Increasing the knowledge of all healthcare professionals involved with diabetes can improve glycaemic outcomes and care transitions. A Diabetes Champion programme was discussed at the American Diabetes Association’s 83rd Scientific Sessions. Lisa Buckingham reports. 

Diabetes education is a key component to positive outcomes for those living with diabetes, but there are not enough diabetes educators to go around and not everyone gets referred to them, said Dr Lucille Hughes, Assistant Vice President of the Diabetes Education and Program Design for Catholic Health, Long Island, New York. It’s therefore critical to develop programmes for the extended care team to be able to develop the skills and knowledge they need to impart information to people living with diabetes. Hence, she said, the Diabetes Champion programme. 

Dr Hughes outlined the programme she created in 2008. It’s a nine-week programme with an hour for each session and around 600 people have completed it so far. Its purpose is to promote and increase knowledge of all licensed care givers in the area of diabetes.

It has eight typical subject areas:

  • Pathophysiology of diabetes 
  • Medications
  • Medical nutrition therapy 
  • Blood glucose monitoring 
  • Diabetes technology 
  • Acute and chronic complications 
  • Problem solving and leadership skills
  • Patient education

What’s key, she said, is to remember that the topics covered should depend on the participants on the course – for example, if the participants are all inpatient staff, when she talks about acute and chronic complications, she would go over insulin-drip protocols and transition from drips to subcutaneous insulin infusion, but if they were care coordinators, the information on complications would be in the context of the information they need to impart to individuals that are newly discharged. 

All participants receive a portfolio with a welcome letter, a pretest, a learning-needs assessment in which they rate their current knowledge and confidence level in various areas (the same assessment is taken at the end of the programme) and a class schedule. Teaching consists of PowerPoints, handouts and a competency exam. She always includes a graduation and gift pack at the end. 

It’s a voluntary programme and no one is forced to attend. She has found that the people that attend want to do more for the patient, but don’t have the knowledge and confidence to do so.

With regard to lessons learned over the years, Dr Hughes discussed what she has changed such as shifting from it from a programme for nurses (it used to be known as the Diabetes Nurse Champion programme) to one for all disciplines; class sizes need to be fairly small (around 20); you must change the curriculum constantly to make sure it’s current, and tailor it based on the needs assessment of the discipline you’re teaching. She also covered the benefits of teaching online – COVID-19 allowed her to pivot to online delivery and this means reaching a much wider audience. Timing is also key, she said – cultivate respect by always starting on time and ending on time, especially as healthcare professionals may worry about courses that run over.

The outcomes have been impressive – for example, pre-test scores on insulin and its administration average at 40% whereas post-test scores are 100%, so it makes a real difference. 

With regard to sustainability, Dr Hughes offers a full-day ‘Keeping the skills alive’ programme once a year. This keeps participants engaged and current in their knowledge, she said. 

The title of the course is ‘Improve glycaemic outcomes and care transitions’ and what she’s noticed over years of teaching is an uptake of referrals from the participants. They often call with questions – perhaps something they’ve learned in class but don’t have the complete confidence to act on it. During each class, the number of referrals to the outpatient Diabetes Education Program increased by an average of five patients per class. 

Providers are also calling, she said, because the Diabetes Champions are telling them that they exist and they’re getting more referrals from those providers. Hypoglycaemic events have also decreased, as measured by the Society of Hospital Medicine. 

In summary:

  • Design the curriculum to meet the needs of the participants.
  • Use the data you collect to truly customise the curriculum – for example, she said, if she gets a majority saying they have zero confidence with inulin pumps, she spends more time on that part of the curriculum.
  • Use the programme evaluation for future classes.
  • The most important lesson she learned was that 100% of participants had either a personal connection to diabetes or a desire to improve their knowledge; advanced degrees did not equate to knowledge regarding diabetes care, management and education.

To learn more, enrol on the EASD e-Learning course ‘Patient education and support’.

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

Two weekly insulins are well into clinical development, with trials showing promising results so far. An expert panel at the American Diabetes Association’s 83rd Scientific Sessions discussed how these new medications might ease the diabetes burden, particularly for those with type 2 diabetes. Dr Susan Aldridge reports. 

The prospect of a daily insulin injection may delay intensification of treatment in type 2 diabetes, as well as adding to diabetes burden. Weekly insulin may alleviate these issues, so promising results from trials with insulin icodec and insulin efsitora have generated excitement in the diabetes community.  “Weekly insulin has been shown to improve health-related quality of life,” said Dr Juan Frias, Managing Director of Velocity Clinical Research. “It has the potential to improve persistence and adherence, and hopefully this will translate into improved short- and long-term outcomes.”

The pharmacokinetic profile of a weekly insulin is flat, meaning fewer hypos, and it can also be co-formulated with a GLP-1 receptor agonist, which has a complementary mode of action. The development of weekly insulins relies on extending the half-life of the insulin molecule which, as a peptide, has a short half-life, requiring continuous infusion or frequent injection. Drug delivery systems can overcome this by creating lipid particle or polymeric systems containing insulin, which allow for slower absorption from subcutaneous tissues.

Efsitora is a fusion protein with two single chain insulin molecules and the Fc region of an immunoglobulin G molecule, with a molecular weight of 50 kilodaltons. Meanwhile, icodec (the other weekly insulin in clinical development) is strongly – but reversibly – bound to albumin, creating a subcutaneous insulin reservoir. Efsitora has been developed by Eli Lilly and is in Phase 3 clinical trials with the QWINT programme, while Novo Nordisk’s icodec is in Phase 3 trials with the ONWARD programme. 

“Efsitora has a half-life of 17 days because of its slow absorption from the subcutaneous space,” explained Dr Frias. “It also has reduced insulin receptor affinity and reduced renal clearance – this leads to a recycling effect, which is important in the prolongation of its action. It achieves a dose-dependent decrease in fasting blood glucose with a nadir between days four and six in type 2 diabetes.” 

Meanwhile, icodec has three amino-acid substitutions in its insulin chain, which reduces enzymatic degradation. It also has lower insulin receptor-binding affinity, which slows insulin receptor-mediated clearance, as well as improved solubility, allowing for a U700 formulation, which is good for weekly administration. 

In summary, molecular modifications and methodologies confer biological properties, including those relating to pharmacokinetics and pharmacodynamics, on these weekly insulins making them suitable for once-weekly dosing. 

Clinical trials update

Ildiko Lingvay, Professor of Medicine at the University of Texas Southwestern Medical Center, reviewed the clinical trials on the two weekly insulins. There have been three Phase 2 trials in the QWINT programme, all involving people with type 2 diabetes, who were either insulin naïve or switching from another basal insulin, with efsitora against glargine as comparator. 

There has also been a trial involving people with type 1 diabetes on multiple daily injections (MDI). Meanwhile, the ONWARDS Phase 3 programme with icodec has also involved people with type 2 diabetes, except for ONWARDS 6, which includes those with type 1 diabetes, and has similarly looked at those who are insulin naïve and switching from another basal insulin against insulin glargine or insulin degludec. Professor Lingvay went on to review the data so far via a series of questions. 

First and foremost, do the weekly insulins lower glucose as you would expect for a basal insulin? “In each of the Phase 2 trials, HbA1c lowering matches – or is even lower than – that of the comparator, and there is the same finding for the Phase 3 programme where we have results,” said Professor Lingvay. “So, yes, absolutely they do.” What about hypos? “Looking at insulin-naïve patients with level 2 or 3 hypos, there were very few, but there is a more mixed picture for insulin-experienced patients making the switch, with a very small absolute increase,” she said. In addition, there was no difference in duration of a hypo between the weekly insulins and their comparators.

For Time in Range and Time below Range, there was very little difference between the weekly insulin and comparator, save for a statistically significant difference in favour of icodec in the ONWARDS 1 trial where Time in Range was better, Time above Range less and Time below Range about the same.  

Since the insulin dose in a weekly insulin is so large, there have naturally been concerns over the impact of accidentally taking an extra dose. There has been a separate study on this, which shows that comparable numbers got clinical hypoglycaemia with an extra dose between the weekly insulin and insulin glargine. “So you might get a low, but it’s not going to be any worse than taking an extra dose of a daily insulin,” said Professor Lingvay. There is also no difference in response whether you inject the insulin in the thigh, abdomen or upper arm. Finally, Professor Lingvay’s analysis of 11 studies shows that people do gain weight when they start the insulin, but this is related more to HbA1c levels than the type of insulin.  

She also referred to the IcoSema Phase 3 trial programme, with a combination of icodec and semaglutide, and hopes results will be ready for next year’s ADA meeting.  

“From my patients’ point of view, the biggest benefit is only having to take one shot of insulin instead of seven in the week,” Professor Lingvay concluded. “Everything else is similar. The weekly insulins are expected to reduce barriers to treatment, reduce treatment burden and improve quality of life. All of these are important features for our patients.” 

Patient and provider perspectives

Chantal Mathieu, Professor of Medicine at KU Leuven, Belgium, and President of the EASD, began by sharing some statements from participants in the weekly insulin trials, such as, “Why are you even asking me whether I would prefer to administer one injection a day or one a week?”.

“One participant in the ONWARD 4 study, who had been on MDI for five years said, at the end of the trial, ‘You need to keep giving me the weekly insulin,’” said Professor Mathieu. “I replied, ‘But what is the difference because you need your daily mealtime insulin anyway’. Her response was, ‘Every injection I can avoid is a plus. What a relief it was that I did not have to give my basal insulin every day during the trial’. I was even more surprised that this participant was so angry with me that I couldn’t keep giving her the weekly insulin. So I saw great enthusiasm for weekly insulins among patients.”

Views among providers were different, though. Endocrinologists feared major stacking of insulin with weekly injections and thus prolonged hypoglycaemia, which would be impossible to manage. Diabetes educators said that with so much insulin on board, people will gain a lot of weight. Primary care providers, on the other hand, were more positive saying: “Oh, this is nice. So we can now give insulin in the same way as we give GLP-1 receptor agonists”. 

“There are some diverse opinions out there,” said Professor Mathieu, “but Ildiko showed the benefits of weekly insulins very nicely in her talk – convenience, improved health-related quality of life and a less overwhelming sense of treatment burden.” 

