SAJDVD Volume 8, Issue 4 by Clinics Cardive Publishing

THE SOUTH AFRICAN JOURNAL OF

Diabetes Vascular Disease OBESITY

LIPIDAEMIA DYS

IN RESISTANCE INSUL

HYPERTENSION

ETES & DIAB

AR DISEASE

HYPER INSULINAEMIA THROMBOSIS

ERGLYCAE MIA

November 2011

HYP

Volume 8 Number 4

ATH EROSCLEROSIS

CUL

Featured in this issue UN call for action on NCDs Outcomes of lifestyle-modification programmes Diabetes patients under-treated for hypercholesterolaemia New guidelines recommend lower LDL target South African legislation on trans fatty acids Oral health in diabetes

Are you looking at every part of diabetes? You might be missing GLP-1. It’s a natural hormone that helps regulate glucose metabolism. It also slows gastric emptying, promotes satiety, and plays a significant role in beta-cell function.1 Its multiple actions throughout the body are critical in diabetes. Unfortunately, your patients might be missing GLP-1, too. Many people with type 2 diabetes may have impaired GLP-1 secretion and impaired beta-cell response to GLP-1.2,3 This could contribute to the pathogenesis of the disease.1 Looking at the whole problem is the most important part of understanding it. That’s why Novo Nordisk is dedicated to ongoing research and development in the management of diabetes.

Diabetes | A whole new perspective

References: 1. Zander M, et al. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and ß-cell function in type 2 diabetes: a parallel-group study. Lancet. 2002;359:824-830. 2. Toft-Nielsen M-B, et al. Determinants of the Impaired Secretion of Glucagon-Like Peptide-1 in Type 2 Diabetic Patients. J Clin Endocrinol Metab. 2001;86(8):3717-3723. 3. Kjems LL, et al. The Influence of GLP-1 on Glucose-Stimulated Insulin Secretion. Effects on ß-Cell Sensitivity in Type 2 and Nondiabetic Subjects. Diabetes. 2003;52:380-386. Novo Nordisk (Pty) Ltd. Reg. No.: 1959/000833/07. PO Box 783155, Sandton, 2146. Tel: (011) 202 0500 Fax: (011) 807 7989 www.novonordisk.co.za NN/DUO/4244/09/10/VER1

ISSN 1811-6515

THE SOUTH AFRICAN JOURNAL OF HYPE

RINSULINAEMIA

Diabetes & vascular disease VOLUME 8 NUMBER 4 â&#x20AC;˘ NOVEMBER 2011 www.diabetesjournal.co.za

Corresponding Editor Dr L Lombard Netcare, Kuilsrivier Hospital, Cape Town DR F MAHOMED Department of Endocrinology, Greyâ&#x20AC;&#x2122;s Hospital, Pietermaritzburg Consulting Editors PROF J-C MBANYA PROF AJ BRINK National Editorial Board DR A AMOD Centre for Diabetes, Endocrinology and Metabolic Diseases, Life Healthcare, Chatsmed Gardens Hospital, Durban SR K BECKERT Diabetes Nurse, Paarl PROF F BONNICI Emeritus Professor, Faculty of Health Sciences, University of Cape Town and President of Diabetes South Africa

CONTENTS

Editorial

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UN call for action: prevention and control of non-communicable diseases L Lombard

Achieving Best Practice

149

Considering the patient perspective for assessing the outcomes of diabetes lifestyle modification programmes: what should we measure, and how?

PROF R DELPORT Department of Family Medicine, University of Pretoria DR L DISTILLER Director of the Centre of Diabetes and Endocrinology, Houghton, Johannesburg PROF WF MOLLENTZE Head of Department of Internal Medicine, University of the Free State, Bloemfontein PROF CD POTGIETER Specialist Nephrologist, University of Pretoria and Jakaranda Hospital, Pretoria PROF K SLIWA Associate Professor of Medicine and Cardiology, Baragwanath Hospital, University of the Witwatersrand, Johannesburg PROF YK SEEDAT Emeritus Professor of Medicine and Honorary Research Associate, University of Natal, Durban International Editorial Board PROF IW CAMPBELL Physician, Victoria Hospital, Kircaldy, Scotland, UK PROF PJ GRANT Professor of Medicine and head of Academic Unit of Molecular Vascular Medicine, Faculty of Medicine and Health, University of Leeds; honorary consultant physician, United Leeds Teaching Hospitals NHS Trust, UK PROF J-C MBANYA Professor of Endocrinology, Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Cameroon and President, International Diabetes Federation PROF N POULTER Professor of Preventive Cardiovascular Medicine, Imperial College, School of Medicine, London, UK DR H PURCELL Senior Research Fellow in Cardiology, Royal Brompton National Heart and Lung Hospital, London, UK

CD Barbosa, B Arnould, JB Gruenberger, PEH Schwarz

Reports

155

South African patients with diabetes are under-treated for hypercholesterolaemia: Survey of in-treatment hypercholesterolaemia highlights the need for intensified treatment in diabetes J Aalbers

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New guidelines recommend lower LDL target in high-risk cardiovascular patients P Wagenaar

Nutrition Focus

159

Avoid these fats: Introduction to South African legislation on trans fatty acids

Case Studies

161

Type 2 diabetes patient without CVD, not achieving lipid targets M Kirby

163

Type 2 diabetes patient with muscle aches on statin therapy P Twomey

Assistant Editor: Special Assignments JULIA AALBERS TEL: (021) 976-4378 FAX: 086 610 3395 e-mail: jaalbers@icon.co.za Development Editor: GLENDA HARDY CELL: 071 819 6425 FAX: 086 610 3395 e-mail: glenda@cvja.co.za Production Editor SHAUNA GERMISHUIZEN TEL: (021) 785-7178 FAX: 086 628 1197 e-mail: shaunag@xsinet.co.za Editorial Assistant and Circulation ELSABÉ BURMEISTER TEL/FAX: (021) 976-8129 e-mail: elsabe@cvja.co.za Production Co-ordinator WENDY WEGENER TEL: (021) 976-4378 e-mail: wendy.icon@wol.co.za

Patient Leaflet

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Taking control of your cholesterol levels

Diabetes Educator’s Focus

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Oral health in diabetes G Hardy

Diabetes Personality

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‘Walking the walk’ to a greater understanding of diabetes

Journal Update

171

Southern African contributions G Hardy

Report

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Controversies at ESC 2011: Dietary approaches for lipid assessment

EASD Watch

178

2011 Update from Lisbon, Portugal

Diabetes News

THE EDITOR PO BOX 1013 DURBANVILLE 7551 or info@cvja.co.za

186

New stem cell cryopreservation laboratory in Cape Town

187

Getting together: a diabetes camp in Stellenbosch

TEL/FAX: (021) 976-8129 INT: 2721 976-8129

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Celebrating World Diabetes Day

The South African Journal of Diabetes and Vascular Disease is published four times a year for Clinics-Cardive Publishing Co. and printed by Tandym Print. Articles in this Journal are sourced as per agreement with the British Journal of Diabetes and Vascular Disease

All correspondence to be directed to:

The opinions, data and statements that appear in any articles published in this journal are those of the contributors. The publisher, editors and members of the editorial board do not necessarily share the views expressed herein. Although every effort is made to ensure accuracy and avoid mistakes, no liability on the part of the publisher, editors, the editorial board or their agents or employees is accepted for the consequences of any inaccurate or misleading information.

SA JOURNAL OF DIABETES & VASCULAR DISEASE

EDITORIAL

UN call for action: prevention and control of non-communicable diseases LANDI LOMBARD

orldwide, non-communicable diseases (NCDs) are currently responsible for more deaths than all other causes combined. Traditionally, high-income populations have borne the burden of NCDs. However, current evidence indicates that the spread of disease is associated with increasing levels of economic development. Low- and middle-income countries now bear a greater burden of NCDs than high-income countries. In Africa, NCDs are projected by 2020 to cause almost three-quarters as many deaths as communicable, maternal– perinatal and nutritional diseases combined. Currently, over 80% of cardiovascular- and diabetes-related deaths occur in low- and middle-income countries. NCDs worsen poverty, while poverty results in rising rates of such diseases. Strong evidence links poverty, lack of education and other social inequities to NCDs and their risk factors. Lower levels of education and residence in urban areas are associated with an increased risk of diabetes. Physical inactivity, daily smoking and regular alcohol consumption are more prevalent in those with the least education. Female blue-collar workers have the highest incidence of the metabolic syndrome, as well as higher rates of obesity. NCDs create serious socio-economic consequences by increasing individual and household impoverishment. Paying for care associated with diabetes can cost lowincome households up to a third of their incomes. Catastrophic hospitalisation expenditures are higher with NCDs compared with communicable diseases. In developing countries, the lack of healthcare capacity and dearth of social protection systems means that people with NCDs are more likely to become sick and die at a younger age. At present, the main focus of healthcare for NCDs in many developing countries is hospital centred. In the case of cardiovascular diseases and diabetes, a large proportion of people at high risk remain undiagnosed. When a diagnosis is made, it is often at a late stage of the disease, when the patient is symptomatic and admitted to hospital with acute events or long-term complications and disabilities. Treatment for advanced-stage disease is expensive as high-technology interventions are required. The impact of NCDs can be prevented through primary healthcare measures to treat those who have contracted or are at high risk of contracting such diseases. This issue of the journal focuses on three areas where primary care can make a difference – obesity, lipid management and food choices.

Correspondence to: Dr Landi Lombard Netcare Kuilsrivier Hospital, Cape Town Tel: +27 0(21) 900-6350 e-mail: lclombard@mweb.co.za S Afr J Diabetes Vasc Dis 2011; 8: 147–148

VOLUME 8 NUMBER 4 • NOVEMBER 2011

Landi Lombard

Cholesterol management in South Africa The CEPHEUS study on cholesterol management in diabetes highlights the contribution that primary care can make to reducing cardiovascular events in patients with diabetes. The strength of this study is that it is representative of the public and private sectors, and the diverse communities of South Africa. Primary-care practitioners, after evaluating the effect of the initial lipid-lowering agents prescribed, should up-titrate statins sensibily and use combination therapy in their diabetic patients. The CEPHEUS study confirms what has already been shown in other countries in the world, that healthcare professionals do not treat lipid levels effectively enough and therefore patients are still exposed to higher-than-necessary risk of cardiovascular disease. Healthcare professionals should know the targets and try harder to achieve these set targets in order to save lives.

New lipid guidelines This issue reports on the new South African lipid guidelines announced recently by the South African Heart Association and the Lipid and Atherosclerosis Society of Southern Africa (LASSA). The new guidelines are more complicated than the previous ones and use a three-tier design based on the Framingham risk score. The first tier of patients (target LDL < 1.8 mmol/l), who should be treated the most intensively, includes a wide variety of patients. This will put more pressure on medical aids for funding, especially combination therapy, but could also potentially save lives. Patients at this level of risk should probably be managed by specialists.

Legislation on trans fatty acids in food The worldwide prevalence of obesity has nearly doubled between 1980 and 2008. Growing globalisation and industrialisation is lead-

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ing to increased consumption of processed food, resulting in an upsurge of saturated fat, trans fats, salt and refined sugars in the diet. In an article on new legislation regarding trans fatty acids in food, we read that Government is regulating this by law. The Department of Health is to be congratulated on this legislation which tries to protect the consumer against unsafe foods. The average South African consumer does not read labels or is unsure of what they mean and how to interpret them. Even healthcare professionals often do not know the recommended intake of the different fats. Removal of these unsafe products in foods should therefore be strongly supported. In this issue, we also provide data from the Nutritional Information Centre, University of Stellenbosch (NICUS), which has responded to the new regulations on trans fatty acids with valuable advice for both health educators and patients.

Intervention Strategies Co-ordinated multisectorial partnerships are required to sustainably prevent and manage NCDs. Government needs to prioritise prevention and control strategies and revitalise primary healthcare. The fact that many NCDs are long-term diseases demands a compre-

hensive healthcare system response that brings together a trained workforce with appropriate skills, affordable technologies, reliable supplies of medicines, referral systems and the empowerment of people for self care, all over a sustained period of time. Sustained primary healthcare measures encompassing essential interventions, palliative and long-term care are required. Preventive and healthcare interventions relating to such diseases should be integrated into reproductive, maternal and child health programmes, especially at the primary healthcare level. The private sector should promote healthy behaviour and improve affordability and accessibility to healthy lifestyle choices. Initiatives by the food industry in reformulation of healthier products and in exercising responsible marketing are crucial. Suggested population-wide interventions include promoting public awareness on diet and physical activity. Civil society should support community awareness campaigns. The knowledge and technology to fight the onset and effects on NCDs, particularly type 2 diabetes, already exists. It’s time for action; the moral, social and economic imperative is clear. Source: Report of the Secretary-General, United Nations General Assembly, sixty-sixth session. Item 119 of preliminary list. Prevention and control of non-communicable diseases.

AFRICA 2012

Celebrating African Excellence Celebration de l’excellence Africaine Important dates:

• Abstract submissions by: 15 November 2011 • Early Bird Registration closes: 30 November 2011 Enquiries:

Parents, Professionals & Nurses Invited International Faculty Professor William L. Carroll (USA)

SIOP Congress Office Telephone: + 27 (0) 11 447 3876 Email: events.suemc@tiscali.co.za

Liesl Hartman (SIOP Africa logo design), Wilfred Schrieff (graphics, WJRS Print Enterprises)

21–23 March Woodstock • Cape Town, South Africa

Dr Scott Howard (USA) Dr Mhamed Harif (Morocco) Professor Rolf Dieter Kortmann (Germany)

www.siopafrica2012.co.za

FINAL ANNOUNCEMENT

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Considering the patient perspective for assessing the outcomes of diabetes lifestyle-modification programmes: what should we measure, and how? CARLA DIAS BARBOSA, BENOIT ARNOULD, JEAN BERNARD GRUENBERGER, PETER EH SCHWARZ Abstract

urrent evidence shows that type 2 diabetes can be effectively prevented and delayed by lifestyle modification. After careful development and pilot testing, a rigorous evaluation of such programmes is crucial to assess their effectiveness prior to large-scale implementation. Integrating the patient perspective in this evaluation is essential. In principle, patient-reported outcomes (PRO) questionnaires can address this key question. However, researchers and clinicians lack a clear framework to make a sound selection of appropriate measures among the large set of possible questionnaires. As a consequence, it is unclear what is the most useful information to be captured from patients when assessing a new programme, so that it can be determined whether the programme can be generalised to a larger population: is it health-related quality of life, satisfaction or something different which could predict the long-term success of the programme? We recommend a specific approach, better adapted to the nature of the intervention, and suggest a selection of a few existing PRO measures that could satisfy the requirements. Keywords: diabetes education, lifestyle modification, measurement instruments, patient-reported outcomes, type 2 diabetes

Introduction Type 2 diabetes has reached epidemic proportions throughout the world. In 2010, approximately 285 million people worldwide had diabetes; this number is projected to increase to 438 million by 2030.1 Major prevention studies have shown that diabetes can be effectively delayed or prevented in individuals with impaired glucose tolerance using lifestyle intervention and/or treatment.2-4 We Correspondence to: Carla Dias Barbosa Mapi Values 27, Rue de la Villette 69003 Lyon, France. Tel: +33 (0)4 72 13 66 56; Fax: +33 (0)4 72 13 51 40 e-mail: Carla.Dias@mapivalues.com Benoit Arnould Mapi Values, Lyon, France. Jean Bernard Gruenberger Novartis Pharma AG, Department of Health Economics and Outcomes Research, Basel, Switzerland. Peter EH Schwarz Division of Prevention on Care of Type 2 Diabetes, Department of Internal Medicine III, Medical Faculty of Carl Gustav Carus, Technical University Dresden, Germany. Originally in: Br J Diabetes Vasc Dis 2011; 11: 187–192 S Afr J Diabetes Vasc Dis 2011; 8: 149–153

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Abbreviations and acronyms ADS ATT DES-SF DMSES HbA1C HCP MEI PAID PRO ProQolid

Appraisal of Diabetes Scale Psychological Adjustment to Diabetes Scale Diabetes Empowerment Scale, Short Form Diabetes Management Self-Efficacy Scale glycated haemoglobin healthcare professional Motivation and Energy Inventory problem areas in diabetes patient-reported outcomes Patient-Reported Outcome and Quality of Life Instruments Database

have learned from these studies that sustained changes in lifestyle in terms of physical activity and diet are crucial for successful type 2 diabetes prevention. Despite evidence of their effectiveness, it is questionable whether implementing diabetes prevention programmes is feasible at a population level.5,6 Economic evaluation has demonstrated the cost effectiveness of primary prevention of type 2 diabetes using lifestyle interventions.7 However, effective implementation of diabetes prevention programmes into clinical practice remains challenging and requires significant financial and human resources.6 Rigorous scientific evaluation of the programmes, prior to large-scale implementation, is fundamental for demonstrating programme effectiveness and feasibility, determining whether or not they are cost effective and providing information for improving existing programmes and designing new ones. Lifestyle modification programmes are usually evaluated through randomised controlled trials that compare the effects of the lifestyle programme versus standard diabetes education using objective measures such as HbA1C, weight reduction and exercise measurement. Unfortunately, many of these evaluation studies do not integrate the patient perspective in their measurement; however, this perspective is fundamental to fully understand the benefits of the intervention programme for patients, increase patient engagement in their care and, ultimately, to maintain behaviour change. Incorporating welldesigned PRO instruments is the best way to assess the effect of intervention from a patient perspective.8 However, to be credible measures, PRO instruments have to be developed and validated following a rigorous and standardised process as recommended in recent US Food and Drug Administration guidelines8 and a European Medicines Evaluation Agency reflection paper.9 This paper addresses two questions, firstly what are the relevant outcomes of diabetes lifestyle intervention programmes from a patient perspective, and secondly what are the most appropriate existing PRO instruments to assess these outcomes?

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Assessing diabetes lifestyle programmes from a patient perspective To successfully assess the outcomes of lifestyle intervention programmes from a patient perspective, relevant key patient outcomes most attributable to the programme must first be identified, followed by a critical review of PRO instruments that would best allow their measurement. Key patient outcomes should be identified with careful consideration of the programme-based theory, the programme objectives, the expected outcomes perceptible by patients, and the target population. The identification and selection of PRO instruments should then follow a structured approach: • identification of PRO instruments from a literature review and consultation with experts • development of appraisal criteria from published documents on the development and validation of health status measures10,11 and with expert psychometric advice • critical appraisal of the identified instruments for relevance, content validity and credibility of quantitative and qualitative methods used for its development and validation. The key appraisal criteria are summarised in Table 1.

Question 1: What are the relevant outcomes of diabetes lifestyle programmes from a patient perspective? For diabetes lifestyle-modification programmes based on empirically supported theoretical models such as Prochaska’s transtheoretical model of behaviour change,12 the behavioural change theory should drive the hypotheses to test for programme evaluation. Prochaska and DiClemente suggest that behavioural change occurs in five distinct stages (precontemplation, contemplation, preparation, action and maintenance) and that movement through these stages is a cyclical or spiral process that involves both progress and periodic relapse. The stabilisation of behaviour change and the avoidance of relapse are characteristic of long-term maintenance of lifestyle behaviour change.

Such transtheoretical model-based lifestyle interventions in diabetes aim to: • prepare and motivate patients for taking an active role in changing their lifestyle (preparation phase) • support them in making good choices and positive changes in their lifestyle (action phase) • support them in maintaining behaviour change (maintenance phase). These interventions are generally proposed to patients ready to change their lifestyle (patients in the preparation or action phases). In this context, the key patient-relevant outcomes identified as most predictive of such programme success and sustained behaviour change are psychological adjustment to diabetes, motivation to change and self-efficacy. Psychological adjustment is the mental response of a person to a dreadful life situation. This concept covers the cognitive and behavioural strategies patients may use to deal with and manage their disease.13 A positive change on psychological adjustment to diabetes is expected as a result of lifestyle-modification programmes. Motivation is the psychological feature that stimulates a person to action toward a desired goal. Motivation plays an important role in successful behavioural change12 and is thus identified as a key concept to evaluate the benefit of a lifestyle programme on patients. Self-efficacy is a person’s perception of their ability to plan and take action to reach a particular goal.14 Self-efficacy was identified as a key concept in order to document and monitor patients’ perceptions of their ability to plan and take action to reach their goals, in this case, eating a healthy diet and increasing physical activities.

Question 2: What are the most appropriate PRO instruments to assess lifestyle programmes in type 2 diabetes? PRO instruments were identified using ProQolid and published literature reviews.15,16 The search was supplemented with instruments recommended by clinical and PRO experts.

Table 1. Key appraisal criteria used to evaluate PRO instruments Questionnaire property

Specific criteria

Explanation

Development methods Patient interviews in population

Were exploratory interviews carried out in the patient population during the development of the instrument?

Evidence of comprehension in patient population

Were comprehension tests carried out in the population during the development of the instrument?

Content validity

Specificity of items for measuring concept in targeted population

Do the items ask specific or general questions? Are the items worded in a way that relates to patients’ experience?

Richness of concept coverage

Do all items in the questionnaire together cover the concept of interest?

Ability to detect differences over time

Does the questionnaire appear to be sensitive to changes over time given its wording?

Appropriateness of recall period

Is the recall period suitable for the study design?

Standard credibility

Populations in which used

Is the questionnaire used in the targeted population?

Specific application in which used

Is the questionnaire used in similar programmes?

Psychometric properties

Construct validity

Is there any evidence that the internal structure is consistent?

Reliability: internal consistency

Are the various items of the score non-redundant?

Reliability: test-retest

Do two independent evaluations by the same patient give the same results?

Sensitivity to change: responsiveness

Is the score able to detect changes over time?

