Diabetes Voice by International Diabetes Federation

Volume 56 –June 2011

Emerging therapies for diabetes

SPECIAL ISSUE

GLOBAL PERSPECTIVES ON DIABETES

DiabetesVoice

CONTENTS

DIABETES VIEWS

DEVELOPING CARE DELIVERY WORLDWIDE

Diabetes Voice is published quarterly and is freely available online at www.diabetesvoice.org.

Building expertise in nutrition and behaviour in the Colombian Caribbean: promising advances against diabetes

Diabetes self-management education: an effective response to the increasing burden in under-served communities

Esteban Mayor Gómez and Astrid Arrieta Molinares

Elizabeth Paz-Pacheco

Appraising the Multi-SAFE approach to low vision and diabetes: a simple technique for saving feet 14

Ann Williams

A multi-partner approach to developing excellence in diabetes management training in four African countries

Joseph Drabo, Assa Sidibé, Serge Halimi, Stéphane Besançon

S C I E N C E AT T H E C U T T I N G E D G E A future of glucose-responsive insulin secretion: bionics versus nature

Pratik Choudhary, John Pickup, Peter Jones, Stephanie A Amiel

Looking for new pharmacological treatments for type 2 diabetes

Cristina Bianchi and Stefano Del Prato

IDF first to address the question: is bariatric surgery good for diabetes?

Carel LeRoux on behalf of the IDF Taskforce on Epidemiology and Prevention of Diabetes

Translating evidence into practice: improving access to HbA1c in sub-Saharan Africa

Diabetes care at the centre of Australia: grassroots care and prevention

Sharing hope and improving care – Haiti builds for a brighter future

Can shared care improve outcomes in women with gestational diabetes?

Eugene Sobngwi and Naby Balde

Elizabeth Barr, Alex Brown Baker, John Boffa, Paul Zimmet

Xilin Yang and Huiguang Tian

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The production of this Special Issue has been made possible thanks to the support of Lilly Diabetes. This publication is also available in French, Spanish and Russian. Editor-in-Chief: Stephanie A Amiel, UK Managing Editor: Olivier Jacqmain, olivier@idf.org Editor: Tim Nolan, tim@idf.org Advisory group: Pablo Aschner (Colombia), Ruth Colagiuri (Australia), Patricia Fokumlah (Cameroon), Attila József (Hungary), Viswanathan Mohan (India). Layout and printing: Luc Vandensteene, Ex Nihilo, Belgium, www.exnihilo.be All correspondence and advertising enquiries should be addressed to the Managing Editor: International Diabetes Federation, Chaussée de la Hulpe 166, 1170 Brussels, Belgium Phone: +32-2-5431626 – Fax: +32-2-5385114 – olivier@idf.org

WAYS F O R WA R D F O R B E T T E R CA R E

John Devlin

International Diabetes Federation Promoting diabetes care, prevention and a cure worldwide

© International Diabetes Federation, 2010 – All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means without the written prior permission of the International Diabetes Federation (IDF). Requests to reproduce or translate IDF publications should be addressed to the IDF Communications Unit, Chaussée de la Hulpe 166, B-1170 Brussels, by fax +32-2-5385114, or by e-mail at communications@idf.org. The information in this magazine is for information purposes only. IDF makes no representations or warranties about the accuracy and reliability of any content in the magazine. Any opinions expressed are those of their authors, and do not necessarily represent the views of IDF. IDF shall not be liable for any loss or damage in connection with your use of this magazine. Through this magazine, you may link to third-party websites, which are not under IDF’s control. The inclusion of such links does not imply a recommendation or an endorsement by IDF of any material, information, products and services advertised on third-party websites, and IDF disclaims any liability with regard to your access of such linked websites and use of any products or services advertised there. While some information in Diabetes Voice is about medical issues, it is not medical advice and should not be construed as such.

ISSN: 1437-4064 Cover photo © Laurence Gough - istockphoto.com

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DIABETES VIEWS

THE EMERGING RESPONSE TO DIABETES

This is particularly important in sub-Saharan Africa and the Indian Subcontinent, where high levels of under-nutrition co-exist with rapid changes in nutrition in young adulthood. India is home to a quarter of the world’s starving people. Yet it also has the second largest diabetes population in the world ‒ over 50 million people and counting ‒ most of these with lifestyle-related type 2 diabetes.

Thirty years ago, when I was a young doctor at the Central Hospital in Yaoundé, Cameroon, a heart attack was highly unusual ‒ so rare an occurrence, in fact, that medical students at the hospital were called in to take a look at any new case. Today, however, cardiovascular diseases, along with diabetes and the other non-communicable diseases, cancer and chronic respiratory diseases, are the most common killers in Cameroon and throughout West Africa. Unaware of the generational damage being done over recent years by the deadly interplay between genetic inheritance and socioeconomic factors (including sweeping rural-urban migration, the rapid loss by large sectors of society of their traditional lifestyles and the proliferation of processed foods), we now find ourselves living in one of the world’s new and unlikely diabetes hotspots. This is happening throughout the developing world: diabetes and other NCDs are striking down working-age people living in the countries that can cope least well. Worldwide, four out of five people living with chronic disease are in one of the low- and middle-income countries. And the epidemic has only just begun. By 2030, the number of people living with diabetes worldwide will be greater than the current population of North America ‒ half a billion!

All of this puts a whole new spin on diabetes care and prevention. We must factor in undernutrition and poverty as well as over-nutrition. We must remove any blame for type 2 diabetes from the shoulders of the individual. And we must find simple cost-effective interventions to avoid the human tragedy and crippling cost of diabetes. The search for such an approach represents one arm of IDF’s response to the burgeoning crisis in health and development, and is the focus of a number of articles in this special issue. Work on some of these projects is in progress; I look forward to reading the results of the translational research underpinning their implementation and assessment in future editions of this magazine. Another hugely important area of our activities, as regular readers will be aware, is in the lead-up to the UN summit on NCDs this September. IDF recently published a set of recommendations that members want to see included in the UN Summit Outcomes Document. The NCD Alliance’s Proposed Outcomes Document contains 34 carefully considered goals and targets that represent our vision of success. To read the Document in full, please visit the IDF website and follow the links.

Yet while overweight and diabetes are on the increase, millions of children go to bed each day hungry ‒ not just pangs of hunger; starving, lacking the essential nutrients for their physical and mental development. Of the two major crises in the world today – financial disarray and soaring food prices – the latter is perhaps the more distressing. Drastic swings in the prices of staple foods are causing ripples of misery and hunger throughout the developing world. A recent report by OXFAM projects that the average price of staple foods will more than double in the next 20 years. The urban poor will assume much of the burden of higher prices by having to spend more and more of their household income on food ‒ at the expense of other essentials like housing, healthcare and education. In many developing countries, the poorest people already spend up to 80% of their income on food. We are now aware of the strong links between a mother’s malnourishment, her baby’s birth weight and the child’s future risk for the constellation of metabolic disorders that leads to diabetes.

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Jean Claude Mbanya is IDF President for the period 2009 to 2012. He is Professor of endocrinology at the University of Yaounde, Cameroon, and Chief of the Endocrinology and Metabolic Diseases Unit at the Hospital Central in Yaounde.

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DIABETES VIEWS

TOWARDS A BRIGHTER FUTURE WITH AND WITHOUT DIABETES

I am particularly pleased to greet Diabetes Voice readers in the pages of this special issue dedicated to potential, novel, newly implemented and recently investigated approaches to diabetes care and prevention. A collection of international authors reporting on their achievements and work in progress either originate from or are working in countries representing all seven IDF regions. The multiethnic cohort of experts is drawn from a variety of fields and reflects the complex and multifaceted and now sadly global nature of the incipient diabetes epidemic – for it is a reasonably new epidemic, and no magic bullet for a cure (yet) exists. All of the emerging therapies and interventions showcased in this magazine – be they lifestyle-related or in search of a pharmacological (or bionic!) solution – describe achievements and achievements in the making made through a great deal of hard work carried out within the rigorous framework of scientific research.

Articles in the ‘Science at the cutting edge’ section explore just that – progress towards a state-of-the-art response to diabetes. Or, in the case of the article on IDF’s position statement on the use of bariatric surgery, towards preventing type 2 diabetes or reversing its disease process. Long-term studies have demonstrated that weight-loss surgery procedures, such as gastric banding, sleeve gastrectomy or gastric bypass, lead to improvements in cardiovascular risk factors and even 'recovery' from diabetes in obese people. The psychological effects of such interventions appear to be positive also. However, some emotional trauma can occur due to the transformation of a person’s appearance – loose skin and facial changes, for instance – and the IDF consensus recommends immediate post-op counselling and life-long follow-up.

Investigators working on the BRIDGES-supported projects, like those described in this issue, are striving to translate knowledge gleaned through clinical research and randomized controlled studies into cost-effective clinical practice in order to implement long-term behavior modification strategies to tackle diabetes and prevent its complications. These are examples of translational research in motion and show the real-world results of IDF’s work, in partnership with public health services and the private sector, to make a difference to the health and wellbeing of vulnerable people with diabetes everywhere.

A team of UK-based researchers debates the merits of two potential paths to restoring insulin secretion in people with diabetes, bringing their blood glucose levels and control back to normal with no risk of hypoglycaemia. Theirs is an informative piece, which manages to demystify some highly specialized science. In the other two sections of this special issue, a number of articles provide an update on research supported by BRIDGES, a major IDF grant programme funded by Lilly Diabetes, whose overarching goal is to improve diabetes care and prevention in the neediest of communities around the world. People living in developing countries face a disproportionate risk from the disturbing, disabling and potentially lethal complications of diabetes. Over the coming decades, the greatest increases in the numbers of people with diabetes are set to occur in sub-Saharan Africa and East and South-East Asia. Latina America and the Caribbean already have worryingly large diabetes populations. For those people, the physical and emotional challenges of managing a complex and life-long disease like diabetes are compounded by daily life in an unhealthy and often unsanitary environment, including a lack of access to healthy food, and a devastating inability to pay for life-saving medications, including insulin.

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Linda Siminerio Chair of the BRIDGES Executive Committee

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Building expertise in nutrition and behaviour in the Colombian Caribbean: promising advances against diabetes Esteban Mayor Gómez and Astrid Arrieta Molinares

Occupying in the northwest corner of South America, Colombia has borders with five countries, including Panama to the north and Brazil to the south, and a Caribbean as well as a Pacific coastline. Colombia, with 45 million inhabitants, has the second-largest population in South America and although it has one of the largest economies on the continent, inequality and unequal distribution of wealth are widespread. Around half the population lives under the poverty line. The authors of this report describe their efforts to improve the prevention and clinical management of type 2 diabetes among communities living in the Caribbean coast region, where poverty, obesity and sedentarism are contributing to a dramatic rise in chronic non-communicable diseases.

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New resources for research will be critical in improving the quality of life of people living in the Colombian Caribbean.

Maria Molina is a young homemaker from a coastal region of Colombia, and, like many of her peers, she is overweight. One morning, Maria was clearing the breakfast dishes and getting ready to send her young son Sebastian to school, when she suddenly had a terrible feeling that the world was falling in around her: a strong dizzy spell was followed by a momentary loss of vision. Alarmed and confused, Maria grabbed a dining room chair to steady herself and called out to her husband, Esteban, who was leaving for the shop where he works a few blocks away in downtown El Pueblito, a suburb of Barranquilla. The disturbing signal that something was wrong with Maria’s body led the young couple straight to the recently inaugurated local health centre that they had heard about only days before. The Camino Sur – El Pueblo clinic is an alternative medical service for the families that make up the large communities that are scattered throughout the towns and villages of the Caribbean region. While household budgets are severely limited, these communities are suffering a growing burden of multiple chronic health problems, which are affecting health and well-being, and contributing to widespread premature death. The dramatic rise in type 2 diabetes in Colombia reflects the worldwide epidemic of this and other non-communicable diseases (NCDs). In 2000, it was estimated that about 171 mil-

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lion people worldwide were living with diabetes; today, according to the International Diabetes Federation (IDF), 285 million people around the world have diabetes and that total is expected to rise to 438 million within two decades.

Undiagnosed type 2 diabetes ‘silently’ causes damage to the eyes, kidneys, nerves and blood vessels. A few days after her first visit, Maria returned to the El Camino clinic to pick up her test results: she was diagnosed with hypertension and type 2 diabetes. Like millions of other people, Maria had been entirely unaware of her condition. Commonly occuring without symptoms, undiagnosed type 2 diabetes ‘silently’ causes damage to the eyes, kidneys, nerves and blood vessels. Acute complications include ketoacidosis, coma and treatment – related hypoglycaemia, and can be disturbing, debilitating and potentially life-threatening. As diabetes progresses without adequate care and self-management, a person with the disease develops disabling and ultimately lethal long-term complications – cardiovascular disease, kidney disease, eye disease, nerve damage. Awareness of the widely documented impact of diabetes is growing in most regions. Interventions based on lifestyle and

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CIIS has developed a bespoke project for the screening, treatment and management of type 2 diabetes.

