A new review in Diabetologia argues that type 2 diabetes in Black Africans differs in some important respects from that found in European populations – findings deserving of further investigation, given that type 2 diabetes rates are set to soar in sub-Saharan Africa in the not-too-distant future. Dr Susan Aldridge reports.

While the prevalence of type 2 diabetes is the world’s lowest in the sub-Saharan Africa (SSA) region, this does vary by country, with the highest numbers in the more affluent countries. The region is also projected to have the greatest rate of increase in type 2 diabetes – 129% by 2045 – compared with other International Diabetes Federation (IDF) regions. This will place additional strain on the region’s already overburdened healthcare systems.

As well as the projected increase in type 2 diabetes and other non-communicable diseases, SSA still struggles with poverty-related health problems, including a huge burden of infectious disease. It is also undergoing rapid rates of urbanisation. These socioeconomic, environmental and lifestyle factors may interact with genetic factors to influence the pathophysiology leading to type 2 diabetes in SSA populations. 

However, much of what we already know about type 2 diabetes comes from studies involving people of White European ancestry. Accordingly, Julia Goedecke and Amy Mendham, for the South African Medical Research Council, have reviewed the current knowledge base underlying the type 2 diabetes risk among Black African populations in SSA, in order to help address current and future challenges in this area. The review highlights similarities and differences between SSA and diasporic Black African populations and seeks out the factors influencing the pathogenesis of type 2 diabetes in SSA, such as social determinants, infectious disease and genetics. 

How type 2 in sub-Saharan Africa may be different

The pathophysiology of type 2 diabetes is still not completely understood. The conventional view is that the process starts with insulin resistance, resulting in compensatory hyperinsulinaemia, eventually leading to beta cell exhaustion, setting the scene for type 2 diabetes. However, an alternative view is that hyperinsulinaemia is the first event, signalled by either oversecretion of insulin from the beta cells and/or reduced hepatic insulin clearance. 

Studies from both SSA and the diaspora suggest that the latter scenario may be more applicable to both populations, for they tend to present with hyperinsulinaemia, rather than insulin resistance. This phenotype has been found in indigenous and diasporic Black African adults and children, independent of adiposity, insulin sensitivity and glucose levels, which suggests that this is a trait that is highly conserved. But it’s not clear whether this hyperinsulinaemia results from exaggerated beta cell function or reduced hepatic insulin clearance. Evidence from West Africa, the UK and the USA suggests reduced hepatic insulin clearance as the main defect leading to type 2 diabetes. This contrasts with recent research, by the authors, in South African women with obesity, which suggests that elevated insulin secretion, rather than low insulin clearance, is behind the presentation with hyperinsulinaemia. 

Based on these and other findings, the authors suggest the following model for type 2 diabetes in SSA. Hyperinsulinaemia, due to a combination of both increased insulin secretion and reduced hepatic insulin clearance, may be the leading factor. This promotes obesity and insulin resistance, leading to more hyperinsulinaemia, then beta cell failure and type 2 diabetes.  

The role of adipose tissue

Distribution of fat differs between Black Africans and their White European counterparts. They have less fat around the middle and more fat around the abdomen and thighs. The authors found this to be linked with some corresponding differences in gene expression that could be significant in the context of type 2 diabetes pathogenesis. 

There is also evidence that Black Africans have lower levels of fat in their liver than White Europeans, consistent with their lower levels of visceral fat. But, with increasing age and adiposity, Black African women do tend to accumulate visceral fat rather than abdominal and thigh fat, and this predicts type 2 diabetes in later life. This raises the question of whether Black Africans might be more sensitive to visceral fat than their White European counterparts. A recent study in Ghanaians suggests that fatty liver increases with increasing urbanisation and this is linked to prevalent type 2 diabetes, supporting the above hypothesis. Clearly the issue of fat deposition in this population and its links to type 2 diabetes is worthy of further research.

Sex differences

There are similar prevalences of type 2 diabetes in SSA men and women, despite significant differences in obesity rates – 41% for women against 11% for men. The authors argue here that Black African men are at greater risk of type 2 than Black African women for several reasons. After adjusting for differences in body fat, men have lower insulin sensitivity, insulin secretion and beta cell function than women. They also have more visceral fat and less abdominal and thigh fat and have a stronger relationship between total and central adiposity and type 2 diabetes than women do. While these disparities may be driven by sex hormones, there have been no studies to support this. 

Recent research by the authors on exercise and diet in this population suggests that moderate-to-vigorous physical activity in men and light physical activity in women were both associated with reduced type 2 diabetes risk. The association of an animal-driven nutrient pattern with body mass index (BMI) was greater among men than women, while the plant-driven pattern, with a higher intake of refined carbohydrates, was associated with increases in abdominal fat in women, but not in men. Further studies are now needed to illuminate these sex differences in type 2 diabetes.  

Lifestyle interventions

We know that lifestyle interventions involving diet and exercise do help in the management of type 2 diabetes, but most studies have been done in White Europeans, with some limited evidence on the diaspora and just one study (by the authors) in SSA. These revealed that African Americans find it harder to lose weight than their White American counterparts. The authors’ study was a randomised controlled trial involving a 12-week aerobic and resistance exercise programme in young black South African women with obesity. Although this found an improvement in insulin sensitivity, that wasn’t matched by a change in insulin response (as has been seen in other studies). Nor was it linked with changes in liver, muscle or pancreatic fat or any other of the mechanisms involved in insulin resistance. 

The authors believe this provides additional evidence that the pathogenesis of type 2 diabetes in Black Africans may differ from that in White Europeans. They say that interventions targeting hyperinsulinaemia, such as very-low-calorie diets and low-carbohydrate diets, may be more effective in SSA populations. Indeed, a study has shown that African American women lost more weight on a lower-carbohydrate diet than on a lower-fat diet, while there was no difference between the two in European women. 

Meanwhile, a study of a very-low-calorie diet to induce remission in people of African descent in Barbados reported less weight loss than in similar studies in Europe. However, 60% of those who achieved 10 kg of weight loss did go into remission at eight weeks and 38% at eight months. Attenuated weight loss in these diasporic populations may arise from hyperinsulinaemia and/or from differences in sociocultural factors affecting adherence to the intervention. No studies have been done in SSA on the impact of dietary intervention upon the pathophysiology of type 2 diabetes (eg remission), so further research into this aspect is needed.

Factors influencing type 2 diabetes in SSA

Social determinants, infectious disease and genetics are listed here as the main influences on type 2 diabetes in SSA. The region is undergoing rapid demographic, sociocultural and economic transitions, which are increasing risk factors. There are differences between people living with type 2 diabetes in rural and urban settings. Those in the former have lower socioeconomic status, younger age of onset and a higher prevalence of childhood undernutrition – but lower prevalence of the traditional risk factors, like obesity. 