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Table 2. Description of patient-reported outcomes instruments (n = 6) Acronym (number of items)

Full name of the questionnaire

ADS Appraisal of Diabetes (n = 7) Scale

Availability of full scale

Languages

Carey et al. Reliability and validity of the appraisal of diabetes scale. J Behav Med 1991;14:43-51 www.musc.edu/dfm/ RCMAR/ADS.html

Original language: US English No translations

Dimensions

One dimension Stressful impact of diabetes

ATT39 Psychological Adjustment Bradley (1994) in Handbook Original language: UK English (n = 39) to Diabetes Scale of Psychology and Diabetes Translations: German, Greek, ATT19 (224-26 and 230-31, Canadian English, French and (n = 19) respectively) Italian

39-item scale. Six dimensions: perceived levels of stress, adaptation, guilt, alienation, illness conviction, and tolerance for ambiguity 19-item scale. One dimension: diabetes integration

PAID Problem Areas in Polonsky et al. Assessment Original language: US English (n = 20) Diabetes scale of diabetes-related distress. Translations: Chinese, Danish, Diabetes Care Dutch, Finnish, German, 1995;18:54-60. Japanese, Portuguese, www.pedsql.org Portuguese for Brazil, Spanish

Four dimensions: diabetesrelated emotional problems, treatment-related problems, food-related problems and social support-related problems

MEI Motivation and Energy Long-form Inventory (n = 27) Short-form (n = 18)

Three dimensions: mental energy, social motivation and physical energy

From author: SE Fehnel, RTI Health Solutions, RTI International, Research Triangle Park, NC 277092194, USA. sfehnel@rti.org

Original language: US English More than 30 translations available

DES-SF Diabetes Empowerment MDRTC, www.med.umich. Original language: US English (n = 8) Scale Short Form edu/mdrtc/ Translations: Chinese, Spanish

Eight dimensions: need for change, developing a plan, overcoming barriers, asking for support, supporting oneself, coping with emotion, motivating oneself, making diabetes care choices appropriate for oneâ&#x20AC;&#x2122;s priorities and circumstances

DMSES Diabetes Management (n = 20) Self Efficacy Scale

Different structure according to language version (three to four dimensions

From author: Dr. Jan McDowell, Queensland University of Technology, Australia. j.mcdowell@qut. edu.au

Of the numerous questionnaires identified, only six instruments were found that addressed psychological adjustment, motivation and self-efficacy and had documented evidence of development methodology and psychometric properties. Three of these assessed indicators of psychological adjustment: the PAID scale,17-19 the ADS20 and the ATT-39/ATT-19.21,22 One measure assessed motivation: the MEI.23 Two measured self-efficacy: the DES-SF24,25 and the DMSES.26-29 These instruments are briefly described in Table 2.

Measures assessing psychological adjustment Of the three measures of psychological adjustment, only the PAID satisfies all criteria. The PAID demonstrates evidence of adequate psychometric testing, responsiveness to change through similar educational intervention19,30-32 and appropriateness to the targeted type 2 diabetes population. In addition, patients were involved in its

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Original language: Dutch Translations: UK English, English for Australia, Turkish and Chinese

development and comprehension testing. The ADS and ATT-39/19 are acceptable tools and meet all except one or two key appraisal criteria. The ADS has interesting content; however, its development did not involve patients and no responsiveness and sensitivity to change data following similar educational interventions are available. The ATT-39 is relatively long (39 items), which can be a burden for patients; it has an item scaling that is often criticised, as respondents are faced with cognitively complex tasks (such as disagree that weight-control is not a problem for them). The ATT-19 is at a relatively early stage of development and more information is needed to assess its sensitivity to detect change in patient psychological adjustment following educational intervention.

Measures assessing motivation The MEI instrument is the only identified instrument that assesses

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Key messages

• Integrating the patient perspective into lifestyle programme evaluation is fundamental to demonstrating the benefits of the programmes for patients. It also provides valuable feedback for HCPs and helps them collaborate with patients to manage diabetes over the course of the disease • Key patient-relevant concepts of greatest interest for lifestyle programme evaluation from a patient perspective are psychological adjustment to diabetes, motivation to change and self-efficacy • Among existing, well-validated instruments, the PAID, MEI and DMSES scales appear to be the instruments of choice to assess the effect of type 2 diabetes lifestyle programmes on patients’ behaviours and perceptions

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our work, the PAID, the MEI and the DMSES questionnaires are the best existing candidates to assess psychological adjustment, motivation to change and self-efficacy, respectively. After evaluation, programmes that have shown beneficial effects at patient level and that have proved to be well designed and cost effective can be generalised and implemented in clinical practice settings. Indeed, setting goals, providing patient education for achieving these goals, and monitoring the patient’s progress using PRO instruments adapted to the context of clinical practice, are critical in clinical practice for maintenance of healthy behaviours, as well as supporting patient adherence and persistence to pharmacological therapies.

References 1.

motivation. It is created to be both responsive to treatment effects and able to discriminate among patients with different clinical characteristics.23 Although the MEI was developed through focus groups and cognitive interviews with individuals being treated for depression, all items are carefully worded to be applicable across various populations, including diabetes patients. The MEI short form, with a recall period of the previous seven days, is expected to be sensitive to behavioural modification programmes and can be used to compare the motivation levels of type 2 diabetic patients over the course of lifestyle intervention programmes.

Measures assessing self-efficacy Two potential candidates to assess self-efficacy were found and meet most of the appraisal criteria: the DES-SF and the DMSES. Although the DES-SF offers comprehensive and coherent coverage of the selfefficacy concept and shows interesting results in educational programme assessment,33-35 the item wording and the item scaling are complex and require considerable cognitive effort from the patients to answer the questions. The DMSES is preferred for its simplicity, although further research on this instrument is warranted to assess its responsiveness over time. This instrument showed a small improvement in confidence in self-care following an educational intervention in primary care in patients with type 2 diabetes.32

Conclusion Health-related quality of life, patient satisfaction, and patient adherence to treatment are important PROs that should improve when using well-designed lifestyle-modification programmes. However, when assessing the effectiveness of a new programme, the primary focus of assessment should be measurable, observable changes at the patient level, which are specific and direct outcomes of the intervention. Psychological adjustment, motivation and self-efficacy are key patient-relevant concepts to consider when evaluating transtheoretical model-based lifestyle interventions in diabetes from a patient perspective. Specific validated instruments exist, which reliably assess these key concepts. Of the instruments identified in

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International Diabetes Federation. Diabetes and Impaired Glucose Tolerance. Global Burden: Prevalence and Projections, 2010 and 2030. www.diabetesatlas. org/content/diabetes-and-impaired-glucosetolerance (last accessed 16 March 2011). Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403. Pan XR, Li GW, Hu YH et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20: 537–44. Tuomilehto J, Lindstrom J, Eriksson JG et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343–50. Ackermann RT, Marrero DG. Adapting the Diabetes Prevention Program lifestyle intervention for delivery in the community: the YMCA model. Diabetes Educ 2007; 33: 69, 74–5, 77–8. Schwarz PE, Schwarz J, Schuppenies A, et al. Development of a diabetes prevention management program for clinical practice. Publ Hlth Rep 2007; 122: 258–63. Hernan WH, Brandle M, Zhang P, et al. Costs associated with the primary prevention of type 2 diabetes mellitus in the diabetes prevention program. Diabetes Care 2003; 26: 36–47. U.S.Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and Radiological Health. Guidance for industry. Patientreported outcome measures: use in medical product development to support labeling claims.www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM193282.pdf (last accessed 21 March 2011). European Medicines Agency. Reflection Paper on the Regulatory Guidance for the Use of Health-Related Quality of Life (HRQL) Measures in the Evaluation of Medicinal Products. Doc.Ref. EMEA/ CHMP/EWP/139391/2004. www.emea. europa.eu/pdfs/human/ewp/13939104en.pdf (last accessed 29 July 2009). Lohr KN. Assessing health status and quality-of-life instruments: attributes and review criteria. Qual Life Res 2002; 11: 193–205. Terwee CB, Bot SD, de Boer MR, et al. Quality criteria were proposed for measurement properties of health status questionnaires. J Clin Epidemiol 2007; 60: 34–42. Prochaska JO, Diclemente CC, Norcross JC. In search of how people change. Applications to addictive behaviors. Am Psychol 1992; 47: 1102–14. Lazarus RS, Folkman S. Stress, Appraisal, and Coping. New York: Springer, 1984. Bandura A. The anatomy of stages of change. Am J Health Promot 1997; 12: 8–10. Duke SA, Colagiuri S, Colagiuri R. Individual patient education for people with type 2 diabetes mellitus. Cochrane Database Syst Rev 2009: CD005268. Eigenmann CA, Colagiuri R, Skinner TC, Trevena L. Are current psychometric tools suitable for measuring outcomes of diabetes education? Diabet Med 2009; 26: 425–36. Polonsky WH, Anderson BJ, Lohrer PA, et al. Assessment of diabetes-related distress. Diabetes Care 1995; 18: 754–60. Welch G, Jacobson AM, Polonsky WH. The Problems Areas in Diabetes Scale. An evaluation of its clinical utility. Diabetes Care 1997; 20: 760. Welch G, Weinger K, Anderson BJ, Polonsky WH. Responsiveness of the Problem Areas In Diabetes (PAID) questionnaire. Diabet Med 2003; 20: 69–72. Carey MP, Jorgensen RS, Weinstock RS. Reliability and validity of the Appraisal of Diabetes Scale. J Behav Med 1991; 14: 43–50.

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21. Dunn SM, Smartt HH, Beeney LJ, Turtle JR. Measurement of emotional adjustment in diabetic patients: validity and reliability of ATT39. Diabetes Care 1986; 9: 480– 489. 22. Welch G, Dunn SM, Beeney LJ. The ATT39: a measure of psychosocial adjustment to diabetes. In: Bradley C (ed). Handbook of Psychology and Diabetes. Amsterdam: Hardwood Academic Publishers, 1984; 223–44. 23. Fehnel SE, Bann CM, Hogue SL, et al. The development and psychometric evaluation of the Motivation and Energy Inventory (MEI). Qual Life Res 2004; 13: 1321–36. 24. Anderson RM, Fitzgerald JT, Funnell MM, Gruppen LD. The third version of the Diabetes Attitude Scale. Diabetes Care 1998; 21: 1403–7. 25. Anderson RM, Funnell MM, Fitzgerald JT, Marrero DG. The Diabetes Empowerment Scale: a measure of psychosocial self-efficacy. Diabetes Care 2000; 23: 739–43. 26. Bijl JV, Poelgeest-Eeltink AV, Shortridge-Baggett L. The psychometric properties of the diabetes management self-efficacy scale for patients with type 2 diabetes mellitus. J Adv Nurs 1999; 30: 352–59. 27. Kara M, van der Bijl JJ, Shortridge-Baggett L et al. Cross-cultural adaptation of the Diabetes Management Self-Efficacy Scale for patients with type 2 diabetes mellitus: scale development. Int J Nurs Stud 2006; 43: 611–21. 28. McDowell J, Courtney M, Edwards H, Shortridge-Baggett L. Validation of the

29.

30.

31.

32. 33.

34.

35.

Australian/English version of the Diabetes Management Self-Efficacy Scale. Int J Nurs Pract 2005; 11: 177–84. Vivienne Wu SF, Courtney M, Edwards H, et al. Development and validation of the Chinese version of the Diabetes Management Self-Efficacy Scale. Int J Nurs Stud 2008; 45: 534–42. Bastiaens H, Sunaert P, Wens J, et al. Supporting diabetes self-management in primary care: pilot-study of a group-based programme focusing on diet and exercise. Prim Care Diabetes 2009; 3: 103–9. Izquierdo RE, Knudson PE, Meyer S, et al. A comparison of diabetes education administered through telemedicine versus in person. Diabetes Care 2003; 26: 1002–7. Sturt JA, Whitlock S, Fox C, et al. Effects of the Diabetes Manual 1:1 structured education in primary care. Diabet Med 2008; 25: 722–31. George JT, Valdovinos AP, Russell, I et al. Clinical effectiveness of a brief educational intervention in Type 1 diabetes: results from the BITES (Brief Intervention in Type 1 diabetes, Education for Self-efficacy) trial. Diabet Med 2008; 25: 1447–53. Lowe J, Linjawi S, Mensch M, et al. Flexible eating and flexible insulin dosing in patients with diabetes: Results of an intensive self-management course. Diabetes Res Clin Pract 2008; 80: 439–43. McCarrier KP, Ralston JD, Hirsch IB, et al. Web-based collaborative care for type 1 diabetes: a pilot randomized trial. Diabetes Technol Ther 2009; 11: 211–17.

OBESITY

LIPIDAEMIA DYS

IN RESISTANCE INSUL

HYPERTENSION

ETES & DIAB

ATH EROSCLEROSIS

CUL

AR DISEASE

HYPER INSULINAEMIA THROMBOSIS

HYP

ERGLYCAE MIA

This peer-reviewed journal is available as full text at all tertiary institutions in South Africa, presenting a great opportunity to submit your good-quality original articles for speedy publication. Recent user research has shown that some 10 000 annual topic searches were done on the SA Journal of Diabetes & Vascular Disease database, which contains seven years of published material.

Call for Articles

The SA Journal of Diabetes & Vascular Disease aims to provide a forum for specialists involved in the care of people with diabetes, to exchange information, promote better management and stimulate research in Africa. This quarterly journal publishes original research and scholarly reviews about prevention and management of diabetes, relating to both general and specific issues. The SA Journal of Diabetes & Vascular Disease invites you to submit your articles online only. Read the Instructions to Authors at www.diabetesjournal.co.za for more information on the journal’s policies and the submission process.

Help your patients love themselves a little more.

CRESTOR® 5 mg is suitable for select patients who need less aggressive lipid lowering1 CRESTOR® is the more effective statin at lowering LDL-C and raising HDL-C2 CRESTOR® 10 mg will get most patients to LDL-C goal1,3 CRESTOR® is well-tolerated and has a favourable benefit-risk profile4,5 S4 CRESTOR® 5 (Tablet) Each CRESTOR® 5 tablet contains 5 mg of rosuvastatin as rosuvastatin calcium. S4 CRESTOR® 10 (Tablet) Each CRESTOR® 10 tablet contains 10 mg of rosuvastatin as rosuvastatin calcium. S4 CRESTOR® 20 (Tablet) Each CRESTOR® 20 tablet contains 20 mg of rosuvastatin as rosuvastatin calcium. S4 CRESTOR® 40 (Tablet) Each CRESTOR® 40 tablet contains 40 mg of rosuvastatin as rosuvastatin calcium. PHARMACOLOGICAL CLASSIFICATION: A. 7.5 Serum-cholesterol reducers INDICATIONS: Primary hypercholesterolaemia, mixed dyslipidaemia and isolated hypertriglyceridaemia (including Fredrickson Type IIa, IIb and IV; and heterozygous familial hypercholesterolaemia) as an adjunct to diet when response to diet and exercise is inadequate. Indicated in patients with homozygous familial hypercholesterolaemia, either alone or as an adjunct to diet and other lipid lowering treatments. CRESTOR® 40 mg should only be considered in patients with severe hypercholesterolaemia and high cardiovascular risk who do not achieve their treatment goal on 20 mg of CRESTOR® or alternative therapy. Specialist supervision is recommended when the 40 mg dose is initiated. REGISTRATION NUMBERS: CRESTOR® 5: 41/7.5/0298, CRESTOR® 10: 36/7.5/0349, CRESTOR® 20: 36/7.5/0350, CRESTOR® 40: 36/7.5/0351. DETAILS OF THE REGISTERED LICENCE HOLDER: AstraZeneca Pharmaceuticals (Pty) Ltd Reg No. 1992/005854/07. No. 5 Leeuwkop Road, Sunninghill, 2157, South Africa. Tel: 011 797 6000. Fax: 011 797 6001. www.astrazeneca.co.za. For full details relating to any information mentioned above please refer to the package insert of CRESTOR® 5 mg, 10 mg, 20 mg and 40 mg. CRESTOR® is a registered trademark of AstraZeneca group. Licensed from Shionogi & Co Ltd, Osaka, Japan. EPI Date: 13/05/2008. Date compiled: March 2011. References: 1. CRESTOR® package insert 2. Jones P, Davidson MH, Stein EA, et al. Comparison of the Efficacy and Safety of Rosuvastatin Versus Atorvastatin, Simvastatin, and Pravastatin Across Doses (STELLAR* Trial). Am J Cardiol 2003;92:152-160. 3. Schuster H, Barter PJ, Stender S, et al. Effects of switching statins on achievement of lipid goals. Measuring Effective Reduction in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study. Am Heart J 2004;147:705-712. 4. Rosenson RS. Statins: can the new generation make an impresssion? Expert Opin Emerg Drugs 2004;9(2):269-279. 5. Shepherd J, Hunninghake DB, Stein EA, et al. Safety of rosuvaststin. Am J Cardiol 2004;94:882-888. 16162

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South African patients with diabetes are under-treated for hypercholesterolaemia Survey of in-treatment hypercholesterolaemia highlights the need for intensified treatment in diabetes J AALBERS

he recently published South African CEPHEUS study has shown that 46% of patients with diabetes who are treated for hypercholesterolaemia do not reach their targets for lowdensity lipoprotein cholesterol (LDL-C).1 This non-interventional study known as CEPHEUS (CEntralised Pan-South African survey on tHE Under-treatment of hypercholeSterolaemia) was conducted between November 2009 and April 2010 in 69 South African study centres and evaluated patients who had received cholesterol-lowering therapy for at least three months. A total of 3 001 patients consented to participate in the survey with only five patients not being entered into the final data set. The study was a single-visit non-interventional study, but also included a doctor and patient questionnaire. The doctor questionnaire was completed prior to patient recruitment. It evaluated the attending doctor’s views on the management of hypercholesterolaemia as seen in his/her patients, and the overall attitude to diagnosis and treatment according to dyslipidaemia guidelines. The patient questionnaire was completed before the investigator assessed the patient. It evaluated the patient’s awareness and perceptions of hypercholesterolaemia, his/her understanding of the lipid-lowering drug (LLD) regimen and compliance with treatment. Table 1. Summary of demographics and patient characteristics at baseline Patient characteristics

Study cohort n = 2 996 (%)

Age (years) 59.4 (11.4) Gender Male 1572 (52.5) Female 1424 (47.5) Ethnic group Caucasian Non-Caucasian Black Mixed ancestry Indian Asian

1385 (46.2) 1611 (53.8) 510 (17.0) 481 (16.1) 576 (19.2) 44 (1.5)

BMI (kg/m2) Waist circumference (cm) SBP (mmHg) DBP (mmHg) Current smoker Diagnosed diabetes Undiagnosed diabetes Diabetes and history of coronary heart disease

30.0 (6.0) 101.0 (14.1) 133.2 (17.7) 80.2 (9.9) 445 (14.9) 1411 (47.1) 71 (2.4) 494 (16.5)

VOLUME 8 NUMBER 4 • NOVEMBER 2011

Table 2. LDL-C goal-achievement targets NCEP ATP III/ 2004 NCEP ATP III

European JEFT IV

South African

Current goal (mmol/l)

< 2.6

< 2.5

Optional goal (mmol/l)

< 1.8

< 2.0

–

< 3.4

< 3.0

Risk category High risk

Medium/low risk Current goal (mmol/l)

Major centres in Johannesburg, Cape Town, Durban and Bloemfontein led the study, with AstraZeneca sponsorship and assistance in the study design. Quintiles, a contract research organisation, provided data management support.

CEPHEUS study methods For each patient, the investigator completed a patient record form, which included information on the patient’s demographics, current LLD treatment and reason for initiating LLD treatment. The investigator also recorded the presence of known cardiovascular risk factors such as smoking, diabetes, family history of premature CHD (defined as definite myocardial infarction or sudden death before 55 years of age in father or other male first-degree relative, or before 65 years of age in mother or other female first-degree relative), arterial hypertension (defined as blood pressure ≥ 140/≥ 90 mmHg or current use of antihypertensive medication) and cardiovascular medical history. Physical examination by the investigator was limited to measurement of height, weight, waist circumference and blood pressure. A fasting blood sample was drawn to evaluate the serum lipid profile [including measurement of apolipoprotein (Apo) AI and Apo B] and glucose levels. It is important to note that this study deliberately attempted to ensure the inclusion of patients of all racial groups, with Caucasians being in the minority (46.2%) (Table 1). The proportion of patients achieving LDL-C target was analysed using target values from multiple guidelines to allow for easy comparison with similar surveys conducted in other countries (Table 2).

Results of lipid-lowering therapy in diabetes patients Only slightly more than half (54.4%) of the diabetes patients reached a target LDL-C of less than 2.5 mmol/l. HbA1c level was also measured in all patients and mean HbA1c in the diabetics was 8.33%, indicating that many diabetics have inadequate glycaemic control. The mean fasting plasma glucose (FPG) in the diabetes

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patients was correspondingly high at 8.16 mmol/l. Only 50% of patients with the metabolic syndrome reached their LDL-C goal of less than 2.5 mmol/l (Table 3). One of the most important lessons for clinical practice from this study is that lipid-lowering therapy was frequently left unaltered, with a total of 63% of patients still on the same agent and dose that they started on. Table 4 lists goal achievement on and the mean dosage according to the statin prescribed. The physician survey showed that most doctors used the South African guidelines. Their failure to treat to target may have been due to additional concerns about drug toxicity, drug formulary constraints, and failure to check lipid levels once LLDs had been started and to titrate LLD dosage when required. Patients showed a good understanding of the need to take their medication, particularly among patients who had had previous cardiovascular events.

Table 3. Patients achieving the LDL-C goals recommended by the guidelines. Patient characteristics

European/South African guidelines n (%)

Overall survey

1557 (52.3)

Age (years) < 40 40–54 55–69 ≥ 70

52 (36.1) 382 (48.5) 822 (54.5) 301 (56.2)

Gender Male Female

854 (54.7) 706 (49.6)

Body mass index (kg/m2) Normal weight (< 25 kg/m2) Overweight (25–29 kg/m2) Obese (≥ 30 kg/m2)

293 (51.3) 584 (54.0) 678 (51.4)

Julia Aalbers, Special Assignments Editor

Coronary heart disease

532 (50.4)

Peripheral artery disease

69 (47.3)

Cerebrovascular atherosclerotic disease

81 (52.3)

Current smoker

213 (48.2)

Diabetes

764 (54.4)

Arterial hypertension

Reference Raal F, Schamroth C, Blom D, Marx J, Rajput M, Haus M, et al. CEPHEUS SA: a South African survey on the under-treatment of hypercholesterolaemia. Cardiovasc J Afr 2011; 22(5): 234–242. Advance published, September 2011.