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behaviour (including diet and physical activity) have proved effective and cost-effective in preventing, halting or delaying the progression of type 2 diabetes. Yet people like Maria continue to suffer. Poverty, resulting among other things in a lack of access to a healthful diet that includes fresh fruit and vegetables, a shortage of trained health personnel and a weak healthcare budget all conspire to undermine attempts to set in motion any effective, long-term programme to improve the health and quality of life of the inhabitants of the region. Establishing the research centre In response to the rise in chronic disease and in the context of these socio-economic difficulties, the Centro de Investigaciones Sanitarias (CIIS) was set up as a health-service provider for the city of Barranquilla. In this initiative, the centre has developed a bespoke project for the screening, treatment and management of type 2 diabetes with the objective of improving the quality of care received by people with diabetes, obesity and/or hypertension in the region. The Centre aims to provide tools for nutritional management, which cover assessment, planning, implementation, coordination and research. Specific objectives include the provision of guidelines for healthcare providers working in primary care on the nutritional management of obesity, diabetes and hypertension, the provision of information on diet and physical activity and nutritional control – and the inclusion of these in medical records; and the provision of a framework for setting treatment goals in primary care centres in the region. Our team of researchers includes the research doctors Astrid Arrieta Molinaro, Tania Acosta, Noël Barengo, Jaakko Tuomilehto, Carlos Ricuarte and the field coordinator, Diana Mayor, all of whom are advised by Pablo Aschner and Rafael Gabriel in collaboration with the Secretariat of Health of Barranquilla. One of the many challenges faced by the team is the shortage – or rather the absence – in the region of health personnel with training in physical activity, nutrition and diet. To overcome this difficulty, the research team is developing the protocol described above. Aimed at a wide range of health professionals, its purpose is to train graduates in medicine, nursing and health sciences who have performed academically well and who are committed to collaborating in this field. Basing their project on IDF’s recommendations for clinical research, the researchers initially identified a group of people at high risk for developing type 2 diabetes using the Finnish

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FINDRISC questionnaire. This group underwent a detailed examination that includes an oral glucose tolerance test and lipid profile, anthropometric measurements and questionnaires on medical history and lifestyle habits. Those who showed impaired glucose tolerance according to the World Health Organization criteria were invited to participate in a clinical trial and randomized into three groups. One group started with an educational intervention with the emphasis on nutrition in the first 6 months; the second group started with an intervention that stresses physical activity, again for the first 6 months. After this period, both groups were standardized. The third group is acting as a control. They receive the care and recommendations that are usually offered at health centres in the region. No rest for the ‘health walkers’ Simultaneously, a survey was launched to determine the status of nutritional management of chronic diseases at health centres throughout the region. Teams of young volunteers, known as ‘health walkers’ because they cover the region extensively, carrying out the FINDRISC surveys and collecting data, using any means of transport available and reaching on many occasions areas that are inaccessible to motor vehicles. Once collected and classified, these data will be used to create the framework for nutritional care targeting obesity, diabetes and hypertension. CIIS is currently seeking support from other organizations in the health sector and local government. New resources will be used to continue carrying out our research activities and develop tools that will be critical in improving the quality of life of people like Maria and their families living in the Colombian Caribbean.

Esteban Mayor Gómez and Astrid Arrieta Molinares Esteban Mayor Gómez is a psychiatrist at the Centro de Investigación Sanitaria CIIS, Baranquilla, Colombia. Astrid Arrieta Molinares is a psychiatrist at the Centro de Investigación Sanitaria CIIS, Baranquilla, Colombia.

Acknowledgement The authors are the principal investigators of this project, which is supported by BRIDGES. BRIDGES is an International Diabetes Federation programme supported by an educational grant from Lilly Diabetes.

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Diabetes self-manag an effective response burden in under-serv Elizabeth Paz-Pacheco

Diabetes prevalence is increasing in leaps and bounds worldwide. In developing countries, where limited healthcare resources are exacerbated by the needs of growing (and ageing) populations, the burden of diabetes is set to have its greatest and most damaging impact. Previously considered a disease of relatively affluent people living in urban areas, diabetes is now on the rise in rural populations. The related health management burden stems from late diagnosis and poor control, specifically glycaemic control and control of the risk factors for cardiovascular events – hypertension, hypercholesterolemia, increasing obesity – owing to poor education and scarce health resources. Elizabeth Paz-Pacheco reports on a four-phase project in a rural community in the Philippines, which aims to overcome these challenges in order to protect the longterm health of the population against the rising tide of diabetes.

Located on the Western edge of the ‘Pacific Ring of Fire’, an enormous belt of seismic and volcanic activity, with Taiwan across the Straits of Luzon to the North and Vietnam across the South China Sea to the west, the Republic of the Philippines is an archipelago of more than 7,000 islands categorized broadly into three main geographical divisions – Luzon, Visayas and Mindanao. The Philippines has a population of approximately 90 million people and, according to the 2008 Philippine National Health and Nutrition Survey, diabetes prevalence among people aged 20 years and older stands at 7.2%. Specialist health resources remain concentrated in the urban centres – Metro Manila for Luzon, Cebu City for the Visayas, and Davao City and Cagayan de Oro for Mindanao, for instance – providing high-quality healthcare for less than 50% of the country. As a result, many thousands of rural communities remain underserved and vulnerable to the increasing human

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ement education: to the increasing ed communities and economic costs of the burgeoning diabetes epidemic. Our medical group became involved with the people of San Juan (in Batangas province), a rural town some 120 km from the capital, Manila, and the adopted community of the University of the Philippines College of Medicine. Although San Juan is predominantly an agricultural town, the University doctors who set up a community medical facility were surprised by the size of the town’s diabetes population.

Although San Juan is an agricultural community, doctors were surprised by the size of its diabetes population. In response to this clear need to control diabetes and its complications, our Section of Endocrinology, Diabetes and Metabolism of the Department of Medicine collaborated with the

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Department of Epidemiology and the Community Health Development Program on a systematic project aimed at increasing understanding of the challenges posed by diabetes and addressing the specific medical needs of the community in San Juan. The cornerstone of care Diabetes self-management education is recognized as a fundamental component of diabetes care. It involves the acquisition by people with diabetes of the appropriate knowledge and skills they require to make effective adjustments to the day-to-day management of medication(s), meal plan, exercise regimen and other factors that impact on blood glucose. To be able to introduce the concepts of self-management and self-management education to people in the community, a good understanding of their knowledge, attitudes and behaviours is essential – to produce culturally relevant and suitable educational tools, for example. In order to affect behavioural change in the long term,

Municipal Hall of San Juan, Batangas

these socio-cultural factors have to be recognized and respected and incorporated into any educational programme. A deep understanding of a community’s knowledge, values and belief systems and the way its members react to new information are essential to enhancing people’s ability to change entrenched patterns of behaviour. With these factors in mind, our group formulated a four-phase,

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five-year comprehensive programme involving the following: t he assessment of knowledge, attitudes and practices (phase I) a community-wide assessment of diabetes prevalence (phase II) a diabetes self-management intervention (phase III) a tailor-made community diabetes prevention programme (phase IV). To date, phases I to III have been completed. The amount of knowledge gleaned from the experience so far has been extraordinary. Phase I highlighted the importance of evaluating knowledge, attitudes and practices in order to (a) understand observed behaviours and (b) guide behavioural change. A cross-sectional study was performed among people with type 2 diabetes in the rural community. Participants were selected using a stratified cluster sampling and data were collected using investigator-administered questionnaires and focus group discussions. A total of 156 people were

Overall diabetes knowledge was low; less than half of the respondents strongly believed in the need for patient autonomy. included. The overall average score on diabetes knowledge was 43%; less than half of the respondents strongly believed in the need for patient autonomy (38%). Only four out of 35 respondents involved in the focus group discussions owned a glucose meter and fewer still were consulting their doctor on a regular basis. Phase II determined the prevalence of diabetes, pre-diabetes and metabolic syndrome. Metabolic disorders were found to be highly prevalent in this rural community, greater in fact than in the Philippine general population. Among the Philippine and broader Asian populations, low HDL cholesterol is the most prevalent component of diabetes and

metabolic syndrome. The increasing age of a population correlates with an increasing prevalence of diabetes, prediabetes and metabolic syndrome. The higher prevalence rates that we saw may not in fact provide true estimates since there was a disproportionate representation among study participants of women working as family carers and homebuilders and people with a family history of diabetes â&#x20AC;&#x201C; and thus a higher risk for diabetes. Nevertheless, the process of screening for and detecting diabetes is an integral aspect of care, and became an important learning point for the healthcare staff working with the community in San Juan.

A typical local health center in the rural town

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Phase I: Focused Group Discus sion

Phase II: Interview, BP and blo od

extraction

lipid profile), health behaviours (exercise, smoking, alcohol consumption, illicit drug use, foot examination) and medication use. These variables were determined at baseline, then after 3 months and 6 months. The self-management education group had a lower average HbA1c compared to the standard care group after 3 and 6 months. In addition, by the third month, there were more participants in the education group performing regular foot examinations than in the standard care group. The final phase of the project aims to look at culturally specific programmes for lifestyle intervention using local diets and exercise programmes.

Sharing the lessons Our group is encouraged by the results so far and excited by the prospect of sharing the lessons learned. Other rural communities in the Philippines or elsewhere will be able to download and use the published documents relating to the San Juan project in order to Phase III: Teaching session by peer educator perform similar investigations. The methodology and data for phase I have been published1; phase II stratePhase III, the educational intervention gies for gathering prevalence data are itself, demonstrated that using a struc- being written up for publication; and tured curriculum delivered by volunteer phase III results have been submitted for peer educators with diabetes consistently presentation at the International Diabetes improved blood glucose control in the Federation World Diabetes Congress in short-term and, therefore, potentially Dubai later this year. Our goal is to make might reduce complications. Baseline and all of these documents readily available to post-intervention variables were assessed as many communities as possible. which included anthropometric measurements (height, weight, body mass in- Into the future dex, waist and hip circumference, waist- A pilot scheme is planned to establish hip ratio, blood pressure); biochemical similar projects in several communimeasures (HbA1c, fasting blood glucose, ties through the regional groups of the

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Philippine Society of Endocrinology and Metabolism. It is hoped that a national programme might implement this approach through the country’s governmental and non-governmental organizations.

Work in early detection and diabetes education is emerging as the first line of defence against the growing epidemic of diabetes. With programmes such as these in place, we might be able to overcome the barriers created by the shortfall in specialists and general practitioners in rural areas and begin protecting the longterm health and improving the quality of life of millions of people living in the Philippines. Work at the grass roots level in early detection and diabetes education is emerging as the first line of defence against the growing epidemic of diabetes in our country and around the world. Elizabeth Paz-Pacheco Elizabeth Paz-Pacheco is Principal Project Investigator of the 4 Phase DM Program in San Juan Batangas, Philippines. She is Associate Professor, UPCM and Chief of Section of Endocrinology, Diabetes and Metabolism at the UP-Philippine General Hospital. She is Past President of the Philippine Society of Endocrinology and Metabolism.

References 1 A rdeña GJ, Paz-Pacheco E, Jimeno CA, et al. Knowledge, attitudes and practices of persons with type 2 diabetes in a rural community: Phase I of the community-based Diabetes Self-Management Education (DSME) Program in San Juan, Batangas, Philippines. Diabet Res Clin Prac 2010; 90:160-6.

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Appraising the MultiSAFE approach to low vision and diabetes: a simple technique for saving feet Ann Williams

The human and economic consequences of diabetes-related foot problems can be harrowing. A person’s foot can become vulnerable due to various complications of diabetes. Nerve damage, vascular problems and delayed wound healing can lead to chronic ulceration. Ensuing infection or the non-healing of an ulcer can result in amputation – one of the most feared and most costly outcomes of diabetes. People with diabetes who also have a visual impairment are at even greater increased risk for serious foot problems and amputation. For those with good vision, efforts to prevent amputation often include education in foot self-examination; people with impaired vision are usually advised to seek assistance from a sighted person for daily foot inspection. Clinical experience suggests that visually impaired people seldom follow this advice. In this article, Ann Williams explains why and reports on a project in the USA in which people with diabetes and impaired vision learn techniques to examine their own feet using a range of senses and, it is hoped, reduce the threat from severe complications, including amputation.

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The global dimensions of the threat from diabetes-related foot problems were highlighted by the International Diabetes Federation in a recent awareness-raising campaign: every 30 seconds a lower limb is lost to diabetes. Treating and caring for a person with diabetic foot disease can be expensive: following an amputation, a person will need prolonged hospitalization, rehabilitation, home care and social services. In developed countries, up to 5% of people with diabetes have foot ulcers and it is estimated that their treatment accounts for up to 15% of the available healthcare resources. In developing countries, the costs of treating people with diabetes foot problems may account for as much as 40% of these resources. With diabetes figures soaring in low- and middle-income countries – the greatest percentage increases over the next 30 years will occur in Africa and Asia

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– where healthcare resources are already limited and ageing populations continue to grow, foot complications are set to become a major drain on emerging economies and a threat to socioeconomic progress in developing regions.