Who should get weekly insulin?

Professor Mathieu turned to an issue that will be of major concern to providers. Which patients do we want to use weekly insulins? “Hypoglycaemia was my biggest fear,” she admitted. “But the clinical data show only a slight increase and this was the biggest surprise. And it was mainly induced by mealtime insulin rather than basal. I do think the jury is still out on the place of weekly insulins in those with type 1 diabetes, but I would give money to have a once-weekly insulin in some of my adolescent patients. However, we will use personalised medicine and decide who with type 1 diabetes can benefit because, in the trials, there was an increase in hypos in those who started with a very nice HbA1c.” 

Turning to efsitora, this increase in hypos in participants with type 1 diabetes wasn’t seen as in ONWARDS 6 with icodec, but Time in Range was only in the 50% range, which is a concern. “So when considering a weekly insulin in type 1 diabetes, I think it depends upon baseline HbA1c,” said Professor Mathieu.

Clinicians will also want advice on initiating a weekly insulin. From the Phase 3 trials on icodec, Professor Mathieu would advise that you do as you would when initiating an insulin-naïve individual on glargine and so a one-time 50% loading dose, then titrate 20U up or down depending on glucose measurements. With efsitora, which is earlier in clinical development, initiating is more of an exploratory process where starting doses are still being evaluated and it is hoped there will be firmer guidance by next year.

What about people on MDI? The ONWARDS 4 trial showed some very interesting data. If you have a weekly insulin on board, you need less mealtime insulin. “This was quite spectacular,” said ProfessorMathieu. “There was almost no titration needed of the mealtime insulin. As clinicians we will have to take this on and bring the mealtime insulin down. It opens up new perspectives for us. Perhaps with once-weekly insulins, we will have fewer people needing MDI. Maybe, if we combine it with a GLP-1 receptor agonist, we can get rid of mealtime insulin, making the burden of insulin treatment in type 2 diabetes a lot less.”

So, in summary, weekly insulins will first and foremost be for people with type 2 diabetes in need of a basal insulin and for some with type 1 diabetes as well. We know that people like weekly insulins as the ONWARDS trials have Patient Reported Outcomes that mention treatment satisfaction, convenience and flexibility. Of course, questions remain and some of the knowledge gaps are about the impact of exercise, intercurrent illness, fasting and hospitalisation. We also need more information about weekly insulins in pregnancy, the elderly and in children. “So we will need communication and education, in particular for primary care, nurses, diabetes educators, dietitians, surgeons, internists, paediatricians and patients,” concluded Professor Mathieu.  

Future outlook for weekly insulins

Dr Ronald Goldenberg of LMC Diabetes & Endocrinology, Toronto, said,“There have been incredible innovations in the half-life of insulins and we’ll probably be able to prescribe icodec sometime in 2024 and efsitora in 2025.” This is because the efficacy and safety data in type 2 diabetes is very encouraging, as is that on therapeutic inertia, adherence and treatment satisfaction. “In fact, efficacy and safety in the ONWARDS trials show superiority for the weekly insulin over the daily comparator.” he said. “So if you have a choice for insulin-naïve patients, I think clinicians will favour the once-weekly. In the type 2 diabetes space, there is good efficacy and safety. The data on efsitora is encouraging too, but we need to wait for the Phase 3 trial results.” 

The ability to prescribe a once-weekly basal insulin really helps in type 2 diabetes. “We know that initiation of insulin is often delayed and 30% of patients decline it, then 38% of the decliners eventually start on insulin, with mean time to initiation of more than two years,” said Dr Goldenberg. Even then, uptitration is slow and insufficient in the six months after initiation. In the trials, the insulin-naïve patients had diabetes duration of 10 to 12 years. The availability of weekly insulin will allow earlier initiation and titration.  

However, Dr Goldenberg sounded some cautions. “There will need to be some education around the fear of high doses. There is also some complexity around different regimes for insulin-naïve patients and those who are switching from another insulin when it comes to initiation and titration, but this can be addressed with apps and smart pens.” 

Then there is the issue of cost and access. “Banting would roll over in his grave if he saw what was happening with the cost of insulin in recent years,” said Dr Goldenberg. “Things are getting better in the US, with various programmes to reduce the cost, but the big question is will weekly insulins be accessible and affordable?”.

And then there is type 1 diabetes, where the go-ahead for weekly insulins is currently at a red light. “We need more information before we can go forward with this,” he said. “We need a deeper dive into the hypos seen in the ONWARDS 6 trial. Who were the patients most affected, what were their characteristics and so on?”.

So, in conclusion, Dr Goldenberg agreed with Professor Mathieu that initiating weekly insulins in type 2 diabetes is a ‘no brainer’ and he thinks that for some patients in the future, the combination of a weekly basal insulin and a GLP-1 receptor agonist could well be the way forward.  

To learn more, enrol on the EASD e-Learning course ‘Management of hyperglycaemia in type 2 diabetes’.

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

When it comes to reducing carbohydrates in the diet, should people with diabetes opt for moderate intake or very low? Two viewpoints were presented at the recent American Diabetes Association’s 83rd Scientific Sessions. Lisa Buckingham reports.

Arguing that moderate carbohydrate eating is best, Dr Carol Kirkpatrick, Clinical Scientist at Midwest Biomedical Research Adjunct Faculty at Idaho State University, began by discussing the variety in definitions of carbohydrate-restricted dietary patterns within randomised controlled trials, which make it hard to evaluate evidence. Her team created a clearer definition and this is what she referred to throughout: Based on 2,000 calories per day: Moderate = 26-44% of calories from carbohydrate per day (130-220 g); Low = 10-25% (50-125 g); Very low = <10% (20-50 g). 

Starting with weight management, she highlighted a study comparing carbohydrate-restricted diets with higher carbohydrate diets, which found that while short-term weight loss was greater with low or very-low-carbohydrate dietary patterns, the effect was lost beyond 12 months. This can be partly due to difficulties with adherence to severe carbohydrate restriction (although we can acknowledge that it’s difficult for patients to adhere to any dietary pattern, she said).

A 2022 meta-analysis looked at the dose-dependent effect of carbohydrate restriction on different cardiometabolic risk factors. There was a significant decrease in bodyweight at six months as carbohydrate intake reduced; however, by 12 months, the significant effect did not remain. 

My stance, said Dr Kirkpatrick, is that moderate carbohydrate is best – this was demonstrated by a meta-analysis, which showed that 35% carbohydrate at 12 months showed the greatest difference in bodyweight compared with the lower and higher intake of carbohydrate. Perhaps, she said, people were better able to adhere to the moderate intake as carbohydrate restriction is difficult to adhere to, especially in the long-term. 

With regard to effect on lipoprotein lipids, a review of the evidence and several meta-analyses since showed that when it comes to LDL cholesterol levels, there is a very low response. Some patients do achieve lower LDL, especially if they’re able to lose adiposity. However, she said, some experience an increase, especially if they have a genetic susceptibility, and a high intake of foods rich in saturated fatty acids can also contribute. It’s therefore important that if a patient chooses to restrict carbohydrates, they replace those foods with unsaturated fats. In general, triglycerides decrease and HDL cholesterol goes up. 

Returning to the dose-response study, the greatest reduction in LDL cholesterol at six months was seen at 40% carbohydrate, which is line with Dr Kirkpatrick’s ‘moderate carbohydrate is best’ stance. 

She drew attention to another 2020 meta-analysis, which showed that a moderate carbohydrate intake resulted in the lowest increase in LDL cholesterol, compared with low- and very-low-carbohydrate intake. For triglycerides, with each reduction in carbohydrate intake, triglyceride levels decreased, so the most significant decrease was seen in the very-low-carbohydrate bracket. 

However, said Dr Kirkpatrick, when it comes to cardiovascular health, we’re not entirely sure what that means – we know that elevated triglyceride levels are associated with cardiovascular risk but what we’re looking for is the overall atherogenic particles in the bloodstream and LDL and non-HDL cholesterol gives us that information. Therefore, we should look at the results in the presence of both triglyceride lowering as well as what’s happening with LDL and non-HDL cholesterol. When we do this, we see that a moderate-carbohydrate intake allows a decrease in triglycerides without an increase in LDL cholesterol. 

Next, she looked at the effect of carbohydrate intake on HbA1c. Research consistently shows beneficial effects at all levels of carbohydrate restriction. The lower they go, the greater the decrease in HbA1c although this does wane at 12 months at all levels of intake.

Dr Kirkpatrick highlighted the PREDIMED and CORDIOPREV studies on cardiovascular health – both of these are dietary intervention studies showing a decrease in cardiovascular events with a Mediterranean dietary pattern – in both, she pointed out, the dietary pattern was moderate carbohydrate. 

In terms of observational studies, which she acknowledged have their limitations, we see that extreme intakes of carbohydrate is associated an increased risk of all-cause mortality – here, she showed a 2018 cohort analysis showing that lower carbohydrate intake of less than 40% was associated with an increased risk of all-cause mortality, compared with a moderate carbohydrate intake of 50%, and at the other end of the spectrum, too high an intake (>70%) was also associated with an increased risk of all-cause mortality.

Her take-home messages were:

  • Benefits of carbohydrate-restricted dietary patterns were achieved at moderate carbohydrate intakes – triglycerides and HbA1c values improve more with severe carbohydrate restriction but the effect wanes with longer duration. 
  • Very low carbohydrate intakes are difficult to maintain and lower carbohydrate intake is associated with increased mortality in cohort studies.  
  • Recommended healthy dietary patterns can be moderate in carbohydrate, with replacement being healthy protein foods and unsaturated fatty acids and the Mediterranean diet pattern has the strongest evidence of benefit.

The argument for very-low-carbohydrate intake

Dr Dina Griauzde, Assistant Professor of Internal Medicine at the University of Michigan, stepped in to present on behalf of Professor William S Yancy from the Duke Lifestyle & Weight Management Centre, to make the case for very-low-carb eating. 

The case for very-low-carb eating centres around improvement of glycaemic control and not increasing cardiovascular risk (likely lowering it). 

Low-carb diets are often referred to as fad diets, she said, but it’s important to note that they have been around for over a century, showing a quote from Dr Elliott Proctor Joslin in 1923 discussing the restriction of carbs. It was the only treatment for type 1 diabetes before the advent of exogenous insulin and the Joslin Diabetic Diet recommended just 15g of carbohydrate per day (2% of daily calories).