However, obesity is on the increase in SSA, as countries start to introduce processed carbohydrate-rich foods, whose consumption, in the context of hyperinsulinaemia, will lead to weight gain, particularly in women. On the other hand, undernutrition, particularly in young children and adults with severe infections, is also a problem. This can lead to malnutrition-related diabetes, an atypical subtype of the condition, found in around 30% of SSA patients. Phenotyping and genotyping experiments would be useful to explore this and other SSA diabetes subtypes.  

Half of the global morbidity and mortality due to infectious disease occurs in SSA, which also has the world’s highest burden of HIV/AIDS, with 67.5% of the total of 37.9 million people living with HIV (PLWH). Now there is anti-retroviral therapy (ART), there has been an increase in life expectancy and non-communicable diseases, such as obesity and type 2 diabetes, among PLWH. First generation ART has been linked to decreased insulin secretion and one of the newer drugs, dolutegravir, to weight gain, which may be risky in an increasingly obesogenic environment. Furthermore, PLWH in Africa often have other infections like TB and hepatitis C, resulting in chronic low-grade inflammation, which also increases the risk of type 2 diabetes. 

Finally, although genome-wide association studies (GWAS) have identified over 400 risk loci for type 2 diabetes, most research in African populations has been done in Europeans. There have been some studies in African Americans, but their genetics and environmental exposures differ from those of people in SSA. Africans have a large amount of genetic diversity, but our knowledge of this is limited. 

However, GWAS of type 2 diabetes in SSA populations have recently been undertaken through the Africa America Diabetes Mellitus study, the Durban Diabetes study and the Human Heredity and Health in Africa Initiative. These have already revealed some novel loci which shed light on the genetic architecture of type 2 diabetes in Africa.  

In summary…

So, the pathogenesis of type 2 diabetes in Black Africans likely differs from that found in people of European ancestry, with hyperinsulinaemia being a key factor. Further studies are, of course, needed to gain a more complete understanding of type 2 in this population. Meanwhile, lifestyle interventions that target hyperinsulinaemia and obesity are recommended to prevent or manage type 2 diabetes in this population. 

To read this paper, go to: Goedecke JH, Mendham AE. Pathophysiology of type 2 diabetes in sub-Saharan Africans. Diabetologia 27 September 2022. 65:1967–1980. https://link.springer.com/article/10.1007/s00125-022-05795-2

For more on the topics covered in this article, enrol on the following EASD e-Learning modules:

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

In the second part of our series on diabetes and under-resourced populations, Dr Susan Aldridge reports on two presentations from the EASD 2022 conference, which explored the particular challenges and solutions prevailing in Europe and Asia.

Europe: Challenges beyond access

Dr Tsvetalina Tankova, Professor of Endocrinology, Medical University, Sofia, reviewed some of the diabetes figures for Europe, with the highest prevalence being in Germany at 15.3% and the lowest in Ireland at 4.4%. Europe also has the highest number of children and adolescents with type 1 diabetes at 300,000 as well as the highest estimate of new onset cases. When it comes to outcomes, 1.1 million people in Europe died of diabetes or its complications in 2021, which accounts for 8.5% of all-cause mortality. “What’s very important is that diabetes and its complications account for 7.7% of all-cause mortality of people under 60,” Dr Tankova said. So, Europe is facing a diabetes pandemic similar to the rest of the world, despite favourable outcomes of prevention studies there.

“Europe is an example of unity in diversity with its different cultures, healthcare systems and levels of resources. There are economic and regional inequalities in access to specialist care, medications and technology,” she said.

She outlined some of the challenges Europe faces. For instance, data is important to ensure people have access to equitable, affordable high-quality diabetes care. National registries are crucial to improving diabetes care in Europe – yet several countries still don’t have one. “Without data it is hard to build accountability and ensure diabetes is diagnosed, treated and controlled,” Dr Tankova warned.

And when it comes to medication, insulin availability is not a problem in Europe, as it is in some other parts of the world. The barriers are of distribution, re-export, tendering and government policies, rather than affordability or accessibility.

For other medications, once they are approved, they are used in a different manner in different countries. In Bulgaria, all new drugs approved by the European Medicines Agency (EMA) immediately go on the ‘positive prescription list’, are 100% reimbursed and are handled by specialist endocrinologists. There are similar variations between countries in use of diabetes technology. These differences arise from cost, disparities in access and psychosocial problems.

Clinical inertia in Europe

Frequent updates in guidelines can be challenging to keep up with and there is a clear discordance between fast-evolving evidence and everyday clinical practice. “Clinical inertia is preventing patients from getting life-saving treatments. That’s why it has to be overcome,” Dr Tankova observed. She gave an example from the Danish diabetes registry on trends in prescriptions of SGLT-2 inhibitors and GLP-1 receptor agonists in people with atherosclerotic cardiovascular disease and obesity, and noted there was no change even after the “amazing” results of recent clinical trials and this was not because of cost, given that the price of DPP-4 inhibitors and GLP-1 receptor agonists is about the same. 

“We need to bridge the gaps between available scientific evidence and clinical practice in Europe at the level of the healthcare system, healthcare professionals and people with diabetes,” she added. She has worked with a group of experts from central and Eastern Europe, looking at the drivers of clinical inertia and they have produced a clinical manifesto called ABCDEFG (https://doi.org/10.1186/s12933-020-01154-w) “With this manifesto we aim to change minds with regard to clinical inertia. We need to increase awareness of the benefits of the new medications.” 

Ending on a positive note, Dr Tankova pointed to the EU’s ‘Healthier together’ initiative on non-communicable diseases initiative. Diabetes is one of five strands and aims to decrease the burden of diabetes and its complications with a focus on data, primary and integrated care and health inequality.

Asia: the diabetes capital of the world

Dr Somia Iqtadar, Associate Professor of Medicine at King Edward Medical University Lahore said. “In Asia, most countries are struggling with GDP growth, a huge economic gap with the rest of the world, besides being affected by climate change at a very rapid pace. But there’s one thing, unfortunately, in which we are leading the world and that is diabetes.”

For Asia has the world’s highest prevalence of diabetes, with figures being particularly high in China, India, Pakistan, Indonesia and Bangladesh. The Asian diabetes phenotype, with its low lean mass and tendency to accumulate visceral fat, is perhaps the most significant cause of diabetes here. 

There is also concern over suboptimal maternal health and uterine programming, which lead to a higher risk of type 2 diabetes and heart disease in the child. And, unfortunately, gestational diabetes and childhood obesity are also on the increase.

“These are things that cannot be controlled overnight – but what we can control is our unhealthy lifestyle, with a lot of carbs and unhealthy fats,” Dr Iqtadar said. “And with globalisation and urbanisation, we now have junk food – all this on top of a body which is prone to accumulating fat. Although Asians tend to have a low body mass, many are now obese. It’s often said that ‘Genetics loads the gun and lifestyle pulls the trigger’.”

