Category: Conferences

There are exciting developments in diabetes technology happening right now, which can help lighten the daily burden of managing the condition. The challenge of making the latest diabetes devices and monitoring more accessible was discussed at ‘Revolutionising Diabetes Care: Celebrating 100 Years of Insulin Therapy’, a recent online conference organised by the Royal College of Physicians and Surgeons of Glasgow. Dr Susan Aldridge reports.

People living with type 1 diabetes are faced with a large number of decisions to make and tasks to do on any given day. “In the words of Professor Simon Heller, ‘type 1 diabetes is the most challenging long-term condition to self-manage,’ and I couldn’t agree more,” said Dr Emma Wilmot, founder of the Diabetes Technology Network UK (DTN-UK). She went on to review the current and future impact of the three types of technology available today to help in the self-management of type 1 diabetes: continuous glucose monitoring, connected pens and closed loop.

Glucose monitoring

In the 100 years since the discovery of insulin, glucose monitoring has transitioned from urine dipstick testing to fingerprick blood testing in the 1970s, which was then the standard of care for many decades. Then, in 2014, the introduction of flash glucose monitoring meant that continuous glucose monitoring (CGM) became affordable and that has led to substantial change.

“If you don’t live with type 1 diabetes, it can be hard to appreciate the difference that CGM can make to your quality of life,” said Dr Wilmot. “Let’s say I want you to drive to Park St in Leeds. I’ll let you have a car and a satnav. No problem? But you can only view your satnav four times during this journey. If that makes you feel a little uncomfortable, that’s great because that’s what we’ve been asking people with type 1 diabetes to do for decades. So what you really want to do is to have unlimited views of your satnav throughout your journey – check where you are, what direction you’re going in and reflect on your journey so far. That’s what continuous access to glucose data allows people with type 1 diabetes to do.”

Clinicians are starting to understand the benefits of CGM for people living with type 1 diabetes – recent research has shown reductions in HbA1c after starting flash monitoring, as well as a decrease in hospital admissions for diabetic ketoacidosis (DKA) and hypoglycaemia, ambulance callouts and severe hypos. “Many international datasets have started to replicate these findings, so as a consequence we’re seeing an increase in access to flash and real-time CGM,” said Dr Wilmot.

However, a key criticism has been that the data from randomised clinical trials came from adults whose glucose was already well-controlled, so there was a call from the National Institute for Health and Care Excellence (NICE) for trials in those with more unstable glucose levels. This led to the Diabetes UK-funded Flash UK randomised controlled trial, which illustrated a 0.5% improvement in HbA1c in the intervention group and an increase in the numbers reaching their target glucose.

The findings led to new NICE guidance in 2022 to offer flash or real-time CGM to adults with type 1 diabetes, depending on their preferences, needs, characteristics and functionality of available devices. “What’s also great is that the ADA/EASD consensus on the management of type 1 diabetes recommends CGM as the standard of care,” said Dr Wilmot. “So there have been huge advances. The challenge now is in delivering CGM.”

In type 2 diabetes, the evidence for CGM is not quite as convincing, so NICE recommends it only in certain circumstances, namely when someone has severe or recurrent hypos, impaired awareness of hypoglycaemia, a disability impairing their ability to self-monitor or needs to do eight or more tests a day.

In the future, a key challenge for clinicians will be choosing a glucose monitoring device. A recent review showed a wide range of new devices coming onto the market – 28 non-invasive optical devices, six non-invasive fluid sampling devices and 31 minimally invasive glucose monitoring devices. Several ‘bloodless’ products are now commercially available. “We, as clinicians, will need to understand what level of evidence is available before we can feel confident offering a device to people with diabetes, as having regulatory approval doesn’t necessarily mean evidence from randomised clinical trials will be replicated in the real world,” Dr Wilmot warned. 

Connected pens

The mainstay of insulin therapy is still multiple daily injections. “Even with better glucose monitoring, we’re often left guessing what insulin doses have been given and when,” said Dr Wilmot. While she advises people to record their doses, either in notes or on an app, she acknowledges that this adds to the self-management burden. “In 2023, surely there are better ways of doing this? That’s exactly what connected pens can offer. In the 1980s, the move from insulin vials to pens was a huge leap forward. The next revolution is here, in terms of more pens giving connected data.”

There are many products in development with all the big insulin companies getting involved. Some healthcare professionals may already have experience of the NovoPen 6, which automatically records insulin doses given. Data from Sweden show that connected pens are associated with fewer missed boluses and more time in range.

The technology also has to make sense to the person living with diabetes for wider take-up. Integration with glucose data will be key, as will decision support with bolus calculation, and recording last dose and insulin on board. This will give more useful and meaningful data reports and, of course, bolus reminders will also be useful going forward.

A consultation with someone using a pen is not as meaningful and data-driven as it would be if they were using a pump. “For me, connected pens are that opportunity to bridge the gap between pen and pump with data reports,” said Dr Wilmot. “You have insulin, carbs and glucose data all in one place.” 

Closed loop

Before closed-loop systems became commercially available, a lot of tech-savvy people with diabetes built their own systems. While these worked well, healthcare professionals often felt uneasy about DIY closed loop because of the medico-legal implications. However, the US Food and Drug Administration (FDA) has now authorised Tidepool, which is an automated insulin dosing loop built from a DIY system, so there has been rapid progress.

There are now three different closed-loop algorithms commercially available (Medtronic 780G, Tandem Control IQ, CamAPS FX), which are licensed for paediatric use onwards. “For me, the key take-home message is that, across a range of trials, they deliver impressive time in range – generally over 70% – with typically half the amount of hypoglycaemia that you’d see with a pump or multiple daily injections,” said Dr Wilmot. “So I think closed loop is the future – people describe them to me in clinic as being life changing. The future is now and it’s about how we deliver this life-changing technology.”

Dr Wilmot and colleagues have been part of the NHS England closed loop pilot study for people on a pump and flash monitor and having HbA1c above 69 mmol/mol. In her own centre, 63 participants started on closed loop between August and September 2021. She gave an example of a young man who was really struggling and was missing a lot of boluses. In just two weeks on closed loop, his time in range increased from 12% to 51% and his glucose management indicator dropped from 91 to 67 mmol/mol. “This may not be as good as results from the randomised controlled trials, but was certainly enough of an improvement to keep this young man freer of complications than he would have been previously,” said Dr Wilmot.

The data from the NHS England pilot has been analysed by the Association of British Clinical Diabetologists (ABCD), submitted to NICE and submitted for publication. “To give you a flavour of the findings, there are the results from the Midlands – Derby, Nottingham, Leicester – where, across our centres, we’re seeing a 16.7 mmol/mol reduction in HbA1c,” said Dr Wilmot. “I cannot think of another intervention that delivers such a staggering improvement in glycaemic control.”

Data like this is opening the doors to wider access. Closed loop is now to be recommended to over 100,000 people with type 1 diabetes as NICE has published draft recommendations covering those with HbA1c of 64 mmol/mol or above using at least one of either pump, flash monitor or real-time CGM, plus those who are pregnant or planning to get pregnant. “This is absolutely huge,” said Dr Wilmot. “The key focus is going to be delivering this technology to people with diabetes over the decades to come.”

She went on to look at where closed loop systems are going in the future. At the moment, systems are linked, but people will want more flexibility in choosing their sensors and pumps and getting them to talk to one another. In 2019, the FDA authorised the first interoperable automated insulin delivery controller and it’s hoped that many devices will go down that route.

Dr Wilmot would also like to see continual evolution of the shape, size, battery life and physical interactions with closed loop systems. Also on the wishlist is infusion sets improved for convenience and longevity and, of course, key to all this is affordability and reimbursement.

With current closed loop systems, there is still a need to count carbs and have it work out the insulin dose, but there is a lot of work going on internationally to go to fully automated systems. Other developments we may see in the future include algorithms adapted to ultra-rapid insulin, alternative routes of insulin delivery, such as intraperitoneal and multi-hormone closed loops. There could also be additional inputs to closed loop systems such as motion sensing and sensing when the user is having a meal, and sensors that look for additional signals such as ketones, active insulin and lactate.

“I think to realise the potential of diabetes technology, we have to overcome some key barriers,” said Dr Wilmot. “For instance, do we have the workforce to deliver closed loop at scale? We also have significant variation across diabetes services in the uptake of insulin pumps and, if we’re to make closed loop more widely available, this drastically needs to change.” 

And, of course, to deliver any of these technologies at scale, healthcare professionals must feel confident in using them. That is one of the key aims of the Diabetes Technology Network UK, which has produced a number of best practice guides (abcd.care/dtn). The Network will continue to make sure the guidance is there to support healthcare professionals who want to increase their confidence in this area.