The first study she drew attention to was a small inpatient feeding study of adults with type 2 diabetes who initially ate a high-carb diet for seven days followed by a transition to a two-week period of a very-low-carb eating pattern (20g of carbohydrate per day). During the low-carb phase, glucose and insulin levels were substantially lower and HbA1c decreased from 7.3% to 6.8% over 14 days. We don’t see that effect with medication, she said – a very-low-carbohydrate diet is the most potent tool we have to help patients achieve glycaemic control.

She then outlined the Carbohydrate-Insulin Model, which explains why carbohydrate is considered more obesogenic:

  • Dietary carbohydrate (sugar or starch) raises serum glucose and insulin.
  • A carbohydrate-restricted diet reduces the diet contribution to serum glucose, which then lowers insulin levels.
  • Insulin is a potent stimulator of lipogenesis (fat storage) and a potent inhibitor of lipolysis (fat burning).
  • Lowering insulin level (or dose) leads to burning of stored body fat, raising serum ketones and lowering body weight. 

The idea that dietary carbohydrate can drive overeating was represented in data from a paediatric feeding trial in which a small cohort of boys with overweight or obesity had three evaluations. During each evaluation period, they consumed a diet with different carbohydrate content. They found that those who had consumed a higher carbohydrate meal ate more and had higher glucose and insulin responses, as compared with those who ate a lower carbohydrate meal. 

Next, she highlighted a systematic review of 13 trials in which dietary carbohydrate was restricted to less than 45% of total daily energy per day and these data were consistent with Dr Kirkpatrick’s data – the degree of improvement in glycaemic status was associated with greater carbohydrate restriction. 

A meta-analysis of 56 trials was next, comparing diet effects on glycaemia in type 2 diabetes with a total of 4937 participants and comparing nine diets. It concluded that: ‘For reducing HbA1c, the low-carbohydrate diet was ranked as the best dietary approach followed by the Mediterranean diet and Palaeolithic diet, compared with a control diet. 

She then moved on to discuss the role of a very-low-carbohydrate diet in relation to cardiovascular disease (CVD). One of the criticisms of this diet pattern is that it’s high in saturated fat and this potentiates CVD risk. However, in a meta-analysis of 21 studies, the intake of saturated fat was not associated with coronary heart disease (CHD), stroke or CVD.

We can take this one step further, said Dr Griauzde, by saying that saturated fat (when consumed as part of a very-low-carb diet) may actually improve key measures of cardiometabolic health. She showed a small study of 40 adults with metabolic dysfunction – it involved 12 weeks of eating 1500 calories per day. Participants on the very-low-carb diet had significantly greater improvements in key measures of cardiometabolic health, such as body mass index and triglycerides. She drew attention to the fact that small LDL (which is more atherogenic than larger LDL particles) increased to a greater extent in individuals following the low-fat diet. Total serum fatty acids (SFAs) decreased to a significantly greater extent in the low-carb group despite a three- to fivefold increase in saturated fat intake. 

The take-home points were: 

  • Low carbohydrate intake leads to rapid reduction in glucose and lower insulin levels.
  • The lower the carbohydrate, the lower the blood glucose trends. 
  • In patients with diabetes, very-low-carb eating also lowers medication requirements more than other eating plans.
  • Blood pressure decreases, serum HDL increases and triglycerides decrease.
  • LDL cholesterol does not typically increase AND small LDL decreases.

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

There are more people on the move around the world than ever before, so it is crucial to understand the specific factors that affect immigrants’ health. An expert panel discussed the latest research on immigration and diabetes at the recent American Diabetes Association’s 83rd Scientific Sessions. Dr Susan Aldridge reports. 

One theme that often comes up when discussing the health of migrants is the ‘healthy immigrant’ paradox, whereby a recent migrant has better health than a native of the country they are arriving in. This benefit tends to disappear over time, with future generations’ health becoming more like that of native people. 

Megha Shah, Assistant Professor at Emory University School of Medicine, took up the discussion with reference to the Hawaii-Los Angeles-Hiroshima study. Started in 1970, this study showed how adapting to a Western diet has led to an increase in diabetes among Japanese people emigrating to the US over the last 50 years compared with those who remained in their native country. “Native Japanese people have a certain lifestyle, but when they emigrate, their risk of diabetes and obesity increases,” said Professor Shah. “But that’s only one community and we have much variation in diabetes risk depending on where someone comes from.” 

The immigrant paradox does not always hold true. There are particular risk factors – namely acculturation, social context and environmental exposures – that the next generations of an immigrant family experience compared with the first generation and these will affect their health going forward. 

Professor Shah went on to give some multigenerational findings in the US that highlight the heterogeneity in the health of immigrant populations. The Sacramento Area Latino Study on Aging (SALSA) showed that second and third generation Mexican adults have a greater risk of diabetes, with acculturation having little impact. However, in the California Men’s Health Study, involving a multi-ethnic cohort, there was a gradient of risk with increasing years in American culture – so there was a greater risk of diabetes for the second generation than for the first. 

Finally, there was the MASALA (Mediators of Atherosclerosis in South Asians Living in America) study, which showed the impact of three different acculturation styles – separation (preference for South Asian lifestyle), integration (equal preference for South Asian and US lifestyles) and assimilation (preference for US lifestyle) – upon type 2 diabetes risk. Women in the integration group had the lowest risk of type 2 diabetes and prediabetes, at 16.4% and 29.7%, while those in the separation group had the highest risk at 29.3% and 31.5%. No such differences were observed among male participants. 

Professor Shah is involved in the Community Engaged Needs Assessment of South Asians in Atlanta (CENSAA) study where they are partnering with the Indian community to collect data and explore their health needs related to cardiometabolic disease risk, looking at differences between those born in India (473 participants) and those born in Atlanta (837 participants). 

A survey was launched, which showed that obesity was higher in those born in the US, although they were more likely to do the recommended 150 minutes a week of physical activity, while those born in India have more hypertension and more diabetes. They went back to the respondents for more detail and found health belief/attitudes, sense of identity and interaction with healthcare systems seemed to be key factors for the prevalence of cardiometabolic disease. “We need future cohort studies to be more diverse, spanning generations,” concluded Professor Shah. “We need to understand diabetes trajectories through the generations to provide etiological insights into the development of diabetes and inform prevention efforts.” 

Tailoring prevention studies

Dr Mary Beth Weber of the Emory Global Diabetes Research Center then spoke about how diabetes prevention efforts could be tailored to take account of cultural influences. For example, we know that South Asians describe food at social events as being very important. Much of it can be very rich, but turning it down on health grounds can lead to tension, eroding the social support that is so important. “Culture is important in driving behaviours,  particularly those of interest for diabetes prevention,” she said. “It impacts self-care behaviour and adherence. So, when designing interventions, do consider cultural aspects throughout the whole process.”

There are several frameworks that can guide researchers with this, such as the ADAPT guidance, which emphasises stakeholder involvement early and often to adapt an intervention to a new context (such as taking cultural influences into account). However, there are still large gaps in provision. A 2015 review of cultural adaptations to the US Diabetes Prevention Programme (DPP) found that very few actually used cultural adaptation frameworks and there was a limited rationale for modifications made. “If you take nothing else away from today, here is the number-one thing we need to do better – we need to document what we are doing to make programmes culturally appropriate because documentation is frequently absent, vague or superficial,” said Dr Weber. “So do report on how or why adaptations were made and link them to the evaluation, so we can see which adaptations are the most effective. I argue that this would be worth its weight in gold for moving this field forward.” 

In addition, it is important to let the community that will be taking up the programme be your guide. “Speak early and often,” Dr Weber continued. “Educate, if needed, but listen too. Work at the ‘speed of trust’, taking the time to build that trust. That needs to be built into the timeline of studies.” 

It is also important to understand your intervention and why it might work for your target population, using feedback from stakeholders. This includes understanding what the core components are that might be driving change. One example of a good prevention programme that reflects these principles is the SHAPE programme, which is an adaptation of the DPP for South Asians, with a focus on portion sizes of foods such as rice and bread. Dr Weber concluded by urging delegates to be sure to write up and publish similar examples to share with the healthcare and wider community. 

Mind your language

Alicia Fernandez, Professor of Medicine at the University of California San Francisco, began her talk on the impact of English proficiency on diabetes care with a simple question to the audience. In a healthcare encounter via a professional interpreter, is patient comprehension, on average, similar to that during an encounter with a language-concordant physician? The answer is no – comprehension is a lot less when an interpreter is involved. 

A study from a New York emergency room compared consultations with two state-of-the-art interpretation systems and a language-concordant physician. When patients were asked if they understood the explanation for their condition, 33% and 39% said yes for the interpreters compared with 59% for the physician. When it came to understanding the instructions for aftercare following discharge, the figures were 33%, 38% and 63%, respectively.  

Dr Fernandez and colleagues have looked at this issue in Kaiser Permanente Latino patients who have diabetes and have either good English or limited English. The two groups were compared and then analysed by whether those with limited English were seen by Spanish-speaking doctors. “There was a big difference, in that those seen by a doctor who did not speak Spanish were more likely to feel lack of trust, that they were treated poorly, not shown respect and that the doctor was not listening,” she said. 

The use of an interpreter instead of a language-concordant physician also has a clinical impact, leading to more medication errors, less understanding of medication labels and less understanding of follow-up and discharge instructions. 

Dr Fernandez also referred to the DISTANCE study, which involved 20,000 Kaiser Permanente patients speaking five languages and including 3193 Latino participants. Ten per cent of White participants had poor glycaemic control, compared with 18% of Latino participants with good English and 21.4% with limited English. And the proportions with poor glycaemic control were 16.1% and 27.8%, depending on whether or not they consulted with a Spanish-speaking physician. No such effect was seen for blood pressure or LDL-cholesterol levels. 

Clearly this issue is worth further investigation but, as Dr Fernandez put it, it is difficult to set up a randomised controlled trial on the basis of patients either seeing, or not seeing, a language-concordant physician, as they would presumably all prefer the former. However, her team was able to carry out a trial looking at the impact of switching from a language non-concordant to language-concordant doctor over the course of the study (as patients are used to seeing different physicians in clinic). At the end, the group that switched to the concordant doctor had much better glycaemic control. 

