Primary Care Reports – improving Diabetes Management – Abbott by Global Business Media

SPECIAL REPORT

Improving Diabetes Management

Understanding the Ambulatory Glucose Profile in Diabetes Re-Thinking Health Care – Prevention of Type 2 Diabetes and its Complications Managing the Diabetic – An Overview Diabetic Complications – Nervous System, Eyes, Kidneys The Artificial Pancreas

Published by Global Business Media

Welcome to Flash Glucose Monitoring. The days of routine glucose testing with lancets, test strips and blood are over.†

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†

FreeStyle and related brand marks are trademarks of Abbott Diabetes Care Inc. in various jurisdictions. Simulated data for illustrative purposes only; not real patient or data. Date of preparation: August 2014. ADCMDP140136r ‡

FreeStyle Libre is currently only available via purchase from Abbott Diabetes Care

IMPROVING DIABETES MANAGEMENT

SPECIAL REPORT

Improving Diabetes Management

Contents Foreword

Dr Charles Easmon, MBBS MRCP MSc Public Health DTM&H DOccMed, Editor

Understanding the Ambulatory Glucose 3 Profile in Diabetes Dr Ramzi Ajjan, associate professor and consultant in diabetes and endocrinology, Leeds Institute for Cardiovascular and Metabolic Medicine; Dr Jez McCole, GP, Sheffield; and Su Down, nurse consultant for diabetes and

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clinical lead for the Intermediate Diabetes Service in Somerset

Introduction The Triangle of Diabetes Care The Ambulatory Glucose Profile Glucose Testing Generating AGP Reports Interpreting the AGP

Re-Thinking Health Care – 7 Prevention of Type 2 Diabetes and its Complications Sophie Levingworth, Medical Correspondent

Taking Control Is Regular Screening the Answer? Effective Management

Managing the Diabetic – An Overview

Dr Charles Easmon, Editor

The Pathology in Diabetes Excess Blood Sugar as the Main Problem Low Blood Sugar as the Secondary Problem of Control Measures Creating a New Homeostasis for the Diabetic and Optimal Care

Diabetic Complications – 12 Nervous System, Eyes, Kidneys Dr Charles Easmon, Editor

The opinions and views expressed in the editorial content in this publication are those of the authors alone and do not necessarily represent the views of any organisation with which they may be associated. Material in advertisements and promotional features may be considered to represent the views of the advertisers and promoters. The views and opinions expressed in this publication do not necessarily express the views of the Publishers or the Editor. While every care has been taken in the preparation of this publication, neither the Publishers nor the Editor are responsible for such opinions and views or for any inaccuracies in the articles. © 2016. The entire contents of this publication are protected by copyright. Full details are available from the Publishers. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical photocopying, recording or otherwise, without the prior permission of the copyright owner.

Type 1 and Type 2 The Nervous System The Eyes The Kidneys Educating the Diabetic and Detecting Early Nervous System, Eye and Kidney Problems

The Artificial Pancreas Sophie Levingworth, Medical Correspondent

The Interplay Between Insulin and Glucagon Automated Blood Glucose Control

IMPROVING DIABETES MANAGEMENT

Foreword I

S IT better to know more? We have tsunamis

in the past 40 years which, in addition to providing

of data that many find difficult to interpret and

the glucose level, provides the direction and rate of

which can cause confusion. Averages can be

glucose change with the push of a button and alerts

very misleading.

users when glucose is too low or too high.

Diabetic patients have a difficult problem. They

It is now available in various forms and formats

need to know their sugar level to decide what to

but, as with any large amount of data, it needs to be

eat, when and how much to exercise and to decide

interpreted and this is the benefit of specific algorithms

whether they need a dose of insulin or glucagon and

designed to make sense of this data. As with web

if so how much? Testing is unpleasant and involves a

pages, data needs a graphical interface that is easy

finger prick at least 3 times daily. Finger pricks need

to interpret. In the West we are used to the colours

needles and needles need to be disposed of safely

of traffic lights and graphical data for diabetics

(as do the needles for insulin). An implant would make

that tells them the red (danger), amber (moderate

sense and especially so if this implant continuously

danger) and green (safe) areas are the best outcome

measured glucose (it will still need occasional finger

from algorithms.

prick checks but not as many and as often). Continuous glucose monitoring is perhaps the most significant breakthrough in diabetes management

Dr Charles Easmon Editor

Dr Charles Easmon is a medical doctor with 30 yearsâ&#x20AC;&#x2122; experience in the public and private sectors. After qualifying as a physician, he developed his interests in occupational medicine, public health and travel diseases.

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Understanding the Ambulatory Glucose Profile in Diabetes Dr Ramzi Ajjan, associate professor and consultant in diabetes and endocrinology, Leeds Institute for Cardiovascular and Metabolic Medicine; Dr Jez McCole, GP, Sheffield; and Su Down, nurse consultant for diabetes and clinical lead for the Intermediate Diabetes Service in Somerset A review of the rationale, role and interpretation of the ambulatory glucose profile in clinical practice.

Introduction The ambulatory glucose profile (AGP) is a tool that allows innovative technology to graphically present dense glucose data. This allows easy identification of patterns and trends in glucose levels and can help healthcare professionals discuss management changes with their patients with diabetes. This article examines the rationale, role and interpretation of the AGP in clinical practice.