“My take-home message for you is that for people living with diabetes, basic care has changed dramatically,” Dr Wilmot concluded. “It should now be CGM plus connected pen. We should then be moving forward and, although we typically think insulin pump at the moment, forget that, for we should be thinking closed loop. That’s what’s coming and I’m very excited about it.”

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

Over the one hundred years since its first use, insulin has undoubtedly saved many lives, yet it still does not fully meet the needs of people living with diabetes. However, there is cause for optimism, according to Melanie Davies CBE, Professor of Diabetes Medicine at the University of Leicester. She discussed improvements in insulin formulation and delivery – past, present and future – at ‘Revolutionising Diabetes Care: Celebrating 100 Years of Insulin Therapy’, a recent online conference organised by the Royal College of Physicians and Surgeons of Glasgow. Dr Susan Aldridge reports.

The original insulin was extracted from the pancreases of cows and pigs. When demand from people with diabetes looked as if it would exceed supply from animal sources, the semi-synthetic insulins were developed and entered general use from the 1970s – several with improved properties are now available. “However, there is still a significant unmet need for insulin,” said Professor Davies. Currently, up to 40% of people with diabetes worldwide – 150 to 200 million people – need it.

Fear of injection may be why there are often delays in initiation of insulin therapy, particularly among people with type 2 diabetes who could benefit. 

“Injections are still undoubtedly a major burden to insulin therapy,” said Professor Davies. Research shows that up to one third of people are not adherent to insulin, 93% would prefer to control their glucose without needing to inject and 59% of physicians identified multiple injections as a difficulty in diabetes care.

Meanwhile, people with type 1 diabetes have between one and three severe hypos per year, and those with type 2 diabetes have around one such event. Severe hypoglycaemia causes many emergency visits every year and has a serious impact on both health and quality of life. 

Innovation in insulins

Modern insulins do go some way to addressing these unmet needs. For instance, longer acting insulins mean fewer injections. They can be injected just once a day and now weekly insulin analogues are in development. “A once-weekly insulin could redefine diabetes management by reducing injections from 365 to 52 a year,” said Professor Davies. And research so far on weekly insulins shows that they can achieve comparable glucose lowering and safety to daily insulins. For instance, the ONWARD series of trials is studying insulin icodec, a weekly insulin. ONWARD2 looked at switching people with type 2 diabetes from insulin degludec to insulin icodec and showed a slight benefit in HbA1c and more participants reaching their 7% (53 mmol/mol) target with icodec, as well as more satisfaction with treatment.

The ideal insulin would be exactly like endogenous insulin and there have been many attempts to create a synthetic insulin that would mimic natural physiology and, in particular, to make it more hepatoselective. Natural insulin is distributed more to the liver than the periphery, whereas with synthetic insulins, distribution tends to be 50:50.

Basal insulin peglispro (BIL) is a more hepatoselective insulin. In the IMAGINE trial, which reported in 2015, BIL was compared with insulin glargine in a 78-week study involving people with type 1 and type 2 diabetes. “The results were really very impressive,” Professor Davies said. Mean HbA1c was 7.06% (54 mmol/mol) on BIL and 7.43% (58 mmol/mol) on insulin glargine. “You don’t often see such an improvement in HbA1c with analogue insulins and a reduction of 0.4% is clinically meaningful,” she continued.

BIL also had the advantage of reducing body weight by around 2 kg on average – another drawback of insulin being weight gain – and it reduced the rate of nocturnal hypos, although it did increase the rate of hypos overall. However, development of BIL had to be discontinued because of lipohypertrophy at the injection site and increases in liver enzymes and liver fat. However, efforts to develop a more hepatoselective insulin continue. 

Focus on insulin delivery

On insulin delivery, “this is where some of the exciting data exists and may be paradigm shifting,” said Professor Davies. For instance, so-called smart insulins are glucose responsive, which can already be achieved to a certain extent with continuous glucose monitoring and responsive pumps.

There are also innovations in insulins formulated in a glucose-sensitive polymer matrix that are in animal or early-stage clinical trials and may be introduced into diabetes care over the next few years. And the technical revolution in terms of apps and connected insulin pens has allowed progress such that 80% time in range is now achievable with hybrid closed loop systems.

Of course, oral insulin is perhaps the ultimate goal when it comes to insulin delivery. Discussions around oral insulin started back in the 1920s and it has always been pursued with enthusiasm. The various barriers in the gastrointestinal tract that prevent the delivery of peptide have been studied in detail and there has been some success with the delivery of oral peptides, such as GLP-1.

There has been development of pulmonary and nasal insulins on the way to an oral version, but these have not been particularly successful. Exubera, an inhaled insulin, was withdrawn from the US market in 2007 for commercial reasons and Afrezza, another inhaled insulin, is beset by practical issues. And then there is Oramed, a nanoparticle-based oral insulin, which got as far as a phase-3 clinical trial in type 2 diabetes. Unfortunately, results reported in January this year showed that Oramed is no better than placebo in lowering HbA1c, so the product has now been withdrawn.

“There have been significant advances in insulin therapy in the last 100 years,” Professor Davies concluded. “While there has been no breakthrough yet in oral insulin, there has been progress in basal insulins, while advances in diabetes technology like pumps and continuous glucose monitoring have improved our ability to make the most of the potential of insulin for people living with diabetes.”

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

Pregnancies complicated by diabetes are on the increase and pose risks for mother and baby. The role of diabetes technology in improving outcomes in these pregnancies was under discussion at ‘Revolutionising Diabetes Care: Celebrating 100 Years of Insulin Therapy’, a recent online conference organised by The Royal College of Physicians and Surgeons of Glasgow (RCPSG). Dr Susan Aldridge reports.

Before the advent of insulin, women with type 1 diabetes and their babies simply did not survive. Then, in 1933, one of the first studies of the use of insulin in pregnancy noted a preponderance of ‘giant babies’ – some weighing more than 5kg – in a cohort of 608 infants born to 155 mothers with diabetes.

Now known as large-for-gestational-age (LGA) babies, 63% of the babies born in this study were affected by this complication. Writing in the New England Journal of Medicine in 1941, Dr Martin Nothmann said, “Diabetes is more unfavourable for the child than the mother – in this regard, insulin cannot accomplish much.”

“The most recent snapshot [from the National Diabetes in Pregnancy audit (NPID)] tells us that today we have one in 10 pregnancies with potentially preventable serious adverse outcomes – that is, still birth, newborn death or birth defect, and this applies across both type 1 and type 2 diabetes,” said Helen Murphy, Professor of Medicine at the University of East Anglia and Chair of NPID. “Early-onset type 2 diabetes has been increasing, so we are now seeing more women in pregnancy with type 2 than those with type 1.”

In 2002/03, at the time of the first Confidential Enquiry into Maternal and Child Health (CEMACH) report, there were 1707 type 1 diabetes pregnancies and only 652 affected by type 2, whereas in 2019-2020, there were 4175 type 1 and 5085 type 2 pregnancies. And this is occurring at a time when NHS maternity services are already stretched.

“What’s also really important is the different patient characteristics,” said Professor Murphy. Women with type 1 are predominantly White, while those with type 2 are more likely to be from ethnic minority groups and are much more likely to live in areas of deprivation. The data shows that 42% of type 2 pregnancies occur among women living in the most deprived areas, while just 5% live in the least deprived areas. “It is vital moving forward that we plan our services such that resources are targeted to these high-risk women,” said Professor Murphy.

Focus on maternal glucose levels

Maternal glucose levels at the time of conception are crucial in determining the outcome of a pregnancy. The National Institute for Health and Care Excellence (NICE) recommends that all women with diabetes aim for an HbA1c of 6.5% (48 mmol/mol). “We know, however, that very few women achieve this,” said Professor Murphy. “But as HbA1c rises – from 7% [53 mmol/mol] and above – there is a sharp increase in congenital malformations among infants born to women with type 1 and type 2. So the single most important message for anyone looking after women of reproductive years is that they should be offered access to safe, effective forms of contraception until HbA1c is as good as it can get for pregnancy.”

Taking adequate folic acid and achieving target glucose levels are key markers in preparing for pregnancy. Half of all women with type 1 diabetes take 5 mg folic acid, compared with only 20% of those with type 2 diabetes. With HbA1c, 15% with type 1 diabetes reach the glucose target and just over 35% with type 2 diabetes. “This means that 65% of those with type 2 do not,” said Professor Murphy. “Most are on metformin, so they are diagnosed but not treated to target and only 18% of these women of reproductive age are treated with insulin before pregnancy. That is something that seriously needs to change.”