People with diabetes who also have a visual impairment are at greater risk for amputation than those with good vision. Yet up to 85% of all diabetes-related foot problems are preventable if appropriate measures are taken. This can be achieved through a combination of good foot care and appropriate education. Amputations and other severe problems can be avoided by people

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who are aware of the importance of appropriate self-care and have acquired the knowledge and skills they need to identify problems at the earliest stage, prevent infection and ultimately amputation, and protect long-term health and mobility. Low vision – increased risk People with diabetes who also have a visual impairment are at even greater increased risk for serious foot problems and amputation. While growing numbers of their peers with good vision in countries around the world have access to preventive, protective education in foot self-examination, people with impaired vision are usually advised to seek assistance from a sighted person for daily foot inspection. Clinical experience suggests that visually impaired people seldom follow this advice. Assistance from a sighted person may

not be available. If it is, a person with impaired vision may prefer to use it for other, more apparently urgent, needs, such as shopping for food or collecting and managing medications. The status of family relationships or local conditions in terms of the provision of home care by public health and social services and/or insurance providers are among the factors that can leave a person with diabetes with impaired vision without the resources they need to prevent disabling foot damage. Consider the situations faced by the real people described in Box 1. Without the ability to inspect their own feet, visually impaired people often simply omit home foot inspections. Protecting feet with multi-SAFE Our group is working to find a costeffective response to this multi-faceted

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BOX 1: CASE STUDIES

ary is a 32-year-old woman with type 1 diabetes. Ten years ago, she lost all vision due to diabetic retinopathy. She completed a comprehensive rehabilitation programme now lives alone in a US city. She works for a large bank, using a computer with a text-to-speech program. She habitually takes a bus or taxi to work or to go shopping. She manages her diabetes using a talking blood glucose meter, an insulin pen and a variety of other tools and techniques for people with impaired vision. Although she is emotionally close to her family, they do not live nearby. When she was told that she needed someone sighted to inspect her feet every day, she replied, "That will never happen. Who could I even ask to do that for me?"

im is a 76-year-old man with type 2 diabetes. Five years ago, he gradually lost much of his vision to age-related macular degeneration. He is a widower and lives near his daughter and her family. They check on him every day by phone. However, because they all lead busy lives, Tim usually sees his daughter in person only once a week – to do grocery shopping and other errands. He is a very independent person and has learned to manage his household and his diabetes using low vision techniques. For example, he uses a large-print blood glucose meter, large coloured dots on his oral medication bottles for identification and a large-print blood glucose record book. When he was told that he needed to have his feet checked daily by a sighted person, he felt he could not ask his daughter for that favour. He does no foot checks at all.

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problem. The Multiple Senses and Foot Examination (Multi-SAFE) technique is a simple, low-tech procedure that uses the senses of touch and smell to carry out thorough, systematic foot selfexamination. The person uses fingers to detect changes in shape and texture of the feet, ankles, toes and toenails; the back of the hand or the forearm to detect changes in temperature; and the nose to detect unusual foot odours that may signal infection (see Box 2 for some more details of the approach). Although this simple technique has been used clinically for some years, it had not previously been formally evaluated using research methods.

Visually impaired people with diabetes often simply omit home foot inspections. We are currently investigating through the Nonvisual Foot Inspection for People with Visual Impairment Study the efficacy, acceptability and feasibility of the Multi-SAFE technique compared with usual care (advice to have a sighted person perform daily foot examinations). Thirty visually impaired adults with diabetes are taking part in the study. At the outset, all the participants received comprehensive diabetes selfmanagement education in small group classes, with special emphasis on all aspects of foot care – regular washing and adequate protection of feet, regular foot inspection, early reporting of any problems to a podiatrist. Regarding regular foot inspection, the experimental group received education on the Multi-SAFE technique, while the control group was advised to have a sighted person check their feet regularly.

Shortly after completion of the selfmanagement education classes, each group came together for a focus group to share feedback on the classes and, in particular, on the foot inspection method they had learned. Another focus group is planned for each class group at the end of the study year to give feedback on actual use of the foot inspection method over a 12-month period. Qualitative information from the focus groups will be compared in order to assess the acceptability of Multi-SAFE compared to usual care. All participants have undergone a comprehensive baseline podiatry evaluation. For the following year, participants continue to undergo a foot evaluation at least quarterly, more often if necessary. For any foot problems that develop, the podiatrists are documenting whether the problem was discovered at home by the participant or a family member, or whether the podiatrist was the first to find the problem. This information is being used to assess efficacy of MultiSAFE compared to usual care for the detection of foot problems. Built-in accessibility Because all the study participants have some degree of visual impairment, the research team has paid close attention to incorporating accessibility into all phases of the investigation. Large print, audio recordings and Braille are used to communicate with and inform participants (according to their preference). Transport is provided to all study activities. In the self-management education classes, the diabetes educators included information about tools and techniques for diabetes care used by visually impaired people, such as talking meters and techniques for identifying medications or for measuring and injecting insulin. In addition,

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CTION FOR NON-VISUAL FOOT INSPE BOX 2: SOME INSTRUCTIONS r feet Follow these steps to check you with your hands.

your 1) Sit in a chair and lift a bare foot to , lap. If you have trouble doing that or you can put your foot on a stool you er, easi hassock. Or, if you find it r. can stand and put your foot on a chai ers 2) Use the sensitive pads on your fing irand thumbs to search your feet for es regularities of texture and differenc in the shape of your toes and feet from

the way they felt the previous day. a) Begin with the large toe, feel the sides, top, and bottom of the toe. , Notice any roughness of the skin calluses, blisters, cuts, swelling, or feelings of soreness as you press

on the skin. r b) Feel the toenail for any irregula il erna shape or ridges. Run a fing

a complete set of handouts covering all areas of diabetes care was given to all participants together with a recording so that they could review the information at home.

It is quite possible that Multi-SAFE may offer benefits to people with good vision. Next steps It is quite possible that the Multi-SAFE technique may offer benefits to people with good vision. Many people, particularly those who are elderly or excessively overweight, have trouble seeing the bottom of their feet despite having perfect eyesight. Moreover, intentional use of more than one sense may enhance daily visual foot inspection.

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can 4) If your fingers are numb, you along the edge of the toenail to feel of probably still feel with the back for any unusual roughness along fore r your hand and the inside of you the edge, or just under the edge. feel arm. You can use these areas to c) Then feel the space between the r you for changes on the surface of large toe and the next toe. to foot. Although you will not be able ord) Continue feeling each toe in es feel between your toes and the edg der, feeling the toes, toenails, and able be still of your toenails, you will spaces between the toes. of to feel the top, sides, and bottom e) Move your hand to the outside edge your foot. of the foot, the heel, and the inside your 5) Repeat this entire process with edge of the foot. other foot. f) Feel the entire surface of the top . of the foot and the sole of the foot back The 3) Next, turn your hand over. of your hand is more sensitive to tem any find perature. You can use it to ch spots that are unusually warm, whi top re enti might be infected. Feel the and bottom surfaces of your foot and toes, and the sides of your foot with the back of your hand.

It is hoped that Multi-SAFE will prove to be a simple, effective, low-cost solution for all people with visual impairment at risk from diabetes foot problems. We are looking forward to some encouraging results. Should this be the case, the investigators plan to develop and expand the study.

Ann Williams Ann Williams is the principle investigator of the Nonvisual Foot Inspection for People with Visual Impairment Study. She is a nurse who has been a certified diabetes educator since 1989 and is currently a faculty member of the Frances Payne Bolton School of Nursing at Case Western Reserve University, Cleveland, USA.

Further reading Boulton AJ, Armstrong DG, Albert SF, et al. Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care 2008; 3: 1679-85. Available from: http://care.diabetesjournals.org/ content/31/8/1679.long.

Acknowledgement The author is the principal investigator of this project, which is supported by BRIDGES. BRIDGES is an International Diabetes Federation programme supported by an educational grant from Lilly Diabetes.

International Working Group on the Diabetic Foot. International Consensus on the Diabetic Foot. International Diabetes Federation. Brussels, 2009. Available from: http://www.iwgdf.org merican Diabetes Association. Foot Care. A ADA. Alexandria, 2008. Available from: www. diabetes.org/type-2-diabetes/foot-care.jsp

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A multi-partner approach to developing excellence in diabetes management training in four African countries Joseph Drabo, Assa Sidibé, Serge Halimi, Stéphane Besançon

Human resources for healthcare in West Africa are among the world’s most limited, severely restricting the capacity of countries in the region to provide effective, equitable public health services to their people. Indeed, the lack of health professionals throughout sub-Saharan Africa has become a significant barrier to achieving the UN’s millennium development goals. While they struggle to deal with a dual burden of disease, African countries have to cope with inadequate distribution of health professionals; despite the growing numbers of people affected by chronic non-communicable diseases like diabetes, heart disease or cancers, the bulk of human resources remain oriented towards the management of infectious diseases HIV/AIDS, malaria and tuberculosis. The authors report on a multipartner project to provide high-quality training in chronic disease management to healthcare professionals in Mali, Burkina Faso, Guinea and Benin.

DiabetesVoice

Diabetes is a life-long condition affecting more than 285 million people worldwide. Already one of the leading causes of death and disability worldwide, diabetes kills 3.8 million people every year. And, according to International Diabetes Federation figures, without concerted action, diabetes is set to affect some 438 million people within two decades. In the developing world, non-communicable diseases (NCDs), mainly diabetes, heart disease, cancers and respiratory diseases, represent a massive and growing problem: already, an estimated 80% of deaths from NCDs worldwide occur in low- and middle-income countries; up to 14 million people die prematurely every year in developing regions due to preventable NCDs; in the very near future, the developing countries will be home to three-quarters of the world’s diabetes population.

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In West Africa, the dramatic rise of diabetes will have a strong negative impact in economic and social terms. This is a disease that increasingly is affecting people during what ought to be their most active, productive years. Diabetes prevalence in sub-Saharan Africa, one of the poorest regions in the world, currently stands somewhere between 3% and 6%. Diabetes is already a major cause of death and disability; it is the leading cause of blindness and provokes 60% of non-trauma-related amputations. In this alarming epidemiological context, there is a clear and urgent need to prepare new health professionals and enhance chronic disease management and care skills of those already in the field.

There is a clear and urgent need to enhance chronic disease management and care in West Africa. Decentralizing care Several years ago, the Mali Department of Health began receiving support from the NGO, Santé Diabète, and financial support from the World Diabetes Foundation. Short training courses in diabetes care and management were given to health professionals in a number of regions. Burkina Faso, with the support of the same partners, initiated a similar process. These initiatives have had a strong impact on the decentralization of diabetes care, which had become a priority for many thousands of people living in outlying areas who require good-quality care. While this multi-partner approach responded to an urgent need, it failed formally to institionalize training in a basic diploma in diabetes care within the mechanisms already implemented by

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these countries. Indeed, with 50 physicians dedicated to the management of diabetes for more than 100,000 people in Mali and less than 40 to more than 110,000 in Burkina Faso, the development of diabetes management of diabetes must occur through continuing professional education and via the establishment of specific degree courses.

established two degree courses to prepare two different levels of specialization in diabetes management: a four-year course to become a specialist in endocrinology and diabetology ‒ the Certificate of Special Studies in Endocrinology and Diabetes a one-year course in diabetes care ‒ the University Diploma of Diabetes.

Specialization and the institutionalization of training In Mali, the Faculty of Medicine, Dentistry and Pharmacy of Mali has

In a context where specialists in the management of diabetes are virtually nonexistent in sub-Saharan Africa, the creation of these two qualifications under the

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auspices of the Mali Ministry of Higher Education and Scientific Research represents an important contribution to ensuring excellence in training for diabetes management. In addition to Mali, three other countries are implementing similar educational initiatives to create diabetes specialists: Burkina Faso, Benin and Guinea.

In addition to Mali, three other West African countries are implementing similar educational initiatives to create diabetes specialists. To ensure medical and scientific excellence, a partnership was established with the French Society of Diabetes. This is an experienced organization with more than 4000 diabetologists,

endocrinologists and diabetes health professionals from a large number of Francophone countries. Several specialists, members of the French Society of Diabetes, are involved in the development of these degrees. They provide support in coordinating educational qualifications and attaining educational objectives, as well as offering the students a period of hands-on training at their hospitals and clinics in France. Twenty students from five countries (Mali, Burkina Faso, Guinea, Benin and Senegal) are currently enrolled in the four-year degree course. The first of the one-year diploma courses will start in January 2011 with an intake of 40 students. These two diploma courses were made possible by financial support from the French Ministry of the Interior. Outlook for the future In only its initial four years of existence, this initiative will train 20 specialists

in endocrinology and diabetology and 40 diabetologists in four countries. This will alter fundamentally people’s access to care and the quality of the care they receive. Moreover, the fact that these degrees are validated at the regional, national and international levels means that diabetes training will be sustained in the long term. Great strides are being made. However, for the moment this training excellence reaches only doctors. A study is underway to develop a similar approach in order to strengthen university courses for paramedics. Opportunities are being explored to create new links between universities in order to prepare related specialists, including dieticians and podiatrists. Joseph Drabo, Assa Sidibé, Serge Halimi, Stéphane Besançon Joseph Drabo is Head of the Department of Internal Medicine at the Centre Hospitalier Universitaire Yalgado, Ouagadougou, Burkina Faso (yjdrabo@yahoo.fr). Assa Sidibé is Head of the Department of Endocrinology-Diabetology at the Mali Hospital, Bamako (sidibe2050@yahoo.fr). Serge Halimi is Head of the Department of Endocrinology, Diabetes and Diseases of Nutrition at University Hospital Centre, Grenoble, France. He is PastPresident of the French Society of Diabetes (SHalimi@chu-grenoble.fr) Stéphane Besançon is Director of the Santé Diabète Mali (santediabetemali@wanadoo.fr).

Further reading Liese B, Blanchett N, Dussault G. Background paper on the human resource crisis in health services. World Bank. Washington DC, 2003. Egger D, Adams O. Imbalances in human resources for health: Can policy formulation and planning make a difference? World Health Organization. Geneva, 1999. I nternational Diabetes Federation. Diabetes Atlas 4th edition. IDF, 2009. aldé NM, Diallo I, Baldé MD, et al. B Diabetes and impaired fasting glucose in rural and urban populations in Futa Jallon (Guinea): prevalence and associated risk factors. Diabetes Metab 2007; 33: 114-20.

