Unlike the well-established causal relationship between excess body weight and type 2 diabetes, obesity is rarely associated with type 1 diabetes. However, epidemiological data refute the former belief that type 1 diabetes predominantly occurs in individuals with normal or low body weight. The prevalence of obesity among adults with type 1 diabetes has reached levels comparable to those in the general population.
The connection between type 1 diabetes and obesity is not only increasingly common but also significantly complicates the management of both conditions and the achievement of adequate metabolic control. It exposes affected individuals to an additional risk of developing microvascular and macrovascular complications. Obesity and obesity-related features of the metabolic syndrome contribute to an increased cardiovascular risk in people with type 1 diabetes.
An Australian study found that for each unit increase in body mass index, the risk of developing diabetic retinopathy increases by 8%.
Several studies have highlighted an association between obesity and diabetic kidney disease in people with type 1 diabetes. A large UK study showed that among individuals with type 1 diabetes who developed diabetic kidney disease, there were twice as many people with obesity compared with those with preserved kidney function.
Recent research confirms that obesity is an important factor contributing to the development and progression of autoimmune diseases, which, like obesity, have seen a dramatic increase over the past few decades.
Several hypotheses have been proposed to explain the association between obesity and type 1 diabetes. It is well known that adipose tissue produces a range of adipokines involved in the regulation of numerous physiological functions, including immune responses. The accelerator hypothesis assumes that excess adipose tissue increases insulin resistance, resulting in glucotoxicity that accelerates beta-cell loss and increases immunogenicity in predisposed individuals. According to this hypothesis, both type 1 and type 2 diabetes are disorders of insulin resistance, representing two extremes of the diabetic spectrum.
The overload hypothesis suggests that beta-cell overload may be mediated by several mechanisms, including obesity-related insulin resistance, which makes beta cells more susceptible to immune system activity. In addition, unhealthy lifestyles supported by an obesogenic environment clearly contribute to the rising incidence of both types of diabetes.
Insulin therapy itself, as an anabolic hormone that promotes fat formation and accumulation as well as protein synthesis, contributes to additional weight gain in insulin-treated individuals, particularly due to the non-physiological subcutaneous route of administration that bypasses portal circulation. It has been shown that people treated with intensified insulin therapy gain an average of approximately 5 kg of body weight.
At present, there is insufficient evidence regarding the most appropriate weight-management strategies for people with type 1 diabetes.
Reduced caloric intake and regular physical activity are essential components of all obesity treatment strategies. In insulin-treated individuals, hypoglycaemia represents one of the main barriers to lifestyle-based interventions. Good education and modern technologies, particularly hybrid closed-loop systems, enable more effective management of these challenges.
Although the use of anti-obesity medications is not contraindicated in people with type 1 diabetes, there is insufficient evidence regarding their safety and efficacy in this population, as individuals with type 1 diabetes have been excluded from randomized clinical trials evaluating these drugs. Nevertheless, it seems reasonable to assume that people with type 1 diabetes who cannot achieve significant and sustained weight loss through lifestyle changes alone may benefit from these medications.
A 3 mg dose of liraglutide (GLP-1), approved for the treatment of obesity, has never been studied in people with type 1 diabetes. However, the efficacy and safety of lower doses of liraglutide have been evaluated in people with type 1 diabetes in the ADJUNCT clinical trials, which demonstrated significant, dose-dependent weight reduction, with an average loss of 4.0 kg with 1.8 mg of liraglutide daily. However, a higher incidence of hyperglycaemia with ketosis was observed with liraglutide. Results from the STEMT study investigating semaglutide at a dose of 1.0 mg once weekly in people with type 1 diabetes showed promising effects on body weight, insulin requirements, and glycaemic control. It should be emphasized that this was a non-randomized study with a small number of participants.
Off-label use of metformin in people with type 1 diabetes and insulin resistance is relatively common in clinical practice.
A meta-analysis of seven randomized controlled trials evaluating the addition of metformin to insulin therapy in people with type 1 diabetes showed a beneficial effect on weight reduction and total daily insulin requirements, but without a consistent effect on glycaemic control.
There is still limited knowledge about the outcomes of bariatric surgery in people with type 1 diabetes and obesity. According to a systematic review including 30 studies with a total of 706 individuals with type 1 diabetes and obesity who underwent bariatric surgery, significant weight loss and reduced insulin requirements were observed, but with an increased risk of hypoglycaemia and diabetic ketoacidosis. Careful monitoring and adjustment of insulin doses are therefore particularly important in the postoperative period.
Conclusion
The increasing prevalence of obesity among people with type 1 diabetes represents an additional risk factor for the development of diabetic complications and poses a major challenge to effective glycaemic and weight management. Given the lack of evidence on the most appropriate obesity treatment strategies in people with type 1 diabetes, there is an imperative need for further research through high-quality, well-designed studies, particularly regarding the use of anti-obesity medications.
Author: Prof. Sanja Klobučar, MD, PhD