Key take-home messages

1136 (53.4)

Family history of premature cardiovascular disease

391 (45.3)

Type of prevention Primary prevention Secondary prevention Diabetes mellitus Familial hypercholesterolaemia

• In South Africa, only 50% of diabetes patients reached the target LDL-C of < 2.5 mmol/l.

722 (54.8) 437 (50.6) 364 (54.6) 34 (26.4)

• Lipid levels are often not checked and medication adjusted following the initial prescription.

Metabolic syndrome (Alberti et al. 2009)

1031 (50.9)

• Patients who reported high treatment adherence were more likely to reach target.

Type of therapy Statin monotherapy Fibrates monotherapy Combination therapy

1485 (53.0) 7 (28.0) 53 (43.8)

• Patients in the 55–70-year age range were more likely to reach target than those under 40, likely due to better adherence.

Risk category High risk Medium/low risk

1086 (50.2) 471 (57.9)

• Many diabetics require high-dose statins or combination lipid-lowering therapy to reach LDL-C targets.

Table 4. Patients on statins achieving the LDL-C goals Atorvastatin (n = 866) Mean dosage (mg)

Fluvastatin (n = 10)

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

(n = 4)

(n = 43)

(n = 371)

(n = 1 526)

20.6

44.0

17.5

23.6

14.7

21.7

Controlled LDL-C NCEP* (%)

Controlled LDL-C Eu/SA* (%)

*Chi-square test; p < 0.05

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SPECIAL REPORT

New guidelines recommend lower LDL target in high-risk cardiovascular patients PETER WAGENAAR

he South African Heart Association and the Lipid and Atherosclerosis Society of Southern Africa (LASSA) held their second joint guideline collaboration meeting on 15 and 16 October 2011. The meeting was attended by representatives of both societies, the funding industry and the Department of Health, as well as various medical specialists. With a view to optimising the management of cardiovascular disease in South Africa, both societies adopted the European Society of Cardiology (ESC)/ European Atherosclerosis Society (EAS) dyslipidaemia guidelines published in the European Dr Eric Klug Heart Journal in June 2011.1 These guidelines are now also the official South African guidelines to determine the most effective and appropriate diagnostic tests and treatments for dyslipidaemic cardiovascular disease. ‘However, we will be tailoring certain dietary recommendations to our own ethnic groups. A major difference is that we won’t be using the SCORE risk assessment Table 1. Recommendations for lipid profiling in order to assess total cardiovascular risk Condition

Classa

Levelb

Established cardiovascular disease

Hypertension

Smoking

BMI ≥ 30 kg/m2 or waist circumference > 94 cm (90 cmc) for men, > 80 cm for women

Family history of premature cardiovascular disease

Chronic inflammatory disease

Chronic kidney disease

Family history of familial dyslipidaemia

11b

Lipid profiling is indicated in subjects with: Type 2 diabetes mellitus

Lipid profiling may be considered in men > 40 and women > 50 years of age SA Guideline Committee has added HIV-positive patients on antiretroviral therapy

Class of recommendation; blevel of evidence; cfor Asian males. BMI = body mass index. a

Amended from ESC/EAS guidelines.1

VOLUME 8 NUMBER 4 • NOVEMBER 2011

Table 2. Recommendations for treatment targets for LDL-C Recommendations

Class a

Level b

In patients at VERY HIGH cardiovascular risk (established cardiovascular disease, type 2 diabetes, type 1 diabetes with target-organ damage, moderate to severe CKD or a Framingham score level ≥ 30%) the LDL-C goal is < 1.8 mmol/l and/ or ≥ 50% LDL-C reduction when target level cannot be reached.

In patients at HIGH cardiovascular risk (markedly elevated single risk factor, a Framingham score level ≥ 15 to < 30%) an LDL-C goal < 2.5 mmol/l should be considered.

11a

In subjects at MODERATE cardiovascular risk (Framingham score level ≥ 3% and < 15%) an LDL-C goal < 3.0 mmol/l should be considered.

11a

Low risk (Framingham score level < 3%). a

Class of recommendation; blevel of evidence.

Amended from ESC/EAS guidelines.1

system, which was developed based on European epidemiological data’, said Dr Eric Klug, vice president of the South African Heart Association. ‘Because South Africa has no comparable data, we’ve always used the Framingham system and will be adopting the new Framingham system in future. Women’s risk was underestimated by the old Framingham system, but the new system has addressed that, in addition to taking the risk of younger people into account. They can now be assessed more accurately.’ The key change in the new guidelines is the downward revision of the target LDL cholesterol level in very high-risk patients (> 30% Framingham risk). It has been lowered to 1.8 mmol/l from 2.6 mmol/l. The definition of ‘very high risk’ has also been expanded to include chronic kidney disease (CKD) in addition to diabetes, established vascular disease (including previous stroke or heart attack) and familial hypercholesterolaemia. CKD, defined as a glomerular filtration rate < 60 ml/minute/1.73m2 for a period of more than three months, is now considered a major cardiovascular risk factor in its own right. In addition, the threshold for ‘high risk’ is now defined as > 15% Framingham risk and the LDL target in that group is < 2.5 mmol/l (Tables 1, 2).1 ‘The INTERHEART study, published in the Lancet in 2004,2 and to which Africa contributed 5% of the 30 000 patients involved, showed that the serum HDL:LDL ratio topped the odds ratio charts in predicting future myocardial infarction. It is therefore a major cardiovascular risk factor which, uncontrolled, will lead to a significantly greater burden of disease’, says Dr Klug. ‘Atherosclerotic cardiovascular disease is the global number one killer and the man-

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agement of dyslipidaemia is therefore vital to addressing the epidemic. We and LASSA are committed to engaging meaningfully with patients and re-establishing the central role of the medical profession in its evaluation, diagnosis and management.’ The new guidelines also take into account the implications of HIV/ AIDS for dyslipidaemia in South Africa. HIV/AIDS is associated with abnormal lipid profiles in some patients and certain antiretrovirals

It's the shell that makes safer.

(ARVs) can exacerbate matters. Already, simvastatin cannot be used in patients on protease inhibitors and the US Food and Drug Administration has now issued an official warning applicable to all patients, regardless of HIV status, that the 80-mg dose not be used in future. Stable patients currently taking 80 mg with no adverse muscular effects can be maintained on the dose. However, physicians need to maintain heightened awareness of potential drug interactions when adding any new medications to a patient’s regimen. The SA Heart Association is affiliated to the ESC and Dr MarjaRiitta Taskinen, emeritus professor of medicine at the University of Helsinki and a member of the EAS guideline committee, was present at the local meeting to advise the SA Heart Association and LASSA. ‘It therefore behoves us to follow its guidelines and not change them’, says Dr Klug. The challenge now is to disseminate the new guidelines effectively to the widest possible audience and the associations are looking to embark on a sustainable marketing campaign in this regard. ‘Strategies to achieve this, including how to reach the “non-converted”, were also discussed at the meeting’, concludes Dr Klug. Peter Wagenaar, Gauteng correspondent

References 1. Safety-Coated R

81mg The ORIGINAL low dose aspirin for optimum cardio-protection pH

Each tablet contains Aspirin 81mg. Reg.No.: 29/2.7/0767 Pharmafrica (Pty) Ltd, 33 Hulbert Road, New Centre, Johannesburg 2001 Under licence from Goldshield Pharmaceuticals Ltd. U.K.

Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2011; 32(14): 1769–1818. Published online June 28, 2011. doi: 10.1093/eurheartj/ehr158. Rosengren A, Hawken S, Ounpuu S, Sliwa K, Zubaid M, Almahmeed WA, et al; INTERHEART investigators. Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364(9438): 953–962. PMID: 15364186 [PubMed - indexed for MEDLINE].

International Society of Cardiovascular Disease Epidemiology and Prevention 44th 10-day International Teaching Seminar on Cardiovascular Disease Epidemiology and Prevention 15–27 January 2012 Cape Town, South Africa The International Society of Cardiovascular Disease Epidemiology and Prevention announces the 44th 10-day international teaching seminar on cardiovascular disease epidemiology and prevention to be held 15–27 January 2012 in Cape Town, South Africa in conjunction with the South African Medical Research Council and the University of Cape Town. Approximately 36 Fellows can be accepted. The Society’s seminar committee will make the final selection. Nominees should ideally be at the postgraduate level with residency training or its equivalent, and be interested in cardiovascular disease epidemiology. Normally, preference is given to younger candidates, with little or no formal training in epidemiology. Tuition, board and accommodation are provided without cost to fellows. Fellows and their sponsors are responsible for their own travel costs to the seminar.

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FLUENCY IN ENGLISH IS AN ABSOLUTE ESSENTIAL Should any accepted Fellow be unable to attend, no substitute not reviewed by the seminar committee may be sent as an alternate by the institution. Applications, including (1) a letter of nomination by the chief of department or institution, or other relevant sponsor, (2) a personal letter of application from the nominee, and (3) the applicant’s curriculum vitae, should be received before 15 September 2011 by the seminar coordinator, address below. Applications can be sent by e-mail but a signed hard copy should follow in the post. Professor Kay-Tee Khaw, Clinical Gerontology Unit, PO Box 251, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge CB2 2QQ, England Fax: +44-1223-336928 • Tel: +44-1223-217292 e-mail: kk101@medschl.cam.ac.uk

VOLUME 8 NUMBER 4 • NOVEMBER 2011

SA JOURNAL OF DIABETES & VASCULAR DISEASE

NUTRITION FOCUS

Avoid these fats Introduction to South African legislation on trans fatty acids

n October 2009, the Department of Health started consulting with stakeholders in order to develop legislation aimed at reducing trans fatty acids derived from partial hydrogenation of vegetable oil used in some foods sold in South Africa. In February 2011, the Foodstuffs, Cosmetic and Disinfectants act of 1972 (act 54 of 1972), as printed in the Government Gazette on 1 March 2010, was amended to include regulations related to trans fats in foodstuffs. On 12 September 2011, Health Minster Dr Aaron Motsoaledi stated at a summit in Boksburg on non-communicable diseases, that the amounts of artificial trans fatty acids found in food should be limited according to legislation. In a written reply to a parliamentary question regarding the new regulations, it was stated that ‘these regulations prohibit the sale, manufacturing and importation of any oils and fats containing partial hydrogenated fats and oils, also referred to as “trans-fats”, in processed foods [with] two grams per 100 g thereof’. Food companies that produce products containing more than the allowed amount of trans fatty acids as stipulated will either have to remove these products from the market, or alter the manufacturing methods and ingredients to comply with the new regulations. The Nutrition Information Centre of the University of Stellenbosch (NICUS) supports the actions of the Department of Health to regulate the trans fatty acid levels of foods to follow in the footsteps of countries such as Denmark and the USA who have already implemented trans fatty acid regulations. The reduction of trans fatty acids in foods will reduce the risk of chronic diseases of lifestyle associated with trans fatty acids. The latest changes in the Foodstuffs, Cosmetic and Disinfectants act of 1972 (act 54 of 1972) creates an opportunity for the Department of Health to assume a central role in implementing regulatory measures that would reduce the intake of artificial trans fatty acids. However, consumers should still make informed choices when choosing foods for themselves and their families, by reading food

labels. A healthy diet, that includes foods low in fat and trans fatty acids, should be a priority for all South Africans in order to reduce health risks and increase quality of life.

What are trans fatty acids? Fats found in food can be classified as saturated, mono- and polyunsaturated fatty acids. Saturated fats are derived mostly from animal products and the unsaturated fats are plant based. Trans fatty acids (TFA) occur naturally in products of animal origin, although to a limited extent. TFA are present in ruminant meat (beef) and milk fats as a result of bio-hydrogenation of unsaturated fatty acids in the rumen. The major trans fatty acid in ruminant meat and milk is vaccenic, with smaller amounts of other trans fatty acids. Processing of vegetable oils such as sunflower oil changes the unsaturated fatty acids into trans fatty acids. This processing is called hydrogenation. Through the process of hydrogenation, previously unsaturated fats become partially or completely saturated. These hydrogenated fats do not occur naturally in food, and are therefore artificial.

Why are there trans fatty acids in food? Products such as cakes, commercial cookies, chips, pies, doughnuts, fried chicken and fish nuggets as well as savoury snack foods such as popcorn, crisps and crackers are made with partially hydrogenated vegetable oils. Traditional vegetable shortening or brick margarine contains trans fatty acids that are formed during production and are therefore artificial trans fatty acids. Trans fatty acids are used by the food industry as they have a higher melting point, which makes them more attractive for baking, and the saturation of these fats extends the shelf life of Table 1. Recommended amounts of fatty acids in the diet.

Dietary factor

South African goal (% of total energy, unless otherwise stated)

Total fat

Up to 30% of energy intake

Saturated fatty acids (SFAs)

< 10% of energy < 7% for those at risk of cardiovascular disease

Polyunsaturated fatty acids (PUFAs)

6–10%

n-6 polyunsaturated fatty acids (PUFAs)

5–8%

n-3 polyunsaturated fatty acids (PUFAs)

1–2%

Trans fatty acids

< 1% By difference*

Mono-unsaturated fatty acids (MUFAs)

Healthy fats

VOLUME 8 NUMBER 4 • NOVEMBER 2011

*MUFA = total fat – (SFA + PUFA + TFAs). Therefore, the MUFA intake resulting may cover a wide range depending on the total fat intake and dietary fatty acid pattern.

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per day. She can therefore consume a maximum of 2.3 g trans fatty acids per day.

How can you reduce the amounts of trans fatty acids in your diet?

Unhealthy fats

baked products. Pressure from health authorities and consumers to decrease the amounts of saturated fats in foods prompted the food industry to replace some of the saturated fats with a stable form of unsaturated fats, resulting in an increase of trans fatty acids in foods.

Reducing total fat intake is important and will in effect reduce your trans fatty acid intake. Opt for liquid vegetable oils such as canola, olive and sunflower oils instead of animal fat such as lard, ghee and butter. Choose soft margarines that are sold in tubs over butter, brick margarine and baking shortening. Soft margarines are high in polyunsaturated fatty acids and typically contain no or very low levels of TFA. Read product labels and choose products free or virtually free (≤ 0.1 g per 100 g) of trans fatty acids. Limit your intake of snacks and confectionary products. Be aware of the term ‘partially hydrogenated vegetable oil’ on ingredients lists of food products and avoid those foods (this refers to trans fatty acids) (Fig. 1).

Nutrition Facts Serving size 1 cup (200 g) Amount per serving Calories 260

Why do we need to reduce the amount of trans fatty acids in our diets?

Trans fatty acids are not essential and have no proven health benefits. A large consumption of trans fatty acids leads to increased weight gain. The overweight or obesity associated with trans fatty acid consumption, as well as the actual intake of trans fatty acids lead to an increase in low-density lipoprotein (LDL) (bad) cholesterol and a decrease in high-density lipoprotein (HDL) (good) cholesterol. Higher LDL cholesterol and decreased HDL cholesterol is a major risk factor for chronic diseases of lifestyle such as heart disease, the metabolic syndrome and diabetes mellitus. The most recent South African demographic and health survey from 2003 showed that the self-reported prevalence of heart disease was 2.7% for men and 4% for women; 2.6% of men reported having diabetes, while the prevalence was reported as 3.9% in women. Elevated levels of serum trans fatty acids have been associated with increased risk of breast and prostate cancer.

Saturated fat 3 g

+ Trans fat 2 g

How much fat can you consume daily? Recent evidence indicates that diets with adequate energy, providing less than 30% of energy from fat, are sufficient to promote normal growth and normal sexual maturation but protect against chronic diseases of lifestyle. Most of the fat in the diet should come from foods that are sources of poly- and/or mono-unsaturated fatty acids such as fish, nuts and vegetable oils, with less fat that is derived from animal products, processed foods and snacks (Table 1).

How much trans fatty acids can you safely consume? According to goals set out for South Africans, trans fatty acids should make up no more than 1% of one’s total daily energy intake. For example, a moderately active 30-year-old woman, 1.65 m tall with a healthy body weight of 61 kg, requires 8 828 kJ

160

Fat 13g

Cholesterol 30 mg

% Daily value 20% 25% 10%

Sodium 660 mg

28%

Carbohydrate 31 g

10%

Fiber 0 g

Sugars 5 g

Protein 5 g Vitamin A 4%

Vitamin C 2%

Fig. 1. Food labels give the breakdown of carbohydrates, fats and proteins in the food.

Conclusion Trans fatty acids occur naturally in some foods, but the majority of trans fatty acids consumed come from foods that are baked, fried or prepared with hydrogenated fats. Trans fatty acids are not essential and a high intake is dangerous to our health. Consumers should read food labels when purchasing food for themselves and their families, and look out for the term ‘partially hydrogenated vegetable oil’ in the ingredients list, as this shows that the product contains trans fatty acids. Choose products that are free or virtually free (≤ 0.1 g per 100 g) of trans fatty acids. A healthy diet that includes foods low in fat and trans fatty acids should be a priority for all South Africans in order to reduce health risks and increase quality of life. For further personalised and more detailed information, please contact NICUS or your specialist. Source: Selected extraction from Facts about trans fatty acids, the NICUS 2011. Available at www.sun.ac.za/nicus.

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Case Study 1 Type 2 diabetes patient without CVD, not achieving lipid targets Presented by Prof Michael Kirby Visiting Professor, Faculty of Health and Human Sciences, Centre for Research in Primary and Community Care and the Clinical Trials Coordinating Centre, University of Hertfordshire, Hatfield, UK Originally in: Prim Care Cardiovasc J 2010; 3(1): S6–S7 doi: 10.3132/pccj.2010.010 S Afr J Diabetes Vasc Dis 2011; 8: 161–162

linical studies suggest that people with type 2 diabetes without cardiovascular disease (CVD) are at the same high risk of a CVD event as those without diabetes but with CVD, although whether this risk is equivalent is disputed by other studies. Despite this, there is clear consensus that individuals with type 2 diabetes should nearly always be considered as being in the high CVD risk category. This excess risk is independently associated with hyperglycaemia together with high blood pressure and dyslipidaemia – typically low HDL cholesterol and elevated triglycerides – which are all components of the metabolic syndrome that is common in these patients. It is important, therefore, that type 2 diabetes patients achieve guideline lipid targets (4 mmol/l for total cholesterol and 1.8 mmol/l for LDL cholesterol) to reduce their risk of CVD events. The management of type 2 diabetes patients with co-existent metabolic syndrome such as James (see Box 1: James, type 2 diabetes for six years

Key points • Patients with type 2 diabetes without CVD should be managed as for secondary prevention patients • Intensive LDL cholesterol lowering should be considered if there is evidence of reduced renal function; concordance may be an issue if targets are not achieved • Lifestyle changes should be encouraged • Add-on treatment with a fibrate will improve mixed dyslipidaemia, i.e. elevated triglycerides and low HDL cholesterol, common in these patients

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• 62-year-old smoker (15 cigarettes/day), shift-worker • Obese (94 kg and BMI 30 kg/m2) • High blood pressure (148/88 mmHg) • Total cholesterol 5.4 mmol/l, HDL cholesterol 0.90 mmol/l, LDL cholesterol 3.27 mmol/l, triglycerides 2.7 mmol/l • HbA1c 7.4% • Moderately reduced renal function (eGFR 50 ml/ min/1.73 m2) • Taking simvastatin 40 mg, aspirin 75 mg, metformin 2 g, enalapril 5 mg daily • UKPDS risk engine: 10-year risk of CHD 40.6%, fatal CHD 26.4%, stroke 15.2% and fatal stroke 2.5%

Box 1) who do not follow lifestyle advice often poses a clinical dilemma for physicians. Possible treatment options for James are summarised in Table 1 and discussed below. CLINICAL OPTIONS According to South African guidelines (see page 155), people with type 2 diabetes considered at high cardiovascular risk should be managed as for secondary rather than primary prevention of CVD, aiming to achieve targets of 4 mmol/l for total cholesterol and 1.8 mmol/l for LDL cholesterol, consistent with the JBS2 guidelines. In patients who fail to achieve these targets, a number of options are recommended (see Table 1). Intensification of cholesterol-lowering therapy (preferably with a more effective statin) is recomTable 1. Expert recommendations for cholesterol management • Switch to a more effective statin; atorvastatin has a stronger evidence base than other higher-intensity statins • To manage his non-LDL lipids, advise James to exercise more, lose weight and eat a healthier, more balanced diet. Adding fenofibrate to statin therapy is an option • Emphasise the importance of adherence to treatment

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mended in patients with evidence of reduced renal function, as is the case for James. To manage his elevated triglyceride levels (2.7 mmol/l, despite statin therapy), James should be encouraged to lose weight and eat a healthier, more balanced diet, as recommended by guidelines. He should increase his intake of high-fibre, low-glycaemic index sources of carbohydrate, low-fat dairy products and oily fish, and limit foods containing saturated and trans fatty acids. His elevated triglyceride levels might also be managed by adding fenofibrate to statin therapy. Encouraging lifestyle change is also important. In accordance with NICE Public Health Intervention Guidance, James should be advised to quit smoking, and offered a referral to an intensive support service. If he is unwilling to accept this, he could be offered pharmacotherapy. EXPERT CONSENSUS It is important that James achieves the lipid targets recommended in guidelines in order to reduce his cardiovascular risk. Given his irregular working hours and unhealthy lifestyle, his compliance with treatment should be checked first as a possible reason for failure. If compliance is an issue, this should be discussed with James. The use of a statin with a longer half-life, such as rosuvastatin or atorvastatin, may be preferable. These higher-intensity, longer half-life statins also provide additional LDL cholesterol-lowering efficacy compared to simvastatin 40 mg. James also presents with the mixed dyslipidaemic profile – elevated triglycerides and low HDL cholesterol – typical of type 2 diabetes, which persists despite statin therapy. Addition of fenofibrate to his statin might be considered to manage his non-LDL lipids, based on guideline recommendations and clinical evidence. Nicotinic acid can have an advantageous effect on serum HDL cholesterol in addition to other lipids, but would not be recommended for James because of possible negative effects on his blood glucose control. The target blood pressure for James should be < 130/80 mmHg given that his eGFR is < 60 ml/min/1.73 m2. With his irregular working hours, his antihypertensive medication should be changed to a once-daily ACE inhibitor or ARB. Ramipril use is supported by findings from the Heart

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Outcomes Prevention Evaluation (HOPE) study, which showed significant reduction in CVD events and the MICRO-HOPE sub-study, which showed reduction in overt nephropathy. Dosage should be titrated to 10 mg daily as used in the HOPE study, with urea and electrolytes being checked after each increase in dose. Lifestyle advice is extremely important in this patient, and he should be actively encouraged to improve his lipid, blood pressure and glycaemic control. Take-home messages: type 2 diabetes patient not achieving lipid targets • Consider the possibility of poor compliance, especially if the patient is not following lifestyle advice. Emphasise the importance of concordance with therapy • Improve lipid control by switching to a longer-acting, higher-intensity statin; consider adding fenofibrate for management of mixed dyslipidaemia • Emphasise the importance of lifestyle intervention

KEY GUIDANCE AND TRIALS • NICE gives specific guidance in type 2 diabetes: CG 87 (an update of CG66), May 2009. http://www.nice.org.uk/CG87 and http://www. nice.org.uk/CG66 • For information on smoking cessation, refer to NICE – Brief Interventions and referral for smoking cessation in primary care and other settings. http://www.nice.org.uk/nicemedia/pdf/PH001_smoking_ cessation.pdf and NICE Public Health Guidance 10. Smoking cessation services. http://guidance.nice.org.uk/PH10/NiceGuidance/pdf/ English • The HOPE Study (Heart Outcomes Prevention Evaluation Study) showed that ramipril significantly reduced the risk of the primary composite cardiovascular outcome (MI, stroke and cardiovascular death) by 25% (95% CI: 12–36, p = 0.0004). The MICRO-HOPE substudy also showed reduction in overt nephropathy by 24% (95% CI: 3–40, p = 0.027). Treatment was well tolerated and most patients continued on the 10-mg dose.