Then there are the environmental factors – urbanisation, smoking and pollution, all of which are strongly associated with diabetes. Air pollution is perhaps the unexplored pathway to type 2 diabetes, but is now becoming a topic of interest. And finally, there are social factors, including poor access to healthcare, low literacy, low adherence to treatment and clinical inertia. 

The way forward in Asia.

“Let’s not lose hope,” Dr Iqtadar said. “There is so much that we can do. We believe that with our actions we can bend the curve and save 111 million cases of diabetes through prevention and control.” This means four levels of prevention: at the population level, for those who are at high risk, then good control among those who already have diabetes and, finally, prevention of complications.   

“Every level of prevention is important to bring the figures down. We need government leadership and multisectorial intervention on strategies, action plans, guidelines, taxes on unhealthy foods and promotion of physical activity,” said Dr Iqtadar.

A focus on maternal and child health is crucial with the message that ‘What you do and eat in the first 1000 days makes a difference for the rest of your life.’ To this end, work on gestational diabetes in India, mentioned in discussion, will be a game changer, but working on the health of mothers will improve that of the next generation.

“We are in this together and will get through this together,” Dr Iqtadar concluded. “Because if not now, when?”

For more on some of the issues dealt with in this article, enrol on the following EASD e-Learning courses:

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

Under-resourced populations bear the biggest burden of diabetes – and are set to bear the brunt of the alarming rise in diabetes prevalence. In the first of a two-part series posting on Horizons this week, Dr Susan Aldridge reports on presentations from three speakers at the EASD 2022 meeting who discussed the challenges faced in their own part of the world – and some of the solutions. First up: a view from the USA.

According to the International Diabetes Federation (IDF), the prevalence of diabetes is rising at an alarming rate, from 4.6% of the world’s population in 2000 to 10.0% in 2021 and is estimated to reach 12.5% (more than 780 million people) in 2045, if no action is taken.

Health inequality and under-resourcing are challenges for diabetes care everywhere, and the USA – despite its wealth and influence – is no exception. Dr Shivani Agarwal, Assistant Professor of Medicine at Albert Einstein College of Medicine, New York, looked at some of the challenges faced here. (Her talk was given by Dr Anne Peters, Professor of Clinical Medicine at the University of Southern California).

In the USA, 11.3 % of the population has diabetes. “Diabetes is a societal disease,” Professor Peters said. “We know there are three key features that interact – income, education and race or ethnicity – and influence having and doing poorly with diabetes.” So, rates are highest in Amerindians and Alaskan natives at 14.5%, compared with 7.4% in White non-Hispanic people. Those with less than a high school education and those with the lowest incomes are also the most likely to develop diabetes. Diabetes is also on the increase among the young in the USA, with type 2 increasing faster than type 1, especially in the Black non-Hispanic population. 

Many factors influence diabetes care and outcomes. It starts at the top with public policy, including research funding and health insurance, then there is the societal level, with factors like structural racism and market forces. Below that is the community, with the social determinants of health like education, neighbourhood and built environment, and economic stability. Finally, there are individual factors like genetics, duration, family history and diabetes care, including monitoring, clinic visits, technology, insulin and nutrition.

Racial and ethnic disparities in the USA

Professor Peters pointed to three trajectories in studies of HbA1c over time with ethnicity. In one, levels stayed the same from diagnosis (though still higher than 7%), the second did less well and the third much worse. Those in the second two groups were more likely to be Black or Hispanic. The same trend is seen in deaths from diabetes. Although these are coming down, there is a long way to go before they are equal to levels in white people.

When it comes to tackling health inequality, how much is wishful thinking and how much is possible? Healthcare professionals are increasingly aware of what needs to be done in education and screening for risk – but is this enough?

“Education is a start, but certainly not an end in itself,” Professor Peters said. “How will theoretical knowledge translate to practical care situations and will dissemination of knowledge be evenly distributed among those who need to know?”  

And how will identification through screening solve the problem of health inequality, without the tools and strategies to address social needs? “I think it is really important that healthcare providers know how to access community resources,” Professor Peters said. “It can be really hard when you’re busy in clinic to know how to get patients connected to the right resources. We need a team of people working with our patients. I really value the social workers and community health workers I work with. And I think it’d be a good idea to pay for all this, because it cuts costs downstream. At present, we don’t necessarily have funding for the kind of care our patients need.”

There is a great need for research in this area – pragmatic studies with stakeholder involvement, looking into the impact of psychosocial stress and resilience, cultural relevance and focusing on implementation and sustainability. “Often these projects are not sustained, and we leave these communities no better off.” Professor Peters said.  “So Shivani says – and I agree with her – that we can focus on individual and relationship issues but often we don’t deal with community issues or society at large.”

Lessons from Los Angeles

Professor Peters went on to show what she and others have been able to do in Los Angeles to change things for their under-resourced patients. “I’m a real believer that if we’re champions we can make a big difference. So we need to unite public health and diabetes care with more collaboration with public health and community organisations.”

Leaders in this kind of work need to be engaged and knowledgeable on the impact of area initiatives on diabetes health, such as housing, encouraging social cohesion, infrastructure (avoid food deserts), food banks and empowering patient advocates and faith organisations to give the underserved a voice.   

“Big problems need big solutions and big players. Everyone in this room needs to make a lot of noise in their own countries to make a difference – get the politicians involved to change government policies.”

Speaking more personally, Professor Peters committed to staying in same place – Los Angeles county – for 30 years, so people could get to know her. She started community participatory research in two under-resourced areas in Los Angeles to try to address people’s needs when it came to healthy lifestyle and, as a result, set up both a ‘safe’ walking group and a farmers market. ­ 

She also created a diabetes working group within the local health department and this created a formulary with GLP-1 receptor agonists, SLGT-2 inhibitors and long and rapid-acting insulins, to provide ‘great care’ to people with diabetes. She also campaigned to get continuous glucose monitoring (CGM) for all patients with type 1 diabetes and their outcomes have improved. “This is a form of health equity and, thanks to a donation, people with type 2 diabetes now also have CGM and we are doing a study on this.”

And finally, she has been mentoring Skyla, a young person at risk due to endemic racism, since the girl – now in college – was eight years old. Working in this way, Professor Peters and colleagues were able to give Skyla an opportunity.

So, big gaps continue to exist in the USA in terms of health equality. The issue is real and multifactorial. “Remember to work with your patients and communities to find out what is needed,” she concluded. “We only know our own solutions, not theirs. We all have to be champions.”

To learn about the Asian and European perspectives on this topic, read part two of this series, tomorrow on Horizons.

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

Analysis of a patient-preference study revealed its efficacy for people with type 2 diabetes at the latest EASD Annual Meeting. Lisa Buckingham reports.