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June 2011 • Volume 56 • Special Issue 1

When you struggle every day to get food and water, imagine how difficult it can be to get insulin.

Lilly Diabetes

For Kandolo, the challenges of obtaining insulin and diabetes supplies can seem insurmountable. To help children and their families living with diabetes in developing countries overcome these personal challenges, Lilly Diabetes supports the International Diabetes Federationâ&#x20AC;&#x2122;s Life for a Child Programme. With help from this programme, local care providers around the world can better provide education, supplies, and insulin. In support of greater awareness, Lilly Diabetes is honoured to produce the second Life for a Child documentary, In the Hearts of Africa, which focuses on how several children, including Kandolo, receive care and support through the programme. Please join us in our support of the Life for a Child Programme by visiting www.lifeforachild.idf.org to find out more. Together, we can make a world of difference.

LD/ELB/05/2011/290

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A future of glucoseresponsive insulin secretion: bionics versus nature Pratik Choudhary, John Pickup, Peter Jones, Stephanie A Amiel

People with diabetes constantly walk a tight rope between strict glucose control to prevent complications and hypoglycaemia. Too often, slight miscalculations result in hypoglycaemia, which can be at best embarrassing and irritating, and may cause injury or even death. New drugs for diabetes and new ways of measuring blood glucose bring hope of easing the burdens of diabetes but the dream for many (and for the researchers trying to help them) is a treatment that restores glucose-responsive insulin secretion so that normal blood glucose concentrations can be achieved with no risk of hypoglycaemia – and perhaps even with no need to think about diabetes all the time. There are two obvious routes towards this Holy Grail: one, for the pure scientist, is the development of the perfect insulin delivery device, driven by the perfect biochemical glucose sensor – the artificial pancreas or ‘bionic solution’; the other accepts that nature got it right the first time and that all we need to do is restore the beta-cells in the islet structures that diabetes destroyed. A group of authors from the UK take a look at the new technologies in diabetes that are bringing us, step by step, closer to one or both of these goals.

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Towards the bionic solution From urine tests, to finger prick blood samples and now to subcutaneously implanted online glucose sensing, our ability to monitor diabetes control has increased enormously. Sensors implanted into the subcutaneous tissue can record either for later downloading (in the manner of 24-hour ECG monitoring) or for display in near real-time. As work progresses towards linking the new glucose monitors to new insulin delivery devices, what has science in store for us? The altered properties of nanoscale structures are being used to develop glucose-responsive insulin delivery. Nanotechnology and nanomedicine are set to make increasing contributions in diabetes care in the coming years, and this will be particularly true of regulated insulin delivery. Nanos is the Greek for ‘dwarf ’. Nanotechnology involves making or measuring things on a very small scale, usually 1-100 nm (a nanometre is 1x10-9 metres) – larger than an atom but smaller than a cell. At this small scale, nanoscale structures and devices often have fundamentally altered properties, including metabolite sensing, controlled porosity, biocompatibility and the ability to target tissues and molecules in the body. Some of these properties are being used to develop glucose-responsive insulin delivery. Despite the progress alluded to above, we still lack a completely reliable and accurate glucose sensor. Alternative technologies to the electrochemical sensors used in current systems are urgently needed. One nano approach that is showing promise is based on fluorescence. Several groups around the world, including in the laboratory at Guy’s Hospital, London (UK), are researching a glucose-binding protein from bacteria, which changes shape on linking to glucose and, when

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tagged with a fluorescent probe, can be used to monitor glucose concentrations. Protein engineering is used to make the molecule operate in the range of glucose levels found in people with diabetes. Detecting nanosecond changes in the fluorescence lifetime (the time taken for the fluorescence to decay after excitation) upon glucose binding, rather than depending on measuring the intensity of fluorescence, has the advantages of stability and lack of interference. Prototypes of the first product, a fibre optic-based sensor implanted in the subcutaneous tissue, have already been tested.

Researchers are thinking of ways to close-couple glucose sensing and insulin delivery in what might be called an ‘artificial nanopancreas’. Could the glucose-binding protein sensor become part of a non-invasive glucose monitor? Researchers at Guy’s have encapsulated the protein in nano-thickness polymer films, making micro-sensors that potentially could be implanted or impregnated in the skin as a kind of ‘smart tattoo’ – with a portable meter held over the glucose tattoo to excite the fluorescence and detect light changes as the tissue glucose changes. Many problems need to be solved before such a system can be commercialized and enter clinical practice but the possibilities are exciting. The distant nano future Coupling detection to treatment in one molecule or nanoscale device is called ‘theranostics’, and researchers are already thinking of ways to close-couple glucose sensing and insulin delivery in

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what might be called an ‘artificial nanopancreas’. This might comprise a glucosesensing molecule like glucose-binding protein embedded on the surface of an artificial cell that contains microvesicles of insulin and with a molecular link from the sensing to insulin delivery. Towards replacing the lost islets Since the publication in 2000 of a report from Edmonton, Canada, on seven people with type 1 diabetes who achieved insulin independence after receiving fresh human islets that had been isolated and donated by multi-organ donors using a novel digestion technique and steroid-free immunosuppression, more than 400 people have received an islet transplant. So where does islet cell transplantation stand today?

Obtaining islets from a donor pancreas is a long and painstaking procedure. The organ undergoes enzymatic and then mechanical digestion before islets are separated from exocrine tissue. This process can take 12 to 15 hours. Islets are then cultured for up to 24 hours and assessed for purity and viability before they are transplanted ‒ introduced into the liver ‘trans-portally’ under local anaesthetic. Prior to transplantation, recipients are given an ‘induction’ treatment to reduce T-cell reactivity and increase immune tolerance to these foreign cells. Immune suppression is then maintained with a combination of drugs such as tacrolimus, sirolimus and mycophenolate mofetil. These are intended to prevent the rejection of the transplant and the recurrence of type 1 diabetes, and need to be continued throughout the recipient’s life. Indeed, most of the risk from islet transplantation comes from the long-term risk of immune suppression.

Challenges for the future In its present form, islet transplantation is not efficient enough for all. The International Collaborative Islet Transplant Registry reports that one year after transplant over 85% of all recipients show detectable graft function (which is associated with almost complete protection from severe hypoglycaemia), and 70% after four years. Nevertheless, only 70% of all recipients achieved insulin independence at some stage, with 55% still insulin independent after two years.

Providing sufficient donor organs will become a major issue as the procedures and the immunosuppression improve. A major obstacle lies in preventing the gradual loss of islet function. This is probably due to a combination of factors: the loss of islets on first infusion; gradual islet death; the recurrence of auto-immunity; the gradual process of organ rejection. Providing sufficient donor organs to supply people with type 1 diabetes is another challenge. This will become a major issue as the procedures and the immunosuppression improve. Novel alternatives are being investigated, ranging from converting exocrine cells into beta cells to obtaining islets from animals. Stem cells are a possible source of new islets. Stem cells are defined by their by their capacity for self-renewal (proliferation) and their ability to differentiate into a number of specialized cell types (pluripotency), properties which make them excellent candidates from which to generate the large numbers of functional beta cells that are required for transplantation. There are three main sources:

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t issue stem cells ‒ found in foetal and adult tissues, where they repair and renew the host tissue e mbryonic stem cells ‒ generated from a blastocyst, which can form all differentiated cell types in the developing embryo induced pluripotent stem cells ‒ similar to embryonic stem cells but generated from adult cells via the forced expression of pluripotency genes. Tissue stem cells Stem cells isolated from many tissues may have the capacity to differentiate into insulin-expressing cells. However, experimental studies using tissue stem cells have so far failed to translate into reliable protocols for generating large numbers of functional beta cells in vitro. Pancreatic stem cells with the potential

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to generate beta cells have been identified in the exocrine pancreas ‒ the pancreatic ducts within endocrine islets. Isolating the stem cells from a human pancreas, expanding them ex vivo and differentiating them into functional beta cells is an attractive therapeutic option but it remains to be demonstrated whether this is technically feasible. Bone marrow stem cells are alternative candidates and are already used therapeutically. They offer the potential for autograft transplantation without immune rejection. Several studies have reported that bone marrow stem cells can be driven towards an insulin-expressing phenotype. Others, however, suggest that the therapeutic benefits of bone marrow stem cells are achieved primarily by their enhancing the regeneration

and survival of endogenous beta cells rather than generating new ones. Liver cells can be induced by the forced overexpression of pancreatic genes to adopt some functional aspects of beta cells. However, it remains to be seen whether these experimental observations will translate to human tissues with sufficient efficiency to generate enough material for therapeutic purposes. Stem cells from a range of tissues – including the central nervous system, intestinal epithelium, dermis, spleen, salivary gland and blood monocytes ‒ have also been reported to differentiate into insulin-expressing cells. But there is little convincing evidence that these cells are capable of the ex vivo expansion required to generate significant amounts of tissue for effective transplantation therapy.

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Embryonic stem cells The differentiation of mouse embryonic stem cells into insulin-expressing cells was first reported more than decade ago. Attention then was focused on how best to drive pluripotent, undifferentiated embryonic stem cells towards a functional beta-cell phenotype. Nowadays, we have detailed knowledge of the sequence of events and developmental cues in the formation of the endocrine pancreas, and this information is being applied to devise differentiation protocols based on the sequential exposure of embryonic stem cells to growth factors and mitogens. These protocols are designed to recapitulate in vitro the important in vivo signals that drive pluripotent cells first towards endoderm, then to an endocrine progenitor and finally to fully differentiated pancreatic endocrine cells. By measuring important staging markers (usually transcription factors) we can assess the effectiveness of the differentiation protocols. This type of research has produced encouraging results but cells generated by these in vitro protocols are in general functionally restricted; they produce either a weak glucose-induced insulin secretory response or none at all. Several studies have demonstrated improvements after transplantation into a person, which suggests that something important is lacking from current in vitro protocols. Identifying the factors involved in the development of the cells in the human body might inform the last stages of an entirely in vitro differentiation protocol for functioning beta cells.

Inconsistencies have also been reported in the development in the body of embryonic stem cells. One likely cause is the disparities in the initial differentiation potential between various lines of embryonic stem cells. This highlights the importance of a systematic evaluation of available human embryonic stem cell lines in order to identify the most suitable starting material. Induced pluripotent stem cells Using induced pluripotent stem cells that are autologous (generated from a recipient’s own body) has the obvious additional benefit that it avoids the use of cells derived from human blastocysts. Directed differentiation protocols have generated insulin-expressing cells from human fibroblast-derived induced pluripotent stem cells. However, these cells are subject to functional limitations similar to those described above for embryonic stem cells. Moreover, there remain other barriers to the clinical use of cells derived from induced pluripotent stem cells, including recent evidence of alterations in gene expression caused by epigenetic modifications of induced pluripotent stem cells ‒ heritable changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA

sequence. Other obstacles include the accumulation of genetic coding mutations in induced pluripotent stem cells and the autoimmune rejection of transplanted cells generated from autologous induced pluripotent stem cells. It remains to be seen whether these obstacles can be overcome to allow induced pluripotent stem cells to achieve their therapeutic potential.

The usefulness of substitute beta cells will depend in part on the development of fool-proof methods of ensuring their safety after transplantation. There are safety issues to consider. The pluripotency of stem cells and their capacity to grow and multiply raise the risk of uncontrolled cell proliferation and the formation of tumours. This is important when considering the transplantation of human islets through intra-portal administration into the liver (the most widely used method at the moment) because the transplanted material is rendered essentially irretrievable in the event of an adverse outcome ‒ a major safety issue.

But we should be wary of overoptimism when interpreting human embryonic stem cell studies using directed differentiation protocols. In terms of differentiation, the effectiveness of similar in vitro protocols varies widely.

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On the left, a section of pancreas seen under the microscope shows a central clump of cells, with dense dark nuclei: the endocrine islet in a sea of dark staining exocrine pancreas cells. On the right, islets have been stained red with a dye that binds to insulin, showing intact islets being separated from the exocrine tissue of the pancreas, before infusion into a patient. The future clinical usefulness of substitute beta cells derived from stem cells will depend not only on their functional competence but also on the development of fool-proof methods of ensuring their safety after transplantation. Problems remain It has become clear that beta cells are gregarious – they work best when collected together if not in formal islets at least in clumps of cells, so-called `pseudo-islets'. When beta cells are isolated, they are not nearly as efficient in terms of secreting insulin in response to glucose as they are when clustered together. And the new beta-cell clusters or islets need to be protected from the recipient’s immune system – which will try to reject them as foreign and destroy them as beta cells – as happened to cause the type 1 diabetes in the first place. Many strategies are being explored to overcome this rejection ‒ and nanotechnology might help. In the Guy’s laboratory, nanofilms applied layer by layer – using alternating layers of positively and

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negatively charged polymers – are being used to encapsulate pancreatic islet cells to improve their chances of survival after transplantation. Using capsules to isolate the islets from immune cells and proteins, preventing rejection, while allowing glucose in and insulin out, has been the subject of research for many decades. Real hope for the future The conventional encapsulation technologies used in the past restricted oxygen and nutrients to the cells and provided incomplete immune protection, severely restricting the islets’ chances of survival. Now, biocompatible nanofilms applied very close to the islet cell surfaces are showing great promise with their adjustable permeability, fast response times and improved ability to admit nutrients. The researchers at Guy’s have already seen significantly improved survival with such nano-encapsulated animal islets transplanted into animals with diabetes. The adoption of new technologies for diabetes will depend on them being

demonstrably as safe and effective as the current therapy, administration of exogenous insulin, which has been used for almost a century. Working together, scientists from different backgrounds are helping to bring us ever closer to such goals.