The Triangle of Diabetes Care Despite advances in treatment, diabetes remains an important cause of morbidity and mortality worldwide, owing to the micro- and macrovascular complications associated with the disease.1 A multifactorial approach is essential

to prevent vascular pathology in diabetes, which includes management of hypertension, dyslipidaemia, obesity and glycaemia.2 Achieving good glycaemic control can represent a particular challenge as, unlike other risk factors, glucose levels can fluctuate wildly and are sensitive to daily activities and food intake. HbA1c has been a useful tool in the quest to optimise glucose levels in diabetes. A drop in this glycaemic marker is associated with a reduction in microvascular complications, an effect that is observed relatively early, and decreased incidence of macrovascular events in the long-term.3â&#x20AC;&#x201C;5 However, reliance on HbA1c alone for glycaemic management runs the risk of ignoring other changes in the glucose profile, namely hypoglycaemia and fluctuations in

If the 10th percentile line lies near the hypoglycaemic value it is important to examine the daily ranges to see if there have been episodes of hypoglycaemia masked by the process of amalgamating the data

THE TRIANGLE OF DIABETES CARE

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A number of interventional and observational studies have shown a link between hypoglycaemia and mortality in diabetes

glucose levels, which are both associated with adverse clinical outcomes.6–10 A number of interventional and observational studies have shown a link between hypoglycaemia and mortality in diabetes.6–8 Although a causal relationship is not always proven, low blood glucose predisposes to cardiac arrhythmias and increases the risk of thrombosis, thereby providing mechanistic explanations for the clinical observations.6 Importantly, HbA1c fails to detect hypoglycaemic episodes and therefore high-risk patients, such as those taking insulin or a sulfonylurea, should be carefully assessed for the possibility of hypoglycaemia. Moreover, fluctuations in glucose levels, commonly referred to as glucose variability, are also associated with adverse clinical outcomes, including increased mortality and longer hospital stay.9,10 Again, HbA1c is unable to address glucose variability, which can only be accurately assessed by regular glucose testing. Taken together, current evidence indicates that whilst HbA1c is a helpful glycaemic parameter, it should be complemented by assessment of hypoglycaemia and glucose variability in order to achieve optimal glucose control. Therefore, we propose a glycaemic management strategy that relies on three measures: HbA1c, hypoglycaemia and glucose variability, in what is best described as the ‘triangle of diabetes care’ (Figure 1). Whilst the evidence supports optimal management of the triangle of diabetes care, in practice it is difficult to comprehensively capture hypoglycaemic events. Moreover, glucose variability can be even harder to assess, particularly in patients who do not perform regular glucose checks. Fortunately, there is a means available to fully evaluate all glycaemic parameters of the triangle, namely the AGP.

The Ambulatory Glucose Profile The AGP is an innovative methodology for interpreting a patient’s daily glycaemic patterns. It uses advances in self-monitoring technology to provide graphic and quantitative information on 24-hour glucose levels, allowing the identification of patterns in glycaemic control. By revealing the trends behind a person’s HbA1c result, the AGP facilitates targeted changes in diet, lifestyle and therapy. The concept of the AGP has been around for some time, ever since attempts were first made to identify patterns in glucose values using the earliest reflective colour meters in the 1980s.11 The vision behind the AGP, first developed by Professor Roger Mazze and colleagues, was to standardise reporting of glucose data, much like a ‘diabetes ECG’. 4 | WWW.PRIMARYCAREREPORTS.CO.UK

Essentially, anyone assessing glucose values attempts to find patterns relevant to day-to-day life, diet, medication and activity. This prompts changes to prevent hypo- or hyperglycaemia.

Glucose Testing Each of the modalities for collecting glucose readings has advantages and drawbacks: HbA1c HbA1c is a single figure representing long-term control. This test has strong evidence for its use, being referenced in trials examining complications and the risk of poor diabetes control. 12 Unfortunately, because it is an average figure, a lot of relevant information may be lost, including the daily fluctuations with which most people with diabetes are familiar. Frequently, clinicians find themselves sitting with a patient, puzzled by an HbA1c value, trying to understand its provenance. Finger-prick testing The advent of blood glucose self-monitoring enabled patients to take greater control of their diabetes, bringing more data to both patient and clinician. Meters with memories and interpretation software further revolutionised the analysis of these data. A variety of bespoke reports can help to spot patterns. Data from at least 14 consecutive days are needed to give a clinically significant picture.13 However, this amount of testing is difficult to achieve and patterns accounting for HbA1c or hypoglycaemia can be buried deep in the readings. Moreover, the diary may be incomplete and/or lack dietary and lifestyle components essential for analysis. Continuous glucose monitoring Until recently, the means to monitor the glucose content of interstitial fluid was not widely available. Continuous glucose monitoring (CGM) delivers a continuous indication of glucose levels, offset by the time it takes for blood glucose to affect interstitial levels. The impact of a meal or medication event can be seen quickly on the profile. Data points are so numerous that evaluation software is almost mandatory, meaning the AGP paradigm is useful to make sense of the data. Flash glucose monitoring An innovative method of measuring glucose levels, flash glucose monitoring, like CGM, measures interstitial glucose. The FreeStyle Libre Flash Glucose Monitoring System is an example of a commercially available sensor-based flash glucose monitor. It is a discreet system, worn on the back of the upper arm which unlike CGM, collects data that is stored on the sensor for up to eight hours, and can then be ‘flashed’

IMPROVING DIABETES MANAGEMENT

THE AMBULATORY GLUCOSE PROFILE

via near-field communication, to a reader for analysis or download. Such dense glucose data as this requires a tool such as the AGP because of its continuous data capture around meals, medications and activity.