Which women are most likely to achieve their glucose target? For type 1 diabetes, it is women in the 35-44 age group and those with the shortest duration of diabetes, therefore having some endogenous insulin secretion. Younger women, those living in deprived communities, those with longer duration and those with higher BMI are the least likely to get to target. The data are similar for type 2 diabetes, although deprivation has less of an impact as most of these women already live in deprived communities.

Professor Murphy then turned to the effects of glucose on obstetric and neonatal complications. If HbA1c is more than 6.1% (43 mmol/mol), there’s a high risk of preterm delivery, which is similar for type 1 and type 2 diabetes. Also, 50% of women with HbA1c between 6.1-6.5% (43-48 mmol/mol) will have a baby that is LGA. “So the key message from this data is that we need to target tighter glycaemia in the second half of pregnancy,” she said. “And, of course, to do that, we need better insulins and better methods for glucose monitoring.”

Rates of stillbirth and neonatal death have decreased in recent years. However, there is concern that stillbirths in type 2 pregnancy may be starting to increase, which needs to be watched very closely in the next few years. “The key modifiable factor in perinatal death in type 1 and type 2 is having HbA1c more than 43 mmol/mol,” said Professor Murphy. Data show a higher risk for women with type 2 diabetes, suggesting that they are particularly vulnerable to above-target glycaemia during the second and third trimesters. If a woman can get to target by 24 weeks, it will significantly reduce the risk of stillbirth.

Continuous glucose monitoring

Using better technology to monitor glucose does help women personalise their insulin delivery. Professor Murphy was involved in the CONCEPTT trial, which compared real-time continuous glucose monitoring (CGM) with fingerstick glucose monitoring in women with type 1 diabetes during pregnancy or pregnancy planning. CGM led to a 7% increase in time in range (TIR), equivalent to an extra 100 minutes a day in range throughout the pregnancy.

The outcomes showed that these small improvements in glycaemic control led to significant benefits for the infant, with reduced rates of LGA, neonatal hypoglycaemia and neonatal intensive care unit admission. “It is this data that led to the UK being one of the first countries in the world to offer CGM to all women with type 1 diabetes to help support them to reach their glucose target and improve neonatal outcomes,” said Professor Murphy. “We are just beginning to see the impact of that as it rolls out across the NHS. We now have national audit data for over 1,000 real-world CGM users and we’re optimistic that some of these benefits we’ve seen in the randomised trial will be replicated in this real-world data set.”

During this rollout, education and support of healthcare professionals is key to helping women understand the importance of reaching their glucose targets. “We have learned that women find these glucose targets, particularly TIR, very intuitive and accessible and, of course, this data sits on their own phones, so they have it to hand,” said Professor Murphy. A series of webinars has been developed to support this rollout, focusing on the use of CGM at the various stages of pregnancy, including delivery and in the postnatal period.

Targets for hyper- and hypoglycaemia are now firmly established in clinical practice for managing women with type 1 diabetes. For TIR (3.5 to 7.8 mmol/l), this should be 70% of the time with less than 25% above 7.8 mmol/l and less than 1% below 3 mmol/l. Women with type 2 diabetes may benefit from aiming for 90-100% TIR.

Mean glucose is also important, where the target should be 6-6.5 mmol/l. ”Achieving these targets, even with the latest CGM and insulin pumps, is hard work and, in my view, automated insulin delivery will take over from insulin pumps and we will have CGM linked to an algorithm that is linked to insulin delivery,” said Professor Murphy. “This will eliminate a lot of the work for women with type 1 diabetes, although with the systems that are available today, carb counting and meal bolusing are still required.”

Hybrid closed loop in pregnancy

Professor Murphy has also been involved in trials of the CamAPS-FX hybrid closed loop system – developed by Professor Roman Hovorka’s team in Cambridge – in type 1 diabetes pregnancy. These have produced some very promising overnight and 24-hour data and the results will be published in the next few months. “What I can share with you today is our experience of supporting women using closed loop,” she said. “Not all women will be able to achieve perfect glycaemic control but, in our experience, with the right education and support, most women should have the same results as outside of pregnancy, which is an increase of 7-10% in TIR.”

Working with colleagues from Scotland, Professor Murphy’s team has done a series of interviews with healthcare professionals looking after women using closed loop in pregnancy. “This is coming and it’s coming soon,” she said. “We’re going to see far more women choosing to use automated or hybrid closed loop systems, so we are starting to look at what we need to do, as healthcare professionals, to roll this out across the NHS.”

The first step in this roll-out is support and education of diabetes teams. One of the messages from the above survey is that all women should be offered these technologies, wherever they’re being looked after. “That does present some challenges, so we need to upskill the workforce right across the UK,” Professor Murphy said. “However, I’m optimistic because we managed to roll out CGM in the real world during the pandemic and I do think that, in the next few years, we’re going to see the rollout of hybrid closed loop for women who are either pregnant or planning a pregnancy.”

Even in the absence of trial data – which will follow shortly – qualitative data from women using the systems is so powerful, she continued. “We’re getting reports of women who are able to stay in paid employment and are having better relationships with healthcare professionals. Most important of all, they’re finding that using this technology allows them to enjoy the pregnancy experience and achieve better glucose outcomes.”

This is illustrated by the words of one woman interviewed, who took six years to become pregnant. “The 246 days of pregnancy meant 17,000 units of insulin, 216 jabs and 70% TIR,” she said. “The technology I was able to use throughout made the journey as stress-free as possible!”

“The challenge for us is to make sure that we can deliver these technologies to all women to improve their experiences of pregnancy and achieve the best possible outcomes for their babies,” Professor Murphy concluded.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

Diabetic retinopathy was one of the hot topics at the recent International Diabetes Federation (IDF) meeting. The session covered the latest research into retinal dysfunction and the challenges of setting up national diabetic eye screening in the Philippines. Dr Susan Aldridge reports.

Diabetic retinopathy is part of the systemic disease that is diabetes, so glycaemic control is particularly important. “The Diabetes Control and Complications Trial showed that intensive therapy reduces the onset and progression of diabetic retinopathy,” said Dr Tom Gardner, ophthalmologist at the Juvenile Diabetes Research Foundation (JDRF) Centre of Excellence, University of Michigan. “I point this out because ophthalmologists should be part of the diabetes team. Even so, the challenge persists – in the US, the number of patients with diabetic macular oedema has continued to increase since 2009 and it is the main cause of vision loss in diabetes.”

In addition, glycaemic control is less than perfect with only a minority of people with diabetes meeting targets for HbA1c, blood pressure and cholesterol. If anything, this proportion is decreasing. 

The advent of anti-vascular endothelial growth factor (VEGF) drugs has made a major impact in vision loss and given another option besides photocoagulation. However, peripheral vision still declines after both treatments. “So the anti-VEGF drug is helpful in stabilising the condition but there’s more to the story,” said Dr Gardner.

The current drugs target only VEGF but there have been attempts to target other molecules involved in vascular degeneration, such as faricimab, which is bivalent against VEGF and angiopoietin-2, and has been shown to be non-inferior to the VEGF inhibitor aflibercept. “This is not a major advance but another step forward in trying to understand vascular pathology of diabetic retinopathy,” Dr Gardner said.

It’s also very important to understand which people with diabetes are most at risk of losing their vision. The FIELD study led the way in this kind of prediction, being a retrospective of sight-threatening diabetic retinopathy analysis using an algorithm involving male sex, diabetic retinopathy at baseline, HbA1c and use of fenofibrate (which reduces risk). It shows where the individual is on the progression curve. This is particularly helpful in selecting people for clinical trials. 

Widespread retinal dysfunction

“So far, the available therapies only target the vascular part of the disease – that’s important but not the whole story,” Dr Gardner said. He gave an example of a patient whose eyes could not adapt to dim light. This was not a vascular condition but meant his rods and cones weren’t functioning properly. “We would not pick that up from a photo or examination,” he said, “so it’s important to look at the whole retina and what’s there besides the blood vessels.”

All the retinal cell types are damaged in retinopathy and this begins in the preclinical stage with vascular leakage and occlusion. There is also neuronal apoptosis – particularly in the inner layer of the retina – and astrocyte dysfunction, which is not well understood but is probably important for regulation of synapses.

Furthermore, microglial activation means that there is activation of the immune system within the retina, as well as other abnormalities that may affect electrical function and morphology.

“It is now becoming clear that the whole retina is affected in diabetic retinopathy, not just the vasculature,” Dr Gardner explained. In his lab in Michigan, they’re now looking for cells in the retina that make the macromolecules essential for function. These experiments are helping them to gain a deeper understanding of how the retina works normally to provide vision and how it’s impaired in diabetes.