Recent guidelines from the ADA/EASD have emphasised the importance of a patient-centred approach to type 2 diabetes treatment, said Beverley Shields, a statistician from the University of Exeter. She highlighted the section about shared decision making and the need to seek patient preference.

She was presenting on patient preferences for type 2 diabetes therapy in the TriMaster trial. The main findings were presented last year, but these were the results of additional analysis of patient preference.

We know that treatment decisions need to balance likely benefits versus adverse effects. Patients vary in their glycaemic response and the side-effects they experience with different drugs, and this cannot be predicted beforehand. The priorities of patients will also vary, with some wanting to lower their glucose while others emphasise wanting to avoid weight gain and hypos.

Most of the information we have on therapies, she said, is from parallel group trials, which help determine at population level what the average response is but they don’t help at an individual level to work out which drug will work best for a specific patient.

The alternative are ‘n-of-1’ trials or crossover trials, where each individual receives multiple alternative therapies, so we can see within-person comparisons. The person can also compare their own lived experience on each drug to establish which they prefer.

The aim of their study was to use this approach to examine patient preference in a randomised, three-way, double-blind, crossover trial of second/third line therapies in type 2 diabetes.

They recruited patients with type 2 diabetes treated with either metformin or metformin and sulphonylureas and with HbA1c of 58-110 mmol/mol, and randomised them into one of six drug order sequences. The drugs used were pioglitazone, sitagliptin and canaglaflozin. Participants completed 16 weeks on each drug with a four-week washout period in between. At the end of each drug period, weight and HbA1c were measured and participants reported any side-effects.

At the end of the trial, the 457 patients who’d completed all three drugs were asked to rank the three drugs they’d tried in order of preference. They were asked to do this twice – once before they’d been given the results of their HbA1c and weight and again afterwards. The cohort was predominantly male (74%) with a median age of 61 and 95% were of white ethnicity.

Mean HbA1c was very similar across all three drugs; pioglitazone had the lowest rate of non-tolerability at 5%, compared with 8.3% for sitagliptin and 7.7% for canagliflozin. Sitagliptin had the lowest number of side-effects at 1.30, compared with 1.59 for pioglitazone and 1.66 for canagliflozin. Canagliflozin was associated with the lowest weight on average, 91.1 kg compared with 93.4 for sitagliptin and 94.9 for pioglitazone.

When patients were asked to rank the drugs before they were aware of their results, 24% chose pioglitazone, 33% chose sitagliptin and 37% chose canagliflozin, with the remaining 6% having no preference.

The predominant reason that patients said they had chosen their preferred drug was that it was the ‘one they felt better on’.

After they had been given their results and chose again, pioglitazone came in at 25%, sitagliptin at 35% and canagliflozin at 38% with 2% having no preference, so fairly similar results to beforehand, but 125 (28%) of patients changed their minds after being given their results. The majority stated that they changed their preference because of the HbA1c result, although reasons differed between drugs with, for example, weight loss being the biggest reason that people chose canagliflozin.

When they looked at the characteristics of people based on their preferred drug, those who had the lowest HbA1c on pioglitazone had chosen pioglitazone as their preferred drug and the same applied for the other two therapies. The same association was seen with side-effects. However, weight seemed to be less of a factor in their decision-making. Regardless of which drug they preferred, patients had the highest weight on pioglitazone and the lowest on canagliflozin.

The advantage to this study, said Beverley, was that they could look at within-person differences. For example, if they’d treated everyone with canagliflozin because that was preferred most on average, they wouldn’t have had as many patients treated with the drug that was best for them in terms of HbA1c and side-effects. The results highlight the importance of taking into account patient preferences and not just making inferences from the mean of the population.

In summary:

  • Patients tend to prefer the drug they felt better on, with the lowest HbA1c and fewest side-effects
  • Weight was less important to patients when choosing their preferred treatment
  • Allocating each individual’s preferred drug compared with the overall preferred drug (canagliflozin) results in patients receiving the drug that results in the lowest HbA1c and side-effects for them

On the basis of this, she said, they propose that a short trial of alternative possible therapies is the optimal way to assess individual preference and that we should let the patient choose.

In the post-presentation questions, she was asked if they’ll work on prediction models based on patients’ characteristics because clinicians will be trying to predict which therapy will be best before it’s started. She responded by saying that the main hypotheses of TriMaster was predicting which characteristics predict response. They found that body mass index and estimated glomerular filtration rate, for example, were able to help predict response and these are results that they will be submitting for publication in the near future. Prediction models are one of the routes we can choose, she said, but the option of allowing patients to try multiple therapies is a good option and one which patients seemed to really like.

She also went back to the issue of weight change and pointed out that many of the studies on patient preference state that weight change is a priority, but it’s often posed as a hypothetical question. They have now seen with this lived-experience study that weight was not the highest priority.

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

A new paper in Diabetologia does not support the hypothesis that exposure to viral infection in the first year of life may trigger beta cell autoimmunity and type 1 diabetes. Instead, the study finds that it is bacterial infections that increase this risk, possibly through an effect on the gut microbiome. Dr Susan Aldridge reports.

The incidence of type 1 diabetes has been on the increase in many countries around the world. And, although we now have immunotherapy with teplizumab to delay onset by a few years, it’s not likely to be available to all for some time – if ever. So primary prevention is crucial. The problem is that the cause – or causes – of type 1 diabetes remain unknown.

Genetic predisposition is significant, but lifestyle and environmental factors also play a part. For instance, there is a marked difference in incidence of type 1 diabetes between the Russian and Finnish parts of the Karelia region, even though the populations share a similar genetic background. Also, migrants tend to show a type 1 diabetes incidence that is similar to that in their new country. The influence of lifestyle and environment is encouraging, as these factors can be modified, with the potential to reduce the incidence of the condition.

There are many environmental factors that might contribute to type 1 diabetes and there is evidence suggesting that exposure to infections in early life might be one of them. Studies have pointed to enterovirus infections, suggesting they may trigger the autoimmune process that leads to type 1 diabetes or accelerate the disease process once it is underway. These infections might also attack the pancreas and, indeed, signs of persistent enterovirus infection have been detected in the newly diagnosed. As well as enteroviruses, upper respiratory viruses have also been implicated as a risk factor for type 1 diabetes. Bacterial infections could also be involved, possibly by affecting the gut microbiota.

So far, however, we don’t have a clear picture of the role of infection in triggering type 1 diabetes. Therefore, Johnny Ludvigsson of Linköping University, Sweden, and colleagues have carried out a study of infections occurring in the first year of life and their link to the subsequent development of type 1 diabetes.