Generating AGP Reports Increasingly, people with diabetes have easier access to technologies capable of producing AGP reports but may lack the expertise to interpret them. The AGP provides graphical and quantitative 24hour data, overlaying multiple days of readings on a single day (Figure 2).14 The AGP report quickly speaks for itself. For example, if there are times when someone is regularly at risk of hypoglycaemia, this can be seen as the 10th percentile touches the 4.5mmol/L line. During a consultation, this can efficiently lead to changes to the insulin/carbohydrate ratios prior to that time period. Similar action can be taken for hyperglycaemic patterns. In this way, expert opinion agrees that the AGP is an effective standard, providing valuable insights into glucose control and the impact of medications, diet and lifestyle choices.15

Interpreting the AGP In order to interpret the AGP report an understanding of the data presented is crucial. The AGP report represents an amalgamation of all glucose values from previous days or weeks and is presented as one 24-hour period. This is referred to as the ‘modal day’.

Features of the AGP report The first element of the modal day is the median curve; this represents the median glucose value at that time point. The median curve indicates the glucose stability seen across the 24-hour period.

Surrounding the median curve are two further shaded areas. The first is the 25th to 75th percentile line within which half of all glucose readings will fall, which is referred to as the interquartile range (IQR). The second, outer area is the 10th to 90th percentile, which captures glucose excursions (Figure 2). Meaningful interpretation of the data presented in the AGP report requires further information with regard to carbohydrate intake and insulin doses, along with other factors affecting glucose such as exercise levels.14 When looking to interpret the data a systematic process should be employed as follows:15 •A ssessing the quality of the data, in particular whether there are ≥14 days of glucose data. • Identifying hypoglycaemic episodes. •E stablishing glycaemic pattern development by time of day. • Evaluating day-to-day variability. •R ecommending any necessary treatment changes. If at any time point in the modal day the IQR is under or on the lower target range, it is imperative that individual daily graphs are investigated to identify hypoglycaemia. Hypoglycaemia, if present, has to be the primary focus of treatment change in order to prevent recurrence. If the 10th percentile line lies near the hypoglycaemic value it is important to examine the daily ranges to see if there have been episodes of hypoglycaemia masked by the process of amalgamating the data.15

It is accepted that AGP can be a useful addition within the consultation to facilitate further education in the understanding of factors that can influence blood glucose variability and self-management of diabetes

Benefits It is accepted that AGP can be a useful addition within the consultation to facilitate further education in the understanding of factors that can influence blood glucose variability and self-management of diabetes (Box 1).14,15 WWW.PRIMARYCAREREPORTS.CO.UK | 5

IMPROVING DIABETES MANAGEMENT

Case scenario15 • 51-year-old male • Weight 93kg (BMI 32) •G lucose measurement HbA1c 73 mmol/mol with daily readings ranging 10–14 mmol/L • I nsulin regimen insulin lispro/insulin lispro protamine 50/50% suspension, 18 units in the morning. Reviewing the AGP report it is noted that there is overall hyperglycaemia throughout the day, especially at night. Although there is no hypoglycaemia, there is a major glycaemic drop in the morning. The patient reports never eating breakfast and so his insulin type is not the most appropriate for his eating pattern. His regimen was changed to a basal–bolus regimen with prandial insulin at lunch and evening meal only. Follow-up At follow-up appointment there has been a dramatic improvement in the overall AGP profile. The median glucose is stable throughout the 24-hour period. There remains a moderate rise after the evening meal with a wide inter-day variation and so dietary advice was given with regard to carbohydrate intake at this meal and dose adjustment to suit as necessary. Further follow-up was suggested with a repeat AGP profile at three to six months.

Meaningful interpretation of the data presented in the AGP report requires further information with regard to carbohydrate

Case scenario for educational purposes only. Individual symptoms, situations and circumstances may vary.

intake and insulin doses, along with other factors affecting glucose such as exercise levels.

The AGP can be of benefit when:14 • Identifying reasons for a mismatch between the patient’s glycaemic profile and HbA1c results.

• Assessing a patient’s glucose levels versus target range. • Understanding the extent and causes of high blood glucose variability. • Assessing suitability of treatment. • Assessing whether it is safe to increase an insulin dose. It can also have particular benefits in patients with reduced hypoglycaemia awareness or in people with a desire to improve their long-term control with improved self-management skills.15 A consensus guide for the interpretation of the AGP specific to the UK is in development and will be a valuable aid to assist healthcare professionals in the clinic setting with this increasingly available technology.

Contact Abbott Abbott House, Vanwall Business Park, Vanwall Road Maidenhead SL6 4UD, UK www.abbottdiabetescare.co.uk 0800 032 1016 Fax 01628 678805

About Abbott Abbott is a global healthcare company devoted to improving life through the development of products and technologies that span the breadth of healthcare. With a portfolio of leading, science-based offerings in diagnostics, medical devices, nutritionals and branded generic pharmaceuticals, Abbott serves people in more than 150 countries and employs approximately 69,000 people.

References: 1.

International Diabetes Federation. IDF Diabetes Atlas. Sixth edition. Brussels, IDF, 2014. Available from: www.idf.org/diabetesatlas (accessed 9 September 2015).

Gaede P, Lund-Andersen H, Parving HH et al. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008; 358: 580–91.

Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control and Complications (DCCT) Research Group. Kidney Int 1995; 47: 1703–20.

Nathan DM, Cleary PA, Backlund JY et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353: 2643–53.

Holman RR, Paul SK, Bethel MA et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359: 1577–89.

Frier BM, Schernthaner G, Heller SR. Hypoglycemia and cardiovascular risks. Diabetes Care 2011; 34 Suppl 2: S132–7.

Elwen FR, Huskinson A, Clapham L et al. An observational study of patient characteristics and mortality following hypoglycemia in the community. BMJ Open Diabetes Res Care 2015; 3: e000094.

Yeh JS, Sung SH, Huang HM et al. Hypoglycemia and risk of vascular events and mortality: a systematic review and meta-analysis. Acta Diabetol 2015 Aug 25 [Epub ahead of print].