Put simply, the different functions of the retina should be integrated but because of the dysfunction of so many cell types beyond the vasculature, disintegration occurs, leading to vision impairment. “The retina is a very highly metabolic, electrical tissue whose job is to provide electrical signals,” said Dr Gardner. “It is a sensory organ, so diabetic retinopathy can be seen as a type of sensory neuropathy.”

Retinal screening in the Philippines

Away from retinal research, Dr Paolo Antonio Silva, ophthalmologist and Chief of Diabetic Medicine at Joslin Diabetes Center, described a joint telemedicine project between the Joslin, Queen’s University Belfast and the Philippine Eye Research Institute. This is known as the UK-Philippines Remote Retinal Evaluation Collaboration in Health: Diabetic Retinopathy (REACH-DR). Its aim is to move retinal screening away from tertiary centres to a wider geographical area, using less expensive, more accessible and portable imaging devices.

These mobile hand-held imaging devices are currently in various stages of development – undergoing validation studies, for example – and can be integrated into smartphone or mobile computing. So far, in the early treatment of diabetic retinopathy, the quality of the retinal image using three different hand-held devices has proven similar to that in a standard retinal photo. 

These hand-held devices can be used in community screening programmes where their size, accuracy and ease of use are particularly useful. “Based on these results, we then wanted to carry out a local cost-effectiveness analysis with the Philippines Department of Health and found that the use of a hand-held camera with mydriasis was the best approach,” Dr Silva said.

The REACH team is also starting to apply artificial intelligence (AI) and deep learning (a machine learning technique that teaches computers to do what comes naturally to humans) at the point of care. This will allow for more effective triage of diabetic retinopathy cases and improvement of workflow with less central load.

However, despite the promise of AI, there is a limited number of publications on its application to diabetic retinopathy and the currently approved AI algorithms are not universally generalisable. “There is an under-representation of some populations, which affects the accuracy of AI,” said Dr Silva. This is because 172 countries don’t have the required publicly available ophthalmic datasets and this may perpetuate health inequality in the application of AI. “So there is a need to create clinically useful AI systems that are based on diverse demographics and understand why, how and when different AI systems work in different settings,” he said.

It may be early days, but the REACH Diabetic Retinopathy team is laying the foundations for retinal screening in a country with limited resources, which is good news for people with diabetes everywhere.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

Around 537 million adults around the world now live with diabetes – an increase of 73.6 million between 2019 and 2021 – according to the International Diabetes Federation (IDF) Diabetes Atlas 2022. More detail on its findings were presented and discussed at the recent IDF meeting in Lisbon. Dr Susan Aldridge reports.

Introducing the latest edition of the IDF Atlas, Professor Dianna Magliano, Head of Diabetes and Population Health at the Baker Heart and Diabetes Institute said: “Diabetes is a threat to global health, which affects all age groups, regardless of geography, language, income.” And, as co-chair of the team that put the report together, she went on to present its main points.

Since 2000, the annual IDF Atlas has been a detailed and authoritative resource for all those concerned with diabetes care. It presents a picture of the global impact of diabetes, including detailed national and regional data. There are also projections for future years and chapters on special topics.  This IDF Atlas 2022, which presents data for 2021, includes chapters on type 2 diabetes in adults and children, and on COVID-19. 

Global diabetes data

Professor Magliano explained that the Atlas is compiled by collecting all reports of diabetes prevalence, both published and unpublished, and including whole population registries. All data meeting the IDF quality threshold is extracted. The IDF uses the United Nations list of countries and territories, currently standing at 215 in number. If a country does not have its own data, an estimate is done using a country similar in demographics, economics and language. 

For the latest Atlas, there were 219 data sources from 144 countries. Of these, 109 were peer-reviewed, 51 were national health surveys, 41 World Health Organisation STEPS studies [surveillance of non-communicable disease risk factors], 16 diabetes registries and two non-peer reviewed government surveys. There were 71 countries lacking their own in-country data.

Key figures from the 2021 IDF Atlas

One in 10 adults aged between 20 and 79 (537 million people) now lives with diabetes, and three in four of them live in low- to middle-income countries. Almost one in two people who have diabetes are undiagnosed, most of whom live in low- to middle-income countries where access to healthcare and resources may be limited.

However, even in high-income countries, nearly a third of those with diabetes do not know they have the condition. Late or no diagnosis is a serious matter, leading to complications, impaired quality of life and increased healthcare expenditure. When it comes to ‘prediabetes’, a total of 319 million and 541 million adults have impaired fasting glucose and impaired glucose tolerance, respectively, which puts them at risk of developing type 2 diabetes.

One in six live births (21 million) is affected by hyperglycaemia in pregnancy, of which 80% is gestational diabetes. Meanwhile, 1.2 million children and adolescents below the age of 20 have type 1 diabetes.

Diabetes also accounts for 11.5% of global health expenditure ($966 billion) and 12% (6.7 million) of all deaths in the 20 to 79 age group. 

In comparison with 2019 data, 73.6 million more adults have diabetes, nearly 150,000 more children have type 1 diabetes and there were 2.5 million more deaths, while there was an increase of $206 billion spent on treating the condition.

“So our data and our projections tell a sobering story,” said Professor Magliano. “We expect to see rises in every region of the world, with the biggest of these increases being in Africa [excluding North Africa, which is grouped with the Middle East], North Africa and the Middle East, and Southeast Asia.”

The projections say that the number of adults living with diabetes is expected to rise by 46% by 2045, from 537 million to 783 million. Diabetes prevalence will increase in Africa by 134%, North Africa and the Middle East by 87% and Southeast Asia by 68%.

Europe is predicted to have an increase of 13%, which would be the smallest in the world. “The drivers for these increases include a rapid increase in urbanisation, obesity and maybe something as yet unknown in the environment,” said Professor Magliano. 

She showed some of the projections that have been made in Atlases in previous years. “The number of people with diabetes has more than tripled since 2000,” she noted. “What’s really interesting is that, in 2003, our projection for 2025 was that there would be 333 million people with diabetes. We had already passed that figure in 2011 when we reached 366 million, so we are actually underestimating.”

Diabetes by country

The Atlas contains a colour-coded map of the world, which displays countries by the number of adults living there with diabetes. Those with over 20 million are China, Pakistan and the USA but, of course, these are the most densely populated. Most of the countries on the map have between one and 10 million adults living with diabetes.

Then Professor Magliano revealed the top 10 countries in the world by numbers of adults living with diabetes. China leads the pack, with 140.9 million people, followed by India, Pakistan, USA, Indonesia, Brazil, Mexico, Bangladesh, Japan and Egypt. “The 2045 projections tell a similar story, with some differences in the ordering of the ranks,’ said Professor Magliano. “Japan drops out and Turkey replaces it but the top six are the same.”

Turning now to percentage prevalence, as opposed to numbers (thereby taking account of the size of a country’s population), the Atlas shows that Egypt, Mexico, Sudan, South Africa, Pakistan, Turkey, Kuwait, Bangladesh, Malaysia and some of the Pacific islands all have a diabetes prevalence of more than 12%. Pakistan leads the top 10 for prevalence with 30.8% prevalence, followed by several of the Pacific islands and Kuwait, with Egypt bringing up the rear with 20.9%.

Diabetes by age

Diabetes has an impact on people of all ages, not just adults. Hyperglycaemia in pregnancy can affect the baby in the womb, both at birth and later in life. In 2021, the majority (87%) of all live births involving hyperglycaemia in pregnancy occurred in low- and middle-income countries where access to antenatal care may be limited.

There were also some regional differences – in Southeast Asia, hyperglycaemia in pregnancy was involved in 28% of live births, while the Middle East/North Africa region had the lowest proportion at 8.6%. Women under 30 accounted for around half of these pregnancies, but the likelihood of a pregnancy affected by hyperglycaemia rises rapidly with age, with the highest prevalence (42%) occurring among women aged 45 to 49. This reflects the increased risk of type 2 diabetes with age.  

Turning to type 1 diabetes in the under-20s, rates are highest in Sweden, Finland and Norway, and there have been significant increases in the Middle East over the past 20 years. However, Professor Magliano noted, there are still many parts of the world where there are no data on type 1 diabetes prevalence. 

Finally, prevalence of diabetes increases with age in every country in the world but differs by income. By the time people reach their eighth decade, one person in five has diabetes in high and middle-income countries and one in 10 in low-income countries.

As the IDF meeting was being held in Lisbon, Professor Magliano took a quick look at what the Atlas says about diabetes in Portugal. Here, the number of people with diabetes is actually falling because the Portuguese population is decreasing, with fewer babies being born. This is fairly typical across the whole of Europe, with age-adjusted prevalence being 10.3% in 2021 and projected to increase to 11% by 2045.