“Switching to a doctor that speaks Spanish improves glycaemic control, but there was no impact of switching on blood pressure or LDL-cholesterol,” noted Dr Fernandez. “So there is something about glycaemic control that is particularly sensitive to language barriers.” 

Analysis of consultations shows that less counselling goes on in discordant languages. Giving examples from her own conversations with Chinese patients who had limited English, she said the conversation is more limited and there are fewer questions, less empathy and less attention given to the patient’s point of view. So this might feed into poorer glycaemic control with less discussion about insulin and diet and, overall, less trust, comprehension and satisfaction.  

Another angle to consider is that with low English literacy often comes low health literacy. Most older immigrants tend to have limited education compared with those who are younger. This can feed into comprehension of health messaging. For example, a survey on knowledge about sugar-sweetened beverages among Spanish speakers showed that while many knew sodas were high in sugar, they did not realise that horchata and agua fresca, which are popular drinks in the community, also contain a lot of sugar.

So what is the way forward? “We obviously don’t all speak all languages, so check back more on comprehension,” said Dr Fernandez. “I will force myself to make an empathic statement and make sure the interpreter makes it too. And always be sure to elicit the patients’ point of view. Arranging for language-concordant diabetes and other health educators is probably one of the most important things we can do.” 

Finally, what about technology? A study of Google Translate translating into Chinese and Spanish and then back into English found potentially life-threatening errors. “If you are going to use this technology, go for simple sentences and plain language, and do not use without oversight from someone,” she warned. Furthermore, machine interpretation by phone technology is not yet ready for clinical use. 

In conclusion, language barriers create difficulties for people with diabetes and their clinicians. They make healthcare less patient-centric, leading to more diabetes distress and may also affect glycaemic control. More needs to be done to facilitate language access and language-concordant diabetes care.  

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

The findings of the SURMOUNT-2 trial were unveiled in a panel discussion at the American Diabetes Association 83rd Scientific Sessions recently. The study showed that weekly tirzepatide leads to significant weight loss and other health benefits in people with type 2 diabetes and overweight or obesity. Dr Susan Aldridge reports.

Professor W Timothy Garvey of the University of Alabama at Birmingham set the scene by reviewing the current therapeutic landscape for treating obesity in type 2 diabetes. “Up to 90% of people with type 2 diabetes also have overweight or obesity,” he said. “They have two diseases and both should be treated effectively.” 

Accordingly, the American Association of Clinical Endocrinology (AACE) guidelines now recommend treating obesity to improve the patient’s health and prevent complications, rather than focusing merely on loss of kilograms. And the AACE/European Association for the Study of Obesity have also come up with a more medical diagnosis of obesity as comprising abnormalities in adipose tissue mass, distribution and function, which create a chronic disease.

Obesity pharmacology ranges from phentermine, back in 1959, to tirzepatide which was approved in May 2022 for glycaemic control in type 2 diabetes, although it is under investigation in many trials, including SURMOUNT, for the treatment of obesity. Tirzepatide is a dual agonist of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptors. In clinical trials with patients without diabetes, tirzepatide can produce up to 22% weight loss, compared with just 15% with semaglutide. “I think these two medicines, which give us weight loss of 15% or more, are transformational in terms of what they bring to the table for our ability to improve the health of our patients,” said Professor Garvey.

The amount of weight loss you need to treat obesity-related disease, such as type 2 diabetes, cardiovascular risk, immobility, sleep apnoea and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), ranges from 10% to 35%, and 10% to 25% is now achievable with medication.  “This is sufficient to prevent and treat a broad array of diabetes complications,” he continued. “So the health benefits that can accrue from this level of weight loss has led me to propose that these drugs be given the title of second-generation obesity medications because they can safely produce more than 15% weight loss in conjunction with lifestyle intervention.”

Obesity in diabetes

Alongside their glucose-lowering effects, GLP-1 receptor agonists and SGLT-2 inhibitors lead to weight loss of around 3%, save for semaglutide, which produces a greater weight loss. “But if we think we’re treating obesity by putting patients on these drugs at doses to treat diabetes, I think we’re fooling ourselves and not doing the best for our patients,” warned Professor Garvey. Also, people with both obesity and diabetes lose less weight than those with obesity alone. This is true for all obesity medications, except for tirzepatide, where we don’t yet have the data.   

Looking at the whole range of weight-loss interventions, at the lower end, lifestyle intervention alone can produce between 2% and 7% weight loss, medication is in the middle with weight loss of up to 22% (in patients without diabetes), while surgery is at the higher end with potential weight loss of 40%.  “We really are lacking that ‘sweet spot’ of drugs that can get us into 15% or more weight loss with type 2 diabetes,” said Professor Garvey. “This is what we want to look for in drugs designed to treat obesity in diabetes.” 

Rationale of medication based on gut hormones

Professor Matthias Tschöp of the Technical University of Munich has been involved in the development of tirzepatide from the start, with Richard DiMarchi, in a bid to achieve 20% weight loss with a medication. “For this, we need to target more than one signalling pathway,” he said. “The gut-brain pathway offers safe and effective targeting of the brain circuits controlling body weight. We need to target more than one gut hormone receptor in the brain and, in my mind, obesity is a brain disease.”

They needed a gut hormone combination in a single compound, he continued. They found that GIP and GLP-1 receptor agonists had a dose-dependent, synergistic, anti-obesity effect in trials in mice and then clinical trials began in 2016. As far as the mechanism of tirzepatide is concerned, GIP is likely the major player, reaching the brain where the antisatiety effect happens.  

Design of SURMOUNT-2

Dr Juan Pablo Frías, Director of Velocity Clinical Research, Los Angeles, noted that tirzepatide has been, and continues to be, studied in a number of metabolic diseases, including type 2 diabetes, obesity, NASH/NAFLD, kidney disease, obstructive sleep apnoea and heart failure with preserved ejection fraction (HFpEF). SURMOUNT-1 was carried out in people without diabetes and showed a 22% decrease in weight over 72 weeks. Other SURMOUNT trials are underway, including SURMOUNT-5, which compares tirzepatide with semaglutide.  

The need for a separate study in type 2 diabetes is that people with type 2 diabetes often lose less weight than those without the condition. The SURPASS series showed that tirzepatide significantly reduced body weight versus placebo or active comparators in people with type 2 diabetes, but these trials were mainly focused on glycaemic control. For a weight-loss trial, BMI should be 27 or more, there needs to be a dietitian on board and it should run for more than 52 weeks. So SURMOUNT-2 was designed to assess the safety and efficacy of tirzepatide for chronic weight management in people with type 2 diabetes and obesity or overweight.

The trial involved 798 people with type 2 diabetes at 77 sites in seven countries, who were randomised to 10 mg or 15 mg of tirzepatide or placebo, along with increased exercise and a reduced-calorie diet. Their mean BMI at the start was 36, mean body weight 100 kg, and duration of type 2 diabetes 8.5 years. The primary objective of SURMOUNT-2 was to show that the 10 mg and 15 mg doses were superior to placebo at 72 weeks for percentage change in body weight and achieving 5% or more reduction in body weight. There were a number of secondary objectives – achieving 10%, 15%, 20% or more loss in body weight, reductions in HbA1c and so on.  

Findings of SURMOUNT-2

Professor Garvey gave out the headline results – for those on 10 mg tirzepatide, mean weight loss was 13.4% (13.5 kg) and it was 15.7% (15.6 kg) on 15 mg. On the 15 mg dose, well over 80% of participants achieved 5% loss of body weight, 45% lost more than 15% and more than 30% of them lost more than 20%. Even more impressive, more than 17% of the participants lost more than a quarter of their body weight. 

“These people are going to need to buy new clothes,” Professor Garvey said, as waist circumference decrease was three to four times greater with tirzepatide than with placebo, while mean change in BMI was around 5.7. “This represents a step down in a whole class of obesity – from Class III to Class II or from obese to overweight,” he continued.  

Meanwhile, HbA1c decreased by 2.1%, with a very rapid increase seen by 24 weeks, which then stabilised at the lower level. Close to 90% of the SURMOUNT-2 participants reached the ADA 7% HbA1c target and around 50% even achieved normoglycaemia. All of this was achieved with no severe hypoglycaemia and very little Level 2 hypoglycaemia. Finally, there were also improvements in lipids and blood pressure, so all primary and secondary objectives of SURMOUNT-2 were met.  

Professor Naveed Sattar of Glasgow University then took the platform to review the safety issues around SURMOUNT-2. “Adverse events, including serious events, were not elevated in the tirzepatide groups compared with placebo, and most treatment-emergent adverse effects were gastrointestinal,” he said. Also of note was improvement in liver enzymes, especially alanine aminotransferase (ALT), which you could expect with weight loss, and suggests tirzepatide has a beneficial effect on liver health. “In summary, the tolerability and safety of tirzepatide in people with type 2 diabetes and obesity is similar to that seen in the SURPASS trials and others on incretin therapies for obesity,” he said. 


Dr Ildiko Lingvay of the University of Texas SouthWestern Medical Center, reviewed the clinical implications of SURMOUNT-2. In comparison, the SURPASS trials were diabetes-focused, with a primary endpoint of HbA1c, with weight loss being secondary, lasted for up to 52 weeks, and BMI was not a factor in inclusion. SURMOUNT had an obesity focus, with HbA1c as secondary, lasted for 72 weeks and BMI had to be 27 or more.  

The SURPASS-3 trial was the most similar to SURMOUNT-2, except that lifestyle interventions were included in SURMOUNT-2 and baseline weight was around 6 kg less. Comparing body weight loss, these were 13.4% and 15.7% in SURMOUNT-2 and 11.4% and 13.9% in SURPASS-3 for the 10 mg and 15 mg doses of tirzepatide, respectively. “This is pretty close and I will speculate that if you were to extend SURPASS-3 to 72 weeks, you would probably get the same percentage body mass loss,” said Dr Lingvay. “The slightly faster response we see in SURMOUNT-2 is probably because of lifestyle intervention in that trial.”  