Lin CC, Li CI, Yang SY et al. Variation of fasting plasma glucose: a predictor of mortality in patients with type 2 diabetes. Am J Med 2012; 125: 416–8.

6. 7.

Mendez CE, Mok KT, Ata A et al. Increased glycemic variability is independently associated with length of stay and mortality in noncritically ill hospitalized patients. Diabetes Care 2013; 36: 4091–7.

10.

Mazze RS, Lucido D, Langer O et al. Ambulatory glucose profile: representation of verified self-monitored blood glucose data. Diabetes Care 1987; 10: 111–7.

11.

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993; 329: 977–86.

12.

Dunn TC, Crouther N. Assessment of the variance of the ambulatory glucose profile over 3 to 20 days of continuous glucose monitoring. Diabetologia 2010; 53 Suppl 1: S421.

13.

Matthaei S. Assessing the value of the Ambulatory Glucose Profile in clinical practice. Br J Diabetes Vasc Dis 2014; 14: 148–152.

14.

Matthaei S, Dealaiz RA, Bosi E et al. Consensus recommendations for the use of Ambulatory Glucose Profile in clinical practice. Br J Diabetes Vasc Dis 2014; 14: 153–7.

15.

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Re-Thinking Health Care – Prevention of Type 2 Diabetes and its Complications Sophie Levingworth, Medical Correspondent

HE RISE of diabetes and the rise of type 2 diabetes go hand in hand. Both have some links to our increased sugar consumption since the era of the slave trade. Public health officials, politicians and the public have key roles in reducing future diabetes and its complications. Taxing sugar has its supporters 1 and its detractors2. Interestingly the threat of sugar taxation has already led to changes in behaviour amongst manufactures3 (leading to a welcome voluntary reduction in sugar content). Education and awareness must also play a role. Many people do not realise the sugar content of a glass of wine4 or that food or drink labeled as ‘healthy’ may have excessive amounts of sugar. It seems odd to tell 5-year olds to cut back on fruit drinks (having previously advised an increase in your 1 in 5!) but that is what we have to do.

Taking Control Weight control is challenging and we now know that one of the healthy generations was the post-

war ‘rationing’ period5. Now in the West there is no shortage of foodstuffs and many of this has to be preserved and processed to travel vast distances. Excess consumption with decreased and more sedentary lifestyles is bound to have consequences on weight gain. However, there are those who believe that the role of gut microbes and antibiotics as contributors to the obesity epidemic are not insignificant6. If we take all these factors into account we have to advise the public on portion control, content control (i.e. ensure quality food stuffs that are not processed), the avoidance of too much ‘junk food’, reduction in human and veterinary antibiotic use alongside a diverse diet with plenty of fibre, pulses and the appropriate microbes. Exercise has its fanatics while there are those who claim not to have time to do any. How do we motivate the ‘sofa surfer”? In my opinion, one step is to explain that the gym is not the key. To use a gym requires a commitment of payment, travel time, change time etc at the end of what might

Everyone (within the bounds of any disability) can do some exercise in their own home whether it be running on the spot or sit ups

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IMPROVING DIABETES MANAGEMENT

already have been a long day. However, everyone (within the bounds of any disability) can do some exercise in their own home whether it be running on the spot or sit ups and, in addition, walking and taking the stairs are to be constantly encouraged.

Is Regular Screening the Answer?

Diabetes is a societal problem on which we should all be advocates for change and optimal care

If we could reduce obesity and increase exercise we would see a corresponding reduction in Type 2 diabetes. However, we would still see some new cases, which raises the question of whether we should introduce a regular screening of those who appear healthy? Many medical publications are negative about the cost-effectiveness of screening but it can be queried whether they have considered a long enough event horizon, since every diabetic detected today has significant potential to gain from the reduced chance of getting costly complications later in life. Once the diabetic knows that they have the condition, the next challenge is to give them accurate and interpretable data as to how well they are controlling their blood sugars. Traditionally, this knowledge has remained with the medical profession but, in the same way that fitness trackers have led to a more personalised level of fitness management, predictably, the next wave for diabetes care is more available data and, for those who cannot manage their own data, there are supportive diabetic communities to help them to manage it better.

Each diabetic needs ideally a percentage score of what is happening to their; Nervous System Eyes Kidneys Feet

Effective Management And alongside this, the knowledge of what can be reversed by better management. They should not be misled into thinking that just one annual check is the key to all their current and future problems. People respond well to feedback and, in the near future, we may better be able to show now the future rewards of better diabetic control. In some areas of health, â&#x20AC;&#x2DC;gamification â&#x20AC;&#x2122; has led to better health management. In summary, diabetes is a societal problem on which we should all be advocates for change and optimal care. The battle against weight gain and complacency around it continues to be challenging and there are industrial forces that will, like tobacco, try to negate any science that advocates change of policy at government level. Diabetic individuals and communities need to be empowered for their own future and they may find better solutions to their health than those identified by doctors.

References: 1.

https://petition.parliament.uk/petitions/106651 accessed 24/1/2016

http://www.cityam.com/232129/a-sugar-tax-would-only-make-the-uk-tax-system-more-incoherent accessed 24/1/2016

3. 4.

http://tiny.cc/4xvu8x http://www.telegraph.co.uk/foodanddrink/10731418/Hidden-levels-of-sugar-in-alcohol-revealed.html accessed 24/1/2016

http://www.theguardian.com/theobserver/2001/jan/14/life1.lifemagazine5 accessed 24/1/2016

http://martinblaser.com/ accessed 24/1/2016

http://searchhealthit.techtarget.com/opinion/Gamification-in-healthcare-isnt-just-about-playing-games accessed 24/1/2016

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Managing the Diabetic – An Overview Dr Charles Easmon, Editor

Diabetes is common and on the increase. If it were an infectious disease it would not just be an epidemic but a pandemic affecting every country in the world.