In conclusion

The IDF Diabetes Atlas is a highly valuable resource but we need to be aware of various limitations in the data and knowledge gaps. The sources of the data are heterogeneous in terms of the year, level of representation of the population and study design, which might have introduced some bias.

Error might also have been introduced by the use of ‘similar country’ data for those countries that have no data of their own. In particular, there is a dearth of data from Africa. And, for the future projections, only age, sex and urbanisation are considered as influences on the data, while there may be many other factors, such as change in lifestyle and obesity, that influence the figures.

Professor Magliano concluded with the following call to action: “There is a strong need for effective intervention strategies and policies to stall the increase in the number of people with diabetes.”

• This presentation and the IDF Diabetes Atlas 2022 are available at www.diabetesatlas.org

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

Continuous glucose monitoring allows a person with diabetes to monitor time in range (TIR), which gives a more complete picture of glycaemic control than HbA1c measurements. So should TIR therefore replace HbA1c in diabetes management or do they complement one another? Speaking at the recent International Diabetes Federation conference, Chantal Mathieu, Professor of Medicine at KU, Leuven, Belgium, gave an expert comparison of TIR and HbA1c. Dr Susan Aldridge reports.

The widespread use of HbA1c measurement in diabetes care started with the Diabetes Control and Complications Trial (DCCT), which revealed the link between higher HbA1c and complications. “It was clear that HbA1c is a good biomarker for glycaemic control and for complications, such as retinopathy, nephropathy, neuropathy and microalbuminuria,” said Professor Mathieu, “and today we use HbA1c to see how the person with diabetes is, when they are sitting in front of us in the clinic. We use HbA1c as an outcome in all our trials evaluating drugs for glucose control and in all our guidelines.”

In other words, HbA1c has now gained status as the gold standard in diabetes measurement, even though its use is relatively recent. However, as all clinicians know, there are many factors that can alter HbA1c, such as short turnover of erythrocytes, physiological states and the use of various medications.

Continuous glucose management (CGM) then came along and it became obvious that HbA1c and self-reported blood glucose values are only a snapshot and do not show the full story. “It’s like driving your car to the airport and opening an eye every now and then,” said Professor Mathieu. “This brought about the idea that we need new biomarkers to add to our measures of glycaemic control.”

HbA1c and TIR compared

A person with diabetes can have the same HbA1c, but different glucose variability and there is now plenty of evidence of the dangers of higher glucose variability. For instance, one of these studies shows an association – although not necessarily causation – between glucose variability and hypoglycaemia, major adverse cardiovascular outcomes and all-cause mortality.

HbA1c and TIR are actually complementary, as follows. HbA1c is a single measurement, usually done every three months. CGM, on the other hand, gives continuous measurements, can be done at any time and measures glucose variability, excursions and time spent in the safe glucose range (neither too high nor too low). HbA1c cannot record the immediate effects of a change in therapy, but CGM does. So, for instance, if you start someone on an SGLT-2 inhibitor, its impact on glycaemia can be seen straightaway. And, as mentioned above, HbA1c is prone to interference, affecting its accuracy, while CGM is not.

Finally, there have been many long-term studies of HbA1c, showing it has a good correlation to clinical endpoints, while there have been far fewer such studies on CGM.

TIR guidelines

The big diabetes societies are now accepting TIR. The abundance of data offered by CGM offers the opportunity to analyse patient data with more granularity than was previously possible, providing additional information to help in reaching glycaemic targets. Accordingly, the American Diabetes Association, for instance, has updated its Standards of Medical Care to include consensus on TIR.

“So is it time to move from HbA1c to TIR?” Professor Mathieu asked. “One thing I learned from COVID-19 was that with all the technology that was around, it was possible to follow people’s glucose control by sharing in the Cloud.”

For people with type 1 diabetes on CGM, TIR is now becoming the gold standard for self-monitoring, especially now that the technology is being integrated more and more with smart insulin pens, which give the time of injections. Then there is also hybrid closed-loop, which integrates CGM with pumps that can shut down and prevent an incoming hypo.

All this has led to new metrics in diabetes management, focused upon times spent in different glucose ranges. TIR itself is usually 70 to 180mg/dl, time below range is 70 to 54 mg/dl, with a hypo being defined as less than 54 mg/dl, while time above range is 180 to 250 mg/dl, with a hyper being defined as glucose above 250 mg/dl.

“These numbers are there for a reason,” said Professor Mathieu. “For instance, the American Diabetes Association says that 70 mg/dl is a ‘warning moment’ where you should consider taking action. A lot of work has gone into these cut-off values, especially the 180 mg/dl cut off.”

The relationship between TIR and HbA1c can be quite complicated. “As more data has been gathered, it has become clear that the same HbA1c can be achieved with very different types of glycaemic control,” said Professor Mathieu. “For example, 70% TIR can be correlated with HbA1c as low as 5.6% and or as high as 8.3%, so TIR gives you the stability of your glucose control. This is very important and tells you why we like this idea of TIR more and more. So we will be aiming for TIR of 70%, as we do for an HbA1c of 7%.”

An international consensus on the use of CGM has come up with a spectrum of different TIR targets, covering people with type 1 and type 2 diabetes, older people and high-risk pregnancies involving type 1 diabetes or gestational diabetes. 

TIR and complications

What about the correlation of TIR with complications? While there are, as yet, no studies like the DCCT for TIR, evidence is growing. For instance, Professor Mathieu highlighted a study from Belgium showing that TIR can be correlated with a range of microvascular and macrovascular complications, as well as hospitalisation for diabetic ketoacidosis and hypoglycaemia.

TIR is also being used as an outcome in medication studies. For example, a trial of insulin degludec versus insulin glargine showed no change in TIR, while a study on insulin Icodec, the weekly insulin, showed an increase in TIR for those previously on a daily insulin.

Then there is the ALERTT1 trial, which is a comparison of intermittently scanned versus real-time CGM with alarms. The findings of this trial show that the latter is associated with an increase in TIR, while the former is not. “So now, gradually, TIR is creeping into our evidence base,” said Professor Mathieu. Very recently, an international consensus paper on metrics and CGM has been published, which will provide guidance on when CGM can be a valuable endpoint in a clinical trial. 

Who should cross the bridge?

The value of TIR in type 1 diabetes is well established and there is now some evidence that it is also valuable in type 2 diabetes. For instance, one trial showed that those with advanced diabetic retinopathy had less TIR and more glucose variability, while another showed that less TIR is also associated with more distal peripheral neuropathy.

There has also been research on macrovascular complications that linked carotid intima media thickness, which can predict cardiovascular disease and major cardiovascular outcomes with TIR. “These studies further validate TIR in my mind as a surrogate marker for the risk of complications,” said Professor Mathieu.

So how important is TIR to people with diabetes? When diaTribe carried out an online survey of people with type 1 and type 2 diabetes, both on or not on insulin, asking them what was really important to them, TIR came out on top and Professor Mathieu knows why. “It gives a real-time view for people with diabetes on how they are doing. I’m sure you all remember when someone with type 1 came into clinic and said, ‘I hope my HbA1c is good’ and now they can say, ‘my TIR is 82%’. It’s very different and it’s really motivating for people, so that is very important for people with diabetes. My gut feeling would have predicted this for people on insulin, not for people not on insulin – but they like TIR as well.”

In conclusion, TIR is a valuable outcome parameter, both in clinical care and diabetes research. The relationship between TIR and complications is becoming clear, but whether the exact relationship is dependent on HbA1c or not is not yet clear. So, Professor Mathieu concluded, “I don’t think that TIR will replace HbA1c in the coming years but it adds to what we learn from it.”

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

In war or during a natural disaster, people with diabetes often go without the care they need because attention is focused upon dealing with medical emergencies. Speakers at the recent International Diabetes Foundation (IDF) meeting discussed what happens when diabetes care becomes a humanitarian issue, with Ukraine as a particular example. Dr Susan Aldridge reports.

Dr Iryna Vlasenko, Vice President of the IDF and a pharmacist working in Ukraine, gave an overview of the impact of the war there on people with diabetes and the action that is being taken to provide the care they need. A record number of Ukrainians have been displaced from their homes by the conflict, which poses a major health challenge, both in the country itself and elsewhere. Inevitably, dealing with trauma and infection takes priority over chronic conditions like diabetes – as has always been the case in a disaster situation.

Before February 2022, diabetes care in Ukraine was in good shape, Dr Vlasenko said, with insulin being reimbursed, other diabetes medications affordable and diagnostic testing widely available. Then, at the outbreak of war, half of the country’s pharmacies were unable to open, hospitals were destroyed and healthcare workers either moved away or could not get to work, while distribution of insulin and other medication was disrupted.