Pratik Choudhary, John Pickup, Peter Jones, Stephanie A Amiel Pratik Choudhary is Senior Lecturer in diabetes at King's College Hospital, London, UK. John Pickup is Professor of Diabetes and Metabolism at King's College London, UK. Peter Jones is Professor of Endocrine Biology at King's College London, UK. Stephanie A Amiel is the RD Lawrence Professor of Diabetic Medicine at King's College London, UK.

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Looking for new pharmacological treatments for type 2 diabetes Cristina Bianchi and Stefano Del Prato

Type 2 diabetes is a heterogeneous disease characterized by multiple pathogenic defects. Impaired insulin secretion and insulin action (insulin resistance) are well-recognized major mechanisms contributing to the development of diabetes. In the past years, intensive research has much improved our understanding of the molecular mechanisms leading to defects of beta-cell function and impaired ability of insulin to promote glucose uptake in muscle and adipose tissue. More recently, other organs have been shown to play a role in the abnormalities of glucose homeostasis. The discovery that the gut, following the ingestion of nutrients, releases factors (incretins) that augment the response of the beta cell and suppress glucagon secretion has opened a whole new area of active investigation to understand its role in glucose homeostasis. The introduction of GLP-1 based therapies is the direct consequence of these discoveries. The role of inappropriate glucagon concentration has found renewed interest as a mechanism contributing uncontrolled hepatic glucose production. Moreover, new players have come onto the stage of the pathogenesis of type 2 diabetes. Maladaptive processes occur at the level of the kidney that may lead to inappropriate reabsorption of glucose in the presence of hyperglycaemia. Finally (for the moment!), more is being learned about the central control of metabolic and hormonal responses by the brain. Cristina Bianchi and Stefano Del Prato from Pisa, Italy, review the changing scene.

DiabetesVoice

In spite of the complexity of the pathogenesis of type 2 diabetes, for many years we have had limited pharmacological tools to treat it, as illustrated in Figure 1. Until the late 1980s, it was metformin and sulphonylureas, but in the past 15 years the number of therapeutic options has grown steadily ‒ with more to come. The expectation is that these new drugs may improve the efficacy-to-safety ratio, resulting in durable maintenance of glycaemic control in the majority of people with diabetes. To achieve such an ambitious, yet much needed, target, new ‘intelligent’ medications should be sought that can target specifically all the mechanisms responsible for hyperglycaemia. New therapies to improve beta-cell function Using the incretin system therapeutically The most recent arrivals into the arena of the diabetes medications are agents targeting the incretin system and, in particular, treatments designed to increase

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The former are injectable molecules while the latter are administered orally. Both approaches yield clinically significant improvements in glycaemic control with trivial risk of hypoglycaemia (a risk only increased when used with insulin secretatogues or insulin). The main difference between the two is the concentration of GLP-1 (or its analogue) attained in blood, which accounts for different effects on body weight. The GLP-1 receptor agonists result in greater GLP-1 concentrations and are associated with some degree of weight loss; the DPP-4 inhibitors are weight neutral. Great efforts are being made to simplify the administration of GLP-1 agonists. In its original formulation, exenatide (a GLP-1 analogue) had to be administered twice a day, but a once-weekly formulation is being considered for approval by

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regulatory agencies. Exenatide once a week retains the positive effect on body weight and it may be even superior as far as glycaemic control is concerned, with fewer side-effects (nausea and vomiting) than the parent molecule. Other molecules with similar properties are suitable for even less-frequent injection (bi-weekly, monthly) are currently under development.

Exenatide once a week may be superior as far as glycaemic control is concerned, with fewer side-effects. The family of the DPP-4 inhibitors is growing as well. The US Food and Drugs Administration has just approved a third agent, linagliptin, for treating type 2 diabetes. As with other DPP-4 inhibi-

tors, linagliptin improves glycaemic control with no risk of hypoglycaemia. A unique characteristic of linagliptin is its primarily non-renal route of excretion: no dose adjustment is required with the reduction of the glomerular filtration rate. Targeting insulin secretion again Improving insulin secretion remains a main target of diabetes treatment. Here, glucokinase ‒ the enzyme that phosphorylates and regulates glucose metabolism in beta cells to drive insulin secretion ‒ represents a potentially attractive therapeutic target. Glucokinase activators increase the enzyme's affinity for glucose and stimulate insulin biosynthesis and secretion, with restoration of early insulin release in response to increasing plasma glucose concentrations. Glucokinase is expressed also in the liver and activators favour hepatic

Figure 1: Classes of drugs for type 2 diabetes in use in the USA during the past 60 years 13 12

Number of medication classes

the availability of the gut hormone glucagon-like peptide-1 (GLP-1). GLP-1 has important physiological actions, including potentiating glucose-dependent insulin secretion and glucagon suppression, delayed gastric emptying, reduction of food intake and loss of body weight. Moreover, GLP-1 prevents beta-cell loss in animals with diabetes. Interestingly, GLP-1 exerts favourable effects on the cardiovascular system and, again in animal studies, it reduces the severity of myocardial infarction. Unfortunately native GLP-1 is rapidly degraded in the blood stream by the enzyme dypeptidil-peptidase-4 (DPP-4). In order to increase the concentration of the hormone in the blood, two approaches have been taken: t he development of agonists of the GLP-1 receptor that are resistant to DPP-4 (exenatide, liraglutide) the use of highly specific DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin).

Dopamine agonists

Bile acid sequestrants

DPP4-I

Amylin mimetics

GLP-1R agonists

Glinides

TZDs

5 4

α-glucosidase inhibitors

Sulphonylureas

Metformin

3 2 1 0

1950

1960

1970

1980

1990

2000

2010

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glucose uptake and glycogen deposition. Although effective, these compounds retain a significant risk of hypoglycaemia. Pancreatic beta cells respond to free fatty acids as well. Orally active synthetic agonists of G-protein-coupled receptors for fatty acids can increase concentrations of cyclic adenosine monophosphate (cAMP) in the beta cells and potentiate glucose-induced insulin secretion and are also being explored for therapeutic potential. New therapies to improve liver glucose metabolism Excessive glucose output from the liver contributes to fasting and post-prandial hyperglycaemia. The liver is very sensitive to the effect of glucagon, which stimulates hepatic glucose output, and is often inappropriately elevated in people with type 2 diabetes. In an attempt to alleviate

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these effects, anti-glucagon treatments based on anti-glucagon antibodies or glucagon receptor antagonists are being sought. Metabolic inhibitors of hepatic glucose production may provide interesting alternative therapeutic approaches.

Metabolic inhibitors of hepatic glucose production may provide interesting alternative therapeutic approaches. New therapies to improve insulin sensitivity Insulin resistance is a main pathogenic mechanism in diabetes. Currently, only metformin and the PPAR-gamma agonists (pioglitazone) are available as insulin sensitizers. The dual PPARalpha/gamma agonists (‘glitazars’)

represent an interesting evolution of ‘glitazones’. Simultaneous activation of PPAR-gamma and -alpha can, indeed, exert positive effects on glucose and lipid metabolism. Aleglitazar represents an example of a dual agonist. Initial studies with this molecule showed an improvement in glycaemic control comparable, if not superior, to that obtained with pioglitazone ‒ with favourable modification of the lipid profile. Fluid retention still occurs but at the recommended clinical dose no case of heart failure was reported. Aleglitazar is being tested in a large-scale clinical trial to assess whether it can reduce the risk of major cardiovascular events in people with diabetes and coronary artery disease. Protein tyrosine phosphatases (PTPs) that function as negative regulators of the insulin signalling cascade (they

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de-phosphorylate the insulin receptor) have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing the abundance of protein PTP1B not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high-fat feeding in animal models. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the conversion of inactive cortisone to active cortisol. The enzyme is expressed in the liver, adipose tissue, brain and placenta, where it plays a critical role in glucocorticoid action. The excess of glucocorticoid results in metabolic disturbances that overlap with those of the metabolic syndrome. This has led to suggestions that increased glucocorticoid activity may play a role in the aetiology of the syndrome, and that 11beta-HSD1 may provide a therapeutic target to normalize glucocorticoid excess in a tissue-specific manner and mitigate obesity, insulin resistance and related metabolic disturbances. Selective inhibitors of 11beta-HSD1 are under development for the treatment of type 2 diabetes and other components of the metabolic syndrome. New therapies to reduce glucose toxicity Chronic hyperglycaemia exerts a toxic effect on the secretion and action of insulin. Reducing plasma glucose concentrations is, therefore, important not just for prevention of long-term complications, but also to preserve crucial homeostatic mechanisms. The sodium glucose co-transporter 2 (SGLT2) inhibitors belong to a novel therapeutic class of glucose-lowering drugs. SGLT2 molecules account for 90% of glucose re-absorption from the forming urine in the kidney. Selective inhibitors of

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We need to understand how to identify the predominant mechanism in each person, so as to tailor treatment regimens most appropriately. SGLT2 inhibitors increase urinary excretion of glucose, causing a reduction in plasma glucose concentration in an insulin-independent manner and with low risk of hypoglycaemia. The loss of excess glucose through the urine leads to weight loss and the mild osmotic diuresis contributes to a reduction in blood pressure. Of the SGLT2 inhibitors under development, dapagliflozin, appears to be in the most advanced phase. Increased rates of infection of the urinary tract, mainly in women with a genital infection, have been reported but these were generally mild and easy to manage with standard interventions. Conclusions After years of quiescence, the pharmacological treatment of diabetes is experiencing a renaissance. Currently, in the USA, and including insulins, there are 13 classes of drugs for diabetes treatment. More have yet to come. Therefore, the palette of diabetes treatment is becoming more and more colourful, offering renewed possibilities to achieve better and more sustained glycaemic control in a larger number of people with diabetes. However, such a large number of treatments will require careful understanding of the heterogeneity of the disease and profound knowledge of the features of each one of these new molecules. Ideally, also, we will need to understand how to identify the predominant mechanism in each person, so as to tailor treatment regimens most appropriately. Finally, careful assess-

ment of the cost-benefit ratio will be mandatory because new drugs will be expensive and the number of people with diabetes will grow, particularly in the poorer parts of the world, which stand to benefit most from better diabetes therapies.

Cristina Bianchi and Stefano Del Prato Cristina Bianchi is clinical researcher in the Department of Endocrinology and Metabolism, Section of Diabetes and Metabolic Diseases, University of Pisa, Pisa, Italy. Stefano Del Prato is Professor of Endocrinology and Metabolism at the School of Medicine, University of Pisa and Chief of the Section of Diabetes and Metabolic Diseases, University of Pisa, Italy.

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IDF first to address question: is bariatric good for diabetes? Carel LeRoux on behalf of the IDF Taskforce on Epidemiology and Prevention of Diabetes

Last year, IDF’s Taskforce on Epidemiology and Prevention of Diabetes convened a working group to review the role of surgery in the treatment and prevention of type 2 diabetes. Bariatric surgery, in which the gastrointestinal tract is operated on with the intention of achieving weight loss, has been shown to have significant metabolic benefit. In December last year, 20 people representing all the IDF regions, and different clinical disciplines, met at IDF’s headquarters to review the available evidence and consider the potential of the procedures for people with diabetes. The meeting had three principal goals: to develop a framework in which bariatric surgery could be assessed in the context of type 2 diabetes; to make recommendations on selection for surgery; and to identify priorities for research, with a global perspective. Carel LeRoux summarizes the findings.

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the surgery

The evidence that obesity surgery can improve metabolic state through weight loss and by other mechanisms has been growing. The idea that an operation can treat – or even prevent – type 2 diabetes has obvious attraction. So last year, IDF convened a working group to consider the place of such surgeries in the global diabetes community. The IDF Taskforce on Epidemiology and Prevention of Diabetes met in Brussels, reviewed the evidence and agreed that bariatric surgery can improve glycaemic control safely and cost-effectively in morbidly obese people with type 2 diabetes. This was not to undermine the importance of population-based efforts, which are essential to prevent the onset of obesity and type 2 diabetes. But it was recognized that in addition to behavioural and medical approaches, bariatric surgery improves diabetes in morbidly obese people and provides a cost-effective approach to treating

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the disease. So bariatric surgery can be considered an appropriate treatment for people with type 2 diabetes and obesity who are not achieving recommended treatment targets with medical therapies, especially when there are other major co-morbidities. The Taskforce report has been accepted by IDF and was published recently.1

Strategies to prioritize access to surgery may be required to ensure that the procedures are available to those most likely to benefit. In many countries, surgery is already an accepted option in people who have type 2 diabetes and a BMI above 35 kg/m2. The meeting did, however, suggest that surgery can be considered as an alternative treatment option in people

with a BMI between 30 and 35 kg/m2 when diabetes cannot be adequately controlled by optimal medical regimen, especially in the presence of other major cardiovascular disease risk factors. This is especially true in Asians and some other ethnicities with increased risk and where BMI action points are now accepted to be reduced by 2.5 kg/m2. This increases the number of people considered eligible for surgery. Although only a minority may be interested in taking up surgery at this stage, strategies to prioritize access to surgery may be required to ensure that the procedures are available to those most likely to benefit. Factors to consider when choosing a procedure Bariatric surgical procedures range from operations designed to reduce the size of the stomach and restrict food entry to the gastrointestinal tract, to procedures designed to by-pass parts of the small

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intestine and alter the body’s responses to food ingestion, with some procedures combining both. The group suggested that Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, bilio-pancreatic diversion and the duodenal switch variant, and sleeve gastrectomy as currently accepted procedures, while only Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding were acceptable for surgery in adolescents with the current level of published data.

expertise. Longer-term surgical and medical complications and the need for

nutritional and lifestyle support, and surgeon’s teams with consistent messages and agreed policies. Presurgical assessment should be comprehensive, including assessment of metabolic, physical, psychological and nutritional health. People need to have realistic expectations of the risks and benefits of surgery, and their lifelong role in lifestyle intervention, nutritional support and follow-up. The multi-disciplinary team needs to understand, seek and recognize any early and/or long-term complications in a timely manner and know when to refer back to the surgeon or others for specific care. Life-long follow-up on at least an annual basis is needed for ongoing lifestyle support, and post-surgical and diabetes monitoring, which should include nutritional monitoring. Where appropriate, follow-up should include a psychological evaluation, support and therapy.