OUNT TO 60 seconds and another 10 people in the world have died of diabetes, which make the disease more deadly than HIV, tuberculosis and malaria combined1. The International Diabetes Federation2 (IDF) estimated that in 2015, 451 million adults worldwide were living with diabetes; an increase of 33 million since 2013 and they estimate that if nothing is done by 2040 the figure will be as high as 642 million. China and India are estimated to have 180 million diabetics between them and the USA has 11% of its population between 20-79 years affected. In 2014, Diabetes UK, estimated that every two minutes, another person receives that diagnosis with 3.9 million affected, projected to rise to 5 million in 20253. The UK General Practitioner no longer has to dip his finger in his patient’s urine to taste if it is sweet as the ancient physicians used to do. The term Diabetes Mellitus means ‘honey siphon’ and is a combination of Greek (diabetes) and Latin (mellitus). The doctor no longer needs to watch helplessly on the sidelines as his Type 1 diabetic in the pre-insulin era (prior to 1922) died of diabetic ketoacidosis or catabolic wasting. The body would break down its own cells and fat to produce energy and with this came excess toxic ketones and acidosis. For their seminal research on insulin, Banting4 and Macleod5 received the Nobel Prize in 1923 (Banting shared his prize money with Best, and Macleod his with Collip).

The Pathology in Diabetes The diabetic could have 1 of several metabolic disorders (Type 1, Type 2 or Gestational) and we now recognise a pre-diabetic condition. The metabolic disorders all involve a problem of insulin, which may be completely or partially

lacking (Type 1) or body cells may be inadequately responsive to its effects (Type 2). In Type 1 diabetes also called Insulin-Dependent Diabetes (IDD) the islets cells of the pancreas are damaged and either produce no insulin or inadequate amounts. Their destruction appears to be caused by an autoimmune process. In Type 2 diabetes, also called Non InsulinDependent Diabetes (NIDD), insulin is produced but the cells fail to respond adequately to it and hence, providing more insulin is not the total solution but improved production may get the cells to respond as they should. In Gestational diabetes, a temporary anomaly occurs during pregnancy but, later in life, diabetes may return. It is estimated to affect 2% to 4% of all pregnancies, with an increased risk of developing diabetes for both the mother and the child. The heavier the baby, the greater the risk to the mother of a return of diabetes (over 4 kg/ 9 lbs) at birth). Treatment may in some case require insulin, but many can be managed by following a healthy diet and appropriate physical activity.

Providing more insulin is not the total solution but improved production may get the cells to respond as they should

Excess Blood Sugar as the Main Problem Despite Type 2 being more common, the key research re the ‘glucose hypothesis’ is based on Type 1. The key study clearly identified raised glucose as the key contributing factor in the risk of micro and macrovacsular damage to the eyes, nervous system, kidneys and cardiovascular system. It is reasonable to extrapolate from this that the same effect of raised sugars will affect those with Type 2 diabetes and hence optimal control for them is as important as it is for Type 16. The relatively short duration of gestational diabetes makes it difficult to assess longterm effects on poor diabetes control during this period. WWW.PRIMARYCAREREPORTS.CO.UK | 9

IMPROVING DIABETES MANAGEMENT

The most obvious effects of low sugars (hypoglycaemia) are tiredness, fainting, possible coma and death but there may be many subtler effects on cognitive and physical ability

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DIABETIC RETINOPATHY

Low Blood Sugar as the Secondary Problem of Control Measures Insulin acts slowly and, as such, too much may be given which will result at some point in the day or night in low blood sugar. In most cases, symptoms will be mild and the diabetic will realise that they need a ’glucose’ load. In severe cases, coma or fits may occur and parenteral glucose or glucose stimulants like glucagon may be required. We eat for pleasure but also for energy because even while sitting still we expend energy. Our basal metabolic rate requires a minimum of calories in both men and in women7. Insulin helps cells get the energy we need. Based on the obvious pathological processes in diabetes, the symptoms will include: • Frequent urination (an osmotic effect) • Extreme thirst and/or hunger • Weight loss (catabolism) • Fatigue • Numbness • Sores that are slow to heal, and • Increased infections Poor control of diabetes can subsequently lead to an increased risk of: • Heart disease • High blood pressure • Stroke • Kidney and bladder failure • Gum disease • Blindness • Foot and leg infections

Creating a New Homeostasis for the Diabetic and Optimal Care8 The cost of complications accounts for over two-thirds of the £5.6 billion a year that diabetes is estimated to cost the NHS.9 The non-diabetic generally does not suffer from sugar levels that are too low or too high but now we can manage the diabetic both are a significant challenge. The most obvious effects of low sugars (hypoglycaemia) are tiredness, fainting, possible coma and death but there may be many subtler effects on cognitive and physical ability which may have effects on safety-critical work or increase accident rates in situations like driving. The high sugar environment has consistently been shown to be harmful to small and large blood vessels. Preventing neuropathy, foot damage, retinopathy, heart disease and stroke are obvious aims of optimal diabetic therapy. The National Institute for Health and Care Excellence (NICE) provides some excellent frameworks for this but, more recently, criticism has been levelled at complacency in the UK about successful Education, Information and Communication (EIC) in diabetes as well as inadequate service provision10,11. Optimal care for the diabetic in the UK is regarded as all nine recommended care processes13 (see below) and all three of NICE’s