Early life infection and type 1 diabetes

The researchers studied children in the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study. This was an international double-blind, multicentre trial,  looking at whether weaning to a hydrolysed infant formula compared with a cow’s milk formula had any impact on the incidence of type 1 diabetes. Of the 2159 participants in TRIGR, 2059 were autoantibody negative and free of diabetes at the end of their first year, and had information on infections during that year. So these children entered the study.

Autoantibody tests were carried out at regular intervals and infections reported by parents were also recorded. These were classified as: upper respiratory, gastrointestinal, urinary tract, middle ear, pneumonia and other. And depending on antibiotic use and other clinical information, the infections were further classified as bacterial or viral. Of the participants, 41.7% developed at least one type of diabetes-related antibody, 11.7% developed multiple antibodies and 6.6% developed type 1 diabetes. When it came to infections, 48.0% had one to three infections, 18.8% four to six infections and 6.5% had seven or more infections during the first year of life. The researchers then had to match these two sets of data to explore the relationship between number of infections and the development of antibodies or type 1 diabetes.   

They found that children who developed at least one diabetes-related antibody had more infections during the first year of their life than those who did not have any infections. Narrowing this down to the type of infection, those with at least one, or with multiple antibodies, and those who went on to develop clinical diabetes were more likely to have had an unspecified bacterial infection.  Finally, timing – children who had had their first viral infections between the ages of six and 12 months were less likely to have multiple antibodies or to go on to type 1 diabetes than those who had had no infections.

Focus on bacterial infections

So, exposure to bacterial infections in the first year of life seems to be a marker for later development of both diabetes-related autoantibodies and type 1 diabetes. The researchers think that the bacteria may affect immune balance, while antibiotic treatment could upset the gut microbiome, which could also influence immunity in a way that promotes type 1. One previous study on a nationwide birth cohort showed that antibiotic treatment during the first two years of life did not increase the risk of type 1 diabetes. However, another nationwide study found the opposite. Bacterial infections could also cause damage to the pancreas.

This new study also does not support the hypothesis that it is viral infections during the first year of life that trigger the autoimmune process underlying the development of type 1 diabetes. In fact, the finding that infants who had their first viral infection after the age of six months were less likely to develop diabetes-related antibodies or diabetes supports the hygiene hypothesis –  which argues that exposure to viruses is protective, helping to develop the immune system.

As this study was exploratory, the researchers caution that it needs confirmation by other studies. To this end, it would be worthwhile including questions about exposure to bacterial and viral infections in early life when taking a history on diagnosis of type 1 diabetes.

To read this paper, go to: Kordonouri O, Cuthbertson D, Belteky M, Aschemeier-Fuchs B, White NH, Cummings E, Knip M, Ludvigsson J. Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals: the TRIGR cohort. Diabetologia 9 September 2022.

https://pubmed.ncbi.nlm.nih.gov/36083343/

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

Tackling sugar intake is a key part of reducing the prevalence of obesity and diabetes, but how best to do it? Evidence for the taxation of sugar-sweetened beverages was presented at the recent EASD Annual Meeting. Lisa Buckingham reports.

We know that unhealthy diets are a major risk factor for obesity and many other diseases, and that price is a key driver of food choice, said Dr Laura Cornelsen, co-director of the Population Health Innovation Lab at the London School of Hygiene and Tropical Medicine. She was presenting on the impact of taxation on obesity and diabetes-related behaviours and outcomes in the UK.

The evidence from tobacco and alcohol is that taxes are effective in both increasing price and reducing consumption. With regard to food and drink, she said, the key questions are whether such tax policies are designed well enough so that price increases sufficiently (the industry often counter-steps and absorbs some of the cost), whether consumers are sensitive to the price increase and buy less and whether governments are willing to implement this policy.

As background, she told the audience that taxes on unhealthy foods and drinks have been modelled in academia since the mid-1990s. It was in the 2000s that focus shifted to sugar-sweetened beverages (SSBs) because they’re a major source of free sugar intake but with empty calories. Now, more than 45 countries have taxes on SSBs. A meta-analysis suggests that these taxes have reduced sales by 15% and consumption by 18%, but evaluating real-life impact on the prevalence of obesity, diabetes and others diseases is difficult because outcomes take time to appear and it’s also hard to isolate the effects of the tax.

Obesity is a burgeoning problem in the UK, with 28% of adults living with obesity in 2019. More recent data on 10-11 year olds shows 26% living with obesity. Between 2012 and 2019, the figures for diabetes have risen rapidly, with a 28% increase in the number of people diagnosed.

Levying the soft drinks industry

Dr Cornelsen moved on to cover the UK’s Soft Drinks Industry Levy, which was announced in 2016 and enacted in 2018. This is a tiered levy on producers of soft drinks depending on the sugar content, with a higher tier for drinks containing 8 g or more of sugar per 100 ml and a lower tier for 5 g and above per 100 ml.

There are four aspects for which we now have evidence, she said, which are availability, prices, purchases and other impacts (revenues, employment, etc.).

For availability, a 2020 study showed the proportion of drinks available in UK supermarkets that have more than 5 g of sugar per 100 ml (almost 50% of the market) and what happened to them when the levy was introduced. There was a remarkable decline in the number available, down to about 15% of the market. Another study on the highest sugar tier (8 g or more) showed a similar trend – the number of drinks available in this category was very much reduced. This was because brands reformulated to lower the sugar content. Interestingly, though, the reformulations took the sugar levels to just below the threshold for the levy (5 g) using a combination of non-caloric sweeteners and sugar, rather than replacing sugar altogether.

The price of the levied drinks increased substantially after the levy came into place. With regard to purchasing, drinks with more than 8 g sugar per 100 ml showed both a drop in volume per household/per week (-155 ml) and a drop in sugar per household/per week of 18 g (46%). For the lower tier of levied drinks, it was -177 ml (86%) and -13 g (86%).

For drinks below the levy threshold, no change in volume was seen but an increase of 15 g sugar per household/per week, which could indicate a switch down to drinks in this market, which previously consisted of diet/zero sugar drinks. However, when all soft drinks were combined, they found no change in volume but -30 g sugar, which equates to 7 kcal per day/per person.

Another study looked at calories purchased and, while volume remained the same, they estimated that 6500 fewer kcal per year/per capita were purchased, which translates to 18 kcal fewer per capita/per day. They estimated that reformulation was responsible for 83% of this reduction and the remaining 17% was down to consumer response to higher prices.

Lastly, Dr Cornelsen showed revenue figures. The UK government estimated that it would raise £520 million a year, whereas the figure for 2018/2019 was £240 million. This does not show the policy to be a failure, she said, but that there was a high level of reformulation to get below the sugar level for the levy.

For those who argued that the levy would put jobs in jeopardy, the reaction in the stock market was that three out of four soft drinks producers listed in the London Stock Exchange saw negative returns immediately following the levy announcement in 2016 but it lasted just a matter of days, indicating a lack of major concerns for the industry.