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Case Study 2 Type 2 diabetes patient with muscle aches on statin therapy Presented by Dr Patrick Twomey Consultant Chemical Pathologist (with a special interest in lipidology), Ipswich Hospital, UK Originally in: Prim Care Cardiovasc J 2010; 3(1): S8–S10 doi: 10.3132/pccj.2010.012 S Afr J Diabetes Vasc Dis 2011; 8: 163–164

Key points • All statins can cause muscle symptoms such as pain, tenderness or weakness, with or without elevation in creatine kinase levels • Hydrophilic statins, such as rosuvastatin or pravastatin, may be less likely to cause muscle symptoms • Ezetimibe, either alone or as add-on to low-dose statin therapy, or nicotinic acid, are options if symptoms persist in the wellcontrolled patient

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tatin intolerance is defined as the presence of clinically significant adverse effects associated with statin therapy that are considered to represent an unacceptable risk to the patient or that may result in compliance being compromised. All statins can cause myositis: muscle symptoms such as pain, tenderness, or weakness accompanied by creatine kinase (CK) levels > 10 times the upper limit of the normal reference range. Statins have also been implicated in the development of myalgia: muscle aches and pains not associated with any significant elevation in CK levels. Box 1: Rose, type 2 diabetes for 10 years • 56-year-old, healthy weight (70 kg, BMI 25 kg/m2) • Good control of glycaemia (HbA1c 6.6%) and blood pressure (132/82 mmHg) • Total cholesterol 5.0 mmol/l, HDL cholesterol 1.30 mmol/l, LDL cholesterol 2.88 mmol/l, triglycerides 1.8 mmol/l • Taking simvastatin 40 mg, aspirin 75 mg, metformin 1.5 mg daily • Complains of generalised aches and pains, particularly when exercising • CK, thyroid function and liver function tests within normal limits; eGFR 55 ml/min/1.73 m2 • UKPDS risk engine: 10-year risk of CHD 7.5%, fatal CHD 4.4%, stroke 3.8% and fatal stroke 0.5%

A patient with type 2 diabetes suffering unexplained muscle aches and pains might consider discontinuing statin treatment, but the well-established evidence base supporting statin therapy for CVD prevention underlines the importance of continuing with LDL-lowering therapy. Managing these patients, such as Rose (see Box 1), poses a dilemma to the physician. Possible treatment options are summarised in Table 1 and discussed below. CLINICAL OPTIONS There are a number of factors to be considered in the management of Rose. Her cholesterol treatment targets should be 4.0 mmol/l for total cholesterol and 2.0 mmol/l for LDL cholesterol, based on the JBS 2 and NICE guidance. However, her reported generalTable 1. Expert recommendations for cholesterol management for Rose If symptoms resolve after discontinuing statin therapy: • Switch to a hydrophilic statin (e.g. rosuvastatin or pravastatin) less likely to cause muscle pain • Re-introduce simvastatin at 10 mg and slowly uptitrate to the optimal dose that does not cause muscle symptoms • Add on ezetimibe to low-dose statin therapy • If symptoms persist, consider ezetimibe monotherapy

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ised muscle aches and pains should first be investigated for possible statin intolerance, as this may influence her treatment options. In this case, measurement of CK and thyroid function in the context of muscle pain, as well as liver-function tests, were all within the normal reference range. She was advised to discontinue statin therapy for one month to investigate whether her muscle aches resolved. After checking for statin intolerance, there are three options for her management (Table 1). South African guidelines recommend statin therapy for CVD prevention in patients with type 2 diabetes, so it is important to continue treatment. (See South African lipid guidelines on page 155.) Switching to a hydrophilic statin such as rosuvastatin or pravastatin may be less likely to cause muscle pain compared to a lipophilic statin. In one study, nearly two-thirds of patients who were intolerant to a particular statin were able to tolerate an alternative statin without side effects. Alternatively, simvastatin could be re-introduced at a lower dose (10 mg) and slowly up-titrated to the optimal dose that does not cause muscle symptoms. Titration to target LDL cholesterol levels could also be achieved by adding ezetimibe to low-dose statin therapy, in accordance with European Society of Cardiology (ESC) guidance. If muscle symptoms persist, ezetimibe monotherapy could be considered and the patient referred for ankle-brachial pressure tests for possible peripheral arterial disease. Glycaemic control, blood pressure and BMI are all good in this patient, suggesting that she is following lifestyle advice appropriately. She is being treated with low-dose aspirin, based on guideline recommendations for treatment in patients with type 2 diabetes aged over 50 years and with blood pressure below 145/90 mmHg. However, it is also important to consider whether the risks associated with aspirin therapy are justified in this patient, given that her 10-year estimated CHD risk is 7.5% and her 10-year risk for stroke is 3.8%. EXPERT CONSENSUS A well-established body of evidence supports the benefits of CVD prevention including LDL cholesterol lowering with a statin in patients with type 2 diabetes. However, this case of possible statin intolerance highlights the need to consider non-statin options for lipid management. Discussing treatment options with the patient to help her to make informed decisions about her therapy is clearly important, as highlighted by South African guidelines. This should involve discussion of the risks and benefits of the various treatment options, as well as the importance of concordance in achieving recommended LDL cholesterol targets and preventing CVD events, including stroke. The importance of adherence to a healthy lifestyle, as already adopted by this patient, in CVD prevention should also be re-emphasised, supported by evidence from the STENO-2 study. If, as in this case, the patient has a low risk score, this information should be communicated carefully to avoid any misperception by the patient that she does not need cholesterol-lowering medication.

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If muscle symptoms return after re-introducing a statin and are likely to influence patient compliance, non-statin treatment options should be considered. In this patient, these would involve a choice between ezetimibe, or a nicotinic acid formulation – ideally one with reduced flushing potential (i.e. in combination with laropiprant, an anti-flushing agent). Although no general recommendations for the use of nicotinic acid in type 2 diabetes patients are given in recent guidelines, this treatment may be considered for Rose as she has good glycaemic control. Nicotinic acid medicinal products have been associated with increases in fasting blood glucose levels, so the patient should be monitored closely, with adjustment of diet and/or hypoglycaemic therapy as necessary. A fibrate is not indicated as a non-statin alternative in this patient because her triglyceride levels are not sufficiently elevated (~1.8 mmol/l). After discussing the risks and benefits of nicotinic acid, the patient might prefer re-introduction of a low dose of statin with add-on ezetimibe therapy for improved LDL cholesterol-lowering efficacy. This approach, which is recommended, may represent the preferred option in this patient. Finally, from a practical viewpoint, the physician should be aware of the risk of relying on ‘normal’ results, especially given the lack of standardisation in measurement of liver function tests across different laboratories. Any elevation in CK needs to be considered in the context of the patient’s usual activities, which in this case include regular exercise. This underscores the need for measurement of CK before starting lipidmodifying treatment to obtain appropriate baseline levels. Take-home messages: type 2 diabetes patient with muscle aches on a statin • Investigate for possible statin intolerance • Consider switching to a hydrophilic statin or add on ezetimibe to low-dose statin therapy • If symptoms persist, consider non-statin options

SUMMING UP: TAKE-HOME MESSAGES • Lowering cholesterol to recommended targets (4 mmol/l for total cholesterol and 1.8 mmol/l LDL cholesterol) is essential in high-risk patients, including in secondary prevention cases, prior CABG, and primary prevention in most type 2 diabetes patients • Treatment options should be discussed with the patient, taking into account informed preference, co-morbidities, multiple drug therapy and the benefits and risks of treatment. The importance of concordance with therapy and lifestyle management should be emphasised • Switching to higher-intensity statins is preferable to up-titrating simvastatin dosage to optimise LDL-lowering efficacy and tolerability. Add-on ezetimibe is an option if targets are not achieved • Where there is evidence of possible statin intolerance, ezetimibe may be a useful non-statin option.

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Patient information leaflet

S Afr J Diabetes Vasc Dis 2011: 8: 165–166.

Keep and Copy Series TAKING CONTROL OF YOUR CHOLESTEROL LEVELS

he first time your doctor/clinic sister tells you that you have high cholesterol levels, it can come as quite a shock, particularly if you are otherwise healthy. Raised cholesterol levels result in a greater risk of heart disease and you will want to avoid this severe complication and hazard to life. High cholesterol can occur for a number of reasons. Eating foods high in saturated fats, exercising too little, being overweight or obese, smoking and regularly drinking too much alcohol are all lifestyle factors that can cause raised cholesterol. Some medical conditions are also known to cause high cholesterol. These include diabetes, hypertension, liver or kidney disease and an under-active thyroid gland. These are all treatable conditions. Medicines prescribed for other reasons may also result in high cholesterol as a side effect. Some of these are birth-control pills, beta-blockers, some diuretics and some antidepressants. Risk factors for raised cholesterol levels that cannot be treated include a family history of coronary heart disease, stroke, hypercholesterolaemia or hyperlipidaemia. Men have a greater chance of having higher blood cholesterol levels than women. Aging and experiencing an early menopause also increase the risk. Some ethnic groups may be more susceptible to high cholesterol levels than others. SO WHAT CAN YOU DO TO IMPROVE THE SITUATION? The first important aspect is to realise that by changing your lifestyle, losing weight, exercising and using natural remedies such as plant stenols (special margarines and natural over-the-counter products

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such as Phytocor), you can lower your total cholesterol level by some 2–3%. This may be enough, and for most of us, this is a better solution than taking medication! So, try this approach for the first three months. Then visit your doctor/sister again and ask that he/she redo your lipid test using the same test as before. Since lifestyle factors are just one of the reasons for high cholesterol levels, sometimes changing your lifestyle is not enough to lower these levels. If your cholesterol levels are still raised, the doctor will explain that medication is essential. You then need to say: ‘Tell me what my lipid levels are’. These include total cholesterol, low-density lipoprotein cholesterol (LDL-C); high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). The general idea is that your total cholesterol must be below 5 mmol/l, the LDL-cholesterol below 2.5 mmol/l, the HDL-C (the good cholesterol) at or above 1 mmol/l and the triglycerides below 2 mmol/l. If you have had a heart attack, stroke or have diabetes, your doctor might want to go even lower on your LDL-C and triglycerides. Make sure he/she explains why he/she wants to do this. The medication he/she prescribes will consist of one or more drugs. Most commonly the first medicine will be a statin but it may also be drugs that interfere with cholesterol uptake, such as ezetimibe or a fibrate. You may even be given one tablet that combines two different classes of drugs. STATIN THERAPY The dose of statin (a drug that blocks the enzymatic production of cholesterol in the body) prescribed by your doctor will depend on your cholesterol

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level. Generally, your doctor will start on a lower dose of statin, called simvastatin (10/20 mg), raising it to 40 mg if needed. He/she will not prescribe an 80-mg dose of simvastatin as this has been shown to be at a disadvantage to newer statins such as atorvastatin and rosuvastatin (the newest and most powerful statin available). HOW WILL I KNOW IT IS WORKING? Studies have shown that statins reduce the risk of heart attacks and strokes. For this reason, there is no need to have a routine blood test to check your lipid levels once your doctor is satisfied that your cholesterol levels are at the target level you and he/she have set. However, your liver function will be tested at three and 12 months to ensure that the drug is suiting you, and your lipid profile will be checked annually. HOW LONG SHOULD I TAKE IT FOR? Your cholesterol level will be lowered by taking the tablets. If you stop taking them, it will rise again. For this reason, we advise that you keep taking the tablets as long as possible, and ideally, for life. One exception may be if you make significant changes to your diet or lose a lot of weight. Substantial lifestyle changes may keep on lowering your cholesterol level without you continuing to take the medication, but don’t make any changes to your lifestyle or medication without speaking to your doctor/clinic sister first. WHAT COMMON SIDE EFFECTS MIGHT I EXPECT? Side effects from statins are surprisingly rare. However, all drugs have

It's the shell that makes safer.

Safety-Coated R

81mg The ORIGINAL low dose aspirin for optimum cardio-protection pH

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Each tablet contains Aspirin 81mg. Reg.No.: 29/2.7/0767 Pharmafrica (Pty) Ltd, 33 Hulbert Road, New Centre, Johannesburg 2001 Under licence from Goldshield Pharmaceuticals Ltd. U.K.

side effects. Even ‘dummy’ pills used in medical trials have been shown to cause side effects in some people, so it is not always the tablet that is to blame. With statins, rare side effects include muscle or joint pains, lack of energy, constipation and indigestion and you should let your doctor, nurse or pharmacist know if these occur. It is important to remember, however, that the likely benefits from statins are greater than the risks, certainly for the majority of people. WHAT IF I TAKE OTHER MEDICINES? It is important to check whether statins interact with any other medicines the doctor has prescribed, or with over-the-counter drugs or supplements. These include herbal and ‘home’ remedies. WHAT IF I DECIDE THAT I DO NOT WANT TO TAKE THESE PILLS? Your doctor or nurse will have advised you to take these tablets because you are likely to benefit from reducing your risk of a heart attack or stroke. High cholesterol does not make you feel unwell so it can sometimes be difficult to understand why you should take a tablet for the rest of your life. Nonetheless, it is worth remembering that large medical trials have proven the benefit of these pills in reducing the risk of heart attack or stroke. EZETIMIBE Ezetimibe is a drug that inhibits absorption of cholesterol by the small intestine. In South Africa, this medicine is often used in a single-tablet combination with simvastatin. The advantage of this statin/ezetimibe single pill is that it is associated with fewer side effects than the equivalent statin-based cholesterol-lowering dosage. For some patients who experience muscle pains on statins, this combination is very useful. FIBRATES (FENOFIBRATE) Fibrates, particularly fenofibrate, are added to statin therapy when cholesterol targets are not reached, but mainly to lower triglyceride levels. While there is more than one fibrate formulation available in South Africa, the cardiovascular and microvascular protection of fenofibrate has led to an evidence-based usage of this agent. Fibrates lower blood triglyceride levels by reducing the liver’s production of the carrier of the triglyceride particle (VLDL) and by speeding up the removal of triglycerides from the blood. Diabetic patients are frequently prescribed a combination of a statin plus ezetimibe/fibrate. Source: Medline Plus

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Diabetes Educator’s Focus ORAL HEALTH IN DIABETES S Afr J Diabetes Vasc Dis 2011: 8: 167–168.

ral care is particularly important for the patient with diabetes. Emerging research suggests that the relationship between serious gum disease and diabetes is two way. Diabetics are more susceptible to serious gum disease, but serious gum disease may have the potential to affect blood glucose control and contribute to the progression of diabetes. Good blood glucose control is key to managing and preventing mouth problems. Poor blood glucose control impairs the functioning of white blood cells, necessary for defence against bacterial infections that can occur in the mouth. The less well controlled the blood sugar levels, the more likely oral health problems will arise, resulting in more frequent and more severe oral disease. Daily brushing and flossing, regular dental check ups and good blood glucose control are the best defence against the oral complications of diabetes. The diabetic patient faces a higher risk of a number of oral conditions Xerostomia (dry mouth) is a common diabetes-related condition that may be a side effect of medicines taken. A dry mouth may make the patient more susceptible to cavity formation, as there is less saliva to wash away bacteria and the acids they produce. Xerostomia can lead to further discomfort; the development of ulcers and tooth decay, and infections of the gums and salivary glands. Simple interventions such as drinking more fluids and chewing sugar-free gum may help keep the saliva flowing. Diabetic patients are at increased risk of gum inflammation. A common complication of diabetes is the thickening of blood vessels, affecting blood flow and slowing the inflow of nutrients to and removal of

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harmful wastes from the cells. The infection-fighting ability of the immune system becomes impaired and results in poor healing of oral tissue. Gingivitis (early-stage gum disease) and periodontal disease, a bacterial infection of the gum and bone that hold the teeth in place, can lead to painful chewing difficulties and even tooth loss. Plaque build up along the gum line hardens and the gums pull away from the teeth. Pockets of infection below the gum cause bone loss, which may result in loosening of the teeth. The frequent use of antibiotics in diabetes makes the patient particularly prone to developing fungal infections of the mouth and tongue. Thrush (Candida) thrives on the high levels of sugar in the saliva, creating painful areas that may turn into ulcers. Thrush presents as white (sometimes red) patches in the mouth, including the palate. It is easily scraped away, but will rapidly regrow. The smoking diabetic patient faces an even greater risk (20 ×) for the development of thrush and periodontal disease. Smoking impairs blood flow to the gums and may affect wound healing in this area. Dentist alert: warning signs for the patient to act on Often gum disease is painless. The patient may not even realise he/she has gum disease until some serious damage has been incurred, so regular visits to the dentist are of great importance. It is essential to pay special attention to any changes in oral health. If one or more of the following problems present, there may be tooth damage and/or gum disease: • pain in the mouth/sinus area that does not go away • white or red patches on the gums, tongue, cheeks or roof of the mouth

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• red, sore, swollen gums • bleeding gums when brushing or flossing. This is not normal. Even if the gums don’t hurt, this must still be checked • pus between the teeth and gums • gums pulling away from the teeth so that they look long; parts of the root may show • loose or sensitive teeth • bad breath • a bite that feels different • dentures/false teeth that do not fit well, or have stopped fitting well • teeth that hurt when eating something cold/hot/sweet or when chewing • dark spots or holes in the teeth. Considerations when visiting the dentist A multidisciplinary health-team approach provides comprehensive care for people with diabetes. Each member of the team contributes particular skills and experience. Collaboration and communication are essential components of a team-care approach, facilitating co-ordination of care. A visit to the dentist may require the involvement of the diabetes doctor; and the diabetes doctor may require information from the dentist. There are some useful points to consider when visiting the dentist: • Acute infections (abscesses) should be treated immediately. Postpone non-emergency dental-care procedures if the blood sugar level is not well controlled. Should orthodontic appliances cut the gums or cheeks, immediately consult with the orthodontist. • Keep the blood sugar levels as close to normal as possible; it is best to eat before the dental appointment. If on insulin, a morning appointment after a normal breakfast is best. • Tell the dentist about your diabetes status at each visit and have a list of the names and dosages of all medications currently being taken. The dentist needs to know if other medications will interact with any prescriptions that may be given. • See the diabetes doctor before scheduling treatment for periodontal disease. If oral surgery is planned, the doctor or dentist will advise on any pre-surgical antibiotics required, changes to meal schedules, or changes to timing and dosage of insulin. • The post-treatment instructions of the dentist must be closely followed. If the mouth is sore after dental work, the patient may not be able to eat or chew for several hours or days. Seek guidance from the doctor on how to adjust the normal routine while the mouth is healing (remember this may be prolonged in the diabetic patient). Most importantly, find out what changes are required with food, drink and diabetes medication. Also find out how often blood glucose levels should be checked. Glenda Hardy

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Day-to-day oral care tips • Brush your teeth after every meal, using a soft-bristled toothbrush. Turn the bristles against the gum line and brush gently. Use small circular motions. Brush the front, back and top of each tooth. Remember to brush the rough surface of the tongue to remove germs. Replace the toothbrush when the bristles are worn or bent, about every three to four months. • Prevent plaque build up by using dental floss at least once a day. Floss reaches places the toothbrush can’t. Using a sawing motion, gently bring floss between the teeth, scraping from bottom to top several times. Never snap the floss into the gum. • If you have dentures, remove and clean daily. • If smoking, talk to the doctor about ways to quit. • Have your teeth and gums cleaned and checked by a dentist twice a year, although the dentist may specifically recommend closer intervals. • Make an appointment with the dentist if you have red, sore or bleeding gums, or gums that are pulling away from the teeth. Also schedule appointments for a sore tooth that could be infected, or pain from dentures.