IMPROVING DIABETES MANAGEMENT

treatment targets (1. HbA1c <58 mmol/mol 2. cholesterol <5 mmol/ mol & 3. target BP). In simplest terms the 9 standards are the development, implementation and monitoring of standards to: 1) Reduce the risk of developing Type 2 diabetes in the population and to reduce the inequalities in the risk of developing Type 2 diabetes. 2) Identify those who do not know they have diabetes. 3) Share and mutually agree care plans for all children, young people and adults 4) Ensure all adult diabetics receive high-quality care throughout their lifetime. Optimising the control of blood glucose, blood pressure and other risk factors for developing the complications of diabetes. 5) As above for children and young people with diabetes, with family and carer involvement for maximal development in not just physical areas but also social, educational, psychological and intellectual. 6) Ensure a smooth transition form child diabetic to adult diabetic services with age appropriate partnership and agreement with the young diabetic. 7) Ensure NHS agreed protocols to rapidly and effectively treat diabetic emergencies by those best trained to do so whilst minimising

complications and recurrences. 8) Ensure children, young people and adults admitted to hospital have effective care for their diabetes with their active involvement in decisions where and when possible. 9) Ensure NHS policies that empower and support women with pre-existing diabetes and those who develop gestational diabetes to ensure the optimal outcomes for any pregnancy. All patients aged 12 years and over should receive all of the nine, NICE recommended care processes. These are the annual checks for the effectiveness of diabetes treatment (HbA1c), cardiovascular risk factors (blood pressure (BP), serum cholesterol, body mass index (BMI), smoking and emergence of early complications (eye screening, foot surveillance and urine albumin/serum creatinine (kidney surveillance)).12 In summary, optimal diabetic care is not rocket science but it does involve monitoring, measurements and interpretation. Any new tools that can aid this process, advance care and reduce future pathologies, mortalities and costs to health services.

Despite Type 2 being more common, the key research re the ‘glucose hypothesis’ is based on Despite Type

References:

2 being more common,

http://tiny.cc/wlxv8x accessed 24/1/2016

http://www.idf.org/ accessed 24/1/2016

the key research re the

https://www.diabetes.org.uk/Documents/About%20Us/annual-reports/Diabetes-UK-annual-report-2014.pdf accessed 18/1/2016

‘glucose hypothesis’ is

http://www.nobelprize.org/nobel_prizes/medicine/laureates/1923/banting-facts.html accessed 23/1/2016

http://www.nobelprize.org/nobel_prizes/medicine/laureates/1923/macleod-facts.html accessed 23/1/2016

http://www.ncbi.nlm.nih.gov/pubmed/10860187 accessed 23/1/2016

http://www.bmi-calculator.net/bmr-calculator/ accessed 24/1/2016

http://www.ncbi.nlm.nih.gov/pubmed/23824944 accessed 23/1/2016

http://www.publications.parliament.uk/pa/cm201516/cmselect/cmpubacc/563/563.pdf accessed 23/1/2016

10. 11.

12.

13.

based on Type 1

http://www.bbc.co.uk/news/health-35374588 accessed 23/1/2016 http://www.publications.parliament.uk/pa/cm201516/cmselect/cmpubacc/563/563.pdf accessed 23/1/2016 http://www.hscic.gov.uk/catalogue/PUB12421/nati-diab-audi-11-12-care-proc-rep.pdf accessed 23/1/2016 http://tiny.cc/8mxv8x accessed 23/1/2016

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Diabetic Complications – Nervous System, Eyes, Kidneys Dr Charles Easmon, Editor

In 2023 it will be only 100 years since Banting and Macleod were awarded the Nobel Prize of the discovery of Insulin1.

Type 2 diabetes represents at least 90% of all cases of diabetes and is on the rise with levels of obesity and changed diet and lifestyles.

HY IS excess sugar (hyperglyceamia) or too lit tle sugar harmful (hypoglyceamia)? The Greek word homeostasis means the maintenance of the ‘same environment’ and this is one of our evolutionary physiological wonders when it works well for temperature or substances like glucose in the body. In nature, the non-diabetic achieves what The American Diabetes Association2 recommends for diabetics, keeping blood sugar levels in the range of: • 70 - 130 mg/dL (3.9 - 7.2 mmol/L) before meals • Less than 180 mg/dL (10.0 mmol/L) two hours after starting a meal keeps glycated hemoglobin (A1C) level less than 7 percent The exact pathophysiology of the damage from excess sugar needs more research and may be more complex than it first seems since there may be specific effects from abnormal levels of insulin and or glucagon.

Type 1 and Type 2 Type 1 Diabetes has evolved from a disease in the pre-insulin era (pre-1923) that was rapidly fatal, to a disease that, if poorly controlled, leads to significant morbidity and an earlier death than for those without the condition. The pre-history of Type 2 diabetes is not as well-known, but the disease was likely to have been less common than it is now because of the shorter life expectancy and the lower levels of obesity. Type 2 diabetes represents at least 90% of all cases of diabetes and is on the rise with levels of obesity and changed diet and lifestyles.