Conclusions

  • There is very clear evidence of reformulation with share of levy-applicable drinks decreasing from the expected 49% to 15%
  • The majority of reformulation moved beverages to just below the threshold (sugar content 4-5 g rather than zero)
  • Prices increased for high-levy, non-reformulated drinks and pass-through was estimated at 31%-100%
  • Prices slightly increased for no-levy drinks
  • Estimated reduction in calories purchased from SSBs ranged from 7-18 kcal per person, per day
  • Manufacturers were able to mitigate brief negative effects and market concerns were short lived
  • Revenues were lower than expected
  • Health impacts are yet to be seen – modelling studies are ongoing and soon to be released

One of the questions after the presentation addressed what Dr Cornelsen called the ‘elephant in the room’ in her response, which is that the reduction in sugar comes with a rise in the use of artificial sweeteners, the health impacts of which (for some sweeteners) are still under debate. She raised the issue that body weight may be a factor in the impact of sweeteners and her concern would be children consuming a lot of these products. However, the official stance is that these reformulations are a positive.

The small reduction in the number of calories consumed per day was also addressed, and while Dr Cornelsen said that the levy would not solve the problem on its own and modelling studies on other policies on, for example, taxing sweet snacks showed more calorie reduction, the levy can be of some help alongside other strategies.

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

Depression is more common in those diagnosed with type 2 diabetes under the age of 40 than those diagnosed later in life. These findings from UK and USA data, reported in a recent issue of Diabetologia, highlight the need for clinicians to screen for depression, particularly in younger people diagnosed with type 2. Dr Susan Aldridge reports.

People with type 2 diabetes are at higher risk of depression than those without the condition. Meta-analyses of the literature suggest that the global prevalence of depression in type 2 diabetes has risen from 20% in 2007 to 32% in 2018. This is important, because depression in type 2 diabetes is associated with poorer adherence to treatment, lower quality of life and increased risk of both complications and mortality.

So, the connection between type 2 diabetes and depression is well known, but what is less clear is whether depression is more likely when someone is diagnosed at a younger age. So-called young-onset type 2 diabetes (YOD) – diagnosed between ages 18 and 39 – is on the increase in many countries, particularly the UK and USA. This is a matter of concern, because YOD is a more aggressive phenotype, with early development of complications. And as they age, with the longer duration of type 2, they are more likely to develop mental health problems and both microvascular and macrovascular complications, with a higher rate of hospitalisation than those with usual-onset type 2, which is diagnosed at age 40 and above. 

The relationship between age at diagnosis and risk of depression in type 2 is complex and needs further research to support effective management in primary care and to reduce healthcare costs. There is also the question of whether the presence of comorbidities like retinopathy and heart disease at diagnosis further increases the risk of depression.

Accordingly, Sanjoy Paul and colleagues at the University of Melbourne, together with William Polonsky, a leading expert in diabetes psychology, have carried out a study which compares the risk of depression in YOD and usual-onset diabetes and whether this is affected by the presence of comorbidities. They also looked at time trends in depression across the age groups. They drew upon electronic medical records (EMRs) from primary care from both the USA and the UK for their data. A total of 230,932 people from the UK and 1,143,122 people from the USA were included in the study. Comorbidities recorded were any cardiovascular disease, microvascular disease, obesity or cancer. The presence of comorbidities, as expected, was highest in the 70–79 group at 70% (UK)/65% (USA) and, in the YOD group, it was 36%/59%.

Trends in depression

The prevalence of depression has gone up over all age groups with type 2 diabetes, in both the UK and the USA, with annual increase rates of 3.8%/2.8%. A similar trend was noted for incidence rates. 

In both the UK and the USA, YOD was associated with a higher risk of developing depression than usual-onset diabetes. In the UK, men with YOD had a 23 to 57% higher risk of depression compared with those who were older. The corresponding figure for women was a 20 to 55% higher risk. These increased risks were similar whether or not comorbidities were present at the time of diagnosis. In the USA, the increased risk for YOD was 5 to 17% in men and 8 to 37% for women, again compared with usual-onset diabetes.

Targeting depression

This study, involving 1.4 million people with type 2 diabetes from population-based EMRs from two different healthcare systems gives us an important new insight into the risk of depression according to age at diagnosis. It is the first to explore the population-level trend in depression prevalence at the time of type 2 diabetes diagnosis across both sex and age groups.

First of all, depression has increased over time in all age groups. And, second, those with YOD have a significantly higher risk of depression compared with those with young-onset diabetes, regardless of the presence of comorbidities at the time of diagnosis. The authors note that their depression prevalence figures are similar to those found for Europe and the USA in other studies. Prevalence and incidence of depression are also significantly higher among women in both the UK and the USA and across all age groups.

This study shows that there are mental health implications of developing diabetes at an early age, whether or not comorbidities are present. The underlying pathophysiology of depression in people with type 2 has been investigated. Risk factors, including obesity, may play a role. Future studies should look into the effects of risk factors before and after diagnosis in different age groups, sex and ethnicity, to explore the underlying causes of depression in YOD further.

And healthcare professionals shouldn’t wait for this research. There is enough in the findings of this new study to highlight the importance of proactive engagement of primary care teams in mental health management of those diagnosed with type 2 diabetes. It’s well worthwhile preventing or catching YOD-related depression, not just for the patient’s sake, but to reduce healthcare costs. One survey from the USA revealed that people with type 2 and depression run up double the expenditure compared with those who have diabetes but no depression.  

Then there is the increase in depression over time in all age groups. This might be because of increased awareness of depression in diabetes as more research and education on the subject emerges. And better record keeping with the transition to EMRs may have allowed for more cases of depression to be captured. Of course, the under-reporting of depression is known to be a problem globally, so the figures here might actually be an underestimate.

Proactive management of comorbid depression in type 2 diabetes, at any age, should involve screening, early diagnosis and prompt treatment with medication and/or talk therapy. This is a worthwhile investment, as it could lead to better glycaemic control and control of other risk, delayed onset of complications and lower healthcare costs. Innovative approaches to identify subgroups of patients most at risk of depression would also be useful to target early intervention.

So, the authors strongly recommend proactive mental assessment in primary care from the time of type 2 diabetes diagnosis, regardless of age or the presence of comorbidities. This should become an essential part of diabetes care. 

To read this study, go to:
Dibato J, Montvida O, Ling J, Koye D, Polonsky WH, Paul SK. Temporal trends in the prevalence and incidence of depression and the interplay of comorbidities in patients with young- and usual-onset type 2 diabetes from the USA and the UK. Diabetologia 5 September 2022. https://pubmed.ncbi.nlm.nih.gov/36059021/

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

The epigenome plays a crucial role in regulating gene expression, cell differentiation and X-chromosome inactivation – and can contribute to disease when dysfunctional. In her new module for EASD e-Learning, Professor Charlotte Ling explores the ways in which epigenetic modifications contribute to type 2 diabetes.