Complication rates in the USA fell from 24% to 15% between 2002 and 2006, despite older and less healthy people receiving surgery.

Managing the risks of surgery Bariatric surgery for people with type 2 diabetes must be performed within accepted guidelines. This requires appropriate assessment for the procedure and multi-disciplinary care, patient education, follow-up and clinical audit, as well as safe and effective surgical procedures. Surgery is not without risks and the 30-day mortality after surgery is between 0.1% and 0.3% ‒ comparable to laparoscopic cholecystectomy. However, the presence of type 2 diabetes has not been found to be associated with increased risk. Reported complications of bariatric surgery include leaks (3.1%), wound infections (2.3%), pulmonary events (2.2%) and haemorrhage (1.7%). A report by the US Agency for Healthcare Research and Quality showed that complication rates fell from 24% to 15% between 2002 and 2006, despite older and less healthy people receiving surgery – perhaps due to to higher hospital volumes, a move to laparoscopic surgery and an increase in banding procedures. Further improvement has been achieved by restricting surgery to centres with high throughput and established

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surgical revisions are not uncommon, some being specific to the procedure used. The key remains early detection and appropriate management. IDF urges national guidelines for bariatric surgery in people with type 2 diabetes and a BMI above 35 kg/m2 together with establishment of national registries of the surgery being performed in order to monitor both short- and long-term outcomes. IDF emphasizes that the morbidity and mortality associated with bariatric surgery is generally low and similar to that of well-accepted procedures, such as elective gall bladder surgery. The risks should be balanced at all times against the range of health benefits, including a reduction in all-cause mortality.

People need to have realistic expectations of the risks and benefits of surgery, and their lifelong role in lifestyle intervention. Considering a successful programme Bariatric surgery should be viewed as a component of the ongoing process of chronic disease management of type 2 diabetes and obesity within high-volume centres with experienced multi-disciplinary teams. The team needs to integrate with primary care, diabetes management,

Criteria for optimal metabolic state and substantial improvement Probably the most significant contribution made by IDF was to shift the goal of treatment away from weight loss or even ‘curing’ diabetes to optimization of the metabolic state ‒ defined as a composite end point of HbA1c at or below 42 mmol/mol (6%), no hypoglycaemia, total cholesterol below 4 mmol/l; LDL cholesterol below 2 mmol/l, triglycerides below 2.2 mmol/l, blood pressure below 135/85 mmHg, greater than 15% weight loss, with reduction in pre-operative medication. A substantial improvement in the metabolic state was defined as the composite endpoint of lowering HbA1c by more than 20%, LDL below 2.3 mmol/l, blood pressure below 135/85 mmHg, with reduced medication from the pre-operated state.

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Sir George Alberti, Prof Francesco Rubino and Prof Paul Zimmet, who, with Prof John Dixon, convened the IDF group.

Research recommendations IDF recognizes that the current level of clinical evidence and the understanding of the underlying mechanisms are insufficient. The working group emphasized the research that is required to advance the field by making the following recommendations: More robust criteria than BMI for predicting benefits from surgery and defining which people would benefit most from which procedures are needed. T he benefit of surgery for people with diabetes and BMI below 35 kg/m2 needs to be established. Studies are needed to establish whether bariatric procedures slow the

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progressive loss of beta-cell function characteristic of type 2 diabetes. T he course of microvascular complications of diabetes after surgery needs to be delineated. T he mechanisms for the success of surgery and the mechanisms associated with recurrence of diabetes need to be investigated. S tudies are needed to define the best regimens for diabetes management post-bariatric surgery. Final clinical recommendations B ariatric surgery is appropriate for people with type 2 diabetes and morbid obesity who are not achieving treatment targets with medical therapies,

especially where there are other obesityrelated co-morbidities. Under some circumstances, people with a BMI of between 30 and 35 kg/m2 could be eligible for surgery. E ach health system should determine whether bariatric surgery is economically appropriate. Surgery is complementary to medical therapies and should aim to reduce microvascular and cardiovascular risk. Experienced multi-disciplinary teams should manage people with long-term support focusing on preventing complications relating to surgery, nutrition and diabetes. G lycaemic control should be optimized peri-operatively and should be closely monitored after surgery. New techniques and devices should be explored in research settings only, while conventional procedures should be more standardized. A minimal accepted data set for presurgery and follow-up should include: HbA1c, fasting glucose and insulin, BMI, waist circumference, retinopathy status, nephropathy status, liver function tests, lipid profile, blood pressure measurement, foot exam, documentation of medications, fasting C-peptide where available, auto-antibody status ‒ for example, anti-GAD where available. A prolonged period of normalization of glycaemic control has benefit even if there is eventual relapse.

Carel Le Roux Carel LeRoux is Clinical Reader/Honorary Consultant, Department of Medicine, Imperial College London and Consultant in Chemical Pathology at King's College Hospital London.

Reference 1 D ixon JB, Zimmet P, Alberti KGMM, Rubino F, for the IDF Taskforce on Epidemiology and Prevention. Diabet Med 2011: 28; 628-42 .

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Translating evidence into practice: improving access to HbA1c in subSaharan Africa Eugene Sobngwi and Naby Balde

The use of HbA1c is becoming mandatory for good-standard diabetes care thanks to scientific evidence generated over the past two decades worldwide. HbA1c as a reflection of chronic hyperglycaemia is also becoming a key indicator increasingly used for the diagnosis of diabetes. However, underserved populations in poor countries have little awareness of or access to this important diagnostic and monitoring tool. As a new technology, the feasibility of large-scale dissemination of HbA1c determination in resource-limited countries, and the cost-effectiveness of its use under those circumstances is questionable. The translation of scientific evidence gathered around HbA1c in poor environments requires appropriate investigation. A multi-centre study in 10 diabetes care facilities in Guinea and Cameroon is ongoing to evaluate the feasibility and benefit of improving access to HbA1c with immediate feedback on diabetes-related outcomes.

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Large-scale and long-term studies in type 1 diabetes and type 2 diabetes have unequivocally demonstrated the benefit of good blood glucose control, among other strategies, for the prevention of vascular complications of diabetes. Over the past two decades, HbA1c has appeared as one of the cornerstones of good diabetes management in all types of diabetes. Since the publication in 1993 of the results of the Diabetes Control and Complication Trial (DCCT) showing the tremendous impact of reducing HbA1c in populations of people with type 1 diabetes on the risk of microvascular complications,1 large bunches of trials have provided the confirmation of this evidence in other types of diabetes and under widely varying circumstances. As a powerful addition to self-monitoring, HbA1c has provided a uniform appraisal of diabetes control worldwide. HbA1c expressed in the percentage of total haemoglobin has thus become a universal language for diabetes specialists and people with diabetes in some settings. However, its interpretation by people with diabetes remained cumbersome ‒ the percentage having no clear relation with the better-known glucose values. In a paper published in 2008, researchers devised an algorithm for relating HbA1c to the results of intermittent blood glucose monitoring measurements over the previous 3 months, plus the average glucose concentration from 48 hours of on-line glucose monitoring, constructing a table by which HbA1c results can be converted into a calculated 'average blood glucose concentration'. This may help people with diabetes make better sense of their HbA1c results. The equation derived from diabetes populations of most continents, including Africa, although it has not been tested in people with heamoglobinopathies.

The cost of equipment to perform the HbA1c assay is prohibitive for resource-limited healthcare facilities. The latest major step taken in the field of HbA1c was its adoption as one of the diagnostic tools for diabetes. On the basis of population-based follow-up data, cut-off points of HbA1c for the diagnosis of diabetes were suggested and validated by international expert committees,3 first in the USA and subsequently by the World Health Organization. Research since then has addressed the issue of identifying people at risk with proposed lower cut-off points. In daily diabetes care practice, HbA1c has been a major step forward. In fact, it gives both the clinician and the person

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with diabetes a clear appraisal of the level of diabetes control over a much longer period of time compared to all other available means of monitoring ‒ and at a very limited cost to the individual and the healthcare system. However, it required heavy techniques, such as high-performance liquid chromatography, that are only available in specialized laboratory settings. The reference methods are time-consuming and technically demanding, with the results of the assay not being available immediately for the purpose of health education and clinical decision-making. Moreover, the cost of equipment to perform these assays is prohibitive for resource-limited healthcare facilities. In response to the limitation of huge technical requirements and length of process, point-of-care instruments were developed and validated for determining HbA1c in a very short time in consultation rooms or at the bedside. Point-of-care HbA1c machines offer the advantage of a valid measure within 10 minutes, using only a drop of capillary blood obtained by a finger prick. HbA1c determination becomes feasible by nurses or doctors not specifically trained in laboratory techniques ‒ even when working in isolation. This equipment is easy to operate, and for some, reagents are cheap and can be stored at room temperature. Therefore, their introduction in underserved populations is becoming more feasible than was the case in the past.

HbA1c determination with immediate feedback enables a perfect match between clinical findings and educational messages. HbA1c determination with immediate feedback to clinicians and people with diabetes enables a perfect match between clinical findings and educational messages in a one-stopshop approach. In the setting of a controlled randomized trial, it has been demonstrated that the immediate feedback of HbA1c results resulted in a significant improvement of blood glucose control at 6-month follow-up and persisted for the 12-month study.4,5 It is known also that the higher the HbA1c before an intervention, the higher the drop obtained through the intervention. Moreover, a meta-analysis of 66 trials of interventions to improve diabetes care showed that interventions in which case managers could make independent medication changes achieved extra 0.5% reductions in HbA1c.6 The attributable

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Clinical trials provide evidence of the effectiveness of various interventions that are sometimes hardly translated in real life with ‘normal’ people.

additional effect of diabetes self-management education was -0.15% HbA1c. Clinician education also showed a significant attributable reduction in HbA1c. Thus, an intervention that combined clinician education, HbA1c determination with immediate feedback to people with diabetes, and targeted diabetes self-management education would provide a much higher reduction in HbA1c than each of these taken separately. Whether such an addition to traditional clinical settings and classical diabetes care processes would improve diabetes outcomes was investigated. The unanswered question is whether this research evidence would translate into real-life clinical benefits. In fact, clinical trials provide evidence of the effectiveness of various interventions that are sometimes hardly translated in real life with ‘normal’ people. This question is one of the foundation stones of translational research. In addition to this, a question that would apply worldwide, we questioned the feasibility and effectiveness of such approach in underserved settings. In fact, Africa is home to 1 billion people with over 12 million affected by diabetes and a projected increase to 24 million by 2030. Specialized diabetes care centres remain scarce in Africa and very few specialized doctors and nurse educators are working in this environment. The proportion of health budgets allocated to NCDs in general, and diabetes in particular, is severely limited and awareness at the population and decision-making levels remains low. As a result, people with diabetes in Africa suffer a higher burden of complications. It is estimated that between 22% and 55% of people with diabetes in sub-Saharan Africa with an average duration of diabetes of 5 years have retinopathy.7 Diabetes is the largest contributor to dialysis in most African settings due to end-stage renal disease. The cost of diabetes

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care in some settings represents one third of family income. Caring for complications is unaffordable to families and healthcare systems in Africa. Thus, the burden of diabetes is even greater because uncontrolled diabetes leads to a high frequency of complications. An unpublished survey conducted by Ayesha Motala confirmed the very low awareness and availability of HbA1c in most sub-Saharan African settings. Thus, more so than elsewhere, the effectiveness of diabetes care would rely on people with diabetes following treatment recommendations alongside implementation of the most cost-effective approaches. Our team is testing whether the introduction in Guinea and Cameroon of routine HbA1c measurement with immediate feedback would improve diabetes control significantly in underserved people with diabetes – known for at least 12 months prior to intervention. We hypothesized an average decrease of 1% in HbA1c in a 1000-person study, with a 20% increase in the number of people reaching treatment goals within 12 months of intervention and follow-up. We therefore aim to determine whether the introduction of routine HbA1c measurement with relevant education alone – without any additional intervention on medication supply, for example – will have a significant impact.

It is crucial to achieve good blood glucose control in all people with diabetes and more specifically in those of African origin. The results of this large-scale translational research in 10 settings in Africa are likely to provide evidence for or against a global effort to improve access to HbA1c in Africa. A 1% reduction in HbA1c on average within 12 months means a major reduction of complications and societal impact of diabetes. Modelling studies show the long-term clinical benefits and economic impact associated with a range of predefined, stepwise improvements in HbA1c, independently of other risk factors. Substantial improvements have been demonstrated in undiscounted life expectancy and quality-adjusted life expectancy, reduced cumulative incidence and costs of diabetes-related complications as well as increased time to onset of complications. Thus, it is crucial to achieve good blood glucose control in all people with diabetes and more specifically in those of African origin, as they seem to be at increased risk for microvascular complications.