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Diabetes Personality ‘Walking the walk’ to a greater understanding of diabetes

D S Afr J Diabetes Vasc Dis 2011: 8: 169–170.

iabetes nurse educator (DNE) Christine Swart believes in ‘walking the walk’ to a deeper understanding and control of diabetes alongside her patients, every step of the way. She is uniquely placed to do this. An insulindependent diabetic herself for more than 20 years, she’s living proof that it’s possible to have diabetes and still lead a normal, healthy life. ‘I believe that ultimately diabetics are people just like everyone else with the same general concerns and challenges. Managing their diabetes is just one additional aspect of their lives and not something that defines them’, she says. Based at Netcare Kuils River Hospital in the northern suburbs of Cape Town, Christine works with three physicians and four gynaecologists, providing diabetes education to all patients admitted to the hospital’s various wards. The population she serves is diverse, ranging from the wealthy to the disadvantaged, but she is committed to giving a good-quality service to all and to working around any constraints related to funding. In addition she runs a monthly support group that addresses topics identified by the patients themselves. ‘Once a year, this takes the form of a dinner at an outside venue – usually with a dietician present. It provides a good opportunity to advise on correct eating choices’, she says. A registered nurse with a background in primary care and community health nursing, Christine first became involved in diabetes when she worked at Netcare Park Lane Clinic in Johannesburg, counsel-

‘Most people don’t really understand what happens in the body when you have diabetes’

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ling pregnant women with gestational diabetes. On her return to Cape Town, she became aware of how many diabetics received inadequate counselling and the prescriptive, unempathetic way they were often treated. She has been a DNE since 1997 and in her current position since 2002. ‘Most people don’t really understand what happens in the body when you have diabetes’, she says. ‘There are many myths and misconceptions that need to be addressed. When a patient comes to me for the first time, I start by assessing how much they know and understand, and sift out the correct information from the nonsense. I then give them a basic course in physiology, using models and pictures of the body so that they become familiar with the various organs and their location. I also have a model hamburger that I dissect in front of them as I explain how eating it affects a diabetic versus how it affects someone without the condition. I tell them how that extra glucose affects the various organs and the potential damage it can do.’ Christine emphasises that it’s important to keep things simple and avoid information overload. To this end, she often educates incrementally in ‘manageable portions’ over successive patient visits and uses tests to assess that patients understand what they’ve been told. ‘I make them aware that the disease will progress and that the pancreas will secrete less insulin over time. This does mean that they will probably need to change their therapy in the years ahead.’ Once patients understand the condition, the next step is to educate them around its treatment. This also takes time, especially when it comes to insulin therapy, which Christine feels requires at least a 90-minute to two-hour conversation. In addition, all patient conversations are individualised and ‘tailor-

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Christine helps a young colleague get to grips with caring for patients with diabetes.

made’, as Christine believes that each patient is different and one cannot use a standardised approach. ‘I can’t stress enough that ensuring compliance takes time and requires ongoing support and motivation. The support of a multidisciplinary team is essential to ensure this.’ An important aspect of the conversation on treatment is to dispel the very human desire for a ‘quick fix’ and to ensure that patients make peace with diabetes being a lifelong, chronic condition. ‘Acceptance does not come instantaneously and it’s a long process.’ Christine expresses concern about untested products available over the counter that make claims to ‘cure’ diabetes. ‘When asked about these products, which usually also have the attraction of being cheaper than prescription medication, I ask the patient what he/she really knows, what research he/she has read, how does this product claim to work and how do its claims align with what I’ve told him/her about diabetes and its management. I never lose sight of how powerful marketing is in this context’, she says. Another particular challenge for Christine is counselling male diabetics

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with erectile dysfunction. ‘It’s become easier over time but it was initially very difficult for me, as an unmarried woman, to broach the subject. But if I don’t ask, I cannot help. However, nowadays I explain exactly what happens in the body and discuss treatment options before referring them back to their doctor for medication.’ Like other DNEs, Christine’s greatest reward lies in seeing patients become compliant and gain control over their condition. ‘One woman in my support group – I’ll call her Mrs J – originally came to me in 2005. She weighed 80 kg and was on oral antidiabetic medication. Today she weighs 62 kg and is off the drugs, controlling her diabetes through a healthy diet and regular exercise. She’s extremely motivated and even accompanied me to the AGM of Diabetes SA this year. I’m so proud of her and her commitment to her way of life. She’s also a great role model for other diabetics and is only too happy to tell her own success story when given the opportunity at support group meetings.’ Peter Wagenaar, Gauteng correspondent

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Journal Update

Southern African contributions

he recent UN summit on non-communicable diseases (NCDs) highlighted the emerging burden of disease in Africa. Particular emphasis was paid to preventable lifestyle choices as risk factors for NCDs, including tobacco use, unhealthy diet, lack of physical activity and alcohol abuse. It appears that the negative consequences of a drift in Africa towards a Western lifestyle is being compounded by a genetic predisposition towards the development of NCDs. These factors and other therapeutic issues are discussed in this update of relevant articles on southern Africa from the world literature.

LIFESTYLE Lifestyle and conventional risk factors responsible for excess burden of sub-clinical vascular disease in black Africans compared to Caucasians in South Africa There is an emerging burden of cardiovascular disease among urban black Africans in South Africa. This rise has been largely explained by the transition from traditional African lifestyles to more westernised behaviour: more sedentary routines, smoking and unhealthy diets, including an excess intake of saturated fats, highly processed foods and alcohol. Existing data has generally shown higher levels of sub-clinical vascular disease in participants from lower socio-economic backgrounds and in blacks. It is difficult to estimate the true contribution of health behaviour from self-reported measures alone as these suffer from considerable reporting bias. From three health behaviours studied in this article, alcohol was the most important risk factor for vascular disease. Low physical activity was associated with a number of other cardiovascular disease (CVD) risk factors, including body mass index (BMI), triglycerides (TGs), blood pressure and C-reactive protein (CRP). The aim of the study was to examine the role of objectively assesed health behaviours in explaining the excess burden of sub-clinical vascular disease seen in urban black Africans compared to Caucasians. The black (192) and Caucasian (206) participants were well matched for age and gender distribution. In general, the blacks demonstrated more risk factors, including higher ambulatory

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systolic and diastolic blood presure, TGs, BMI, CRP and a higher prevalence of the metabolic syndrome. In addition, blacks were less physically active and more likely to smoke. The black sample reported lower use of alcohol, although both black alcohol users and nonusers demonstrated higher levels of gamma glutamyl transferase than Caucasians. This might suggest the presence of alcohol-induced liver damage from previous alcohol abuse in blacks who reported non-drinking status. Alternatively it may reflect a greater prevalence of non-alcoholic fatty liver disease in the blacks. Results further revealed a higher prevalence of hypertension in the black sample. Black Africans demonstrated higher mean carotid intima–media thickness (mCIMT) compared with Caucasians, although the difference was considerably attenuated after adjustment for conventional and behavioural risk factors. This attenuation suggests that the emerging burden of CVD among urban black Africans in South Africa is largely caused by modifiable factors. Key take-home message: Higher ambulatory systolic and diastolic blood pressure, and raised triglycerides and body mass index are the major factors driving vascular disease in black South Africans. Source: Hamer M, Malan L, et al. Conventional and behavioural risk factors explain differences in sub-clinical vascular disease between black and Caucasian South Africans: The SABPA study. Atherosclerosis 2011; 215: 237–242. DOI: 10/1016/j.atherosclerosis.2010.12.015.

South African black smokers demonstrate greater cardiovascular dysfunction than Caucasian smokers Globally, the prevalence of smoking-related CVD is higher in Africans than Caucasians. Many studies have reported the effect of smoking on the metabolic syndrome, and together they cause dyslipidaemia, increased CRP levels and endothelial dysfunction. Smokers are therefore characterised by high serum TG and low-density lipoprotein cholesterol (LDL-C), with significantly lower high-density lipoprotein cholesterol (HDL-C) than non-smokers. Nicotine intake leads to increased blood pressure and decreased oxygen-carrying

capacity of the blood, which may in turn cause ischaemia and hypoxia. This stimulates increased red blood cell production, contributing to increased viscosity and consequently inflammatory and coagulatory processes. Inflammation and coagulation are associated with atherosclerosis and cornonary heart disease. All of these factors contribute negatively to increased risk for CVD. This study aimed to determine the association between smoking and measurements of vascular function in African and Caucasian people of South Africa. Anthropometric and cardiovascular variables, serum creatinine and CRP levels were measured. African smokers had significantly increased arterial stiffness, which was not found in Caucasian smokers. Africans also showed more associations between smoking and cardiovascular dysfunction than the Caucasians. A high degree of urbanisation among Africans, coupled with higher smoking prevalence might be to blame for the high prevalence of CVD in the African population. Key take-home message: Smoking results in more vascular damage in black compared to white South Africans. Source: Zatu MC, Van Rooyen JM, Schutte AE. Smoking and vascular dysfunction in Africans and Caucasians from South Africa. Cardiovasc J Afr 2011; 22(1): 18–24.

Xylitol a better sweetener for the diabetic patient Chronic consumption or overconsumption of refined sugar may cause severe physiological and clinical problems such as overweight, obesity, diabetes and other diseases related to the metabolic syndrome. As a result, sugar substitutes are gaining popularity in the market, several of which have been found to have mild to severe side effects. Studies have pointed to the carcinogenic effects of saccharin in humans; others have shown aspartame to have significant effects in causing gastric, pancreatic and endometrial cancers and migraines. Aspartame has also been reported to be responsible for lymphomas, leukaemias, cancers of the bladder and brain, chronic fatigue syndrome, Parkinson’s and Alzheimer’s disease, multiple sclerosis, autism and systemic lupus.

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Of several sugar alcohols widely used as sugar substitutes, xylitol has been considered a safer sweetener, lacking the gastrointestinal side effects of the other sugar alcohols. Numerous studies have confirmed the effect of xylitol in the prevention of dental caries, plaque and oral biofilm production. The effects of xylitol on glycaemic control has also been reported. Compared with sucrose, xylitol has similar sweetness but relatively lower caloric value. Xylitol has a significantly lower glycaemic index (13) compared with sucrose (65), with the potential for reduction of diabetic hyperglycaemia. The overall antidiabetic effects of xylitol as a sugar replacement on diabetes-associated parameters have not yet been investigated. Data from this University of KwaZulu/Natal Department of Biochemistry study suggests that xylitol not only reduces the blood glucose concentration but also significantly improves the glucose tolerance level compared with sucrose in non-diabetic rats. Seventeen Sprague-Dawley rats were randomly divided into three groups, supplied for three weeks with drinking water ad libitum (control group), 10% sucrose solution (sucrose group) or 10% xylitol solution (xylitol group), respectively. Between the sucrose and xylitol groups, food intake was not significantly different, but drink intake and body weight were signifcantly increased in the sucrose group. Blood glucose data suggested that xylitol could maintain both the non-fasting and fasting blood glucose levels in a physiologically safer and more stable condition compared with sucrose. The significantly better glucose tolerance ability of the xylitol group confirmed that it has better effects in blood glucose and diabetes management compared with sucrose. The xylitol group also had significantly higher liver glycogen concentrations. Key take-home message: Xylitol can be a better sweetener than sucrose to maintain diabetes-related parameters at a physiologically safer and more stable condition. Source: Shahidul Islam M. Effects of xylitol as a sugar substitute on diabetes-related parameters in nondiabetic rats. J Medicinal Food 2011; 14(5), 505-511. DOI: 10.1089/jmf.2010.0015.

GENETIC STUDIES Increased obesity-related insulin resistance in black South African women has genetic basis Adipogenesis is controlled by a sequential activation of transcription factors. Peroxisome proliferator-activated receptor γ (PPARγ) and

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CCAAT/enhancer-binding protein α (C/EBPα) function with other adipogenic transcription factors to regulate the expression of lipogenic genes. The adipogenic capacity of subcutaneous adipose tissue (SAT) has been proposed as a potential mechanism underlying the link between adiposity and insulin resistance. Reduced adipogenic capacity of SAT is typically associated with increased adipose cell size, apoptosis, inflammation, reduced vascularisation and insulin signalling within adipose tissue, and peripheral insulin resistance. Despite a high prevalence of insulin resistance, black South African women have less visceral adipose tissue (VAT) and more peripheral (gluteal–femoral) SAT than their white counterparts. Although increased VAT is considered a major determinant of insulin resistance, peripheral SAT deposition has been shown to be protective, being inversely associated with fasting insulin levels in overweight and obese pre-menopausal white women. The mechanisms underlying this apparent paradox are unkown. The authors hypothesised that a reduction in the expression of lipogenic genes may be associated with insulin resistance in black South African women. This study sought to measure expression of the genes involved in adipogenesis and lipogenesis in abdominal VAT and gluteal SAT depots and determine their relationships with insulin sensitivity in normal-weight and obese black and white South African women. The black and white women were well matched for percentage of body fat and waist circumference, whereas obese black women had less VAT and more superficial SAT (SSAT) than white women, but similar deep SAT (DSAT). Obese black women had greater gynoid fat mass. Fasting glucose levels were not different between ethnic groups, but black women had higher fasting insulin levels than white women. Circulating adiponectin levels did not differ by ethnicity, nor did average abdominal and gluteal adipocyte size. Novel findings of the study were that the expression of PPARγ and PPARγ-responsive genes were down-regulated to a greater extent with obesity in black compared with white women. Furthermore, expression of these genes, mainly in the gluteal and DSAT depots, was associated with insulin sensitivity in black but not white women. An ethnicspecific adaptation is suggested from the observation that expression of PPARγ and PPARγ-responsive genes was down-regulated to a greater extent with obesity in black compared with white women. The expression of the major adipogenic transcription factors and PPARγ-responsive genes was correlated

with insulin sensitivity in black but not white women. These gene associations with insulin sensitivity were significant only in the gluteal and, to a lesser extent, the DSAT depot. Novel findings of this study indicated that gynoid fat mass was negatively correlated with insulin sensitivity in black but not white women, contrasting with the prevailing hypothesis that peripheral (gluteal–femoral) SAT deposition is protective.The findings of this study add to the weight of evidence refuting the hypothesis that black women display healthy obesity due to their greater peripheral fat distribution, but instead suggest that obesity in black South African women impairs gluteal SAT adipogenesis and storage, potentially leading to insulin resistance and an increased risk of type 2 diabetes. Key take-home message: Gluteal fat depositon in black women is related to insulin resistance, while visceral fat depostion in white women is the determinant of risk of type 2 diabetes. Source: Goedecke JH, Evans J, et al. Reduced gluteal expression of adipogenic and lipogenic genes in black South African women is associated with obesity-related insulin resistance. J Clin Endocrinol Metab 2011; 96(12). DOI: 10.1210/jc.2011-1576.

EVIDENCE FOR CLINICAL PRACTICE Simple anthropometric measures suitable for determination of metabolic risk – a South African study Central obesity, specifically the accumulation of VAT, is linked to the development of several metabolic diseases, including hypertension, dyslipidaemia and insulin resistance. Waist circumference (WC) is used as a proxy measure for VAT; however, ethnic differences exist in the relationship between WC and VAT. Few studies have looked at the ability of central obesity measures to identify metabolic risk factors in southern African populations. Recent studies in Europeans and Asians have shown that waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) have a greater ability than WC alone to identify patients with hypertension, dyslipidaemia and type 2 diabetes. Black South African women are on average shorter and have more peripheral fat than white South African women. With increasing WC, black women accumulate less VAT than white women, yet black women are more insulin resistant and paradoxically, present with lower TG and total cholesterol (TC) levels than white women. Similarly to WC and VAT, the ethnic-specific

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associations between WHtR and WHR with known metabolic risk factors remain to be explored in a South African population. The present study compared the diagnostic ability (sensitivity and specificity) of obesity measures (WC, WHtR, WHR and VAT) to identify black and white South African women with or without elevated blood pressure, dylipdaemia and insulin resistance; and to identify thresholds of obesity measures that best identify risk in these women. Apparently healthy, pre-menopausal South African women (241 black and 188 white) were assessed on basic anthropometric measurements and blood pressure. Blood sampling after an overnight fast determined plasma glucose, serum insulin, TC, HDL cholesterol and TG concentrations. Insulin resistance was calculated from fasting glucose and insulin levels. There were no ethnic differences in body weight; however, the white women were significantly taller and had a lower BMI and WHtR than the black women. There were no ethnic differences in WC or WHR; although black women had less VAT than white women. For both black and white women there were no differences in blood pressure, and fasting glucose levels were within normal ranges. The white women had higher mean fasting glucose and lower fasting insulin levels than black women. White women had significantly higher TG, TC and HDL-C levels. All measures of central obesity were found to be better indicators of metabolic risk in white compared to black South African women. These findings suggest that factors other than body composition, such as inflammation or environmental factors, contribute to increased metabolic disease in black women. Another important finding was the significant differences in the diagnostic ability between VAT and anthropometric measures for identifying metabolic risk thresholds. It was found that WC was better than VAT for identifying black and white women with insulin resistance. Conversely, VAT was significantly better than WC for identifying elevated TG levels in white women and elevated blood pressure in black women. WC and VAT thresholds were lower in black compared to white South African women. Considering WC and WHtR can be used to identify equivalent metabolic risk, and given the high cost and risks of radiation exposure associated with CT scans, it may be more clinically applicable to use these simple anthropometric measures over VAT for identifying metabolic risk variables.

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Key take-home message: Simple anthropometric measures of WC, WHtR and WHR for determining metabolic and subsequent risk of diabetes are not as useful in black as in white South African women. Source: Evans J, Micklesfield L, et al. Diagnostic ability of obesity measures to identify metabolic risk factors in South African women. Metabol Syndr Relat Dis 2011; 9(5): 350–360. DOI: 10.1089,met.2011.0034.

Mild symptomatic hypoglycaemia does not adversely impact on beliefs about diabetes or health status over the long term Improved glycaemic control is required to minimise long-term complications of type 2 diabetes but carries the risk of hypoglycaemia. Periods of moderate to severe hypoglycaemia and accompanying symptoms (sweating, palpitations, tremor, cognitive impairments, behavioural changes and coma) are distressing and may lead to changes in the way patients manage and think about their diabetes. Reports on the impact of mild hypoglycaemia are sparse, resulting in this study, with contributions from the Division of Endocrinology and Metabolism of the University of the Witwatersrand. Beliefs about illness may unfavourably change in response to mild hypoglycaemia in ways modified by external social factors, education and experience. Collectively, these may influence self-care behaviour and adherence to medical regimen. Self monitoring of blood glucose has the potential to confirm or refute subjective feelings of hypoglycaemia, as well as identify asymptomatic episodes of low blood glucose. The aim of this study was to evaluate the association betweeen experience of mild hypoglycaemia and changes in beliefs about diabetes, self-reported well-being, health status and health behaviours over a period of 12 months. The study randomly allocated 453 wellcontrolled, non-insulin dependant type 2 diabetes patients into one of three interventions: (1) standardised care with threemonthly HbA1c measurements; (2) use of a blood glucose meter with minimal education or training and with clinician interpretation of results; and (3) use of blood glucose meter with extensive education and training in self interpretation and application of the results to diet, physical activity and medication adherence. Self-reported questionnaires assessing beliefs about diabetes, well-being, health status and health behaviour were

collected at baseline and one year. Experience of grade 1 hypoglycaemia (self reported with no accompanying symptoms) was associated with a small increase in selfreported personal control over diabetes, but no other significant changes in beliefs about diabetes or self monitoring of blood glucose were identified. There was no evidence of long-term adverse impact on health status from the experience of mild, symptomatic hypoglycaemia. Previous studies have suggested a much larger impact of hypoglycaemia on quality of life than identified in this study. This study shows neither a significant association between health status and reported experience of hypoglycaemia, nor changes in experience of hypoglycaemia over time. Regular monitoring with subsequent regulation of lifestyle and medication may add to a sense of personal involvement and responsibility. However, those experiencing symptoms of hypoglycaemia did not share the same changes in personal control. The wider benefits of increased perceptions of personal control in supporting self management of diabetes need further evaluation. Key take-home message: There is no evidence of a long-term adverse impact on beliefs about diabetes or health status in those patients experiencing mild symptomatic hypoglycaemia when self monitoring blood glucose. Source: Malanda UL, Bot SD, et al. Experience of hypoglycaemia is associated with changes in beliefs about diabetes in patients with type 2 diabetes. DIABETICMedicine 2011. DOI: 10.1111/j.1464-5491.2011.03340.x.

DRUGS AND THERAPEUTIC REGIMENS Addition of alogliptin to metformin and pioglitazone effective for inadequate glycaemic control in type 2 diabetes Treatment goals of type 2 diabetes aim to achieve and maintain glycaemic control to mitigate the risk of microvascular and macrovascular complications. Dual oral therapy with metformin and pioglitazone is a well-established treatment option for patients with type 2 diabetes. Metformin lowers blood glucose, primarily by increasing hepatic insulin sensitivity. Pioglitazone increases peripheral and hepatic insulin sensitivity and potentially preserves β-cell function. Largely due to progressive decline of β-cell function, most patients initially achieving treatment goals eventually experience a dete-

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rioration of glycaemic control. Such secondary treatment failure necessitates escalation of drug doses or the use of a combination of drugs with complementary mechanisms of action to maintain glycaemic control over time. Current treatment guidelines indicate that patients with inadequate glycaemic control may benefit from the addition of a third oral antidiabetic drug before initiating insulin therapy. Dipeptidylpeptidase-4 (DPP-4) inhibitors inhibit the degradation of incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, thereby increasing insulin secretion and decreasing glucagon secretion after meals. These drugs may also improve β-cell function. Given the distinct but complementary mechanisms of action of alogliptin (DPP-4 inhibitor), metformin and pioglitazone, triple oral therapy with these drugs has the potential to address both insulin resistance and Islet dysfunction. South Africa’s Helderberg Diabetes and Medical Centre has made a contribution to the study of efficacy and safety of triple oral therapy in the diabetic patient with inadequate glycaemic control. The aim of this study was to assess the efficacy and safety of adding alogliptin 25 mg (triple oral therapy) versus uptitrating pioglitazone from 30 to 45 mg for 52 weeks in type 2 diabetes patients with inadequate glycaemic control on metformin (≥ 1 500 mg or maximum tolerated dose) and pioglitazone 30 mg. Triple oral therapy in patients with inadequate glycaemic control provided clinically relevant and superior improvemnt in A1c compared with uptitrating pioglitazone, without increasing safety or tolerability concerns. The glycaemic benefits of triple therapy were seen as early as week four and maintained throughout the 52-week period. Clinically relevant improvements were observed regardless of age, gender, ethnicity, race and baseline BMI. Key take-home message: Adding alogliptin to an existing metformin–pioglitazone regimen provides superior glycaemic control and potentially improves β-cell function with no clinically important differences in safety, compared to uptitrating pioglitazone. Source: Bosi E, Ellis GC, et al. Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study. Diabetes, Obesity Metabol 2011; (in press). DOI: 10.1111/j.14631326.2011.01463.x.