As a principal investigator in the Epigenetics and Diabetes Unit at Lund University Diabetes Centre, Sweden, Professor Charlotte Ling is more than amply qualified as a guide to the epigenetic mechanisms implicated in type 2 diabetes. Over the last decade or so, her research group has pioneered this field of investigation, making several ground-breaking discoveries – such as genome-wide epigenetic modifications in the pancreatic islets, skeletal muscle, adipose tissue and liver of people with type 2.

“We have identified epigenetic modifications in pancreatic islets from donors with type 2 diabetes compared with controls,” says Professor Ling. “However, the question is which is the chicken and which is the egg? Do these epigenetic modifications contribute to the development of type 2 diabetes? Or are they just a consequence of the disease?”

To investigate this question, she and her team have performed a series of experiments, testing whether exposure to high glucose and lipids had direct effects on the DNA methylation and gene expression patterns already seen in pancreatic islets from non-diabetic human donors. Much of this module details the results of those studies and a wealth of other evidence in support of epigenetics playing a causal role in the pathogenesis of type 2 diabetes.

The basic science subject matter takes the lead in this module, but always with a watchful eye on how this work might be applied to clinical care. Throughout the module, basic research is interspersed with clinical application scenarios and case studies, demonstrating its relevance to clinical practice. As Professor Ling says: “It is very important to try to use our basic research – to bring it to the clinic. That is the ultimate goal.”

In this case, Professor Ling and her team have their sights set on developing blood-based epigenetic markers and new therapies. “We have analysed DNA methylation in the blood trying to develop blood-based epigenetic markers that can predict future type 2 diabetes, future diabetic complications and response to therapy in people with type 2 diabetes. Some preliminary data look promising but future research will look into this further.”  Other work by her and her team supports the tantalising prospect that epigenetic mechanisms might also provide new therapeutic targets for type 2 diabetes.

Find out more about this fascinating topic by enrolling on Professor Ling’s module, Epigenetics and the beta cell – module 2 in the EASD e-Learning Beta cell biology course.

For more on this topic, see module 1 of the Beta cell biology course, Stimulus-secretion coupling in pancreatic cells.

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

Remission of type 2 diabetes is now seen as a real alternative to a lifetime of medication and worry about complications. The down side is that it may not last, and the issue of relapse was in the spotlight at the Diabetologia symposium on remission at EASD 2022.

Relapse of type 2 diabetes is currently defined as the resurgence of diabetes after a period of remission. It differs from not achieving remission in the first place and may be influenced by different factors. Speaking at this year’s EASD Annual Meeting, Dr Blandine Laferrere, Associate Professor in the Division of Endocrinology at Columbia University Medical Center, said: “It’s difficult to discuss relapse, because we don’t have a lot of data on it. It’s easier – and more interesting – to publish on remission.”

There are two important aspects to relapse, she continued. First, there is the temporal aspect, which depends on how often someone is monitored. So it may be difficult to know how long someone has been in remission or relapse. But time spent in remission before relapse could be very important – and the longer the better. There will also be degrees of relapse. Some will have an HbA1c just above the diagnostic level and just need to go back on metformin. They will be very different from those with higher HbA1c, who may need to go back on insulin. 

Relapse scenarios

People arrive at type 2 remission by different routes. Dr Lafererre went on to describe some scenarios and how they affect the chance of later relapse. For instance, in a meta-analysis of trials of short-term intensive insulin therapy (IIT), 60 to 70% went into remission, but 30% of these relapsed after 12 months. In another study of ITT, followed by either a GLP-1 receptor agonist or placebo, duration of diabetes was found to be a significant factor in the likelihood of relapse. At three months of follow-up, the relapse rate was 40% for those with diabetes duration of less than two years, and 90% for those with a longer duration than this. The influence of diabetes duration is similar to what is found in remission – the shorter the duration, the higher the chance of remission.

An animal study shed some light on what might be happening here. In diabetes, the beta cell de-differentiates, but in insulin therapy it differentiates again. So the mechanism of relapse on IIT might be that the beta cells de-differentiate again after insulin is discontinued. And beta cell function is likely to be worse in those with a longer duration of diabetes. 

Some people achieve type 2 remission after pharmacotherapy – particularly with GLP-1 receptor agonists. Dr Lafererre referred to a study where participants were given exenatide or nothing for 12 weeks after a remission intervention with either intensive lifestyle change or insulin. Those on exenatide did not relapse, until they were taken off it – when they relapsed at the same rate as the controls. Many other GLP-1 receptor agonists have shown the same. “So, there is no permanent benefit of the GLP-1 receptor agonists on the beta cell,” Dr Lafererre noted.

Then, with lifestyle intervention, there is the problem of sustainability. Dr Lafererre has extracted some data from the Look AHEAD trial, although it was not actually aimed at remission or relapse. Over 4,000 people were randomised to either intensive lifestyle intervention or to diabetes education. One third of those in the lifestyle group relapsed per year, and half of those in the education group, over the course of follow-up. 

“What could be the mechanism here?” she asked. “We don’t have measures of beta cell function in Look AHEAD, unfortunately. There was over 8% weight loss in the lifestyle group. Weight regain could perhaps explain some of the relapse, although this is an association and not a mechanism.”

Finally, for those who have achieved remission through bariatric surgery, there is a lot of data to mine the factors affecting relapse. For instance, it seems that the treatment someone has before surgery is important – with insulin giving higher relapse rates than either diet or oral hypoglycaemic agents. “Pre-operative insulin was shown to be a factor in predicting relapse in almost all the studies,” Dr Lafererre noted.

Duration of diabetes is also a factor, with a recent study showing relapse rates at 10 years after surgery of 20% for those who had had diabetes for less than four years, but 94% for those who had had the condition for longer than this.

Of course, it is hard to make direct comparisons, as rates of relapse after bariatric surgery vary tremendously – between 12% and 94% – depending upon the time of follow-up of the study.

Although there is little information about the mechanism of relapse after surgery, Dr Lafererre believes it involves poor beta cell function at the start – which could be indicated by someone having to take insulin long term before they have surgery. This function continues to decline over time, in some people, despite surgery and weight loss. 

Her own lab has looked at beta cell function over time. “I wish more people would do this,” she said. One question they looked at was whether beta cell function recovers fully in clinical remission. For this, they selected people whose duration of diabetes was less than two years, to make sure they went into remission. They were then studied three years after surgery. “The beta cell function did not normalise and this surprised me tremendously, because they were all in full remission.”

So, clearly there is more to be learned about the role of beta cell function in relapse. Other possible mechanisms include insulin resistance, weight regain or lower weight loss after surgery. “And no-one has studied the possible role of being less fit or poor diet. There is also genetics and socioeconomic status to consider, and decreased sensitivity to incretins, where glucose toxicity comes back,” Dr Lafererre concluded.