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If proven effective, this approach would spur national and international actors to distribute point-of-care HbA1c en masse in resource-limited diabetes care settings. Preliminary results indicate a high participation rate, with over 1300 people enrolled and a drop-out rate of less than 20% after an average 9 months of follow-up. Results will be released at the end of 2011.

Eugene Sobngwi and Naby Balde Eugene Sobngwi is Senior Lecturer in Epidemiology at the University of Newcastle upon Tyne, and Consultant Endocrinologist at Yaoundé Central Hospital, Cameroon. Naby Balde, Department of Endocrinology and Diabetes, Donka University Hospital, Conakry and NCD Department, Ministry of Health, Republic of Guinea.

References 1 T he Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977-86. 2 N athan DM, Kuenen J, Borg R, et al; A1c-Derived Average Glucose Study Group. Translating the A1C assay into estimated average glucose values. Diabetes Care 2008; 31: 1473-8. 3 N athan DM, Balkau B, Bonora E, et al. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009; 32: 1327-34. 4 C agliero E, Levina EV, Nathan DM. Immediate feedback of HbA1c levels improves glycemic control in type 1 and insulin-treated type 2 diabetic patients. Diabetes Care 1999; 22: 1785-9. 5 F erenczi A, Reddy K, Lorber DL. Effect of immediate hemoglobin A1c results on treatment decisions in office practice. Endocr Pract 2001; 7: 85-8. 6 S hojania KG, Ranji SR, McDonald KM, et al. Effects of quality improvement strategies for type 2 diabetes on glycemic control: a meta-regression analysis. JAMA 2006; 296: 427-40. 7 M banya JCN, Motala AA, Sobngwi E, et al. Diabetes in sub-Saharan Africa. Lancet 2010; 375: 2254-66.

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Diabetes care at the centre of Australia: grassroots care and prevention A report on the 2010 symposium on Indigenous peoples’ health held in Alice Springs, Australia Elizabeth Barr, Alex Brown Baker, John Boffa, Paul Zimmet

The Baker IDI Heart and Diabetes (Baker IDI) Institute of Australia was established in 2008 following the merger of two eminent clinical academic bodies, the Baker Heart Research Institute and the International Diabetes Institute. Baker IDI is Australia’s first multidisciplinary organization tackling the deadly trio of obesity, diabetes and cardiovascular disease through research, education and care. In 2007, Baker IDI established a research group in Alice Springs in Central Australia under the leadership of Alex Brown, a leading Indigenous doctor/ researcher, to conduct cardiovascular and diabetes research focusing on improving health outcomes for Aboriginal and Torres Strait Islanders. One of the key objectives of the Alice Springs facility is to provide educational activities to health and community workers involved in the prevention and management of cardiovascular disease and diabetes among Indigenous people. The authors report on one of its several projects: a symposium held in 2010 on issues such as service delivery, prevention and management to reduce the disproportionate burden of diabetes experienced by Australian Indigenous people.

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The key presentations Primary prevention Paul Zimmet (Baker IDI) discussed the epidemiology and public-health impact of diabetes, highlighting the significance of the epidemic globally as well as locally. He showed that type 2 diabetes and prediabetes combined are estimated to affect between 3 and 4 million Australians. Diabetes alone is associated with an annual cost of AUD 8 billion. The impact of diabetes is magnified in Indigenous Australians, in whom it is associated with other chronic conditions, such as cardiovascular and renal disease, nonalcoholic steatosis of the liver and sleep apnoea. He pointed out that prevention strategies are of paramount importance and need to incorporate lifestyle, diet and exercise, but also improved child

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and maternal health. Under-nutrition in an unborn child, a factor affecting many Indigenous pregnancies, may increase its risk for diabetes in adult life. John Boffa, representing the Central Australian Aboriginal Congress, outlined the importance of comprehensive primary healthcare, encompassing several aspects of social care and healthcare, especially improving early childhood health and educational development. Gary Sinclair of the Northern Territory Department of Health emphasized the importance of a population approach to the primary prevention of diabetes and chronic disease in Central Australia based on New Zealand’s experiences. This implies a whole-community, wholelife-course and whole-family approach that is sustainable, has a focus on ethnicity and involves community partnerships. Christine Connors, also of the Northern Territory Department of Health, outlined the policy interventions that have already been undertaken in the Northern Territory to reduce risk factors for diabetes and cardiovascular disease. She explained that while the programmes for tobacco control were quite well developed, programmes for obesity required more attention. Nevertheless, several were in operation in the Northern Territory, including retail licensing and quality improvement, increasing the availability of fresh food, replacing soft drinks with diet versions, an ‘Eat Better Move More’ campaign and increasing the numbers of sport and recreational officers. Complications of diabetes Mark Cooper (Baker IDI) provided an overview of diabetic complications, not only the usual cardiovascular diseases, kidney disease, eye disease, foot ulceration and amputations, but also dental

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disease, Alzheimer’s disease and cancer. He highlighted the high prevalence of rapidly progressive kidney disease in Indigenous Australians, stating that the mechanisms for rapid progression are largely unknown. Although controlling blood pressure and cholesterol are paramount to reducing the risk of renal and cardiovascular complications, there are still significant gaps in the literature on the efficacy and safety of treatments for kidney disease specifically in Indigenous Australians. David Goodman from St Vincent’s Hospital in Melbourne highlighted recent research showing that the burden of kidney disease may be increasing and is associated with low birth weight, which again emphasizes the importance of improving the status of maternal health. He discussed the significant medical, logistic and social difficulties in managing Indigenous people with end-stage kidney disease who require dialysis, suggesting that dialysis treatment should be made available closer to the person’s home. Tim Henderson from the Northern Territory Clinical School and Flinders

University discussed eye disease, noting that although the prevalence of diabetic retinopathy is similar in Indigenous people compared to their non-Indigenous counterparts, a significant number of Indigenous people with diabetes were not having their eyes checked. Jonathan Shaw (Baker IDI) emphasized the need to improve foot screening, quoting Australian research which shows that screening for foot complications was considerably worse for Indigenous Australians – and this despite clinical guidelines from Australia’s National Health and Medical Research Council, which recommends that Indigenous people with diabetes have their feet checked at every health visit. It is unlikely that financial constraints are to blame for this lack of cover: the equipment needed for a foot examination is far from expensive. Primary care systems – the role of care planning A subsequent session focused on systems currently being implemented in primary care to improve the prevention and management of chronic diseases in Indigenous communities. Flinders

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University‘s Malcolm Battersby discussed self-management programmes in diabetes: the Flinders Program has received AUD 5 million from the Federal Government’s ‘Closing the Gap’ campaign to train health professionals for implementation in Indigenous settings. Gaynor Garstone, a diabetes educator with the Northern Territory Department of Health, outlined a successful case-conferencing programme for the management of renal disease and diabetes that is being used in remote Northern Territory communities in conjunction with the Royal Darwin Hospital. The programme comprises case conferences in which the endocrinologist and diabetes educator in Darwin (who both have experience of community outreach) confer with the rural medical officer, nurse and/or Aboriginal health worker, with the patient’s consent. This has helped hospital staff to develop a better understanding of the issues affecting people who live remotely. Moreover, under this programme, people receive specialist care without having to travel. This begins to address a range of challenges, including the following: i solation h igh health-staff turnover v ariable understanding of diabetes, culture and society by health workers in the Northern Territory d ifficulty liaising with hospital staff providing care for people who do not want to travel to city medical facilities

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Joanna Smith and colleagues from the Santa Teresa Clinic then provided an inspiring case study on the successful implementation of multidisciplinary care at Santa Teresa in Central Australia to improve awareness and treatment of chronic diseases. Lifestyle change and the real world – making a difference What strategies can help people adopt healthy lifestyle behaviours? Kevin Rowley and colleagues from the University of Melbourne outlined an ‘ecological’ health promotion programme that was implemented by Indigenous communities in the State of Victoria to improve physical activity and nutrition using a wide variety of settings, targets and strategies. The programme’s successes were underpinned by community leadership and participation and the programme’s alignment with community values, local knowledge, social structures and organizations. David Dunstan (Baker IDI) discussed the health risks of sedentary behaviour, including prolonged TV viewing, which are associated with overweight and obesity, high blood glucose and cholesterol and an increased risk of heart disease and premature death. He explained that in addition to vigorous physical activity, being involved in light-intensity activities is beneficial to health both because of associated increased metabolic activity and by occupying time that would otherwise be taken up by sedentary activities! Michael Kyrios of the Swinburne University of Technology explained the influence of pre-historical, historical,

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cultural, socioeconomic and political dimensions on Indigenous Australians’ health – influences not fully considered in conventional theories about barriers to behavioural change. Programmes for Indigenous people need to include individual health-related behavioural changes as well as multifaceted approaches that encompass these external influences. Maternal and child health Clair MacVicar, a paediatrician with the Central Australian Remote Health Service, revisited the importance of genetic and environmental influences on the risks of developing chronic diseases and explained that the risks increased when there was a mismatch between genetic make-up and environmental influences. Louise Maple-Brown of the Menzies School of Health Research and Royal Darwin Hospital reported that compared to non-Indigenous Australians, Indigenous Australians experience obesity and type 2 diabetes much younger, and that, given the paucity of evidence on the efficacy of medications in young people, their management was complex. Prevention strategies for young Indigenous Australians need further development.

Jeremy Oats, a senior obstetrician at the Royal Women’s Hospital in Melbourne and a member of the Victorian Consultative Council on Obstetric and Paediatric Mortality, discussed current recommendations for the diagnosis and management of gestational diabetes, summarizing the findings from the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study. This showed a continuous relationship between carbohydrate intolerance in pregnancy and adverse pregnancy outcomes that were independent of ethnicity. The new criteria for gestational diabetes are likely to identify more women and babies at risk in most populations; health services will need to plan for this increased demand. A high-risk initiative for the diabetes in pregnancy clinic at the Alice Springs Hospital was described by another obstetrician, Simon Kane from Canberra Hospital. The Diabetes Antenatal Care and Education Clinic (DANCE) is multidisciplinary and includes an obstetrician, midwife, diabetes educator and physician. Management takes place in the community to limit the need for women to travel large distances. The programme is audited to inform future changes in clinical practice and examines rates of

a lack of medical specialists in remote centres. The model is transferable and is being considered to improve diabetes management in pregnancy.

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gestational diabetes, the percentage of women presenting early in pregnancy, the percentage of women undergoing a 22-week ultrasound, and delivery and neonatal outcomes (such as birth weight). Glynis Dent, a diabetes educator at Alice Springs Hospital, later explained that DANCE facilitates a collaborative, holistic approach to care, using different antenatal care models, including hospital, general practitioner and midwife clinics. Barriers addressed particularly by allowing women to telephone clinic staff from their community setting have included dealing with mobile and remote clients, the lack of midwives working remotely, and the difficulty of encouraging people to monitor blood glucose and use insulin when living conditions were not supportive. Integrating primary and tertiary care The symposium ended with a session on the integration of primary and tertiary care in Indigenous health. Peter Fitzpatrick of the Borroloola Health Clinic outlined the challenging roles of the general practitioner, which incorporate both clinical and population health improvement and can change over time and across communities. Roles include

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leadership and encouraging Indigenous people to be leaders in their communities; involvement in infrastructure planning of housing and recreational facilities; advocacy on behalf of Indigenous people; improving integration between clinical services in communities and hospitals; conveying information on chronic diseases in an uncomplicated manner; and building relationships with community members. Challenges facing general practitioners include poor communication between remote clinic and hospital staff where staff turnover is high; inadequate linkage between electronic health records; poor engagement with Indigenous people; and breakdowns in well-coordinated primary care systems. Neale Cohen, an endocrinologist at Baker IDI, outlined the role of the specialists as important components of a multidisciplinary team. He emphasized that although the majority of people with diabetes can be managed in primary care, some develop more complex problems. People requiring a specialist referral include those with kidney or eye disease, neuropathy, people initiating insulin, using pumps or with psychological needs and pregnant women with diabetes.

Conclusions The overarching objective of the 2010 Alice Springs Symposium, to promote engagement between local healthcare providers, educators, researchers and policy makers in order to expand knowledge of evidenced-based care and thus reduce the ill health and mortality caused by the complications of diabetes, was successfully achieved. One aspect that we hope to improve on in future meetings is the level of attendance by Indigenous health professionals. Barriers to attendance could have related to the need for people to travel to Alice Springs, or leaving their community understaffed by health workers. The project will investigate the possibility of conducting some of the future Department of Health and Ageing educational symposia in remote communities in the Northern Territory.

Elizabeth Barr, Alex Brown Baker, John Boffa, Paul Zimmet Elizabeth Barr is an epidemiologist at the Baker IDI Heart and Diabetes Institute (Elizabeth.Barr@bakeridi.edu.au). Alex Brown Baker is Head of Indigenous Health Research at the IDI Heart and Diabetes Institute. John Boffa is Public Health Medical Officer with the Central Australian Aboriginal Congress. Paul Zimmet is Director Emeritus and Director of International Research at the Baker IDI Heart and Diabetes Institute.

Acknowledgment

The symposium was funded by the Australian Government Department of Health and Ageing.