The Nervous System To understand the pathology of diabetes on the nervous system it is useful to review this 12 | WWW.PRIMARYCAREREPORTS.CO.UK

fascinating and complex condition. Centrally we have the brain and the spine, which are sensibly called the Central Nervous System (CNS). Everything outside the CNS is the Peripheral Nervous System (PNS), which itself can be subdivided into 1) the Sympathetic Nervous System 2) the Autonomic Nervous System and 3) the Enteric Nervous System. If the brain and the spine are the control centre, there is traffic within and to them that would resemble a 3-dimensional chessboard. Inside the brain and the spinal cord, data is collated and coordinated as well as inputs received (sensory) and outputs given (motor, endocrine, glandular etc.) Each part of the system consists of nerve cells (sensory, motor or more complex) and supporting cells (neuroglia). The sense organs for vision, taste, smell, hearing, and balance and sensory receptors for the general senses like touch, temperature, and pain carry information to (and in most cases from) the brain and spinal cord to be processed and integrated. Various receptors maintain key functions. There are receptors for touch, blood pressure, pressure, vibration, light, chemical balance, heat, hydration, cold, tissue damage, taste, smell and pain. We do not need to think when we eat, breathe, pump blood around arteries and secrete from glands such as the digestive organs. These functions are controlled by our autonomic nervous system (ANS) and are labeled ‘involuntary’, although they can be consciously controlled. The up-regulating part of the ANS is famously described as the ‘fight or flight’ mechanism and also known as the ‘Sympathetic Nervous System’ in which the heart rate increases, breathing rate increases,

IMPROVING DIABETES MANAGEMENT

DAMAGE CAUSED BY DIABETES

digestion decreases and stress hormones and adrenaline are released. The balancing “Parasympathetic System”, as expected, reduces heart rate, breathing rate, increases digestion and effectively ‘down-regulates’ the effect of the Sympathetic System. The digestive system and organs have an interesting interplay of both Sympathetic and Parasympathetic systems. Diabetes may damage a single nerve (mononeuropathy), a specific localised nerve group and hence muscle as in diabetic amyotrophy with pain/muscle wasting in the hip and thigh or buttock or more commonly cause ether peripheral neuropathy or autonomic dysfunction3. Why the feet and legs are affected first in most diabetic peripheral neuropathy is unknown, but lack of sensation, altered sensation, loss of balance and coordination, loss of reflexes and infections are well known complications. Diabetic damage to the autonomic system can and does cause a wide range of symptoms since this system controls the heart, bladder, lungs, gastro-intestinal tract, sex organs and eyes. In the gastro-intestinal tract, symptoms can vary from constipation, to diarrhea, slow gastric emptying, difficulty swallowing and sometimes the perverse problem of sweating when eating. In men erectile dysfunction may be an early feature of microvacsular disease and in women this may feature as vaginal dryness or abnormal sweating.

The Eyes High blood sugars can cause damage to the blood vessels at the back of the eye and prevent the retina getting appropriate nutrients. At the earliest stages of diabetic retinopathy,

blood vessels leak fluid and distort sight but at the later stage of proliferative retinopathy weaker new blood vessels grow around the retina and into the clear vitreous humor that fills the eye. More bleeding occurs as well as clouding of vision and scars that detach the retina occur if untreated’ with the additional risks of retinal detachment and macular oedema.

The Kidneys The main cause of kidney failure is diabetes and it may affect up to a third of those with diabetes4. In type 1 this damage may take 10 years to develop but in Type 2 some damage may already be present at the time of diagnosis. The kidney damage caused by high sugars can be compounded by high blood pressure, raised cholesterol, blood vessel damage and infections. As toxins previously cleared by the kidney build up in the body, the need for dialysis or a kidney transplant becomes essential for life.

In men erectile dysfunction may be an early feature of microvacsular disease and in women this may feature as vaginal dryness or abnormal sweating

Educating the Diabetic and Detecting Early Nervous System, Eye and Kidney Problems Diabetes is one of the most important chronic disease states for which education of the individual and prevention of predictable future complications is of paramount importance. Young adolescents diagnosed with diabetes often struggle with the restrictions that it imposes and the sad consequence of damage 10-20 years later is always regrettable. What the diabetic needs to know is not esoteric. They need to know that there is a reason that their blood sugars should stay within a certain range. They need to know that a low sugar level WWW.PRIMARYCAREREPORTS.CO.UK | 13

IMPROVING DIABETES MANAGEMENT

Lack of sensation, altered sensation, loss of balance and coordination, loss of reflexes and infections are well known complications.

could kill or cause complications. They need to know how to detect a low sugar level and how to adjust for it. The new algorithms will help them detect episodes that even they were not aware about. They need to know that the range of symptoms and signs is wide and that if they get something otherwise inexplicable they should assume it as a consequence of the diabetes until proved otherwise (in many cases they will also need to educate their own doctors of these facts). They need to know that the annual checks are designed to detect early problems, which can then be addressed. In an ideal world we would have tools that allow the diabetic to assess the function of their nervous system, eyes or kidney or at least tools that are closer to the point of care than hospital appointments. One advance that could help assess retinopathy quickly and cheaply is the invention of Dr Andrew Bastawrous5 of the London School of Hygiene and Tropical Medicine. Via various funders and a campaign on crowd fundraising site â&#x20AC;&#x2DC;indiegogoâ&#x20AC;&#x2122;6 his team will release this year a device that can attach to mobile phones (PEEK7).

References: 1.

http://tiny.cc/noxv8x accessed 18/1/2016

http://www.mayoclinic.org/diseases-conditions/diabetic-neuropathy/basics/symptoms/con-20033336 accessed 24/1/2016

http://www.webmd.com/diabetes/guide/diabetes-kidney-disease accessed 24/1/2016

5. 6. 7.