She then put SURMOUNT-2 into context with other weight-loss drugs. So, for instance, there is STEP-2 with semaglutide, with nearly identical study populations, where the rate of change of weight loss is clearly greater with tirzepatide. And, in the pipeline, there is orforglipron, an oral small-molecule GLP-1 receptor agonist, which looks promising with a 10% reduction in a 26-week Phase 2 trial.  

Meanwhile, a Phase 2 trial of the long-acting amylin analogue cagrilintide showed a mean weight loss of 15.2% in participants with type 2 diabetes. Finally, retatrutide, a triple agonist of GLP-1, GIP and glucagon (GCG) receptors produces around 10% weight loss in a Phase 2 trial. “So I am very hopeful about the next generation of weight-loss agents,” said Dr Lingvay. “It’s such great news for our patients as there is a great need for these medications.”  

To learn more, enrol on the EASD e-Learning course ‘Obesity and diabetes’.

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

Optimal medical therapy, as recommended in clinical guidelines, is underused in high-risk patients with type 2 diabetes and cardiovascular disease, heart failure and chronic kidney disease. The COORDINATE-Diabetes trial, which aims to close this prescription gap, was discussed by an expert panel at the recent American Diabetes Association’s 83rd Scientific Sessions. Dr Susan Aldridge reports. 

COORDINATE-Diabetes is a randomised trial aiming to improve the care of people with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) who are attending cardiology clinics. Jennifer Green, Professor of Medicine at Duke Clinical Research Institute (the coordinating centre for the trial), set the scene. She noted that rates of many serious diabetes complications fell between 1990 and 2010, thanks to better control of blood pressure, glucose and lipids. However, the number of events has not decreased because there are so many more people with diabetes. “Even if we treat everyone to target, there remains a residual risk because diabetes, cardiovascular disease and kidney disease frequently coexist, and the presence of more than one substantially increases the risk of adverse outcomes,” she said. “This is not fully addressed by traditional risk-reduction strategies.” 

The most recent ADA/EASD guidelines recommend the use of GLP-1 receptor agonists and/or SGLT-2 inhibitors with known cardiovascular benefit for people with type 2 diabetes with ASCVD, heart failure or chronic kidney disease (CKD). The COORDINATE-Diabetes team carried out some background work on 150,000 patients to see how far these guidelines were already being followed and how patients were being cared for in the community. 

They found that 24.7% were on a high-intensity statin, 53.1% on an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and 9.9% were on an SGLT-2 inhibitor or GLP-1 receptor agonist. Only 2.7% were on all three classes of recommended medication, while 37.4% were on none of them. “These medications are substantially underused in clinical practice,” said Professor Green. “These patients had insurance and the statins, ACE inhibitors and ARBs are not new or expensive, and all of these medications have been shown to improve outcomes.” 

She continued that the usual response is to say that there is a problem of access, but she does not believe this is the whole story. Data from Veterans Affairs centres shows that SGLT-2 inhibitors have been widely available there since shortly after the EMPA-REG trial results in 2015. If they can do this, then why is it not happening in the community and how can this be changed to improve outcomes for people with type 2 diabetes and ASCVD? These are the questions that COORDINATE-Diabetes set out to explore. 

Setting up COORDINATE-Diabetes

The objective of COORDINATE-Diabetes was to test the impact of a clinic-level, multifaceted intervention on the prescription of the three key groups of evidence-based therapies (statins, ACE inhibitors/ARBs and SGLT-2 inhibitors/GLP-1 receptor agonists) in people with type 2 diabetes and ASCVD Unlike a conventional clinical trial, the focus was not upon efficacy, but on improving the quality of care that these patients received.

Dr Neha Pagidipati, Director of Duke Cardiometabolic Prevention Clinic, took to the stage to talk about the design and conduct of the trial. “An important part was the multidisciplinary and extremely engaged steering committee, which included diabetologists, primary care physicians, diabetes specialist nurses, pharmacists and cardiologists,” she said. “That was the key component and why the trial has worked so well.”

Forty-three cardiology clinics took part, all working with a local diabetes specialist, with 20 randomised to the intervention and 23 to usual care, following guidelines. The participants had type 2 diabetes and ASCVD, peripheral arterial disease and/or cerebrovascular disease. The primary outcome was prescription of all three key groups of medication during six to 12 months of follow-up. Secondary outcomes were prescription of agents in each medication group and clinical outcomes such as blood pressure, HbA1c and hospitalisation.  

There were three components of the intervention. First, a team consisting of a nurse, cardiologist and endocrinologist visited each site to assess local practices and barriers to prescription of the key medications. Second, various strategies were put in place to encourage an increase in take-up of the medication, including patient and clinician education and development of pathways. And, finally, there was audit and feedback.  

A successful outcome

Dr Christopher Granger of the Duke Clinical Research Institute presented the results of COORDINATE-Diabetes. “There is nothing more important in the health of our patients than to implement what we know is effective,” he said. The barriers to implementation uncovered by the trial were many: patient, provider and system factors, cost, inertia, lack of education, fragmented care and lack of ownership. Exploring these led to opportunities for alignment, leadership and engagement, while behaviour-change strategies included feedback, incentives, education and simple tools such as reminders. 

The proportion receiving all three of the key medications actually improved in both groups to 37.9% in the intervention group and 14.5% in the usual care group. This represents a 23.4% absolute improvement when the researchers were aiming for 10%, said Dr Granger, so it’s a better-than-expected outcome. 

There were also increases in statin, ACE/ARB and SGLT-2/GLP-1 prescriptions in both groups, with greater increases in the intervention group. The biggest shift was in the SGLT-2 inhibitors, with use increasing from 10.9% to 34.8% in the intervention group. There were no significant improvements in blood pressure, lipids or HbA1c, but that was not the intention of the study. “More importantly, we did see a tendency for improvement in clinical outcomes, including all-cause mortality or hospitalisation for myocardial infarction, stroke, decompensated heart failure or urgent revascularisation,” said Dr Granger. “This was a 21% risk reduction, which was non-significant but nonetheless in the range of what we’d expect, given the change in medication.” 

He added that while the trial was not resource-intensive, it did need a ‘champion’ to ensure its success. The next step is to scale it up. He concluded: “As Bill Gates has said, ‘Humanity’s greatest advances lie not in its discoveries, but in how those discoveries are applied’ and we think that this project has provided some meaningful information on how we might be able to do that.” 

The endocrinologist’s point of view

Ildiko Lingvay, Professor of Medicine and Endocrinology at the University of Texas Southwestern Medical Center, noted that the prescription gap is also very high for patients seen in endocrinology and primary care. She carried out a study of 11,000 people with type 2 diabetes and ASCVD, heart failure or CKD and looked at the proportion receiving prescriptions for SGLT-2 inhibitors or GLP-1 receptor agonists. For primary care, endocrinology, cardiology and nephrology, the figures were 20.1%, 24.8%, 20.3% and 18.3%, respectively. “So there is a 75% gap in how we, as endocrinologists, should be treating our patients,” she said. 

However, the COORDINATE intervention can be applied to any specialty, particularly with the three-pronged approach targeting the patient, provider and system, where everyone involved is responsible for ensuring that best-care practices are followed. She strongly recommends team-based care where, if another specialist initiates the treatment, other specialties should help with titration, side-effects and encouraging others to initiate them. “The results of COORDINATE-Diabetes are absolutely fantastic, but we have a long way to go,” she said. “Our role is to make sure the uptake goes to 100%. Why care about COORDINATE-Diabetes? Because we all want our patients to get the right treatment for the best outcomes.” 

Spreading the word

COORDINATE-Diabetes shines a light on the goals of care in cardiometabolic disease – prolong life, keep the patient out of hospital and improve their quality of life. “Absolutely, we have the tools to achieve this and we have never had more tools,” said Dr Mikhail Kosiborod, Executive Director of the Cardiometabolic Center Alliance (CMCA) at St Luke’s Mid America Heart Institute, who was chairing the panel. “Do the guidelines tell us what we should be doing? Yes. Every major professional society, including the ADA, has undergone substantial revisions and have all given the highest level of recommendations to these treatments.” Yet, at least according to a study of 5000 patients in the US from 2016 to 2018, less than 7% are actually receiving optimal medical therapy.  

Cost and access are issues, of course, but studies show that making medicines cheap or even free only leads to a modest increase in adherence. There are numerous other barriers, including a lack of effective clinical care models with poor communications, inadequate patient support, lack of accountability, education gaps and misaligned incentives. “We now have proof of concept on what happens if you address these issues,” said Dr Kosiborod. “Addressing systemic barriers can improve prescription rates and address clinical inertia.”

COORDINATE-Diabetes was a good start but not a ‘silver bullet’ – 62% in the intervention group were still not on optimal therapy. However, there are many other initiatives underway on team-based comprehensive care. For instance, the CMCA has some new data on a type 2 diabetes/ASCVD ‘bundle’, consisting of optimal, guideline-directed medical therapy, which shows an increase in the proportion of patients receiving it from 28.2% to 67.1% in a six-month period. Similar data apply to patients with type 2 diabetes and CKD.

“The questions that remain are: is this sustainable, is it scalable to more and more centres around the country and will it have a lasting impact on care transformation?” said Dr Kosiborod. To address these questions needs changes in the system and among stakeholders, such as the pharmaceutical industry, patient and professional organisations.

He took inspiration from one example where rapid care transformation was actually achieved in the US. The D2B (door-to-balloon) Alliance dramatically reduced the waiting time for interventional radiology after myocardial infarction in five years.   

So, in conclusion, cardiometabolic disease is a huge public health threat. Many tools exist to treat it and there has been a fundamental shift in management when it comes to optimising medical therapy. However, these disease-modifying therapies are underused in high-risk patients. A shift in focus to comprehensive risk reduction is needed, as set out in clinical guidelines, but implementation has been slow. “COORDINATE-Diabetes and the CMCA signal the start of care transformation,” said Dr Kosiborod, “and I certainly hope that we will see transformation in my lifetime like the one we have seen for myocardial infarction.”

For more information, go to

To learn more, enrol on the EASD e-Learning course ‘GLP-1 receptor agonists’.

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

The impact on calorie intake of portion size, energy density and plant-based and ultra-processed foods was discussed at the American Diabetes Association’s 83rd Scientific Sessions held in San Diego recently. Recent research findings on eating behaviour could help tackle the mounting challenge of obesity more successfully. Dr Susan Aldridge reports. 