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Ultra-long-acting insulin degludec provides comparable glycaemic control to daily insulin glargine without additional adverse events Despite the availability of many therapies, many people with diabetes are unable to reach guideline-recommended rates of glycosylated haemoglobin (HbA1c). Insulin degludec is an ultra-long-acting basal insulin analogue in clinical development. Pharmacokinetic properties of insulin degludec result in an ultra-long-action profile, making possible new applications of alternate-day or three-times weekly injection of this insulin. This can potentially help with acceptance and early initiation of insulin therapy for some people with type 2 diabetes. This clinical proof-of-concept trial aimed to assess the efficacy and safety of insulin degludec once a day or three times a week, compared with insulin glargine once a day in combination with metformin. The study subjects were insulin-naïve type 2 diabetics who were inadequately controlled on oral antidiabetic drugs. Participants were randomly allocated to receive (1) insulin degludec (900 nmol/ml) three times a week, or (2) insulin degludec (600 nmol/ml or 900 nmol/ml) once a day, or (3) insulin glargine (600 nmol/ml) once a day; all in combination with metformin. Insulin degludec provided once a day or three times a week as add-on to metformin did not differ from insulin glargine in terms of glycaemic control. There were no apparent treatment-specific patterns or clustering of adverse events. Source: Zinman B, Fulcher G, et al. Insulin degludec, an ultra-long-acting basal insulin, once a day or three times a week versus insulin glargine once a day in patients with type 2 diabetes: a 16-week, randomised, open-label, phase 2 trial. Lancet 2011; 377: 924–931. DOI: 10.1016/ S0140-6736(10)62305-7.

Benefits of fibrates in reducing cardiovascular events for type 2 diabetic patients questioned Lowering the concentration of LDL cholesterol with statins substantially reduces the rate of cardiovascular events among patients with underlying CVD or other risk factors. Yet a substantial risk persists, suggesting that additional lipid-modifying interventions may be needed. High TG levels and low levels of HDL cholesterol independently correlate with increased cardiovascular risk. There remains considerable controversy over the clinical efficacy of fibrates in overall cardiovascular

benefit. Fenofibrate has been approved for use in reducing LDL cholesterol, TG, total cholesterol and apolipoprotein B levels; as well as increasing HDL cholesterol levels in patients with primary hypercholesterolaemia or mixed dyslipidaemia. Fenofibric acid (the active ingredient of fenofibrate) is the only fibrate approved for use with a statin for reducing TG levels and raising HDL cholesterol levels in patients with mixed dyslipidaemia and coronary heart disease or those who have equivalent risk levels and are receiving optimal statin therapy. To date, there is no data on direct clinical outcomes to support this indication. The ACCORD-Lipid substudy was designed to determine whether combination therapy with a statin plus fenofibrate would reduce the risk of cardiovascular events, compared with statin monotherapy. After a follow-up of almost five years, fenofibrate plus simvastatin had not significantly decreased the rate of the primary outcome of fatal cardiovascular events, non-fatal myocardial infarction or non-fatal stroke, compared with simvastatin alone. However, a sub-group analysis of patients with baseline TG levels above 204 mg/dl and HDL cholesterol levels below 34 mg/dl showed a 31% reduction in the rate of primary outcome. The question of the appropriate way to handle the approved indication for fenofibric acid for co-administration with a statin is controversial. The ambiguity for physicians who must make individualised decisions for patients needs to be removed. It is suggested that until sufficient evidence emerges, physicians prescribing combination statin–fibrate therapy should selectively target high-risk patients only after optimal control of LDL cholesterol has been achieved with statin therapy. A properly designed trial is warranted to test the hypothesis that adding fenofibric acid to statin therapy significantly reduces the risk of cardiovascular events among highrisk patients who have reached their LDL cholesterol goal with a statin but have residual mixed dyslipidaemia. Key take-home message: Fenofibrates work to lower cardiovascular risk in patients with TG levels raised above 2.3 mmol/l and HDL cholesterol levels below 1.0 mmol/l. Other type 2 diabetes patients do not show benefit from fenofibrate addition. Source: Goldfine AB, Kaul S, et al. Fibrates in the treatment of dyslipidemias – time for a reassessment. New Engl J Med 2011; 365(6): 481–484.

Glenda Hardy

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Controversies at ESC 2011: Dietary approaches for lipid assessment From: Br J Prim Care Nursing 2011, published online. S Afr J Diabetes Vasc Dis 2011; 8 : 175–177.

t this year’s Congress of the European Society of Cardiology (ESC), 27–31 August in Paris, France, experts debated a number of controversial issues. A key session was the debate on dietary approaches for lipid assessment, chaired by Prof Rory Collins, Oxford, UK and Dr Mikael Rabaeus, Clarens-Montreux, Switzerland.

Is food supplementation with plant sterols useful to prevent cardiovascular disease? Prof Eric Bruckert, Institute of Endocrinology and Prevention of Cardiovascular Disease, Pitié-Salpêtrière Hospital, Paris, France argued the case for this motion. The effect of individual dietary changes on cardiovascular disease (CVD) risk is difficult to evaluate in short-term (< 5 years) clinical studies. Therefore evidence to support dietary recommendations is based on a more complex approach. Extensive data show that consumption of plant sterols (1–2 g/day)* has been consistently associated with reduction in plasma concentrations of low-density lipoprotein (LDL) cholesterol by ∼10%. This was recently reaffirmed by a meta-analysis of 84 randomised, controlled studies in 6 805 patients.1 Indeed, recent dyslipidaemia guidelines by the ESC and European Atherosclerosis Society recommend inclusion of foods supplemented with phytosterols (1–2 g/day) in individuals with elevated total LDL cholesterol for whom total cardiovascular risk assessment does not justify the use of pharmacotherapy.2 * According to the European Food Safety Authority dossier, the efficacy of phytosterol supplementation is proven with a daily dosage in the range of 1.5–2.4 g.

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Building on his argument, Prof Bruckert showed that there is overwhelming evidence from population studies, clinical outcomes trials and genetic studies to confirm the cardiovascular benefits of a long-term 10% reduction in LDL cholesterol.3,4 In a meta-analysis of 58 dietary and drug trials involving nearly 15 000 subjects, long-term reduction in LDL cholesterol of 1.8 mmol/l (∼70 mg/dl) reduced the risk of ischaemic heart disease by about 60%.3 Therefore, by extrapolation, he implied that lowering of LDL cholesterol levels by ∼10% with dietary plant sterol supplementation is likely to be useful in preventing CVD. In the second part of his presentation, Prof Bruckert focused on issues relating to the risk versus benefit of plant sterol supplementation. He emphasised that the safety dossiers for phytosterol-supplemented products have been extensively reviewed by numerous regulatory agencies, including the US Food and Drug Administration. Overviewing the data, he concluded that there was no consistent evidence of accumulation of plant sterols in tissues, oestrogenic effects or effects on the gut morphology or physiology. Instead, the data suggested that dietary phytosterol supplementation may be associated with possible anti-atherogenic effects, based on three key lines of evidence. • First, recent studies in large numbers of patients using appropriate adjustment of confounders showed no association between increased plasma levels of plant sterols and risk for ischaemic heart disease.5-7 For example, in the Longitudinal Aging Study Amsterdam, high plasma levels of sitosterol, a marker of plant sterols, were associated with a markedly reduced risk for coronary heart disease (CHD), suggesting that plant sterols might have protective anti-atherogenic effects.6 • Second, extensive experimental data consistently showed beneficial effects on stabilisation or regression of atherosclerosis.8 • Third, a systematic meta-analysis including data from 17 studies in 11 182 subjects did not indicate an association between serum levels of plant sterols and increased risk of CVD.9 In summing up his case, Prof Bruckert emphasised that phytosterol-supplemented

foods have been recognised as effective and safe in almost all countries. Dr Oliver Weingärtner, University Hospital of Saarland, Homburg at Saar, Germany argued the case against the motion. He suggested the need for caution in extrapolating that lowering of LDL cholesterol with dietary plant sterol supplementation translates to reduction in CVD risk. To highlight his point, he referred to the ILLUMINATE trial with the cholesteryl ester transfer protein inhibitor torcetrapib.10 Although effective in raising high-density lipoprotein cholesterol and lowering LDL cholesterol, torcetrapib was also associated with an increase in risk for major cardiovascular events. Additional research suggested that this adverse effect was most likely attributable to off-target pharmacological effects on the adrenals, resulting in hyperaldosteronism and hypertension.11 In a key point, Dr Weingärtner highlighted the fact that while the human body has very efficient means of eliminating sterols in a normal diet, plant sterol supplementation has been shown to more than double serum sterol levels. The biological signiﬁcance of this effect has been the subject of much debate. Dr Weingärtner overviewed data from two studies. In one small study, dietary supplementation with plant sterols increased plasma sterol levels and sterol concentrations in aortic valve tissue in patients with aortic stenosis.12 Another study showed that common genetic variants at the ATP-binding cassette hemitransporter ABCG8 and ABO blood group, gene loci were associated with increased sterol levels and coronary artery disease risk.13 However, these data are not definitive as these variants were also associated with elevated cholesterol levels. In his rebuttal, Prof Bruckert highlighted the need to consider the weight of evidence as a whole to avoid over-reacting to the results of individual studies. There are also methodological issues; in the case of animal studies it is important that the effects of plant sterols are compared against a standardised level of cholesterol intake. Dr Weingärtner suggested that dietary plant sterol supplementation may be associated with impairment of endothelial function, based on experimental evidence in apolipoprotein E-deficient mice. This study

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also showed increased deposition of sterols in the central nervous system of these mice, suggesting that plant sterols may be able to cross the blood–brain barrier.14 However, he acknowledged that the data are not clear, as other studies have not shown this.15,16 Whether methodological issues, notably differences in the cholesterol content of the diets used in these studies, may explain this is not clear. In his rebuttal, Prof Bruckert once again argued for a cautious approach when considering data from a single experimental study. In respect of the effect of plant sterols on endothelial function, he highlighted evidence from numerous human studies indicating that consumption of plant sterols is instead associated with anti-inflammatory effects, as shown by reduction in levels of C-reactive protein (CRP).17 However, he did agree that there was a need for further study to better understand how and to what extent dietary plant sterols might modify inflammation and the immune system. In summing up, it was acknowledged that there was a considerable weight of evidence for the LDL-lowering effects of dietary phytosterol supplementation, providing a firm basis for recommendations made by the recent joint ESC/EAS dyslipidaemia guidelines. Beyond LDL cholesterol lowering, there is also some evidence to suggest that dietary plant sterols may exert beneficial effects on other lipids and biomarkers, such as CRP. Whether these effects translate to prevention of CVD requires further analysis. For a definitive answer, long-term, randomised, placebo-controlled studies would be the ideal, but are probably unlikely from a practical perspective.

Is diet alone sufficient to reduce cardiovascular risk? This motion was debated by Prof Steven F Horowitz, Stamford Hospital, USA (for) and Prof Peter Sleight, Oxford, UK (against). This

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debate was less combative, as both of the participants agreed that diet is an important part of lifestyle intervention to prevent CVD. The debate therefore hinged on the word ‘alone’. Prof Horowitz argued the case that diet is a major determinant of the risk for CVD, supported by epidemiologic data. For example, he cited the Lyon Diet Heart Study,18,19 in which adoption of a Mediterranean diet by myocardial infarction survivors resulted in ∼70% reduction in mortality compared with a comparator group treated with a prudent diet. These data led to termination of the trial. This difference in mortality was evident from three months, was not related to the extent of LDL cholesterol lowering, and the benefit persisted at follow up four years later. Subsequent studies showed that adherence to a Mediterranean diet was inversely associated with CHD risk. Specifically, consumption of plant-based foods, and the ratio of mono-unsaturated to saturated fats in the diet were linked with lower cholesterol levels and in turn reduction in the risk of CHD.20 Diet, as part of intensive lifestyle intervention, has also been shown to regress atherosclerosis and improve risk for CVD, in part due to beneficial effects on endothelial function and inflammatory markers of atherosclerosis.21 In his conclusions, Prof Horowitz said that these data clearly argue for an early, proactive approach using diet, as part of a comprehensive lifestyle-modification programme, to prevent CVD. Indeed, this approach is already regarded as a fundamental first step in current guidelines.2 However, as argued by Prof Sleight, longterm adherence is problematic, even among highly motivated individuals. As an example, he referred to the Nurses’ Health Study in 84 129 women free of diagnosed CVD, cancer and diabetes at baseline. Only 3% of the sample was able to maintain a healthy lifestyle (i.e. not smoking, moderate alcohol consumption, at least 30 minutes of moderate physical activity/day, and maintaining a healthy body weight and diet) over the long term.22 Furthermore, he emphasised that in individuals at high risk of CVD, the magnitude of LDL cholesterol reduction achieved with lifestyle is usually insufficient. In such individuals pharmacotherapy is also clearly indicated, in line with recent guidelines, with statins the recommended first-line therapy.2 Prof Sleight concluded his presentation by highlighting the need for new

approaches in motivating people to adopt a healthy lifestyle, possibly involving nurseled intervention programmes, as well as collaborative approaches across the spectrum of healthcare professionals. In conclusion, both participants of the debate agreed that diet, as part of intensive lifestyle modification, is a fundamental first step in the prevention of CVD. An early, proactive approach is key to reducing lifetime cardiovascular risk. However, it was recognised that motivation and nonadherence are the most important stumbling blocks in the long term. Additionally, in high-risk patients, diet alone is usually insufficient to achieve sufficient reduction in LDL cholesterol levels as recommended by guidelines.

References 1.

Demonty I, Ras RT, van der Knaap HC, et al. Continuous dose–response relationship of the LDLcholesterol-lowering effect of phytosterol intake. J Nutr 2009; 139: 271–284. 2. Reiner Z, Catapano A, de Backer G, et al, ESC/EAS guidelines for the management of dyslipidaemias. The Task Force on the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; doi: 10.1093/eurheartj/ehr158. 3. Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low-density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. Br Med J 2003; 326: 1423. 4. Benn M, Nordestgaard BG, Grande P, Schnohr P, Tybjærg-Hansen A. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease. J Am Coll Cardiol 2010; 55: 2833– 2842. 5. Wilund KR, Yu L, Xu F, et al. No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler Thromb Vasc Biol 2004; 24: 2326–2332. 6. Fassbender K, Lütjohann D, Dik MG, et al. Moderately elevated plant sterol levels are associated with reduced cardiovascular risk – the LASA study. Atherosclerosis 2008; 196: 283–288. 7. Escurriol V, Cofán M, Moreno-Iribas C, et al. Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort. J Lipid Res 2010; 51: 618–624. 8. Trautwein EA, Demonty I, Ras RT. Plant sterols – a dietary approach for effective blood lipid lowering as part of a heart healthy diet. Curr Topics Nutraceut Res 2010; 8: 137–148. 9. März W. Plant sterols and cardiovascular disease: A systematic review and meta-analysis. Latebreaker abstract, EAS 2011, Gothenburg, Sweden, June 2011. 10. Barter PJ, Caulfield M, Eriksson M, et al; ILLUMINATE investigators. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007; 357: 2109–2122. 11. Forrest MJ, Bloomfield D, Briscoe RJ, et al. Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br J Pharmacol 2008; 154: 1465–1473.

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12. Weingartner O, Lutjohann D, Ji S, et al. Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol 2008; 51: 1553–1561. 13. Teupser D, Baber R, Ceglarek U, et al. Genetic regulation of serum phytosterol levels and risk of coronary artery disease. Circ Cardiovasc Genet 2010; 3; 331–339. 14. Weingartner O, Ulrich C, Lutjohann D, et al. Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE2/2 mice. Cardiovasc Res 2011; 90: 484–492. 15. Plat J, de Jong A, Volger OL, Princen HM, Mensink RP. Preferential campesterol incorporation into various tissues in apolipoprotein E*3-Leiden mice consuming plant sterols or stanols. Metabolism 2008; 57: 1241–1247. 16. Jansen PJ, Lutjohann D, Abildayeva K, et al. Dietary plant sterols accumulate in brain. Biochem Biophys Acta 2006; 1761: 445–453.

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17. Othman RA, Moghadasian MH. Beyond cholesterol-lowering effects of plant sterols: clinical and experimental evidence of anti-inflammatory properties. Nutr Rev 2011; 69: 371–382. 18. De Lorgeril M, Renaud S, Mamelle N, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 1994; 343: 1454–1459. 19. De Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 1999; 99: 779–785. 20. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 2003; 348: 2599–2608. 21. Dod HS, Bhardwaj R, Sajja V, et al. Effect of intensive lifestyle changes on endothelial function

and on inflammatory markers of atherosclerosis. Am J Cardiol 2010; 105: 362–367. 22. Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med 2000; 343: 16–22.

This report has been funded by an educational grant from Danone.

Diabetes diary for 2012 congresses DATE

PLACE

CONFERENCE

8–11 February

Barcelona, Spain

5th International conference on advanced technologies and treatments for diabetes

15–17 February

Istanbul, Turkey

1st American Society of Nutrition Middle East Congress ‘Nutrition in Health and Disease’

7–9 March

Glasgow, UK

Diabetes UK professional conference 2012

19–22 March

Harrogate, UK

Society for Endocrinology BES 2012

22–25 March

Rio de Janeiro, Brazil

2nd Latin America congress on controversies to consensus in diabetes, obesity and hypertension

29–31 March

Riga, Latvia

AdiT 2012 – 4th International conference on advances in diabetes and insulin therapy

19–22 April

Bantry Bay, South Africa

SEMDSA/NOFSA 2012 congress

5–9 May

Florence, Italy

European congress of endocrinology

9–12 May

Lyon, France

19th European congress on obesity

24–27 May

Bonita Springs, USA

27th Annual clinical conference on diabetes

8–12 June

Philadelphia, USA

72nd American Diabetes Association scientific sessions (ADA)

23–26 June

Houston, Texas, USA

ENDO 2012

22–24 July

South Africa

Centres for Diabetes and Endocrinology (CDE)

13–16 September

Heidelberg, Germany

EMBO/EMBL Diabetes and obesity symposia

1–5 October

Berlin, Germany

48th European Association for the Study of Diabetes annual Meeting (EASD)

10–13 October

Istanbul, Turkey

ISPAD 2012 – 38th annual Meeting of the International Society for Pediatric and Adolescent Diabetes

7–9 November

Leeds, UK

40th Pacific Paediatric Endocrine Society biennial scientific meeting

22–25 November

Athens, Greece

Controversies to consensus in diabetes, obesity and hypertension

4–6 December

Dubai, UAE

1st American Diabetes Association Middle East Congress ‘Diabetes Prevention and Treatment’

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EASD WATCH SUMMARIES

2011 UPDATE FROM LISBON, PORTUGAL European Association for the Study of Diabetes Contributors: L Lombard, G Hardy, J Aalbers

DIABETES EPIDEMIC DEMANDS GLOBAL ACTION: FROM THE UN SUMMIT ON NON-COMMUNICABLE DISEASES Diabetes remains on its relentlessly upward trajectory. The International Diabetes Federation (IDF) figures for 2011 are 366 million people with diabetes globally. Deaths due to diabetes will number 4.6 million, with one person dying every seven seconds of complications related to diabetes. The global diabetes community expects commitment from international political leaders at the UN Summit on Non-Communicable Diseases (NCDs) focusing on the challenge posed by diabetes, cancer, heart and lung diseases. The Summit has the intention of creating concrete actions and measurable targets for prevention and control of NCDs worldwide, with particular focus on developing countries. Leading experts attending the EASD meeting demanded increased funding for research as a key commitment arising from the Summit. IDF President Jean-Claude Mbanya and EASD vice-president Andrew Boulton (South Africa) have jointly commented that ‘without urgent research into improved care and prevention models, we stand little chance of meeting any longterm targets that arise from the Summit’. Research into strengthening health systems should include developing and evaluating approaches for building care capacity, as well as integrating diabetes care with primary healthcare services that offer management of chronic infectious diseases and maternal and child health. Source: UN/NCD press release

Novel treatments In a session on novel agents in development for the management of type 2 diabetes, interesting new molecules were described. These included a GPR40 protein agonist

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(TAK-875) studied in a phase-two trial and compared to 4 mg glimepiride.1 There were 426 patients in the 12-week study, which achieved a 1% lowering in HbA1c levels, equal to that of glimepiride 4 mg. More than 40% of the patients achieved an impressive ≥ 1.5% lowering in HbA1c levels. There were fewer incidents of hypoglycaemia compared with glimepiride and few reported side effects. This molecule holds promise for the future. Another agonist, GPR119 (PSN-821) was also presented in a phase 1 trial. This receptor is present on the beta-cells as well as in the gastrointestinal tract.2 Previous studies have shown increased levels of insulin, GLP1, GIP and PYY. This study showed lowering of LDL cholesterol and of fasting blood glucose of 2 mmol/l.

It was a small study with only 25 patients who experienced no serious side effects. There was a tendency towards weight loss. HbA1c levels were not assessed and there were small changes in both fasting and postprandial glucose levels reported. The results were less impressive than the above study, although it was only in phase 1. Another product developed and tested in a phase 1 trial was a glucokinase activator in the liver. It showed several side effects and it appears that further development will not continue.3 Two speakers presented data on glucagon receptor antagonists. Although showing slight increases in liver enzyme levels, they displayed good lowering in HbA1c levels of 1–1.5%. One of the drugs has a very long half-life.