Conclusions

To achieve remission and prevent relapse it’s important to intervene very early, prior to starting insulin, and try to sustain those lifestyle changes. There is also a role for pharmacotherapy such as short-term insulin, tirzepatide, and a metformin/SGLT-2 inhibitor combination, all of which may preserve beta cell function. “I believe pharmacotherapy should be looked at in a very positive way here,” Dr Lafererre said. “It would be very interesting to have more studies on short-term sequential insulin therapy to see if we can sustain the improvement in beta cell function, which is really the goal of preventing relapse.”

For more on this topic, see the following EASD e-Learning modules:

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

A fascinating insight into diabetes stigma and how it can be tackled was presented at the recent EASD conference. Lisa Buckingham reports.

Dr Noriko Kodani from the National Centre of Global Health and Medicine in Japan described how her own diagnosis of type 1 diabetes after the birth of her daughter and how that drove her change from working for a pharmaceutical company to work in the field of addressing diabetes stigma. As part of an East-West forum, she presented on social and internalised stigma to people having diabetes in Japan.

Historically, psychiatric disorders and conditions such as tuberculosis and HIV were the target of social stigma, she said, and people were labelled as social deviants, discriminated against and isolated as a result. Obesity and diabetes have recently been added to this list – not because these conditions are intractable but because they’re mistakenly regarded as the result of poor self-discipline.

Dr Kodani highlighted a 2013 review article published in Patient discussing this and an interesting point it makes is that people without diabetes do not consider it to be a stigmatised condition, whereas the experience of people with diabetes is very different and they report feeling judged and constantly monitored.

Being given a misunderstood label can mean that people face difficulties with self-care, with a lack of a suitable environment and support, their identity and self-esteem are denied by others, and they become socially isolated and experience loneliness. Medical, social and psychological isolation can then result in suboptimal clinical outcomes.

Stigma against people with diabetes is a universal phenomenon and is not specific to Japan. She cited a Diabetes UK statistic that one in six people with diabetes is discriminated against in the workplace and that this is brought about because employers lack knowledge about diabetes and do not understand its impact. It goes on to say that everyone deserves to work in an environment where they can ask for the support they need.

‘Belongingness’

Dr Kodani expanded on this workplace issue by connecting it to the experiences of people with diabetes in Japan. Culturally, group affiliation (belongingness) is prioritised over social inclusion; there is a social pressure to be a ‘group member’ and the status of having diabetes is regarded as a social deviation. This makes ‘coming out’ as having diabetes very challenging and research by her colleague Dr Hashimoto shows that, in the workplace, the people he interviewed would do things like inject insulin stealthily in the bathroom while others said that they couldn’t ask for healthy food choices to be provided at work events serving foods like fried chicken and cakes and had to eat the food provided, concealing their diabetes status.

However, the younger generation’s attitudes are changing, she said, and they are learning to speak out and ask for what they need while till following the rules of Japanese society.

To demonstrate what people with diabetes in Japan are up against, Dr Kodani presented a 2013 quote from a public meeting spoken by the Minister of Finance and Vice Prime Minister: ‘It is not fair that I have to pay public medical insurance premiums for those who indulge themselves in eating and drinking, and get diabetes eventually. It is frustrating to see such guys and imagine that someday I have to pay for them.’ This provoked many comments on Twitter accusing people of diabetes of being a threat to public health care.

This was nine years ago but it is only in the recent past that stigma towards people with diabetes came to professional attention in Japan, said Dr Kodani. She drew attention to a qualitative study by Dr Asuka Kato and colleagues that details the impact of internalised stigma (also known as self-stigma) on type 2 diabetes self-management. Self-stigma is strongly interrelated with social stigma and is particularly strong in Japanese people. If diabetes treatment isn’t working, they will often blame themselves when, in fact, there can be multiple reasons. This can then affect their diabetes self-management and we need to understand that this so-called ‘non-compliance’ can be a result of internalised stigma.

‘Language creates reality’

She moved on to discuss the importance of the language used by healthcare professionals. For example, a position statement from Diabetes Australia states that healthcare professionals (HCPs) should focus on the achievable, inform but don’t judge and remember that language creates reality, and NHS England guidance says that HCPs should become aware of the use of terminology such as compliant or non-compliant and try to find out about a patient’s current situation and how it might be affecting their diabetes. HCPs, said Dr Kodani, should be the centre of advocacy to mitigate social stigma against people with diabetes.

In Japan, tackling this issue has a long way to go. A recent web survey of physicians by a medical journal asked: what do you think about using the word ‘diabetics’ in your clinic conversations? The majority (64%) said they had never thought about and 11% said it wasn’t a problem. Only 12% said it was problematic and they’d never use it, with the remaining 11% recognising it as problematic but saying they would still use it.

In addition, there seems to be a divide among patients. People with type 1 diabetes may have an ‘us and them’ attitude to people with type 2 diabetes because type 1 diabetes is etiologically different and they don’t want to be treated like them, and may also express things like wanting a different diagnosis name so that they’re not associated with diabetes. Dr Kodani said that she is slowly seeing a change in this attitude among patients, especially among the younger generation.

As a sign of progress, the Japanese Diabetes Association and Japanese Association for Diabetes Education and Care issued a statement in national newspapers in 2019 stating that ‘People with diabetes can be socially active like you. Your appropriate understanding on diabetes is wanted’. Whether this enlightenment approach is enough to mitigate social stigma is a matter for debate and needs empirical research, said Dr Kodani.

What, then, should be the target for action? Our common enemy, she said, is the etiological beliefs about diabetes and the concept of it being a ‘lifestyle-related disease’, which puts so much focus on the patient. Diabetes is shaped by complex interactions between bio-medical determinants, socially bound behaviours and physical/social environments. A full understanding of this is what’s needed to ensure fair treatment of people with diabetes.

Japan is moving slowly towards this. Another quote from a public meeting in 2018 by the same Minister of Finance took the same attitude as the previous one. This time, however, the major liberal papers and blogs raised a voice against it and asked ‘Can diabetes be attributed simply to self-discipline and responsibility?’.

She concluded that advocacy for tackling social and self-stigma needs to include the following:

  • Medically precise understanding of diabetes etiology is necessary but not enough
  • Action beyond ‘enlightenment’ is wanted but it should not be mere information dissemination
  • Advocacy against both social stigma and self-stigma is indispensable
  • Domestic and global alliance across private and public sectors is required, taking into account social and economic backgrounds (including cultural backgrounds) and professionals must be organised to reach out to make changes
  • We need to be more supportive of people diabetes, helping them be more self-affirmative, maintain their self-esteem and be able to live a happy life

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