Eating behaviour is complex and food intake is affected by several factors, including energy density, portion size and variety, which are relatively well researched. Palatability, macronutrient content, processing and food form also influence food intake, but less is known about these factors. Dr Barbara Rolls of Penn State University said: “Research shows that intake of almost all foods, even fruit and vegetables, is affected by how much is served. People tend to assume that if they overeat in one meal, they will compensate by eating less at another.” This is not so, according to a study she was involved with, where adult participants accumulated an extra 4,000 to 5,000 calories during an 11-day exposure to a diet where food portions were increased by 50%. This lack of a compensatory response was also found in research on young children, previously believed to have an innate ability to self-regulate their food intake.

Behavioural strategies are therefore needed to help people address the issue of portion size for managing food intake. For instance, they can simply be encouraged to eat less, be advised on what specific foods to downsize or consume pre-portioned foods to reduce exposure to large servings. When these three approaches were tested in a clinical trial, those in the pre-portioned group did significantly better than those in the other two groups, maybe because they didn’t have to ‘learn’ anything. Then there was the usual weight-loss plateau and all three ended up losing around 6% of their body weight. 

Focus on energy density

Dr Rolls noted that there was a lot of action on portion size – political activity and initiatives around providing information, including labelling and MyPlate (a nutrition guide published by the United States Department of Agriculture that guides people on how much to eat of each food group) tools. “We need to modify environmental cues, give more choice on portion size and provide ‘to-go’ containers at the start of a meal, which has shown some success,” she said. “But if we could reduce the energy density of the foods people were eating, we wouldn’t have to worry so much about portion size.”

Fat and sugar reduction can, of course, reduce the energy density of food. So, too, can adding water, an approach that is only now coming to the fore. Dr Rolls illustrated this with two trays of food, matched for calories and macronutrient composition, but with the energy density of one reduced by increasing the proportion of water-rich vegetables. “Here’s the surprise – but one which has been replicated in many labs – people tend to eat similar volumes of foods, so if the energy density is less, they will be eating fewer calories spontaneously, and there is no sign of a compensatory response.”

A clinical trial has shown that this approach led to significant weight loss and Dr Rolls’ team also did a secondary data analysis on the PREMIER trial, which compared the DASH (Dietary Approach to Stop Hypertension) diet with advice/counselling following national guidelines on hypertension control. This analysis revealed that energy density was the key factor in weight loss. In another study in children, lower and higher energy diets and a control diet were compared. Those provided with the higher energy density foods ate more and those with lower energy density ate less. 

To show how powerful these effects are, Dr Rolls cited a study on how energy density and portion sizes affected the intake of popular foods, such as chicken, macaroni cheese and apple sauce, in preschool children. The study had a three by two design, with three portion sizes – 100%, 150% and 200% – and higher and lower energy densities – 100% and 142%. These combinations varied in calorie content from 455 to 1290 kcals and the meals all looked similar. The results showed that portion size and energy density combine to affect intake. This meant that between the smallest lower energy density meal and the largest higher energy density meals, there was a 79% higher accumulated calorie intake. “So energy density and portion intake act independently, and can combine and have very powerful effects,” said Dr Rolls. “Eating behaviour is complex and we’ve shown that individual factors can affect intake.” 

Strategies for reducing food intake according to energy density include increasing portions of palatable vegetables and fruit and lower energy-dense foods. Portion sizes of energy-dense foods can also be controlled with strategic use of the MyPlate tool. “We’ve done studies to show this works and it’s very effective to show people how much they can still eat if they lower the energy density of their diet,” Dr Rolls concluded.  

Animal or plant?

Plant-based diets have gained in popularity in recent years, but do they help people lose weight? Christopher Gardner, Rehnborg Farquhar Professor of Medicine at Stanford University, did a quick comparison. Animal foods have more protein and are more energy dense, while plant foods have more carbohydrate and more water. When it comes to nutrients, animal foods contain more calcium, zinc and iron, but plants have more fibre, unsaturated fat and antioxidants. 

On the down side, animal foods have more saturated fats and cholesterol, while plants are the source of added sugars and refined grains. Finally, when it comes to healthy foods, there are fish and yogurt in the animal domain; broccoli and chickpeas in the plant domain. And, on the unhealthy side, breaded chicken and processed red meat, and sodas and pastries. 

Translating this into clinical trials, Professor Gardner cited work at Harvard on healthier and less healthy plant-based diets, which showed that the healthier version is associated with less diabetes. There is also work with the Zoe group in the UK, revealing the striking microbiome differences between healthy and unhealthy animal and plant-based diets.

Plant-based diets

Professor Gardner was lead investigator in the SWAP MEAT (Study With Appetising Plant food Meat Eating Alternative Trial), which was the first significant study of plant-based meat products. In this 16-week crossover trial, 36 adults ate two servings per day of a Beyond Meat (a plant-based meat alternative) product or an organic meat product. As far as nutrients are concerned, the two were very similar. Those on the plant-based meats lost a small but significant amount of weight and lowered their LDL-cholesterol. 

Professor Gardner has also been involved in a comparison study of the impact  on HbA1c of a low-carb, ketogenic diet versus Mediterranean diet. On the keto diet, to get to the required 5% carbohydrate, you need to get rid of fruits, legumes (including beans) and whole grains, which can all be kept in the Mediterranean diet. Both diets avoid added sugars and refined grains, and include non-starchy vegetables – namely, those grown above ground. The central question in the trial was, after eliminating added sugars and refined grains, are there additional benefits to eliminating legumes, fruits and whole grains? 

This was a crossover trial with 20 participants in each arm with prediabetes and diabetes. “Both lowered their HbA1c but there was no difference between them,” said Professor Gardner. “They did it by getting rid of the added sugars.” Other measures, such as lipids, glucose and weight, also improved. However, LDL-cholesterol was worse on the keto diet, which is quite commonly seen because of its high fat content. 

In conclusion, does it matter whether you go for an animal or plant-based diet? On the basis of research so far, Professor Gardner recommends the best of both. “Choose a whole-food, plant-based Mediterranean diet, eliminate added sugar and refined grains, and add yogurt, fish and eggs.”

The challenge of ultra-processed foods

The NOVA classification groups all foods according to their degree of processing – namely unprocessed or minimally processed; processed culinary ingredients, such as sugar or butter; processed food and ultra-processed foods. This last group consists of combinations of ingredients, including either original or chemically modified foods from the fractioning of original foods and various additives. These combinations are designed to be palatable – or even ultra-palatable – convenient and low cost. Therefore, they are ubiquitous and widely consumed, but what is their impact on people’s health? 

“There is a link between consumption of ultra-processed foods, regardless of nutrient content, and obesity, type 2 diabetes, cancer and all-cause mortality,” said Dr Kevin Hall, a researcher at the National Institute of Diabetes and Digestive and Kidney Diseases. These foods are high in fat, sugar and salt and low in fibre, which is what drives people to overeat them. A National Institutes of Health study prepared nutrient-identical, ultra-processed and unprocessed versions of a diet and used them in a two-week crossover study, where leftovers were analysed to see how many calories were consumed of each version. “To feel satisfied, participants needed to eat 500 calories more on the ultra-processed version, which suggests that ultra-processed diets lead to increased intake,” said Dr Hall. Moreover, those on the unprocessed diet lost weight, while those on the ultra-processed version gained both weight and fat. 

However, there was individual variability in how much more those on the ultra-processed version actually ate and those who ate more calories, unsurprisingly, gained more weight. But some people ate the same number of calories on both diets, so they were not susceptible to whatever it is about the ultra-processed diet that is so appealing. 

Digging deeper, more fat and carbohydrate were being consumed in the ultra-processed diet and this was done by eating more calories in the main meals, but not in the snacks. “This is surprising because it’s usually the snacks that we think of as driving overeating,” said Dr Hall. “Everyone has an opinion about what is causing overconsumption of ultra-processed foods. We now need to do a study where we start to take apart these hypotheses.”  

He reviewed various hypotheses. First, maybe people just like ultra-processed meals more. However, in the study above, there were no differences in pleasantness of familiarity. Second, the ultra-processed foods were eaten more quickly, which might lead to eating more calories. Finally, when beverages – added to balance the fibre content of the two meal versions – were taken out of the analysis, the ultra-processed version had much higher energy density, which made the eating rate more complicated because people were then eating more slowly, but were also consuming more calories per minute.  

Further studies, however, suggest that energy density may be only part of the hypothesis around the appeal of ultra-processed foods. Hyper-palatability may also play a part. This is defined as the presence of certain proportions of fat, simple sugars and salt in ultra-processed foods, which drive over-consumption.

Analysis of foods in the ultra-processed versus unprocessed diet trial, described above, showed that 70% of the calories from the former actually fell into the hyper-palatability category. A new study is therefore underway involving four test diets, differing in hyper-palatability and energy density, to tease out the impact of these factors on energy intake. “We don’t know the answer yet, so stay tuned,” Dr Hall concluded.  

To learn more, enrol on the EASD e-Learning course ‘Lifestyle intervention’.

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

Chronic kidney disease (CKD) and heart failure in type 2 diabetes were under discussion at the recent Primary Care Diabetes Europe conference. Screening and implementing the latest research need to be prioritised in primary care to improve the prognosis for those living with cardiorenal complications. Dr Susan Aldridge reports.

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function that are present for three months or more and, in diabetes, is characterised by a urine albumin-creatinine ratio (UACR) of ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR) of ≤ 60 ml/min/1.73 m2. Professor Per-Henrik Groop from the Department of Nephrology at Helsinki University Hospital said: “Kidney disease is so important. It’s so common and the consequences are grim. Convey this to all your friends and colleagues because GPs are the ones that should take care of this. If a patient has to see me, it’s too late, for I’m a nephrologist – and nephrologists are interested in dialysis and transplantation.” 

Prevalence, consequences and management of CKD

In a study in which 27,000 people with type 2 diabetes worldwide were screened at random, at least half of them had CKD. “So it’s extremely important to screen for the presence of CKD,” said ProfessorGroop. “The majority of people you see in the clinic are microalbuminuric and these can be handled very nicely by GPs, but stages 3, 4 and 5 of CKD will have to involve the nephrologist.”