TABLE OF CONTENTS DIABETES EPIDEMIC DEMANDS GLOBAL ACTION: FROM THE UN SUMMIT ON NON-COMMUNICABLE DISEASES.......................................................... 178 Novel treatments................................................. 178 SGLT-2 inhibitors.................................................. 179 Exenatide vs liraglutide......................................... 179 46th Minkowski lecture....................................... 179 ADVANCES IN IMPLEMENTING LIFESTYLE CHANGES Improving health outcomes through peer diabetes education: lessons for primary healthcare.......... 180

INCRETIN MIMETICS: THE FUTURE OF TYPE 2 DIABETES MANAGEMENT................................. 182 Once-a-year GLP-1 dosage passes phase 2 trial.... 182 Liraglutide, the human GLP-1 analogue: safe in mild and moderate renal impairment in type 2 diabetes............................................................ 182 Achieving weight loss with incretin-based therapies, GLP-1 agonists and DPP-4 inhibitors.................. 182 Maintaining weight loss with liraglutide on adding insulin detemir: one-year follow-on results........ 182

BRAIN CONTROL OF SATIETY AND APPETITE Brain responses to food....................................... 180

The promise of DPP-4 inhibitors: use them early in the disease process....................................... 183

Gastric bypass alters central appetite control........ 180

CARDIOVASCULAR FOCUS IN DIABETES Provocative suggestion: that DPP-4 inhibitors could have a cardiovascular protection affect?............ 183

Other consequences of bariatric surgery: insulin sensitivity improves only in DM patients............ 180 High risk of depression in type 2 diabetics: motivation for monitoring of emotional well-being in collaborative care models............. 181 NUTRITION AND TYPE 2 DIABETES....................... 181 CLINICAL TRIALS OF INTENSIVE GLUCOSE LOWERING End-stage kidney disease (ESKD): ADVANCE trial.... 181 Understanding cardiovascular risk at HbA1c levels below 7%: ACCORD trial.................................. 181 UKPDS UPDATED RISK MODEL............................. 181

Type 2 diabetes patients with non-albuminuric renal impairment are still exposed to coronary events.183 Nephropathy........................................................ 183 Cardiovascular events and risk in type 2 diabetes: the latest insights and clinical trials . ....................... 183 MICROVASCULAR COMPLICATIONS: PERIPHERAL NEUROPATHY AND THE DIABETIC FOOT........... 183 Charcot foot........................................................ 183 FIELD study: fenofibrate reduction of amputations explored........................................................... 184

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Unfortunately, increased LDL and total cholesterol levels might be a worry for the future. These were also early phase 1 and 2 trials and we await new developments on these products.4,5 Source: 1. Viswanathan, et al. A randomised, doubleblind, placebo- and active-controlled, dose-ranging study to determine the efficacy and safety of the novel GPR40 agonist TAK-875 in subjects with type 2 diabetes mellitus. Presentation 187. 2. Goodman ML, et al. Orally administered GPR119 agonist PSN821 shows clinically significant glucose lowering and other potential cardiometabolic benefits in patients with type 2 diabetes. Presentation 188. 3. Bue-Valleskey JM. LY2599506, a novel glucokinase activator (GKA), improves fasting and postprandial glucose in patients with type 2 diabetes mellitus. Presentation 189. 4. Prince MJ, Short-term treatment with glucogon receptor antogonist LY 2409021 effectively reduces fasting blood glucose (FBG) and HbA1c in patients with type 2 diabetes mellitus. Presentation 190. 5. Engel SS. Efficacy and safety of the glucagon receptor antagonist, MK-0893, in combination with metformin or sitagliptin in patients with type 2. Presentation 190

SGLT-2 inhibitors A whole session was dedicated to selective glucose transporter-2 (SGLT-2) inhibitors, which are a new class of agents that inhibit glucose re-uptake in the proximal tubule of the nephron of the kidney. Dr Henry presented an eloquent talk on dapagliflozin with or without metformin.1 This was a 24-week randomised, double-blind, active control study with 640 patients in the trial. The results showed a 2% lowering of HbA1c levels with a 5-mg combination dose of dapagliflozin and metformin. This was more or less equal to the 10-mg dose, where about 3.3 kg weight loss was achieved. The main side effects were increase in incidents of vulvovaginitis, as well as balanitis, a slight increase in haematocrit, and lowering in uric acid level and systolic blood pressure of 3–4 mmHg. There were no hypoglycaemic incidents in the study. Another study on dapagliflozin combined with metformin, presented by Dr Bailey, was a randomised, double-blind, placebo-controlled trial over 102 weeks.2 Compared to the study presented by Henry, the results was positive. The results with 5 mg dapagliflozin combined with metformin were not as impressive (0.58% lowering in HbA1c levels) as 10 mg dapagliflozin plus metformin, which showed a 0.78% lowering in HbA1c levels. Body weight reduction was similar to that of the Henry study, with a weight loss of between 2.8 and 3.4 kg. Another new agent, empagliflozin, was

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explored in studies by groups from America and Germany, presented by Prof Julio Rosenstock.3 This was a dose-finding study in 495 patients over a period of 12 weeks. This was compared to sitagliptin and showed more or less equivalent HbA1c lowering of –0.6% and a 1.5-kg weight loss. Fasting blood glucose levels were lowered more than with sitagliptin. Source: 1. Henry R, et al. Dapagliflozin, metformin-XR or both together to initiate pharmacologic therapy for type 2 diabetes. Presentation 145. 2. Bailey CT, et al. Sustained efficacy of dapagliflozin when added to metformin in type 2 diabetes inadequately controlled by metformin monotherapy. Presentation 146. 3. Rosenstock J, et al. ENCORE: efficacy and safety of BI 10773, a new sodium glucose co-transporter-2 (SGLT-2) inhibitor, in type 2 diabetes patients inadequately controlled on metformin. Presentation 147.

Exenatide vs liraglutide The DURATION-6 trials evaluating exenatide once a week versus liraglutide head to head in a 1.8-mg dose with a 26-week follow-up period were presented. The liraglutide was up-titrated to a dose of 1.8 mg per day and exenatide was used in a 2-mg per week formulation. The primary objective was lowering of HbA1c levels after 26 weeks of follow up; 912 patients were randomised. GLP-1 analogues are known to have significant gastrointestinal side effects and withdrawals on many of these trials have been problematic in the past. Compared to exenatide once a week, there was slightly more withdrawals due to side effects in the liraglutide group. However liraglutide was more effective than weekly exenatide, which lowered HbA1c levels by 1.28% after 26 weeks, with a 2.68-kg weight loss (both statistically significant). Liraglutide lowered HbA1c levels 1.48% with a 3.58-kg weight loss. Both of these results were superior to the exenatide once-a-week dosage, although with slightly more side effects. Both exenatide and liraglutide lowered systolic blood pressure, as was showed in previous trials. The side-effect profile of liraglutide was significantly worse than the once-a-week exenatide, but the effect was slightly superior. None of these agents is currently available in this form in South Africa. Liraglutide is soon to be launched by Novo Nordisk in our country and it is unknown when exenatide once-a-week dosage will be

available. Both of these treatments will add significantly to our armamentarium and are keenly awaited. Source: Buse JB, et al. Efficacy and safety of exenatide once weekly versus liraglutide in subjects with type 2 diabetes (DURATIO-6): a randomised, open-label study. Presentation 75.

46th Minkowski lecture Prof Naveed Sattar from Glasgow presented a lecture titled ‘Exploiting biomarkers in large datasets for insights into diabetes and cardiovascular disease’. One of his first conclusions was that ALT levels, as a marker of liver dysfunction, increase with more metabolic abnormalities, while AST levels tend to stay fairly stable. In a meta-analysis, ALT was also shown to be a predictor of future diabetes risk. NAFLD (non-alcoholic fatty liver disease) has been shown to have a 2.5 hazard ratio for the development of diabetes. ALT was also shown to be linked to diabetes, with a 2.02 hazard ratio for the top quartile compared to the bottom quartile of ALT as a predictor of developing type 2 diabetes. The profile of fatty liver disease associated with diabetes is usually with ALT levels raised more than those of AST. Gamma GT is usually also raised, while HDL cholesterol is low, with the patient being overweight and glucose levels being abnormal. It was also shown that accumulation of liver fat could be decreased by regular exercise and increased fibre intake. Sattar also showed data on the complexity of the interaction between adiponectin and insulin resistance and suggested that the association between adiponectin and diabetes is not as simple as previously thought. He also stated that 50 to 70% of patients with type 2 diabetes have a variant of fatty liver disease. He went on to challenge the statement that type 2 diabetes is a cardiovascular risk equivalent, and showed data to suggest that this is not true at diagnosis. However, the diabetic person’s lifetime risk for cardiovascular disease is definitely increased and the duration of the disease is an important component of this risk. He also showed that when fasting glucose was used as a predictor of cardiovascular risk, cardiovascular disease (CVD) only increased when fasting glucose exceeded 6 mmol/l. Below this level, fasting glucose was not associated with increased CVD. Further data showed that of all the CVD

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risk factors, blood pressure lowering is the most efficient way of lowering cardiovascular risk, compared to glucose lowering and treatment for high cholesterol levels. Another interesting statistic recently published was that statin therapy increased the incidence of diabetes. For every three cardiovascular events prevented by using statins, one new diabetic was produced. Therefore patients with low cardiovascular risk and high risk of developing diabetes should not necessary be treated with statins. Source: 46th Minkowski lecture, EASD, Prof N Sattar.

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ulcers (DFU) was examined in China, where 33% of DFUs result in amputation. Findings indicated that individualised diabetic education may decrease the incidence of DFU, retard the progress of diabetic foot and reduce amputation rate and mortality. Source: Zhenghua X, et al. Individualised diabetic education can contribute to decrease the incidence of diabetic foot and avoid amputation: results of a 9-year prospective study. Presentation 61.

BRAIN CONTROL OF SATIETY AND APPETITE Satiety signalling in type 2 diabetes

ADVANCES IN IMPLEMENTING LIFESTYLE CHANGES Improving health outcomes through peer diabetes education: lessons for primary healthcare Diabetes requires a life-long process of selfcare, treatment and lifestyle changes. It is commonly accepted that diabetes patients should be made aware of the signs, symptoms and consequences of the disease. Studies relating to peer education for improving health outcomes in diabetes are rare in developing countries. An exception was the presentation of the recent Bangladesh study on the effectiveness of diabetes education with professional versus peer leaders. Among the peer leader group, significant reductions in systolic blood pressure, fasting blood glucose and HbA1c levels were found. Educational intervention by professionals also resulted in significant reductions in HbA1c levels. Fasting blood glucose was more significantly reduced in the peer leader group compared to the professional group. Study subjects of the professional group had significantly better diastolic blood pressure compared to the peer leader group. This emphasises the value of South Africa’s approach of using lay community workers to support the healthcare team. Source: Khan F, et al. Effectiveness of diabetes education on improving glycaemic achievement by professionals versus peers. Presentation 66.

Improved peer education outcomes for diabetic foot The significance of diabetic education on prevention and prognosis of diabetic foot

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Altered central satiety signalling in type 2 diabetes may be a barrier to weight loss. A surrogate marker of neuronal activation (changes in regional cerebral blood flow) has been used to examine the effect of type 2 diabetes on neuronal responses to feeding. Findings indicated that altered central satiety signalling in T2DM may be a barrier to weight reduction and lifestyle management in the treatment of T2DM. Source: Lee S, et al. Impact of type 2 diabetes on hunger and brain responses to eating: a continuous arterial spin labelling functional magnetic resonance imaging study. Presentation 135.

Brain responses to food Eating behaviour is also controlled by corticolimbic responses to food cues, which mature in man from childhood to early adulthood. Changes in such higher-functioning brain responses observed in obesity and type 2 diabetes may be implicated in their aetiology. Central control of appetite is an attractive target for weight reduction and diabetes control. Considering the increased risk of obesity and type 2 diabetes as an individual ages, Cheah and colleagues have investigated the effect of advancing age in adults on corticolimbic responses. It is established that BMI influences regional brain responses to food cues. Age may independently influence neural network responses to food that control appetite and eating behaviour. Reduced activation of these pathways may result in reduced control of food intake, which may be involved in the increased risk of obesity with rising age. Source: Cheah YS, et al. Both ageing and body mass modulate the human brain response to food cues. Presentation 133.

Gastric bypass alters central appetite control The role of the proximal intestine in the pathophysiology of type 2 diabetes mellitus has been the subject of growing interest. Gastric bypass surgery has been shown to resolve type 2 diabetes but the underlying mechanisms are incompletely understood. Studies have examined the improvement in glucose metabolism after gastric bypass surgery. Hunt and colleagues proposed that changes in gut-to-brain communication following Roux-en-Y gastric bypass (RYGB) may modulate central control of appetite. Findings indicate that the pattern of central neuronal deactivation in response to food ingestion is similar in those who have had RYGB and individuals of normal weight, but different from obese individuals who have not had surgery. These patterns may explain increased satiation with eating and the weight loss seen post-RYGB. Source: Hunt KF, et al. The brain’s response to food ingestion after Roux-en-Y gastric bypass: a [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) study. Presentation 137.

Other consequences of bariatric surgery: insulin sensitivity improves only in DM patients Svehlikova and colleagues quantified changes in insulin sensitivity1 before and shortly after gastric bypass surgery in type 2 diabetic (DM) patients and non-diabetic patients (non-DM) with severe obesity. Improvement in insulin sensitivity was marked in DM patients, independent of duration of disease. No such post-operative changes were observed in the non-DM group. Despite a markedly enhanced GLP-1 response in an oral glucose tolerance test, there was only a mild improvement in insulin secretion, which still remained impaired when compared to non-DM patients. An unexpected enhanced rise in glucagon levels during OGTT points to a substantial stimulatory effect of gastric bypass on alpha-cell function. The hypothesis that intestinal insulin resistance is an important factor in the pathophysiology of type 2 diabetes was investigated by Makinen and colleagues.2 Their aim was to non-invasively quantitate intestinal insulin-stimulated glucose uptake (GU) in obese patients before and after bariatric surgery.

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This study demonstrates that obese subjects with and without type 2 diabetes have significant insulin resistance in the proximal intestine. Jejunal GU is improved in line with whole-body and skeletal muscle insulin sensitivity after bariatric surgery and the recovery of diabetes. The findings suggest that intestinal insulin resistance is an important factor in T2DM. Source: 1. Svehlikova E, et al. Improved glucose metabolism early after gastric bypass surgery relies primarily on enhanced insulin sensitivity. Presentation 182. 2. Makinen J, et al. Intestinal insulin resistance associated with obesity and type 2 diabetes. Presentation 185.

High risk of depression in type 2 diabetics: motivation for monitoring of emotional well-being in collaborative care models The risk of depression is doubled in individuals with type 2 diabetes, often presenting as a chronic condition. The incidence and recurrence/persistence of depression and significant predictors thereof have been examined in a cohort of 2 460 primary-care patients with type 2 diabetes. Female gender, low levels of education, microvascular disease, other co-morbid conditions and stressful life events were all positively associated with incident depression. Low educational level was the only significant predictor of recurrent/persistent depression.1 Diabetes has a considerable impact on health-related quality of life (HRQL). A prognostic link between self-reported HRQL and unfavourable outcome has not been well explored in patients with type 2 diabetes and acute myocardial infarction. It was found that a low self-reported HRQL score is of prognostic significance and can therefore serve as an easily obtained indicator of patients at high risk for all-cause and cardiovascular mortality. The predictive value appeared to be higher in men.2 Source: 1. Kjellstrom B, et al. Health-related quality of life predicts survival in patients with type 2 diabetes and myocardial infarction: a report from the DIGAMI2 trial. Presentation 6. 2. Nefs G, et al. The course of depression in primary care patients with type 2 diabetes: results from the DiaDDZoB study. Presentation 213.

NUTRITION AND TYPE 2 DIABETES There is still limited understanding on how dietary macronutrient composition is linked

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with long-term risk of obesity-related chronic disease. Diets high in protein have shown promising results on short-term weight reduction and glycaemic control. However, high-protein diets were associated with increased risk of type 2 diabetes. Replacing protein with carbohydrates, particularly fibre-rich breads and cereals, was inversely associated with type 2 diabetes.1 The increased consumption of a Western diet high in refined sugar and fat has led to increased rates of obesity, insulin resistance and type 2 diabetes mellitus. The effect of high sugar intake in adolescence is less well demonstrated. Lewis and colleagues have studied the effect of sugar intake in early teenage years on glucose tolerance and insulin resistance in early adulthood. Higher dietary sugar intake in early teenage years independently affected longer-term glucose metabolism and was associated with higher fasting plasma glucose and relative insulin resistance. There was no such association for high dietary sugar intake in early adulthood. These findings indicate a potential legacy effect of the adolescent diet and a need to address dietary advice in this age group The ability to identify obese subjects who will lose weight in response to energy restriction is an important strategy in clinical care of obesity. Kong and colleagues have concluded that individual responses to hypocaloric high-protein, fibre-rich dietary programmes could be predicted by plasma insulin, IL-6, leukocyte numbers and adipose tissue HAM56 levels prior to diet.3

trial found that an intensive blood glucoselowering regimen (HbA1c < 6.5%) based on gliclazide MR reduced the risk of ESKD, but the effects on other renal outcomes were less clear.

Source: 1. Ericson UC, et al. High intake of protein and processed meat is associated with increased incidence of type 2 diabetes. Presentation 13. 2. Lewis AS, et al. A prospective longitudinal observational study on the effect of dietary sugar intake in adolescence and early adulthood on measures of glucose metabolism in early adulthood. Presentation 237. 3. Kong L, et al. Plasma insulin and inflammatory markers prior to weight loss can predict dietary responders. Presentation 16.

The United Kingdom Prospective Diabetes Study (UKPDS) outcomes simulation model for type 2 diabetes predicts development and consequences of diabetes complications, enabling economic evaluation of interventions. This model has been extended and enhanced, with additional risk factors. Micro- or macroalbuminuria was a significant covariate in eight equations (including death and renal failure); peripheral vascular disease was significant in seven equations (including death and amputation) and white blood cell count in four equations (including first stroke and blindness). Notably, atrial fibrillation was associated with high risk of first stroke and heart failure.

CLINICAL TRIALS OF INTENSIVE GLUCOSE LOWERING End-stage kidney disease (ESKD): ADVANCE trial Blood glucose levels have been linked to the risk of kidney disease, but the effects of intensive glucose control on major kidney outcomes among people with diabetes are not known. An analysis from the ADVANCE

Source: Zoungas S, et al. Intensive glucose lowering and end-stage kidney disease: new data from the ADVANCE trial. Presentation 39.

Understanding cardiovascular risk at HbA1c levels below 7%: ACCORD trial The ACCORD trial reported significantly higher mortality in type 2 diabetes patients treated with intensive glucose lowering (target HbA1c < 6%) versus standard treatment (target HbA1c 7â&#x20AC;&#x201C;7.9%). The ACCORD findings are contextualised with outcomes estimated from other data sources, by comparison of relative risks of non-fatal MI, non-fatal stroke, heart failure and all-cause mortality. Relative risk of all-cause mortality in ACCORD was significantly different from previous data. This difference was not seen in the other endpoints, was not consistent across recent studies and was not fully explained by hypothesising a lower limit of 7% for HbA1c benefit. Observed mortality effects in the ACCORD trial may have been related to factors other than glucose lowering. Source: Foos V, et al. Comparison of ACCORD trial outcomes with outcomes estimated from modelled and meta-analysis studies. Presentation 3.

UKPDS UPDATED RISK MODEL

Source: Hayes AJ, et al. An improved model to estimate lifetime health outcomes of patients with type 2 diabetes using 30-year follow-up data from the United Kingdom prospective diabetes study. Presentation 4.

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INCRETIN MIMETICS: THE FUTURE OF TYPE 2 DIABETES MANAGEMENT A miniature osmotic pump the size of a matchstick may revolutionise treatment of type 2 diabetes with insulin mimetics (and perhaps other agents).

Once-a-year GLP-1 dosage passes phase 2 trial The DUROS subcutaneous delivery system is currently being used with exenatide in phase 2 trials. This system offers patients and their healthcare systems a once-a-year non-injectable exenatide, which delivers continuous and consistent levels of this GLP-1 agonist. The investigational study of ITCA 650, as it is called, has now determined a likely dose regimen for phase 3 trials on an initial three-month ITCA 650 dosing of 20 µg/ day, followed by the subcutaneous implantation of a second device for 6- and 12-µg duration supplying 60 µg/day. The phase 2 trial results showed consistent plasma levels of exenatide up to 48 weeks with undetectable levels within 24 hours of device removal. Patients in the trial showed sustained reductions in HbA1c levels, FPG and weight reduction. Side effects were greatly reduced and there were no discontinuations due to nausea. The DUROS device is also in phase 2 clinical studies in prostate cancer research, delivering androgen reduction therapy. Source: Luskey K, et al. Presentation 77. EASD Oral Presentation

Liraglutide, the human GLP-1 analogue: safe in mild and moderate renal impairment in type 2 diabetes A meta-analysis of seven clinical trials has assessed the safety and efficacy of oncedaily liraglutide in mild (estimated creatine clearance < 90 ml/min) renal impairment. This review showed that reductions in HbA1c levels were similar regardless of renal impairment. The proportion of any patients experiencing major hypoglycaemic episodes was very low (0–0.2%) and not related to renal function. Minor hypoglycaemic events seemed lower in the renalimpaired group and overall, liraglutide was effective and well tolerated in these type 2 diabetes patients.

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Key notes on macrovascular complications

• Advanced glycation end products (AGE) are not found in higher concentrations in the atherosclerotic plaque of diabetics, compared to patients without diabetes undergoing carotid endarterectomy (Presentation 1264). • An HbA1c level of 6.3% has the lowest risk of cardiovascular events and mortality, according to a study of 40 000 type 2 diabetes patients in a Swedish registry (Presentation 153). • The use of a serum glycated albumin (GA)/HbA1c ratio was found to be useful in type 2 diabetes Japanese patients, with values above 3% being indicative of presence of plaque (Presentation 1265). • The newly developed Canadian iScore, used after ischaemic stroke, has been shown to have a high predictive accuracy also in diabetes patients (Presentation 1254). • In non-diabetics who are at high risk of developing diabetes, a yearly increase in the normal HbA1c level (5.7%) of 0.1% was associated with an increase in aortic stiffness comparable to being two years older (Presentation 152). • Obesity without insulin resistance does not raise and seemed to lower cardiovascular disease risk, according to a six-year follow-up study comparing ‘metabolically benign obesity’ to normal-weight individuals with insulin resistance (Presentation 222). • Non-alcoholic fatty-liver disease (NAFLD), as measured by liver ultrasound scan and biochemically, is a major risk factor for cardiovascular events in patients with type 2 diabetes. These patients should be treated and cared for by both an internist and a cardiologist, as their cardiovascular events are three times that of type 2 diabetes patients without NAFLD (Presentation 246).