Within the first few days of hostilities, Dr Vlasenko began to mobilise and co-ordinate support in her role as Vice President of the IDF, working with the Ministry of Health to get government authorisation for their activities “Volunteers and patient organisations played a big role and I had so many calls from around the world offering help,” she said. Many people and organisations got involved, including the World Health Organisation (WHO), charities, NGOs, foreign governments and, of course, the IDF. “I would like to underline how much the IDF associations around the world helped us,” she added. “It shows that we are like family.”

Two to three weeks into the conflict, it became apparent that there was going to be limited access to diabetes healthcare, including pharmacy supplies (although glucometers and testing strips were still available). People needed more short-acting insulin, probably because of the stress they were under, while the mass migration underway called for an overall increase in supplies. Direct Relief, to whom Dr Vlasenko offered her “big thanks”, stepped in and has supplied 950 tons of medical aid, including insulin syringes, needles and medication, since 24 February 2022.

Meanwhile, the Ministry of Health organised a crisis hotline for people with diabetes from the start of the war and made insulin free rather than reimbursed (until July), as well as providing daily online updates of pharmacies that had insulin supplies.

Two to three weeks after that, outpatient clinic and pharmacy access improved in those areas where there were no active hostilities. However, drug prices had gone up 20% by then and hospitals were still providing mainly urgent care. “We also need to remember issues like dialysis, which may be hard if someone is on the road as a refugee,” Dr Vlasenko said. “And, of course, there is mental health as people are under stress all the time.”

As a pharmacist herself, she noted the important role the profession can play in a disaster situation. “They can provide immediate healthcare to affected communities as they [pharmacies] are more accessible than even supermarkets or banks.”

Meanwhile, refugees to neighbouring countries such as Poland are in need of support and thanks are due to IDF Europe who, in partnership with the United Nations High Commissioner for Refugees (UNHCR), have been working to improve services for them. At home, there has been a ‘medical collapse’ in the occupied territories, which is still a problem. However, mobile teams, consisting of a GP, a psychologist and a nurse, have been going out to look after people with diabetes. After two years of COVID and now war, there is concern about mounting diabetes complications, so the teams are looking at eyes, feet and cardiovascular health.

Looking back

On reflection, how does Dr Vlasenko assess the response to the diabetes challenge posed by the war? There are certainly some positive points. “Healthcare providers and institutions have proven highly resilient in this situation,” she said. “We managed a co-ordinated humanitarian response.”

Inevitably, though, it has been hard to overcome some of the challenges. For instance, service delivery has had to be reactive rather than being driven by the proactive outreach that is a feature of good diabetes care. And, inevitably, healthcare worker capacity is still stretched. “The full burden of diabetes, particularly that of complications and psychosocial suffering, is not being addressed,” said Dr Vlasenko. Two key issues are the need for better management to avoid diabetes mortality and the logistics of providing a continuous supply of treatment, especially insulin.

Future priorities for diabetes care in Ukraine, whether or not peace comes, include health promotion, improving access to medication, HbA1c testing, adherence to treatment plans and more work on mental health. And, of course, the consequences of the war will be an increase in diabetes and its complications and economic burden. “Thank you for your support,” Dr Vlasenko concluded. “We really appreciate it. Please stay with Ukraine. We could not survive without you.”

Diabetes, disaster and the wider world

Dr Nizar Albeche, former Chair of IDF Middle East and North Africa region, who has also worked at Aleppo Hospital, Syria, brought a wider context to diabetes and disaster, both natural, such as hurricanes, tsunamis and floods, and man-made. Diabetes is always a low priority in these situations. People with diabetes have many needs and will inevitably suffer both immediate and long-term consequences when they are caught up in a disaster.

“What affects the outcome for people with diabetes is whether the disaster is occurring in a low-, middle- or high-income country,” he said. “Location is also very important.” He noted that Ukraine lies within a developed area of Europe and there has been lots of help coming in through various programmes, as Dr Vlasenko mentions above. “The courage of the Ukrainian people has been remarkable,” he said. “They were also quick to get worldwide support and set us an example of how to deal with a disaster through resilience and co-ordination.”

The opposite is true in Syria, a low-income country involved in a war that has lasted for 11 years. Millions have been displaced, hospitals destroyed and there have not been enough donations from outside. The health system there has all but collapsed – and it was not in good shape before the war began.

Many Syrian refugees went to neighbouring countries such as Lebanon and Iraq – which were not prepared for the accompanying healthcare burden – and found themselves without jobs or income. Refugees with diabetes, including children, had urgent needs for medication such as insulin.

However, things are changing. The WHO has set up a framework for addressing diabetes challenges and needs in humanitarian crises in low- and middle-income countries, and the IDF also has a Diabetes and Disaster Plan and is working with the WHO on this issue. Then there is the Boston Declaration, a new initiative for diabetes (see below). However, Dr Albeche concluded, lack of resources in a disaster situation remains an important challenge for low- and middle-income countries.

The Boston Declaration

The world is now dealing with the highest number of people ever displaced by disaster in history and 80% of them are from low- and middle-income countries. In the future, 1.2 billion could be displaced by climate change and natural disasters. In these situations, people with type 1 diabetes, in particular, are at acute risk of death and disability. “We need to deal with this on top of the projected increase in diabetes,” said Sylvia Kehlenbrink, director of the Non-Communicable Diseases in Conflict Program at the Harvard Humanitarian Initiative, USA. “Non-communicable diseases are always a small part of foreign health aid. A sustained and collaborative commitment is now needed from many players.”

This necessary commitment has been initiated by the Boston Declaration, signed by 40 international organisations after a meeting at Harvard University in 2019, when 100 people came together as a community wanting action on diabetes in disaster situations. The declaration has four declared targets: advocacy, universal access to insulin, improving diabetes data and seeking unified clinical and operational guidelines for diabetes in humanitarian crises.

To achieve these goals, the International Alliance for Diabetes Action (www.iadadiabetes.org) has been set up with a diverse group of stakeholders including NGOs, academia, charities and the private sector. It is hoped that the group can help provide quality care for all those with diabetes who find themselves caught up in a disaster situation.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

Prevention and remission of type 2 diabetes is crucial for tackling the projected increases in incidence in coming years. The logistics of setting up a large-scale programme in England and the challenges of achieving similar success elsewhere were discussed at the recent International Diabetes Federation meeting in Lisbon. Dr Susan Aldridge reports.

While the oral glucose tolerance test (OGTT) is often used to identify those at risk of type 2 diabetes, NHS England uses a two-stage approach. First, a risk assessment tool is used and then, if needed, either HbA1c or fasting blood glucose is measured. Results between 42-47 mmol/mol or 5.5-6.9 mol/l, respectively, identify a high-risk individual who would be eligible for the NHS Diabetes Prevention Programme (DPP).

There is a big evidence base for interventions to delay or prevent the onset of type 2 diabetes from Finland, India, Japan and the USA, where the OGTT is used to identify those at risk. However, recent work from England used HbA1c and found a 43% reduction in type 2 diabetes with lifestyle intervention. “We now have evidence that defining risk this way and introducing lifestyle intervention does have good randomised clinical control evidence behind it,” said Professor Jonathan Valabhji, National Clinical Director for Diabetes and Obesity at NHS England, who played a leading role in setting up the NHS Diabetes Prevention Programme (DPP).

Back in 2014, the Five Year Forward View report expressed concern about the sustainability of the NHS, placing much more emphasis upon prevention. Professor Valabhji saw an opportunity to set up a national diabetes prevention programme and it was fully supported and funded after the 2015 General Election.  

Setting up the NHS DPP

Early stages of the NHS DPP saw the establishment of a reference group, a service specification and procurement of providers. The service specification was similar to the US DPP, consisting of a nine-month group-based programme with 13 sessions based around losing weight, healthy eating and increasing physical activity. After a gradual roll-out across England, full coverage was achieved by the summer of 2018. “Referral was by GPs and they are very good at targeting those most in need of these interventions,” said Professor Valabhji. “We were also able to show that our attendees adequately represented high-risk groups, such as those in more deprived areas, South Asians and Afro-Caribbeans.”

Outcomes of the NHS DPP

Data on the first 350,000 participants showed a mean weight decrease of 3.3 kg and a mean HbA1c decrease of 2.0% for completers of the programme (those who had attended 60% or more of the sessions). “This is taxpayers’ money, so there is a huge responsibility for those of us who implemented the programme to make sure it does what it says on the tin,” said Professor Valabhji. The National Institute of Health Research funded and commissioned an independent study, published at the Diabetes UK conference earlier this year, and it showed that the relative risk reduction of completers compared with those attending none of the sessions is 37%. “Even more pleasing was that the independent analysis was able to demonstrate a 7% reduction of type 2 diabetes incidence in the English population, not just attendees at the NHS DPP,” he added. 