Screening rates around the world vary and are less than optimal everywhere. And the consequences of not detecting CKD early are grim, according to Professor Groop. These include increased risk of premature death, end-stage kidney disease (ESKD), cardiovascular events and hospitalisation for heart failure. For instance, years of life lost for diabetes alone, diabetes plus cardiovascular disease, and diabetes, cardiovascular disease and CKD are six, 12 and 16 years, respectively.  

Professor Groop reiterated the ‘Five-Finger Rule’ for managing CKD. The five components are: optimise blood glucose, use an ACE inhibitor or angiotensin receptor blocker (ARB), control blood pressure, manage lipids and stop smoking. Research shows that achieving these multiple treatment targets is associated with a lower risk of death and end-stage kidney disease (ESKD) than achieving three or fewer. “This standard of care does work, but one of the problems is that we don’t always provide the optimal standard of care,” he said. So, for example, one study shows that 42% of people in the USA with CKD do not receive the standard of care – many still do not receive ACE inhibitors or ARBs, despite these drugs being introduced in the 1980s, and only a minority are receiving more recent therapies, such as SGLT-2 inhibitors.   

Clinical trials

Recent clinical trials have shown the value of SGLT-2 inhibitors in CKD. For example, the EMPA-REG cardiovascular outcomes trial showed a 39% reduction in composite kidney outcomes and a slowing of the natural decline in eGFR with empagliflozin. There have also been dedicated kidney trials, such as CREDENCE, which involved patients with albuminuria and had a primary composite end point of ESKD, doubling of serum creatinine, kidney or cardiovascular death. The findings of a 30% reduction in this endpoint were “absolutely wonderful,” according to Professor Groop. 

Meanwhile, DAPA-CKD involved patients who did not have type 2 diabetes. Then there was EMPA-KIDNEY, with 6609 participants of whom 54% did not have diabetes, 27% had cardiovascular disease and 35% had an eGFR of less than 30. In this trial, empagliflozin led to a 28% reduction in the primary endpoint of kidney-disease progression or cardiovascular death. With these kind of results, Professor Groop noted that dialysis could be postponed by as much as 10 years with an SGLT-2 inhibitor. 

Then there is finerenone, a non-steroidal mineralocorticoid receptor antagonist, which can offer extra protection to the kidney. FIDELITY is a large, pooled, pre-specified data analysis of the FIDELIO-DKD and FIGARO-DKD trials on finerenone involving 13,171 participants, which includes patients with microalbuminuria and those with relatively preserved kidney function. “These are like the majority of people you have in your clinic,” noted Professor Groop. “This is why I say primary care physicians are the ones that should pick up these patients and start to treat them.” FIDELITY showed that finerenone, compared with placebo, reduced cardiovascular and renal outcomes in patients with type 2 diabetes and all stages of kidney disease.  

The final message on CKD

It is imperative to screen for the presence of CKD. The SGLT-2 inhibitors and finerenone are effective tools for improving the prognosis of patients with type 2 diabetes and CKD on top of the standard of care because they reduce the risk of adverse cardiac and kidney outcomes. And the GLP-1 receptor agonists reduce albuminuria, while providing cardioprotection. “My humble wish to all of you is – screen, screen, screen, implement, implement, implement,” he concluded. “As Anton Chekhov said, ‘knowledge is of no value unless you put it into practice’.” 

Diabetes and the heart

Heart failure has reached pandemic proportions and is now affecting 64 million people around the world. This number is likely to increase as the population ages and rates of type 2 diabetes increase. Heart failure is a leading complication of type 2 diabetes, where it is more common than either myocardial infarction or stroke. 

Francesco Cosentino, Professor of Cardiology at the Karolinska Institute, spoke about the concept of the cardiovascular continuum, a chain of events that starts with diabetes and other risk factors such as hypertension and obesity, and progresses ultimately to ESKD, heart failure and cardiovascular death. “This concept is clinically very relevant because interruption anywhere can provide cardiorenal protection,” he said. “A major paradigm shift has taken place in the management of cardiovascular risk in type 2 diabetes because of the increase in the evidence base for new treatments.”  

For example, following findings on SGLT-2 inhibitors from cardiovascular outcome trials, these are now recommended to patients with cardiovascular risk and type 2 diabetes. “Looking at the hospitalisation for heart failure outcomes in the cardiovascular outcome trials, the intervention and placebo curves diverge very early on,” he noted. “These are stunning results.” A meta-analysis also came up with very consistent findings of a reduction of around 32% in time to hospitalisation for heart failure (HHF) with SGLT-2 inhibitors. 

The results of recent and upcoming heart failure trials are likely to move the treatment landscape on even further, added Professor Cosentino. These include DAPA-HF, which shows a relative risk reduction of 26% in cardiovascular death and HHF with dapagliflozin in nearly 5000 patients with heart failure with reduced ejection fraction (HFrEF), an effect independent of diabetes status – and there were similar findings in the EMPEROR-Reduced trial. Then there is the SOLOIST-WHF trial, which has shown that sotagliflozin reduces cardiovascular death and HHF compared with placebo in people with type 2 diabetes and worsening heart failure.  

Heart failure with preserved ejection fraction

Until recently, there was little clinical trial evidence for the management of heart failure with preserved ejection fraction (HFpEF), so this was basically diuretics and management of comorbidities. Then the EMPEROR-Preserved trial showed a 21% reduction in the composite endpoint of cardiovascular death and HHF with empagliflozin and there were comparable results for dapagliflozin in the DELIVER trial. “So we can now say ‘one size fits all’ across the spectrum of left ventricular ejection fraction,” said Professor Cosentino. 

Analysis of the data across EMPEROR, DELIVER, DAPA-HF and SOLOIST-WHF, covering 22,000 patients, shows combined cardiovascular death/HHF down by 23%. “The data points to a consistent signal of efficacy with SGLT-2 inhibitors,” said Professor Cosentino. “So basically we have been witnessing an evolving role of SGLT-2 inhibitors in cardiorenal protection.” 

The results support European Society of Cardiology guidelines to prioritise the use of SGLT-2 inhibitors, independent of blood-glucose control considerations, in patients with or at high risk of cardiovascular and renal complications. “There has been a shift in trials to a cardiorenal focus and adequate management of this type of patient is only possible by building bridges aimed at improving collaboration between cardiology, diabetology, primary care and patients,” Professor Cosentino concluded.  

To learn more about these areas, enrol on the EASD e-Learning courses ‘Diabetes and the kidney’ and ‘Cardiovascular health and diabetes’.

To hear more from Professor Groop, listen to ‘The Briefing Room’ in which five leading experts discuss cardiorenal metabolic challenges in type 2 diabetes.

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

David Matthews, Professor Emeritus in Diabetic Medicine at the University of Oxford, gave the Paul Cromme Award Lecture at the recent Primary Care Diabetes Europe (PCDE) conference in Barcelona. Professor Matthews took this opportunity to explore a new way of looking at the challenge posed by the growing pandemic of type 2 diabetes. Dr Susan Aldridge reports. 

Professor Matthews opened by reflecting upon the Black Death, which swept through Europe between 1346 and 1353 and became the world’s greatest ever demographic disaster – until COVID-19 came along. With his daughter Philippa, a professor of infectious diseases at Oxford, he wrote a paper back in 2011 with the provocative title ‘Type 2 diabetes as an infectious disease: is this the Black Death of the 21st century?’. “We looked at the fact that we are currently facing a global epidemic of obesity and diabetes,” he said. “In some settings, prevalence is up to 50% and half of those affected will die of complications.”

Professor Matthews’ theme is that there are significant resonances and comparisons between type 2 diabetes and infectious diseases. COVID-19 has undoubtedly been a huge catastrophe – with 80 million infections in 2020 alone – that transformed society with schools and industries closed down, society in lockdown, and daily messaging on mask wearing and social distancing. Meanwhile, the International Diabetes Federation report revealed that prevalence of type 2 diabetes was 537 million in 2021, which is 6.5 times more than the number with COVID-19 the year before. 

“So why did COVID-19 cause massive societal change, but diabetes has not?” asked Professor Matthews. Maybe because COVID-19 was all about headlines, while diabetes is more about trends, which we tend to ignore. In the UK, the trend means that between now and 2030 the number of people with diabetes will go up by one million – a 25% increase.  

What type 2 diabetes, a non-communicable disease, and COVID-19, a communicable disease, have in common is that both are demographic, economic and personal catastrophes. COVID-19 spreads like an epidemic and so does type 2 diabetes, the difference being that COVID-19 can spread in days, while diabetes takes decades and this slow spread tends to get ignored. COVID-19 can kill in a matter of days while diabetes will take 10 years or more. “So you discount the diabetes because it’s in the future,” Professor Matthews said. In 2020/2021, there were 2.5 million COVID-19 deaths, but 6.7 million dying from diabetes.   

Is type 2 diabetes infectious?

For COVID-19, there was a clear pathogen involved and Professor Matthews believes this is also the case for type 2 diabetes – it’s not an infectious agent, that we know of, but rather the toxic environment we live in. “We can think of type 2 diabetes as an infectious plague of the 21st century,” he said.  

People traditionally think of epidemics as involving communicable disease. In 1990, half the deaths and disability in the world were due to communicable disease, but two-thirds of health problems today are related to chronic diseases, also known as non-communicable diseases, and infectious disease is no longer a dominant cause of death in developing countries. So the term epidemic can be applied to communicable and non-communicable diseases.

How does the way COVID-19 was dealt with compare with how we address type 2 diabetes? With COVID-19, the first steps were data collection and assembly of emergency teams. Primary prevention measures were then set up and treatments identified, while the basics of transmission were established with ways of breaking the infectious cycle, including immunisation.  

Now, looking at type 2 diabetes in comparison, data is collected of course, but this is very diffusely spread across countries. There is some primary prevention work and, when it comes to identification of possible therapies, we do know how to treat type 2 diabetes. “So we wait for it to happen and then start to treat it, instead of preventing it,” said Professor Matthews. “It’s all brilliant science, but it’s treating something that’s already happened.” 

In type 2 diabetes, we still haven’t established the basics about what’s going on, especially with insulin resistance. Nor is there real action on breaking the cycle of ‘infection’ or immunising against the toxic environment. 