Source: Gough S, et al. Reductions in HbA1c and the incidence of hypoglycaemic episodes are not affected by renal impairment in patients with type 2 diabetes, treated with liraglutide. Presentation 822.

Achieving weight loss with incretin-based therapies, GLP-1 agonists and DPP-4 inhibitors This study of the data of approximately 1 200 patients treated in two large, randomised trials was used to determine the number of patients reaching the target HbA1c level of less than 7% and weight loss after 26 weeks of treatment with either liraglutide 1.8 mg or 1.2 mg daily on top of metformin and/or sulphonylurea therapy. Patients receiving the higher dose of liraglutide were most likely to reach target HbA1c levels and achieve weight loss (–3 kg) than on the other two therapies. This was a post-hoc evaluation, which supports available clinical trial data on these agents. Source: Zinman, et al. Achieving glycaemic control and weight loss with incretin-based therapies. Presentation 798.

Maintaining weight loss with liraglutide on adding insulin detemir: one-year follow-on results The issue of weight loss in the face of adding insulin to a type 2 diabetes patient’s regimen is one that troubles patients and their clinicians. Further follow up of patients on metformin and liraglutide (1.8 mg) for 12 weeks (run-in period) who were not achieving their HbA1c target levels and then randomised to continue on oral therapy (keeping HbA1c < 8%) or to receive 10 U insulin detemir daily has shown no weight increase with the addition of insulin detemir in the following 52 weeks. Weight loss continued in those receiving oral therapy only. Minor hypoglycaemic rates were very low in both arms and no major hypoglycaemic episodes occurred in the one-year treatment period. Source: Bain SC, et al. Adding insulin detemir (I Det) to liraglutide and metformin improves glycaemic control with sustained weight reduction and low hypoglycaemic rates: 52 weeks. Presentation 73

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SA JOURNAL OF DIABETES & VASCULAR DISEASE

The promise of DPP-4 inhibitors: use them early in the disease process An 18-month study of patients presenting with type 2 diabetes who were not yet on treatment has shown that initial therapy with saxagliptin plus metformin (dual oral therapy) achieved more sustained glycaemic control than monotherapy using either of these agents. This randomised, phase 3, double-blind parallel group study1 included 1 300 patients with type 2 diabetes inadequately controlled with diet and exercise. Patients were randomised to oral saxagliptin 5 mg or metformin; 10 mg saxagliptin plus metformin; 10 mg saxagliptin; or metformin only. The mean duration of type 2 diabetes was 1.7 years and patients were young (mean age 52 years). The initial dual therapy with saxagliptin (5 or 10 mg) and metformin consistently resulted in more patients achieving glucose control over 18 months than those on metformin only, regardless of the baseline characteristics of the patient. The results of this approach suggest that glucose control may be more likely when dual oral therapy is initiated early. A second study (PROMPT) used saxagliptin (5 mg/daily) instead of up-titrating metformin from 1.5 g/day to 2.5 g/day. The saxagliptin addition was better tolerated and achieved similar HbA1c reductions to the larger metformin dose.2 Source: 1. Frederick F, et al. Clinical characteristics and sustained glycaemic control: a 76-week, randomised double-blind study of saxagliptin and metformin in treatment-naïve patients with type 2 diabetes. Presentation 829 2. Hermans MP, et al. Effects of saxagliptin added to sub-maximal doses of metformin compared with dose calculation of metfomin in type 2 diabetes: results from the PROMPT study. Presentation 828.

CARDIOVASCULAR FOCUS IN DIABETES Provocative suggestion: that DPP-4 inhibitors could have a cardiovascular protection affect An evaluation of all available trials with DPP-4 inhibitors used for longer than 24 weeks in type 2 diabetes patients was done to assess issues of cardiovascular safety. Major cardiovascular events (MACE) were fewer in the patients given DPP-4 inhibitors compared to placebo or another treatments. While suggesting little more than no adverse events, this arena will require much more attention in randomised controlled

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EASD WATCH

trials for diabetes drugs, as suggested by many cardiovascular experts. Source: Lamanna C, et al. DPP-4 inhibitors and CV events: a protective effect? Presentation 244.

Type 2 diabetes patients with nonalbuminuric renal impairment are still exposed to coronary events This study of 9 865 type 2 diabetes patients from the Renal Insufficiency and Cardiovascular Events (RACE) trial showed that non-albuminuric renal impairment was more strongly associated with myocardial infarction and the need for coronary revascularisation than with stroke or the need for carotid revascularisation. However, patients with micro- or macroalbuminuria had higher rates of coronary events. Source: Pugliese G, et al. Association of Normoalbuminuric renal impairment with cardiovascular disease. Presentation 38.

Nephropathy In an interesting talk from the Netherlands, Dr I Drion presented data from a study on diabetic individuals over 75 years of age (Zodiac-24 study) with decreased kidney function. Estimated glomerular filtration rate (GFR) was calculated by the MDRD and Cockcroft-Gault formula. It is well known that albuminuria and decreased GFR in type 2 diabetes patients is associated with increased cardiovascular mortality. This has not been studied in this age group. Estimated GFR is often decreased in this older population group. During this study on 347 patients over 75 years, a large percentage died. The patients were stratified into three categories, those with estimated GFR < 45 ml/min/1.73 m2, those with GFR 45–60 ml/min/1.73 m2 and those with > 60 ml/min/1.73 m2. The study showed that patients with albuminuria had increased risk of mortality, but not those with only GFR 45–60 ml/ min/1.73 m2 in the age group over 75 years. Source: Drion I, et al. Chronic kidney disease and mortality risk among elderly diabetic individuals (ZODIAC-24). Presentation 37

Cardiovascular events and risk in type 2 diabetes: the latest insights and clinical trials Osteoprotegerin (P-OPG) a bone-related glycopeptide produced by vascular smooth

muscle has been shown to be a useful independent predictor of the presence of coronary artery disease in asymptomatic type 2 diabetes patients with microalbuminuria. This Danish study used myocardial perfusion imaging and CT angiography to correlate the presence of arterial disease with P-OPG levels in 200 asymptomatic type 2 diabetes patients. Importantly, patients with low levels of P-OPG did not have significant artery stenosis. Source: Reinard H, et al. Osteoprotegerin and CAD in type 2 diabetic patients with microalbuminuria. Presentation 1283.

MICROVASCULAR COMPLICATIONS: PERIPHERAL NEUROPATHY AND THE DIABETIC FOOT Peripheral neuropathy, a significant microvascular complication of diabetes, leads to impaired quality of life, and is a primary determinant of lower-limb ulcer formation and amputation. In the UK, it has been found that diabetic patients of South Asian origin have one-third the risk of foot ulceration compared to Europeans. In an attempt to define differences in predisposing risk factors for ulceration, Fadayi and colleagues found that despite worse glycaemic control, Asian patients had better small-fibre function and structure compared to European diabetic subjects. Furthermore, they had higher foot skin oxygenation and hyperaemic blood flow response to heating, which may protect from the development of foot ulceration. Source: Fadavi H, et al. Potential explanation for lower incidence of foot ulceration in Asian compared to European patients with type 2 diabetes. Presentation 7.

Charcot foot The mechanisms of pathological bone resorption in acute Charcot osteo-arthropathy are not fully understood. It has been demonstrated that receptor activator of nuclear factor κβ ligand (RANKL) plays an important role as an activator of osteoclastic resorption in acute Charcot osteo-arthropathy. However, it is not known whether RANKL-mediated osteoclastic resorption can be modulated by the pro-inflammatory cytokines TNF-α and IL-6. Peripheral blood mononuclear cells, which act as osteoclast precursors, were cultured in vitro on bovine disks in the pres-

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ence of (1) macrophage colony-stimulating factor (M-CSF) and RANKL, (2) M-CSF, RANKL and neutralising antibody to TNF-α, and (3) M-CSF, RANKL and neutralising antibody to IL-6. The addition of neutralising antibody to TNF-α to the cultures with M-CSF and RANKL led to a marked decrease in the osteoclastic resorption only in patients with Charcot osteoarthropathy. The addition of neutralising antibody to IL-6 had a variable effect on the osteoclastic resorption in the three groups. It led to a significant decrease in osteoclastic resorption in patients with acute Charcot osteoarthropathy and to a non-significant decrease in healthy controls. Unexpectedly, it led to a significant increase in bone resorption in patients with diabetes.

The potential role of agents reducing pro-inflammatory cytokines remains uncertain in treatment of Charcot foot. Source: Petrova NL, et al. The proinflammatory cytokines TNF-α and IL-6 modulate RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. Presentation 11.

FIELD study: fenofibrate reduction of amputations explored In this large study of type 2 diabetes patients on treatment with co-micronised fenofibrate 200 mg per day, foot sensation as measured by monofilament test improved. This is likely to be the basis of the 37% reduction in amputations found in the added fenofibrate arm of the FIELD study.

The presence of peripheral neuropathy was assessed by standard 10-G monofilament at baseline, year two, and at study close after five years; 17.2% of participants had features of peripheral neuropathy at baseline (1 125 with symptoms only, 564 had abnormal monofilament assessment). Prevalence of abnormal monofilament test at the end of the study was significantly lower in the fenofibrate arm (6.9 vs 8.2%). The NNT to avoid a first on-study amputation over the five-year study was only 16. Source: Keech AC, et al. Predictors of peripheral neuropathy and effects of fenofibrate among 9,795 subjects with type 2 diabetes: the fenofibrate intervention and event lowering in diabetes (FIELD) study. Presentation 180.

Novo Nordisk (Pty) Ltd. Reg. No.: 1959/000833/07. PO Box 783155, Sandton, 2146. Tel: (011) 202 0500 Fax: (011) 807 7989 NN/DUO/4145/07/10/VER1

Cardiovascular diary for 2012 congresses DATE

PLACE

CONFERENCE

1–3 February

New Orleans, USA

Internatioanl Stroke Conference www.heart.org

18 February

Frankfurt, Germany

TrenD 2012 – Transcatheter renal denervation www.ici-congress.org

18–21 April

Dubai, United Arab Emirates

World Congress of Cardiology www.world-heart-federation.org

3–5 March

Southern Sun Cape Sun, Cape Town, South Africa

17th Biennial Congress of the SA Hypertension Society Congress (SAHS) www.hypertension.org.za

17–20 May

Berlin, Germany

Congress on cardiac problems in pregnancy (CPP 2012) www.cppcongress.com

27 June

Frankfurt, Germany

ICI 2012 – Imaging in cardiovascular interventions www.ici-congress.org

28 June

Frankfurt, Germany

CSI 2012 – Catheter interventions in congenital and structural heart disease

19–22 July

Sun City, South Africa

13th Annual SA Heart Congress www.saheart.org

25–29 August

Munich, Germany

2012 ESC – European Society of Cardiology Congress www.escardio.org

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Diabetes News

New stem cell cryopreservation laboratory in Cape Town

he use of stem cell technology in the therapeutic arena is an increasingly tangible objective in medical science. Currently, the are 70 medical conditions (primarily blood diseases) that can be treated by the application of stem cell technology, with more than 3 000 clinical trials in progress. Future medical applications are continuously being researched and discovered, among which are some showing promising results in human diabetes therapy. As genetic understanding of type 1 diabetes increases, the value of stem cell storage could become a reality. The incidence of type 1 diabetes is on the increase globally. Recent research among children with a family history of type 1 diabetes shows that Western lifestyles and associated overweight/obesity may trigger increased risk of Islet autoimmunity, with associated increased insulin resistance.1 Internationally, trends reflect the importance of stem cell banking. These stem cells can mean the difference between life and death in the case of future threats to the health of the donor. Saving stem cells at birth is truly a once-in-a-lifetime opportunity for baby, siblings and parents. There is a one-in-four chance of the tissue matching the siblings and a one-in-eight chance of the tissue matching the parents. In the USA, transplants performed on patients younger than 18 years of age show that more than 50% of stem cell transplantations have cord blood as the cell source. It is legislated in 27 American states that expectant parents have to be informed of the possiblity of stem cell storage by their attending medical expert. Cryo-Save NV, the leading international family stem cell bank, represented in 40 countries on four continents, already stores 185 000 samples from cord blood and umbilical cord tissue for newborns, and adipose tissue for adults. Cryo-Save South Africa has opened a state-of-the-art stem cell processing and storage laboratory in Cape Town, providing best-practice medical services with sound governance and commercial practice. Cryo-Save South Africa has employed professional, dedicated and highly-skilled staff to operate the new laboratory. Key personnel have undergone specialised train-

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ing at Cryo-Save’s state-of-the-art facility in Belgium. The Cape Town laboratory will immediately process and store cord tissue as well as stem cells from cord blood. To ensure that extracted stem cells are viable, flow cytometry testing is performed prior to storage. Cryopreservation storage facilities are not dependant on electricity supply and are isolated from external power cuts. Clients have

the option to store in South Africa or Belgium, or to select dual storage of a sample in South Africa and in Europe. G Hardy 1.

Couper JJ, Beresford S, Hirte C, Baghurts PA, Pollard A, Tait BD, et al. Weight gain in early life predicts risk of Islet autoimmunity in children with a firstdegree relative with type 1 diabetes. Diabetes Care 2009; 32(1): 94–99.

Case study A patient with a family history of type 1 diabetes mellitus is delighted that her daughter is pregnant. With the knowledge that the grandchild may be at risk of inheriting this condition, the practitioner feels it suitable to advise stem cell storage from the grandchild. Future stem cell therapy may be beneficial to the lifelong health of the grandchild. • On registration, a collection kit and information pack are sent to the client. • Umbilical cord stem cells are collected immediately after birth by the attending medical professional with no risk to either mother or child. The procedure is painless and non-invasive and does not affect the natural sequences of birth at all. • Specialist medical couriers deliver the sample to the Cape Town laboratory within 24 hours, where the cells are professionally processed and stored according to the highest international standards. Contact Tel: 0860 STEM CELLS (0860 7836 2355) Tel: +27 11 803 4409 Fax: 086 219 9157 e-mail: info@cryo-save.co.za Web: www.cryo-save.co.za

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SA JOURNAL OF DIABETES & VASCULAR DISEASE

DIABETES NEWS

Getting together: a diabetes youth camp in Stellenbosch

he Journal was recently invited to attend a diabetes youth camp in Jonkershoek, arranged by Sister Kamaretha Beckert and Dr Nickie Bernard. A multi-disciplinary team also volunteered their services at the camp. Some 40 children between the ages of 6 and 16 years had the opportunity of attending and learning how to cope and thrive despite their diabetes. These youth shared experiences and fears in a safe environment. Among the emotions experienced by the child with diabetes are anxiety, anger and depression, as well as fear of needles, death, hospitalisation, rejection and humiliation, and these require careful handling. Ms Rosemary Flynn, clinical psychologist who is also diabetic, had advice for parents. ‘Find a place for the diabetes where it neither rules, nor is neglected. Because of their diabetes, these children may develop special aptitudes. But they are still children of their particular age, confronting other issues independent of and possibly exacerbated by their diabetic status.’

Flynn recommends developing a childcentred approach within the context of authoritative parenting. ‘Be warm, accepting and loving, but clear about the boundaries. As parents, you need to cultivate in the diabetic child self control, initiative and an outgoing approach to life. ‘By listening carefully, accepting the child’s view and not getting hooked on the parental agenda, being patient and expressing your delight in your child’s achievement, big or small, fears and anxieties can be dealt with and placed in a non-dominant sphere’, she concluded.

Innovative support for diabetic lifestyles Do you know about the following useful resources for your young diabetic patients and their parents? • The Blackberry application: Calorie counter by Fat Secret can really help with carb counting for insulin calculation. The application supplies calorie totals and macro-ingredients of meals from popu-

lar restaurants (Wimpy, St Elmo’s pizzas, Steers and many others) as well as the calorie levels of common foods bought in stores throughout the country. • The Emotion of Children with Diabetes: this useful and practical guide for parents is by Rosemary Flynn. A CDE-sponsored publication, this book provides a practical guide to coping with the emotional ups and downs of children with diabetes. • Diabetes vir Kinders: for Afrikaans families, Sr Kamaretha Beckert has created an information file targeted at those children who have recently been diagnosed with diabetes. Available at all Medi-clinics who have partnered in this educational project, this colourful file helps children to understand and manage their condition, with simple clear explanations about the biology and day-to-day requirements of their disease. • Accu-Chef Cookbook: published by AccuCheck, this is a beautifully illustrated and clearly set out book. The teenager or young adult is likely to find inspiration from this collection of easy-to-make recipes.

Dr Landi Lombard chatting to the teenagers about hypoglycaemia.

Exercise and outdoor activities are essential for staying healthy with diabetes.

Young people who attended the diabetes youth camp with their mentors.

Parents and their children getting much-needed support and advice.

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Celebrating World Diabetes Day ‘Act on Diabetes Now’ 2011 marks the third year of the five-year focus on ‘diabetes education and prevention’, the theme selected for World Diabetes Day from 2009 to 2013. The campaign calls on all those responsible for diabetes care to ‘act on diabetes now” With the first-ever UN high-level meeting on non-communicable diseases held in September, World Diabetes Day will provide the platform to cement the decisions and outcomes of global decision makers. At the same time, World Diabetes Day will provide impetus and inspiration for the diabetes community when they gather for the World Diabetes Congress in Dubai in December. With 2011 being a milestone year for the over 300 million people living with diabetes, five key messages have been developed to inform the outputs and deliverables of this 2011 campaign: • Diabetes kills: one person every eight seconds, four million people a year. • Diabetes doesn’t discriminate: all ages, rich and poor, all countries are affected. • Diabetes can no longer be ignored: four million lives are lost a year, one million amputations a year, millions are lost in income and productivity. • Life-saving care, a right not a privilege: education, medicines and technologies are needed, particularly in the developing world. • Choose health: the general public needs to demand healthy food and environments, and to keep active and eat well. You can make a difference.

November, leading up to World Diabetes Day, on 14 November this year. The campaign reinforces the importance of exercise in managing diabetes. People with diabetes are encouraged to do the Big Blue Test on any day between 1 and 14 November at midnight Pacific Time, by testing their blood sugar, getting active, testing again, and sharing the results online at bigbluetest.org. Remember: just 14 minutes of exercise decreases participants’ blood sugar levels between 15 and 20%. In 2010, more than 2 000 people did the Big Blue Test. Over 120 000 people watched the Big Blue Test video. Roche Diabetes Care, makers of Accu-Chek® diabetes products and services, funded the production of the video and incentived participation by donating 75 cents for each of the first 100 000 views, resulting in a total donation of $75 000. The donation provided insulin and supplies to more than 2 000 people with diabetes in developing countries. In 2011, in proportion to the number of people that do the Big Blue Test, another donation from Roche Diabetes Care will benefit more than 8 000 needy people with diabetes. Five non-profit organisations, focused on helping underserved areas with a high incidence of diabetes in the USA, will each receive $10 000, while $25 000 will go to support the work of the International

Diabetes Federation’s (IDF’s) Life for a Child Programme in Latin America. World Diabetes Day Blue Monument Challenge In 2010 the IDF encouraged a Monument Challenge on 14 November. More than 1 000 iconic sites and buildings around the world were lit up in blue, honouring World Diabetes Day. They encouraged a further challenge for 2011 with already 900 monuments scheduled to go blue. Buildings joining this challenge include: the AAMI Park in Melbourne, the Eye in London, Yula River bridge in China, California State Capital building, USA, and Burj-al-Arab in Dubai. South Africa’s very own Voortrekker Monument in Pretoria has joined the cause by also going blue. Visit Flicker under World Diabetes Day Blue Monument Challenge to view the magnificent sites. What did South African Diabetes leaders do? Novo Nordisk arranged a Changing Diabetes concert, which was held on 5 November. This concert featured South African artists such as Tshepo Mosese, Danny K, Teargas and Kabelo. Their Changing Diabetes bus was also on site for free diabetes screening, creating awareness of the disease.

While the campaigns last the whole year, 14 November is the official day, celebrating Frederick Banting’s birthday. He, along with Charles Best first conceived the idea which led to the discovery of insulin in 1922.

What is the world doing for World Diabetes Day in 2011? Here are just a few of the main events commemorating World Diabetes Day. The Big Blue Test – you can join in! The Big Blue Test is a diabetes awareness programme celebrated in countries such as the USA, UK and Spain. The Big Blue Test was started by the non-profit Diabetes Hands Foundation, and takes place every

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A really effective diabetes screening initiative, Novo Nordisk’s bus is popular whereever it goes, often into rural areas in South Africa.

VOLUME 8 NUMBER 4 • NOVEMBER 2011

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No other basal insulin can offer you more References 1. Blonde L et al. Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets – the TITRATE™ study. Diabet. Obes. and Metab. 2009;11:623–631. 2. Philis-Tsimikas A et al. Comparison of Once-Daily Insulin Detemir with NPH Insulin Added to a Regimen of Oral Antidiabetic Drugs in Poorly Controlled Type 2 Diabetes. Clin Ther 2006;28(10):1569–1581. 3. Rosenstock J et al. A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetologia 2008;51:408–416. 4. Hermansen K et al. A 26-Week, Randomized, Parallel, Treat-to-Target Trial Comparing Insulin Detemir With NPH Insulin as Add-On Therapy to Oral Glucose-Lowering Drugs in Insulin-Naïve People with Type 2 Diabetes. Diabetes Care 2006;29(6):1269–1274. 5. Klein O et al. Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profiles but less variability than insulin glargine in type 2 diabetes. Diabet. Obes. and Metab. 2007;9:290–299. 6. World IMS Data, September 2009. Proprietary Name: Levemir®. Scheduling Status: S3 Composition: Insulin detemir 100 units /ml. Indication: Treatment of insulin requiring patients with diabetes mellitus. Registration Number: 38/21.1/0084. For full prescribing information refer to package insert approved by the medicines regulatory authority. Novo Nordisk (Pty) Ltd. Reg No. 1959/000833/07. PO Box 783155, Sandton 2146. Tel: (011) 202 0500 Fax: (011) 807 7989 www.novonordisk.co.za NN/DUO3817/02/2010ver1