14 | WWW.PRIMARYCAREREPORTS.CO.UK

http://www.nobelprize.org/nobel_prizes/medicine/laureates/1923/banting-facts.html accessed 18/1/2016

http://www.lshtm.ac.uk/aboutus/people/bastawrous.andrew accessed 24/1/2016 https://www.indiegogo.com/projects/peek-retina-help-fight-avoidable-blindness#/ accessed 24/1/2016 http://www.peekvision.org/ accessed 24/1/2016

IMPROVING DIABETES MANAGEMENT

The Artificial Pancreas Sophie Levingworth, Medical Correspondent

We live in an age of wearable technology and advances are happening in leaps and bounds

DIALYSIS MACHINE

UPPORTING A failed or failing organ is a modern achievement of great complexity that saves and extends life. In the past. when both kidneys failed, death was inevitable as experienced by 1930’s actress Jean Harlow at the tender age of 26 (probably secondary to scarlet fever1). But now we have transplants and dialysis, which can be blood or peritoneal based. The inventor of the Segway, Dean Kamen, has added extensively to the safety and portability of dialysis devices2. When the Islet cells of the pancreas fail in type 1 diabetes, the harmful effects of sugar lead to death and morbidity via kidney failure (which, as noted, can be supported), nervous system, eye and cardiovascular complications. What if we could replace the function of the pancreas artificially? This has been the goal of scientists and researchers for many years. There have been several false dawns but one device3 (the collaborative efforts of teams from Boston University and Massachusetts General Hospital) now has approval from the United States Federal Drug Administration service4 (FDA). FDA regulation is tight and once something is approved, if it applies for European regulation or regulation with the MHRA it will often succeed over time.

The Interplay Between Insulin and Glucagon “Water, water, everywhere, And all the boards did shrink; Water, water, everywhere, Nor any drop to drink.” Samuel Taylor Coleridge, The Rime of the Ancient Mariner (replace “water’ with’ glucose’ and ‘drink’ with ‘use as energy’) Insulin works slower than glucagon. The wellfunctioning pancreas produces both. However, both are reduced in Type 1 diabetes wherein the islet cells of the pancreas are reduced in number through an autoimmune disorder. To achieve homeostasis of glucose (normal range), the body needs both insulin and glucagon. After exercise or if a low glucose level is detected then glucagon promotes the breakdown of glycogen in the liver (glycogenesis) to glucose. The broken-down glycogenproduced glucose prevents the low level that would occur, because exercise (noninsulindependent) leads to the uptake of glucose into muscles and prevents low glucose uptake by insulin sensitive tissues. The low glucose effects of diabetes are important as they can cause

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The Bionic Pancreas Team of Boston University and Massachusetts General Hospital have worked as a collaborative group to make automated blood glucose control a reality

unconsciousness, coma, hyper stimulation of the compensatory sympathetic nervous system and, if untreated, brain damage and death. Insulin is a hormone enabler that helps glucose get into the body cells where it is used to make energy. In Type 1 diabetes there is partial or complete lack of insulin production by the body and in the Type 2 diabetics the problem is more one of lack of cell responsiveness to insulin. With the shortage of insulin or its lack of effect, a potential fuel, glucose, circulates into the blood stream and effectively becomes a toxin and, in addition, has the other effect that in a sea of abundance there is no key source of energy and so to get energy the body needs to break down other things (catalysis) and this is obviously harmful. Microbes love sugar and the excess in diabetes can lead to the proliferation of pathogenic types, which promotes infection and we have all seen the horrendous pictures of diabetic feet that have not been properly attended to.

Automated Blood Glucose Control There are 2 types of Artificial pancreas devices 1) those that actively dose insulin alone and 2) those that also use glucagon to prevent and treat hypoglycemia (bihormonal artificial pancreas). The Bionic Pancreas Team of Boston University and Massachusetts General Hospital have worked as a collaborative group to make automated blood glucose control a reality. The team has succeeded and in the USA and an FDA approved product is now available. Key to the success of an ‘artificial pancreas’ has been Continuous glucose monitoring, which can record 288 decisions per day, 7 days per week, 365 days per year. For Continuous glucose monitoring (CGM) to work, three components are required 1) a small

‘Continuous Glucose Monitoring (CGM) is an FDA-approved device that provides real-time glucose readings, throughout the day and night, allowing people with diabetes to see their glucose levels and track how quickly they’re increasing or decreasing. CGM has been an established technology since 2006 and performance advances throughout the years have made today’s systems increasingly accurate. A typical CGM provides up to as many as 288 glucose readings per day (once every 5 minutes). CGM does not completely eliminate the need for blood glucose meter readings but provides additional information for more informed treatment decisions and improved glucose control. CGM can be used by people with Type 1 or Type 2 who are concerned with their diabetes management.’5

sensor to measure glucose levels (in the skin/ eyeball/earlobe etc) 2) a transmitter to send data (ideally wirelessly) to a receiver and 3) a receiver/ display device which gives the result usually in a graphical or colour coded fashion. We live in an age of wearable technology and advances are happening in leaps and bounds6,7. Apart from an FDA and UK approved device8, we are aware of much research, device testing and collaboration in this space, which includes a Google patent for contact lenses that measure glucose. The future for the diabetic with continuous glucose monitoring is promising in that algorithms and forms of artificial intelligence can inform when problems will and have occurred and these can be corrected.

References: 1.

http://www.jeanharlow.com/about/biography.html accessed 23/1/2016

2. 3. 4. 5. 6.

7. 8.

16 | WWW.PRIMARYCAREREPORTS.CO.UK

http://www.dekaresearch.com/homechoice.shtml accessed 23/1/2016 http://sites.bu.edu/bionicpancreas/ accessed 23/1/2016 http://www.fda.gov/MedicalDevices/default.htm accessed 23/1/2016 http://www.dexcom.com/continuous-glucose-monitoring accessed 24/1/2016 http://sites.bu.edu/bionicpancreas/files/2014/07/G4__Enlite__Nav_comparison_Damiano_JDST_2014.pdf accessed 23/1/2016 http://tiny.cc/3rxv8x accessed 23/1/2016 http://www.dexcom.com/en-GB accessed 23/1/2016.

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