Change your mind: obesity and type 1 diabetes

Diabetes is a chronic disease of carbohydrate, fat and protein metabolism that results from the inadequate action of insulin. It affects an estimated 463 million people worldwide and is predicted to rise to approximately 578 million people by 20301. Dangerous acute complications of diabetes include diabetic ketoacidosis and severe hypoglycemia (low blood glucose), which can lead to a trip to the emergency room or worse.  In the long-term, chronic hyperglycemia (high blood glucose) can lead to a number of micro- and macro- vascular complications, including nephropathy, retinopathy, coronary artery disease, stroke and peripheral neuropathy.

There are two major types of diabetes, type 1 diabetes (T1D) and type 2 diabetes (T2D). T1D develops due to a deficiency of insulin following the autoimmune-mediated destruction of the insulin-producing beta cells in the pancreas. T2D, the significantly more common form of the disease (accounting for ~90% of diabetes cases worldwide1), is characterized by insulin resistance, whereby an individual’s capacity to respond to insulin is impaired. It is often thought that T2D is strictly a disease of obesity and T1D is only seen in lean people; but it’s not so! While obesity is an important risk factor for T2D there are complex environmental and genetic factors at play, and the rate of obesity in people living with T1D is comparable to that of the general population4.

What does obesity mean for people with T1D? It is not yet clear, but we know this is an important question that must be investigated. Weight gain in people living with T1D may trigger the same metabolic disturbances as those seen in people living with T2D, such as insulin resistance. In fact, much like the rates of obesity, the prevalence of insulin resistance in people living with T1D is also increasing5. People living with T1D who develop insulin resistance and/or obesity often clinically resemble people with T2D, and this may have important consequences for how they should be treated. These patients rarely achieve glycemic control, even with higher doses of therapeutic insulin, and are at higher risk of experiencing obesity- and diabetes-related complications5.

So, why is the prevalence of overweight and obesity increasing in T1D patients?

In addition to the lifestyle and diet factors that have driven the global rise in obesity in people with and without diabetes alike, there are also obesity drivers intrinsic to T1D physiology and management. People with T1D must sometimes eat extra carbohydrates to avoid or resolve hypoglycemia; some people with T1D also choose to consume low carbohydrate, high fat foods to prevent spiking blood glucose levels. Intensive insulin therapy—the mainstay of diabetes management— drives weight gain through the hormone’s anabolic effects on the body, and the difficulties of controlling blood glucose during exercise may create a barrier to working out. Finally, the satiety hormone amylin is reduced or absent in people with T1D, which may cause further weight gain. In sum, the causes of overweight and obesity in people with T1D are numerous and complex, and demand a further investigation!

But what about the influence of obesity on T1D development and outcomes?

Does obesity increase the risk of developing T1D as it does for T2D? Previous research suggests that obesity can initiate disease onset and possibly accelerate the pathogenesis of T1D6. This may be due to inflammation and metabolic changes from obesity. However, not enough studies have been done to draw firm conclusions, and not all studies have reached the same outcome; the contribution of obesity to the development of T1D remains an important question. A key aim of our work is to address this problem head on. Similarly, not enough is known about what obesity means for glucose control and long-term health in people with T1D. How big a factor is obesity in these outcomes? Can we learn how to predict which people living with obesity and T1D will have negative health outcomes? What are the mechanisms mediating the effects of obesity on T1D outcomes? We will find out!

SOPHIA Work Package 4—T1D and obesity

While obesity has long been known to contribute significantly to T2D progression, its prevalence, consequences and physiological attributes in T1D patients are poorly understood. Work Package 4 of SOPHIA aims to further our understanding of the complex interplay between obesity and T1D. We are investigating the role of obesity in accelerating T1D onset, how obesity affects T1D outcomes such as blood glucose control and long-term complications, and conversely, how the presence of T1D affects outcomes associated with obesity. To answer these complicated questions, we are working with collaborators around the world to pool knowledge, fresh ideas, and data sets for analysis. The result of this work will be a better scientific understanding of the intersection between T1D and obesity that can optimize care for a population that has been under-studied for too long. Additionally, we aspire to remove the stigma around obesity. Obesity in all populations, including people with T1D, is not a personal failing but a complex disease and must be treated as such; recognition of this fact will not only ease the psychosocial burden felt by many living with obesity, but also pave the way for improved clinical care.

  1. Saeedi P et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the international diabetes federation diabetes atlas, 9th edition. Diabetes Research and Clinical Practice 2019; 157:1-10
  2. Kahn BB and Flier JS. Obesity and insulin resistance. The Journal of clinical investigation. 2000; 106(4):473-481
  3. Zatterale F et al. Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes. Frontiers in Physiology. 2020; 10:1-20
  4. Fellinger P et al. Overweight and obesity in type 1 diabetes equal those of the general population. The Central European Journal of Medicine 2019; 131:55-60
  5. Cleland SJ et al. Insulin resistance in type 1 diabetes: what is ‘double diabetes and what are the risks? Diabetologia. 2013; 56:1462-1470
  6. Overweight, obesity and the risk of LADA: results from a Swedish case-control study and the Norwegian HUNT study. Diabetologia. 2018; 61:1333-1343

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This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875534. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and T1D Exchange, JDRF, and Obesity Action Coalition.

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