Digital delivery

From the beginning, there was huge political pressure to deliver NHS DPP digitally. “We always said the programme would be evidence-based and, when we set it up in 2015, we didn’t think the evidence was strong enough to deliver digitally,” said Professor Valabhji.

Then a pilot study of a 12-month digital programme with peer support, a telephone service and a website was set up in nine areas with five providers and 3,500 participants. This led to significant reductions in weight and HbA1c.

Since these findings were ready by the onset of the pandemic, the NHS DPP providers were able to adapt the entire programme to digital or remote delivery and recruitment soon picked up to pre-pandemic levels after a sharp dip at the start.

In a paper on baseline weights from April 2017 to April 2021, a very rapid rise – most marked in younger people, women and those living in deprived areas – was noted at the onset of lockdown and this has still not returned to pre-pandemic baseline levels.

By early 2022, around 117,000 people had been referred to the remote programme and 25,000 to the digital programme. Average weight losses were 3.3 kg for remote and 5 kg for digital, compared with historical data of 3 kg for the original face-to-face option. It is not clear why so much more weight was lost in the digital group, who tended to be younger, but were also starting from a higher baseline weight. The digital programme is done by the participant on their own, while the remote option is done in groups (like a Zoom meeting). It may be that the digital programme is preferred by those who feel there is stigma attached to obesity and overweight, and would prefer to work alone in their weight loss, while others prefer the support of a group. 

Type 2 remission on the NHS

The NHS Type 2 Diabetes Path to Remission programme was set up in 2019 and is based on evidence from the DiRECT and DROPLET studies of low-calorie diets involving total meal replacement (TMR) consisting of soups and shakes. The model of the remission programme is similar to that of the NHS DPP. Participants receive TMR for three months, followed by two months of food re-introduction, then seven months of behavioural support to maintain their weight loss.

After a six-month delay because of the pandemic, the programme was rolled out in September 2020 to 25% of England and earlier this year reached 50% of the country. NHS England is now in the process of putting providers in place for the rest of the country.

“Five thousand people have started the programme so far and we are pleased to see an excess of referrals from the most deprived areas,” said Professor Valabhji. “The most common BMI among participants is 30 to 35 and, while participants in DiRECT were mainly white, our programme includes people from different ethnic groups, with 20% Asian and 6-8% Afro-Caribbean.”

Retention rates are “very encouraging” with 56% completing the programme. And when it comes to weight loss, this is very similar to that reported in the trials at an average of 10.3% of body weight and 11.4 kg at 12 months. This data is being linked to the National Diabetes Audit, which will give HbA1c and prescription findings, enabling the rate of type 2 remission to be revealed sometime in the next six months, so watch this space. 

Do prevention strategies really work?

Findings from NHS England are encouraging but what about type 2 prevention programmes elsewhere? Dr Timotheus Dorh, who recently served as Chair of IDF North America and Caribbean region, is from St Lucia and has a special interest in non-communicable diseases, such as diabetes. He has reviewed evidence from around the world to put together some ideas about what does – and does not – make an effective prevention strategy.

“We know, as scientists, that the prevention strategies can decrease the risk of diabetes,” he said. “Almost every country in the world has some form of diabetes prevention now.” But how do you determine the success of these programmes? Incidence rates of type 2 diabetes have decreased in the US between 2001 and 2019 and one could assume that this is because of the prevention programme. However, the IDF Atlas shows that prevalence and mortality have generally increased.

“I think there is really not enough data to determine the success of our strategies,” said Dr Dorh. “More than one third of countries in the world have no reliable mortality data and estimating mortality due to diabetes is also challenging. If someone dies of a complication, diabetes may not appear on the death certificate. Many people with diabetes are also living longer. So we might be looking at the wrong data. It would maybe help to look at some mixture of incidence and prevalence.”

There is also wide variability in enforcement of prevention strategies by country and, often, a lack of co-ordination in efforts. On this point, Dr Dorh noted that the Centers for Disease Control and Prevention (CDC) in the US had trained community organisations in prevention, which had increased patient support. In contrast, this approach is harder to sustain in low- and middle-income countries and, as a result, patient support can be poor, which impacts the success of the prevention strategy. Finally, there is sometimes lack of funding. “Even though the interventions themselves are cheap, the associated education costs money,” said Dr Dorh. “IDF could pay, but the onus for this is really on governments.”  

Recommendations for successful prevention

Dr Dorh made a number of recommendations based on his review. First, countries should implement programmes that score highly in the PIPE impact metric. This means Penetration, which is the ability of the programme to reach the people who need it, involving scaling up. Implementation and Participation means ability to set up the programme and get people involved. And, finally, Effectiveness, which would cover weight loss, completion of the programme and, most importantly, reduction in type 2 diabetes incidence.

Furthermore, the programme should be implemented in its entirety and involve all stakeholders in planning and discussion. In many countries, health insurance is a big problem, so insurers should be approached to increase coverage. Finally, governments should invest in research and data analysis, as well as support groups run by organisations such as the IDF, and volunteers should be encouraged to work on prevention programmes. 

“In conclusion, I would like to say that data analysis and collection is crucial to determine how successful current prevention strategies are,” said Dr Dorh. “Often, even when successful studies are published, there is no infrastructure available to carry out the cost-effective strategies recommended. Remember, what works in your country may not work elsewhere because of economic, social and cultural factors.”

He finished with a quote from Nelson Mandela, which could be applied to type 2 diabetes prevention work: ‘If you talk to a man in language he understands, that goes to his head. If you talk to him in his own language, that goes to his heart’.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

Advances in diabetes technology should help reduce the frequency of hypoglycaemia and the distress it can cause but does the clinical evidence for this stack up? And what about the psychological barriers to the successful use of diabetes technology? Both aspects were under discussion at the recent meeting of the International Hypoglycaemia Study Group. Dr Susan Aldridge reports.

There are many automated insulin delivery (AID) products, mostly using closed-loop with manual mealtime bolusing. All tend to show increased time in range of around 10%, reduced hyperglycaemia and hypoglycaemia, improved quality of life, decreased mean glucose values and decreased glucose variability. Professor Tim Jones, of the University of Western Australia, reviewed the clinical evidence on how AID impacts hypoglycaemia.

One of the early studies was the Diabetes Camp study, with 54 participants, where there were seven hypos in the AID group and 22 in the control group. Another hospital/clinic study involving afternoon exercise showed a significant reduction in overnight hypos on AID. More recently, there was a six-month, randomised controlled trial in Australia, involving 120 adults on either AID or manual insulin and fingerprick testing. This showed that AID does offer significant protection against hypoglycaemia exposure, as measured by time in range. “Clearly, there are still some limitations to prevention of hypoglycaemia by AID systems, as they reduce it, but do not eradicate it,” said Professor Jones. 

Addressing hypos through improved technology

One of the limitations of AID – as far as hypoglycaemia is concerned – arises from insulin pharmacokinetics. It acts for ‘too long’ in an AID system because it continues to be absorbed from the subcutaneous site. There are also counter-regulatory hormone deficits in people with diabetes, and predisposing factors, such as exercise, alcohol, diet, missed insulin and sometimes a combination of all of these, which come into play and precipitate a hypo.

There are various strategies for reducing, or even eliminating, hypos with AID. A more physiological insulin delivery route, such as via the peritoneum, might help, as would faster-acting insulin or a dual-hormone system, although this would require a more complicated pump.

Then there is a prospect of automatic detection of sleep and exercise, with corresponding adjustment to insulin delivery. Finally, you can never have too much patient and clinician education when it comes to preventing or eliminating hypos.

There is one instance, though, where current AID technology has really hit the mark – it has had a big impact on nocturnal seizures. “These are very rare on closed-loop, whereas in the past they were much more common,” said Professor Jones. “With a sensor-augmented pump with low glucose suspend, the incidence of nocturnal seizures in people with impaired awareness of hypoglycaemia was reduced to zero.”

Addressing fear of hypoglycaemia

It is not just the number of hypos that AID can prevent that is important. It’s also about whether these systems can improve people’s confidence about hypoglycaemia. “We asked our patients what worries them about having a low,” said Professor Jones. “Some of the comments were disturbing – concern about passing out and dying, going so low that you go into a coma, being alone when you have a hypo. So we have to consider if closed-loop can decrease this fear of hypoglycaemia, as this is an important quality-of-life issue for people with diabetes.”