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Sharing hope and improving care – Haiti builds for a brighter future John Devlin

Established in 2000, Konbit Sante Cap-Haitien Health Partnership is a US-based volunteer initiative to improve healthcare in northern Haiti. Konbit Sante works with the Haitian Ministry of Health and with Haitian healthcare professionals to strengthen the capacity of the public system to provide care for Haitians. In Haitian Creole, ‘konbit’ is a traditional Haitian method of working together to till the fields of others as well as one’s own – a cooperative effort. ‘Sante’ means health. The author reports on his experiences with Konbit Sante and describes their efforts after the devastating earthquakes of January 2010 to rebuild, reinforce and improve healthcare provision for people with diabetes in Haiti.

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I first visited Haiti in 2000 principally to become acquainted with Konbit Sante and assess first-hand the degree of need of the Haitian diabetes population. My initial efforts involved unloading large containers of much-needed medical supplies and equipment at the Hôpital Universitaire Justinien, a 250-bed teaching hospital operated by the Haitian Ministry of Health. Serving an estimated 825,000 people, it is the largest healthcare provider in northern Haiti. During this initial visit, I also had the opportunity to meet a number of Haitian colleagues, give a series of lectures and observe the diabetes clinic in operation. During this and subsequent visits, I was able to assess the level of diabetes care available to the fortunate few with the means to travel to and pay for a clinic visit. It was apparent that Haitians arrived at late stages of disease; had little if any regular follow-up care; could not afford the complex medical regimens being prescribed; and had very poor control of their diabetes and blood pressure. It was reported to me that lower-extremity amputations were

being performed at an average rate of one per week.

For the majority of Haitians, a diagnosis of type 1 diabetes is a death sentence. The situation for people receiving hospital treatment was equally desperate. Although a limited supply of glucose test strips was sometimes available, laboratory measurements could be performed only once daily ‒ and often were unavailable due to frequent power cuts. Family members were required to pay out-ofpocket for all laboratory tests. With the economic poverty among the majority of Haiti’s population, it was common for a person to be admitted with suspected diabetic ketoacidosis but without having even electrolytes to confirm the diagnosis. For the majority of Haitians, a diagnosis of type 1 diabetes is a death sentence because they cannot afford to buy insulin.

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A young girl learns the proper hand-washing technique at a Konbit Sante cholera education site.

Despite these challenges, healthcare providers in Haiti are proficient and professional and highly dedicated. Resident physicians must show ingenuity in order to perform seemingly simple procedures, such as an X-ray, ECG, or lumbar puncture. Things taken for granted in wealthy countries like the USA were simply unavailable to Haitian personnel, including most medical supplies, properly functioning equipment, clean water and electricity. Fortunately, through Konbit Sante’s ongoing efforts, generators now provide a steady source of back-up electricity, there is clean water for hand-washing if not for drinking, and important pieces of medical equipment are maintained in working order.

Haïtienne de Diabete et de Maladies Cardio-Vasculaires (FHADIMAC) headquarters. Nancy is an endocrinologist and Project Coordinator at FHADIMAC; Philippe, her husband, is one of the country’s leading epidemiologists. It was immediately apparent that I had met individuals who were not only eminent clinicians and researchers, but who also shared a passion to improve the well-being of Haitians struggling to live with diabetes.

I was able to meet two Port-au-Prince diabetologists, Nancy Charles Larco and Philippe Larco at the Fondation

The purpose of my visit was to discuss plans to submit an IDF BRIDGES grant application focused on improving

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Healthcare providers in Haiti are proficient and professional and highly dedicated.

diabetes care in Cap-Haitien. Nancy and Philippe proved to be invaluable resources for understanding the cultural context of diabetes care among Haiti’s urban and rural populations. Along with their FHADIMAC colleagues, they had published the only well-designed study of diabetes prevalence in Haiti. Among adults aged between 40 and 64 years, 10.6% of men and 14.4% of women were found to have diabetes. Disturbingly, less than 25% of adults aged 40 or older had a normal blood pressure. A collaborative working group including these Haitian diabetologists, the executive director of Konbit Sante, the head of the Hôpital Universitaire Justinien’s internal medicine residency programme and colleagues at the Maine Medical Center Research Institute, Maine, USA, submitted a BRIDGES

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application in July 2009. The primary aim of our project is to improve the three diabetes-related outcomes shown to be most cost-effective (all are cost-saving) in resource-poor countries: b lood glucose control in people with HbA1c greater than 9% b lood pressure control in people with blood pressure is above 160/95 p reventive foot care in those at high-risk.

proposed starting date of 1 April could be delayed indefinitely until the country had time to deal with the quake’s after-

illiterate population. We also developed, in conjunction with residents in internal medicine, stepped-care algorithms in French for foot care and the management of blood glucose and blood pressure. We will determine how well we can translate evidence-based diabetes care into this most challenging of environments using the RE-AIM framework of Russell Glasgow, which examines the reach, effectiveness, adoption, implementation and maintenance of an intervention.

We have developed culturally appropriate educational materials to provide education to a largely illiterate population.

As we awaited final news on the status of our application, Haiti was devastated by the Richter 7.0 earthquake of 12 January, 2010. As members of IDF and their international partners made intensive efforts to ensure that an adequate supply of insulin reached Portau-Prince, I learned that our project had been funded. It was a bittersweet moment in the midst of such a tragedy, but the context served to accentuate the urgency of the work we were proposing to do. Although we were advised that the

math, I discovered upon returning to Cap in March that everyone from the Hôpital Universitaire Justinien chief of staff down was eager to begin the project without delay. With the invaluable contribution of qualified nursing staff and community health workers, we have developed culturally appropriate educational materials in Haitian Creole, and others using pictographs provided by FHADIMAC, to provide education on the principles of nutrition, exercise, medications and preventing complications to a largely

Those of us who have had the privileged of getting to know the Haitian people feel a little saddened each time we have to leave the country, and look forward to our return. Perhaps it is their indomitable spirit and strength of character that is so much in evidence ‒ an unstoppable force for a brighter future for all people living with diabetes in Haiti.

John Devlin John Devlin is a diabetologist at the Maine Medical Centre, Maine, USA, and principal investigator of the Improving Diabetes Care in Cap Haitien project.

Further reading Charles-Larco N, Charles R. Solidarity with Haiti: the global diabetes response. Diabetes Voice 2010; 1: 47-9. Jean-Baptiste ED, Larco P, Charles-Larco N, et al. Glucose intolerance and other cardiovascular risk factors in Haiti. Prevalence of Diabetes and Hypertension in Haiti (PREDIAH). Diabetes Metab 2006; 32: 443-51.

Acknowledgement

A view of the Cathedral from the entrance to the hospital

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The author is the principal investigator of this project, which is supported by BRIDGES. BRIDGES is an International Diabetes Federation programme supported by an educational grant from Lilly Diabetes.

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Can shared care improve outcomes in women with gestational diabetes? Xilin Yang and Huiguang Tian

Gestational diabetes, which is defined as ‘any degree of glucose intolerance with onset or first recognition during pregnancy’, damages the health of millions of women and their babies during the perinatal period and later in life. Like type 2 diabetes, gestational diabetes is on the rise worldwide. However, the management of gestational diabetes is less developed than the management of type 1 diabetes and 2 diabetes. In this report, Xilin Yang and Huiguang Tian describe a translational study into the effects of shared care versus usual care in Tianjin, China, the aim of which is to develop an effective and sustainable care model for managing gestational diabetes.

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Pregnancy-induced hypertension is a major concern for women with gestational diabetes. Many studies have reported the effect of gestational diabetes in increasing risks for hypertension and pre-eclampsia. The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) investigation, a huge, multinational, multi-centre study, revealed three principal findings:1 Strong associations exist between maternal glucose levels (fasting, 1-hour and 2-hour) during pregnancy and pre-eclampsia. T here are strong and continuous associations between maternal plasma glucose levels, increased birth weight and cord-blood serum C-peptide levels with no apparent thresholds. G lucose levels during pregnancy are associated with primary caesarean section, premature delivery, birth injury (such as shoulder dystocia), intensive neonatal care, and jaundice.

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Babies born to mothers with gestational diabetes are more likely to develop obesity by the ages of between 8 and 10 years and impaired glucose tolerance between 10 and 16 years. Indeed, a baby born to a mother with gestational diabetes may exhibit early features of metabolic syndrome ‒ high blood pressure and low high-density lipoprotein cholesterol. Women with gestational diabetes are also likely to develop type 2 diabetes in later life. In a large Canadian population-based database of deliveries collected over a 7-year period between 1995 and 2002, the probability of developing diabetes after gestational diabetes was 3.7% at 9 months after delivery and 18.9% at 9 years after delivery.2

the north of China, about 130 km southeast of the capital, Beijing, with a population of more than 10 million people. Antenatal care is shared by a three-tier prenatal care system consisting of approximately 90 hospitals, six district-level women’s and children’s health centres, and a city-level women and children’s health centre. All pregnant women are registered at the hospitals and in the 32nd week of pregnancy, they will be referred to one of the women and children’s

A baby born to a mother with gestational diabetes may exhibit early features of metabolic syndrome. The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) was a seminal randomized clinical trial which addressed the effectiveness of managing gestational diabetes.3 In this large randomized study, 490 women with gestational diabetes diagnosed at 24 to 34 weeks of gestation were randomly assigned to intensive therapy involving dietary advice, blood glucose monitoring and insulin therapy as needed, while 510 women with gestational diabetes were assigned to routine care. The trial demonstrated that intensive care of gestational diabetes can reduce significantly the rate of serious perinatal complications (defined as death, shoulder dystocia, bone fracture, and nerve palsy) compared to the routine care. The Tianjin study Tianjin is a metropolitan port city in

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health centres for management until delivery. Women with a high-risk pregnancy can be referred to a health centre at any point during gestation. The Tianjin Women and Children’s Health Centre heads the three-tier prenatal care system and is responsible for the organization, co-ordination and implementation of research into women’s health, as well as the promotion, via the six district-level women and children’s health centres, of projects in the antenatal care units of the 90 hospitals. In late 1998, a universal system for the screening and management of gestational diabetes was introduced into the antenatal care network as an initiative to improve the well-being of pregnant women and their babies.4

Gestational diabetes care was inadequate; blood glucose self-monitoring during pregnancy was not widely available. By 2009, the programme had screened 128,125 pregnant women. During this period, the system witnessed a rapid increase in the prevalence of gestational diabetes in Tianjin. For example, the adjusted prevalence of gestational diabetes increased nearly three-fold between 1999 and 2008, from 2.4% to 6.8%.5 On the other hand, care for women with gestational diabetes in Tianjin was inadequate and blood glucose self-monitoring during pregnancy was not available to the majority of women. The three-tier antenatal care system did not have specialized diabetes nurses or specialized dieticians who could provide medical counselling to help pregnant women keep blood glucose levels under control. The Randomized Translational Study to Examine the Effects of Shared Care

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versus Usual Care in Management of Gestational Diabetes in A Three-Tier Prenatal Care Network in Tianjin, China (The RTSESU study), is a populationbased clinical trial to translate the established gestational diabetes management protocol of the ACHOIS study into a shared-care model. RTSESU will examine the effectiveness, cost-effectiveness and sustainability of the shared-care model in reducing high birth weight (defined as larger than or equal to 4500 g) as the primary endpoint; and macrosomia (defined as birth weight greater than or equal to 4000 g) and pregnancy-induced hypertension as the secondary endpoints. The study will screen pregnant women at 24 to 28 weeks using a 50 g 1-hour glucose test. Those with a positive result are referred to a centralized gestational diabetes clinic, where they will undergo a 75 g 3-hour oral glucose tolerance test. The International Association of Diabetes and Pregnancy Study Group’s diagnostic criteria are used to diagnose gestational diabetes: fasting plasma glucose at or above 5.1 mmol/l; or 1-h plasma glucose at or above 10.0 mmol/l; or 2-h plasma glucose at or above 8.5 mmol/l.6 A total of 920 of women with gestational diabetes will be randomly assigned to receive shared care or the usual antenatal care. The fieldwork began on 1 July 2010 and will end on 30 June 2013. By that time, we will be able to demonstrate the effectiveness of shared care in reducing the primary and secondary endpoints, and the cost-effectiveness of the model and its sustainability. It is hoped that using these results, a management model for improved and effective delivery of care for women with gestational diabetes might be established in other parts of China and elsewhere in the world.

Xilin Yang and Huiguang Tian Xilin Yang, Department of Medicine and Therapeutics, the Chinese University of Hong Kong Special Administrative Region, China. Huiguang Tian, the Tianjin Women and Children’s Health Centre, Tianjin, China.

References 1 M etzger BE, Lowe LP, Dyer AR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991-2002. 2 F eig DS, Zinman B, Wang X, Hux JE. Risk of development of diabetes mellitus after diagnosis of gestational diabetes. CMAJ 2008; 179: 229-34. 3 C rowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 4 Y ang X, Hsu-Hage B, Zhang H, et al. Gestational diabetes mellitus in women of single gravidity in Tianjin City, China. Diabetes Care 2002; 25: 847-51. 5 Z hang F, Dong L, Zhang CP, et al. Increasing prevalence of gestational diabetes mellitus in Chinese women from 1999 to 2008. Diabet Med 2011: 28: 652-7. 6 M etzger BE, Gabbe SG, Persson B, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010; 33: 676-82.

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“Believe it or not, it made learning about diabetes fun.” Diabetes Conversations is an exciting programme featuring Conversation Map™ education tools that has people with diabetes talking. Diabetes Conversations is much more than a series of engaging education sessions. From facilitator training to support resources and follow-up materials, this comprehensive programme provides many components that work together to assist you in helping people with diabetes achieve greater success in managing their disease. Please contact your Lilly representative or visit www.diabetes.healthyi.com to learn more about this dynamic programme and to find out about training sessions in your area.

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