“What is the causative agent in obesity/type 2 diabetes, if it is an infectious-type disease?” asked Professor Matthews. “Type 2 diabetes is related to the obesogenic environment that surrounds us. It is transmissible by the society that you and I, government and industry – especially the food industry – construct. It’s not related to any moral failings, it’s about a toxic environment where it is hard to make healthy choices.” 

As a simple example, Professor Matthews asked delegates to raise their hands if they’d eaten more breakfast in the conference hotel than they normally would. Several did. It was beautifully laid out, but it still represented a toxic environment because if you expose people to multiple choices then they will consume more, as has been proved in animal experiments. “Stimulus is everywhere and size is everything,” he said. “This is the way society is changing and infecting you, for industry upsizes and supersizes and makes profits from that.”   

Focus on fast food

Obesity is now a pandemic and the causes are obvious. “Government, scientists, health workers and individuals use excuses as to why no action is needed,” Professor Matthews said. “For instance, government says that food is the responsibility of the individual. That is nonsense and we have to call it out.”

Meanwhile, some scientists say that obesity is genetic. There may be some truth in this but what has been going on in our population over the last five years or so cannot be explained by genetic change. People living in poverty will say, ‘the best value meal I can find is fast food’. “I’m afraid that’s completely true,” said Professor Matthews. “So we’ve got a society that is obesogenic where poverty is forcing you to be overweight and that’s a political problem.” 

We are changing what we eat, with an accelerating trend towards a diet high in saturated fat, sugar and refined foods, but low in fibre. And average food consumption per person is due to go up from 2680 calories in 1997-1999 to nearly 3000 calories in 2030. Eating habits are changing too. Eating together as a family is less common, while snacking on the go is on the increase. Portion sizes are up too and more food is eaten outside the home or in the form of ready-meals.  

Intervention is key

Stepping back into history again, Professor Matthews recalled how, in 1854, John Snow removed the handle from the Broad Street pump and stopped a serious outbreak of cholera. “He intervened and that’s what we need to do,” he said. “The Diabetes Prevention Program shows that lifestyle intervention gives you delay and prevention, but at a cost of €11,000 per case of diabetes prevented because this was a medical model involving dietitians and encouragement delivered by healthcare professionals. This cannot be translated to the community. We need societal interventions.”

He cited Community Interventions for Health (CIH), a large, comprehensive multinational study for community interventions – its goal was to create sustainable interventions that prevent and control leading chronic diseases by addressing risk factors. The CIH study has collected data on smoking, physical activity, diet, biometric data and environmental scans, and developed interventions in schools, workplaces, neighbourhoods and health centres. 

These ran for two years with follow-up, involved over 12,000 people and looked at knowledge, attitudes, behaviours and locus of change. Professor Matthews showed many examples of the CIH study’s work, such as healthy meals in workplace canteens, outdoor gyms and even one that could be applied in the PCDE conference venue – namely, ‘decision prompts’ to take the stairs. “If you want a quiet time here, sit on the stairs,” he noted. “No one is going up and down them.”

As mentioned earlier, governments fear interventions might make it look as if they are telling people what to eat, but there are other approaches that could be adopted, such as taxing certain foods or making food labels more prominent by putting them on the front of packets, instead of in small print on the back. Calorie labelling on menus, once fiercely opposed by restaurants but now adopted in some places, could save thousands of lives and billions in healthcare expenditure.  

The CIH study has shown that effective interventions must be culturally sensitive, context specific and involve partnerships between local stakeholders and communities. Their success depends on a range of factors, including sustained commitment, stakeholder engagement and a tailored approach.

Besides taking these learnings on board, Professor Matthews urged delegates to also get involved with the European Diabetes Forum, the World Health Organisation and the Global Alliance against Chronic Disease. Health education, social marketing, community mobilisation and structural change are all needed to engineer societal change at the level of the individual, family, community and society.

As Michelle Obama put it, ‘We, as parents, are our children’s first and best role models and this is particularly true when it comes to their health. We can’t just lie around on the couch eating French fries and candy bars and expect our kids to eat carrot sticks and run around the block’. Healthcare professionals can set an example too. “So do use the stairs and not the lift here,” Professor Matthews urged delegates.  

Non-communicable diseases, including diabetes, kill 36 million people a year, nine million of them before age of 60 when they are in the prime of life as breadwinners. “But we can prevent this, as we know the problems are tobacco, alcohol, unhealthy diet and inactive lifestyle solutions,” said Professor Matthews. “And we can afford it. From just $1 per person per year, even poor countries can turn the tide. It’s a global issue requiring a global response from government, the United Nations, civil society and the private sector, with all countries committing to high level political action to reduce exposure to risk factors, strengthen health systems, improve access to care, set targets and measure results.” 

In conclusion, we can learn from COVID-19 by treating type 2 diabetes as a transmissible disease. “Let’s not have our grandchildren say, ‘between 1980 and 2035, a huge plague of diabetes wrought havoc throughout the world. It was understood, but not prevented. It was the greatest ever demographic disaster’,” concluded Professor Matthews. “We must all play our part in making sure this doesn’t happen.” 

To learn more about promoting lasting behaviour change, enrol on the EASD e-Learning course ‘Lifestyle intervention’.

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

Type 2 diabetes is increasingly being diagnosed among people under the age of 40. Early-onset diabetes is associated with an increased risk of complications and requires more intensive intervention, according to Professor Melanie Davies, speaking at the recent Primary Care Diabetes Europe Conference in Barcelona. Dr Susan Aldridge reports.

Professor Davies, Consultant Diabetologist at University Hospitals, Leicester, noted that early-onset type 2 diabetes is being described in different ways. In Leicester, their youngest type 2 diabetes patient is only eight years old, but early-onset may also refer to type 2 diabetes in those aged 18 to 25, or diagnosed in someone under the age of 40. “However early-onset type 2 diabetes is described, we know that it represents a different phenotype from later-onset type 2 diabetes,” she said. “If diagnosed under the age of 40, type 2 diabetes has worse outcomes.” 

She referred to a ‘fairly typical’ case study, who has obesity, hypertension, polycystic ovary syndrome (PCOS) and acanthosis nigricans. “This is the scary reality for people living with early-onset type 2 diabetes,” she said. “Obesity is almost always a comorbidity. Around half present with hypertension, one in four have PCOS and half have acanthosis nigricans.” 

Early-onset type 2 diabetes is now on the increase in most regions of the world, bringing a worrying burden of complications and premature mortality. A recent paper based on data from the Swedish Diabetes Registry shows that younger age at diagnosis of type 2 diabetes worsens outcomes for cardiovascular disease, including acute myocardial infarction and heart failure, and for chronic kidney disease. “So age at diagnosis is prognostically important for survival and cardiovascular risk,” said Professor Davies. “This has implications for the timing and intensity of interventions. We need to approach this group differently and more proactively.” 

The TODAY study

In 2004, The National Institute of Diabetes and Digestive and Kidney Diseases in the US set up a study to find the best way of treating early-onset type 2 diabetes, with an initial 699 participants aged between 10 and 17 years. The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study compared metformin, metformin plus rosiglitazone and metformin plus intensive lifestyle intervention. This showed that metformin therapy is inadequate, beta cell decline is rapid and response to intensive lifestyle interventions is minimal in this group. “Although there is some fantastic data here, it is also really very sad when you look at the incidence of complications in this study,” said Professor Davies. 

TODAY showed that some young people already have complications at baseline and these were set to get worse over time. The second phase of the TODAY study was published in 2021 and involved 500 participants diagnosed with early-onset type 2 diabetes at a mean age of 13 and followed up for 13 years, by which time two-thirds had hypertension, over half had dyslipidaemia and over half had diabetic kidney disease. Meanwhile, 32% had neuropathy and 51% had retinopathy, which had increased from 13% in 2011. In summary, by the age of 26, 50% of this population had one complication and 28.4% had at least two.   

The study also showed that young women with type 2 diabetes had 260 pregnancies. Only 13.5% were using contraception and 65% experienced pregnancy complications. One-quarter of the pregnancies was lost pre-term, and there was a very high incidence of small or large offspring. So the TODAY findings so far show that this cohort with early-onset type 2 diabetes has a very high risk for poor outcomes overall.  

A different approach

Professor Davies and colleagues have been doing their own research on early-onset type 2 diabetes in Leicester. For example, they have just published some data on depression in this population. “Those diagnosed around age 20 have a high level of depression and diabetes distress, and less self-compassion,” said Professor Davies. “Self-compassion is a good predictor of outcomes, so we need to get better at boosting self-compassion.” 

Their research showed that heart function was already impaired in people with early-onset type 2 diabetes, independent of obesity. The team has also carried out a study among people in their early 40s, offering either routine care, a DiRECT-type low-calorie diet or supervised exercise training. The exercise arm, but not the diet arm, showed an improvement in diastolic dysfunction. “So we are now doing an ongoing study,” said Professor Davies. “These people are asymptomatic, but may already have markers of early diastolic dysfunction. We need to be thinking about early interventions to address that.”

However, when it comes to choosing interventions, there is an issue with the evidence base. People in the younger age groups account for less than 5% of participants in diabetes clinical trials. In cardiorenal trials, the proportion drops to 0.97% and is not much higher in trials of lifestyle interventions and self-management. “This means that much of the evidence we base our practice on is not from people in these younger age groups,” noted Professor Davies.  

She recalled speaking about early-onset type 2 diabetes back in 2013 and observing that this group is ‘under-screened, under-supported and under-treated’. “I am not sure that things have really moved on since 2013,” she said. In the UK, recent audit data showed that take-up of care processes and the evidence base around early-onset type 2 is still poor. “The traditional outpatient clinic approach is not appropriate,” she continued. “We need to engage more around activity, psychological support and community. We also need to look at the way we build cities and work in schools.” 

To this end, Professor Davies’ team has a programme grant now in its second year, which involves the design of a new approach in Leicester, with multi-site interventional development to address multimorbidity in early-onset type 2 diabetes. “I think we really need to grasp this challenge of early-onset type 2 diabetes,” she concluded. “It is continuing to increase and those affected have a higher burden of complications and worse outcomes.” 

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