In a randomised clinical trial involving 120 adolescents, AID improved time in range compared with controls, although not as much as is seen in adults. Quality of life also improved, but there was no significant impact on fear of hypoglycaemia. “So this is more complex than just reducing hypoglycaemia exposure and needs to be dealt with appropriately,” said Professor Jones.

What about impaired awareness of hypoglycaemia? In a six-week trial of closed-loop, the time at glucose less than 3.9 mmol/l was reduced from 5.2% to 1.7%, and time at glucose less than 3 mmol/l went from 1.9% to 0.3%. However, there was no improvement in hypoglycaemia awareness, despite decreased exposure to it. So, again, as with fear of hypos, there is a need to think of effective strategies to address lack of awareness beyond just technology use, Professor Jones concluded. 

Psychology, AID and hypoglycaemia

Some people with diabetes get more benefit from AID than others and some avoid it altogether. Dr Linda Gonder-Frederick, Associate Professor of Research in Psychiatric Medicine at the University of Virginia, looked at the psychological factors involved in the successful use of diabetes technology. “From a psychologist’s perspective, it’s a very complicated process,” she said. “It involves adoption, continuation of use and outcomes.”

According to the technology adoption theory, which was not developed with diabetes in mind but applies to it very well, adoption and continuation depend on ease of use, usefulness and trust, all of which are subjective and individual.

A study of readiness to use technology in people with type 2 diabetes showed five different profiles, from high to low readiness – this included medium-high readiness, but with high levels of diabetes distress, and also medium-high readiness, but with low health literacy. This suggests that support to start on AID, with the goal of reducing hypoglycaemia and associated distress, should be individualised with these profiles in mind.

There is also the issue of perceived benefit of technology vs the burden associated with its use. “This is an important concept in health-belief models,’ said Dr Gonder-Frederick. “Behaviour is an outcome of that benefit vs burden analysis. For example, for many adolescents, the perceived burden of wearing something on your body that others can see overcomes the perceived benefit of using it.”

One interesting study shows that perceived psychological benefit may sometimes be more important than actual clinical benefit. A group of 158 multiple daily injection users with less than optimal control started on CGM and, after 24 weeks, there was an improvement in diabetes distress and confidence about hypoglycaemia that was not related to glycaemia outcomes. This contrasts with the studies discussed above by Tim Jones, which suggest fewer hypos does not necessarily equate with less fear and greater awareness. These different findings maybe show how variable people’s experience of diabetes technology and hypoglycaemia can be. 

Continuing support

Sometimes, people do not continue with CGM and insulin pumps. For instance, one study involving adolescents on closed-loop found that 30% of them discontinued its use within three to six months. The major reason given was that the system was too time-consuming to use. A survey showed that ease of use is very important going forward. Alarms and discomfort can both cause problems that might lead someone to give up on their technology. “This shows that people with diabetes need ongoing support, not just to get started on technology,” said Dr Gonder-Frederick. “Often, people have unrealistic expectations about AID. For instance, if it’s called an ‘artificial pancreas’, that gives the impression that if they use these devices they’re not going to have to think about their insulin very much. So it’s very important to have an alignment between expectations and experience.”

In another study, those with best outcomes from AID were the ones who gave themselves more meal and correction boluses. “This was a nice example of diabetes engagement,” said Dr Gonder-Frederick. “Putting in time and effort is still a requirement after starting to use the most sophisticated diabetes technology if you want to achieve the very best results.”

Finally, she looked at the A2A (Attitudes to Awareness) tool from Stephanie Amiel’s lab. “What they found with folks who were still having problems with severe hypoglycaemia was that they prioritised avoidance of hyperglycaemia and hypoglycaemia concerns were minimised,” she said. “This tells us that, even with use of the most sophisticated technology, those beliefs and psychological factors are still going to be in operation and may interfere with people achieving the goals they would like to achieve from using technology.” 

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy

A recent study discussed at the 2022 EASD Annual Meeting found that modifiable risk factors, including HbA1c and BMI, are consistently associated with severe influenza, pneumonia and COVID-19 infection outcomes in people with type 2 diabetes. Lisa Buckingham reports.

Rhian Hopkins, a PhD student from the University of Exeter, began with what we know – that people with diabetes are twice as likely to be hospitalised or to die from an infection-related death compared with the general population. Diabetes is also one of the most important risk factors for COVID-19.

Population-based research in the UK has identified risk factors for COVID-19 mortality within people with diabetes. However, said Rhian, it’s unclear whether these risk factors are specific to COVID-19 or reflect severe respiratory infection in general. Understanding this may be vital should a new respiratory infection emerge.

The key question they wanted to answer in their research was this: are risk factors for severe COVID-19 outcomes similar to other respiratory infections in people with type 2 diabetes? Their aim was to compare clinical and sociodemographic risk factors for COVID-19 with risk factors for influenza and pneumonia.

They studied large scale, population-based data from the UK, using routinely collected health records from the Clinical Practice Research Datalink (CPRD). It contained largely representative primary care data from the UK population alongside individual level linkage to hospital records, allowing the researchers to identify causes of hospitalisation.

They identified over half a million adults with type 2 diabetes for each of their three cohorts: COVID-19 (pre-vaccination); influenza and pneumonia (both from a period just before the pandemic so that COVID-19 infection would not impact outcomes).

They chose to use infection-specific hospitalisation as their outcome, as opposed to mortality (which many early studies chose as an outcome), and used Cox proportional hazard models to explore patterns of association and identify risk factors for each infection. Their models were multivariable and encompassed a wide range of potential risk factors, including 19 co-morbidities, including diabetes features such as microvascular complications.

However, the presentation focused on their most interesting findings on socio-demographic features and the clinical risk factors of HbA1C and body mass index (BMI).

Overall, they saw over 6000 hospitalisations for COVID-19 during the study period, 1354 for influenza and 13,971 for pneumonia. The vast majority were in the older age groups for all three infections, as expected.

With regard to socio-demographic risk factors, they compared the risk between groups for each infection and looked first at male vs female. They found that being male was associated with a greater risk of hospitalisation from COVID-19, compared with influenza and pneumonia where there was less difference between male and female.

For age, they saw that a 10-year increase in age was associated with a greater increase in hospitalisation for pneumonia compared with COVID-19 and influenza, which were similar.

For ethnicity, they replicated previous studies by finding that non-white ethnicity was a risk factor for severe COVID-19 infection outcomes, but they didn’t see this association for the other respiratory infections.

Their results showed a clear differential association between COVID-19 and pneumonia with non-white ethnicity being a greater risk of hospitalisation for COVID-19 and a lesser risk for pneumonia; for influenza, they saw an association only with South Asian ethnicity.

When looking at deprivation, they saw that an increase in deprivation was more strongly associated with hospitalisation for COVID-19 than for pneumonia and no association was observed with influenza.

Once the differences were established, they looked at clinical risk factors. HbA1c and BMI are potentially modifiable and easy-to-measure clinical features that have previously been associated with poor COVID-19 outcomes in people with diabetes, said Rhian. They found that high HbA1c was independently associated with hospitalisation for COVID-19 with increasing risk with high HbA1c starting at a level of 55 mmol/mol. Around 40% of the cohort had an HbA1c above this level.

High HbA1c was also associated with hospitalisation for pneumonia and influenza. The influenza associations looked very similar to those for COVID-19 but for pneumonia, the point at which risk starts to increase was around 80 mmol/mol. An HbA1c of this level was associated with increased risk of hospitalisation for all three infections, but risk starts to increase at a lower level for influenza and especially for COVID-19.

The same analysis was repeated for BMI and it was found that BMI is independently associated with increased risk of hospitalisation for all three infections and that severe obesity is an important and consistent risk factor across the infections.

With COVD-19, however, the risk rises more rapidly from a BMI of 30, suggesting that risk at lower BMI levels may be more important for COVID-19, particularly when compared with pneumonia.

Overall, modifiable risk factors of HbA1c and BMI are broadly consistent between respiratory infections. In contrast, there were clear differences in sociodemographic associations for the three infections:

• There was a stronger association of male sex with COVID-19
• Age was more strongly associated with pneumonia
• There was an association between non-white ethnicities and COVID-19 but not for pneumonia
• Deprivation was more strongly associated with COVID-19

The message we can take from this, she said, is that approaches to identify people with diabetes at higher risk of severe COVID-19 outcomes may not be entirely applicable to other respiratory infections, and that good glycaemic control may lower risk of all of the severe respiratory infections outcomes that were studied.

After the presentation, the question of vaccination was addressed as the cohorts studied were not vaccinated and this would be an interesting comparison to make in future studies, especially in light of the fact that vaccination rates vary widely across UK populations.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.