Shattering myths: Study reveals new insights on type 1 diabetes and obesity link

In a recent review published in the International Journal of Obesity, researchers reviewed recent advancements in epidemiological data about type 1 diabetes (T1D) and weight disorders. They explore the challenges scientists and clinicians face in studying and treating these associations. Their findings debunk multiple myths regarding T1D, most notably that the chronic condition only affects lean adolescents. Finally, this review presents recommendations for therapeutic interventions against T1D and guidelines for future research on the topic.

Study: The emergence of obesity in type 1 diabetes. Image Credit: Monkey Business Images

Obesity and diabetes – a brief history

Weight-related disorders, the most common of which are overweight and obesity, present substantial clinical and socioeconomic burdens globally. More than 1 billion individuals worldwide suffer from obesity, with the condition estimated to have claimed more than 5 million lives in 2019 alone. Alarmingly, changing trends in diet and physical activity are driving significant increases in obesity rates, with current obesity prevalence almost triple that of 1975. Western countries are worst affected by this negative trend, with reports highlighting that United States (US) obesity rates have seen a fourfold increase since 1980.

Compared to the far more prevalent type 2 diabetes (T2D), type 1 diabetes (T1D) is a rare, usually genetic condition affecting between 3-10% of people with diabetes. It is thought to be an autoimmune disorder and is characterized by the reduced or complete inability of the pancreas to produce insulin, resulting in a toxic buildup of sugar in a patient's bloodstream. Because its onset was historically noted in adolescents, the condition has been called 'juvenile' diabetes, but recent research has discovered that T1D can develop in individuals of any age group.

In the US, T1D is reported to affect 5.6% of all diabetic patients. A popular clinical notion was that T1D affects only lean individuals, with overweight and obese individuals immune to the condition. Given this notion and the post-coronavirus-2019 (COVID-19) trend of increasing overweight prevalence, T1D prevalence was expected to reduce. However, recent research has debunked this view and found a positive cyclic feedback association between excess weight disorders and T1D. This leads to predictions that T1D prevalence will increase from its current 3.7 million to more than 17 million by 2040.

T1D remains the less-studied diabetes version, with research into the disease a fraction of that into T2D. Improving professional and public knowledge about the disease, its causative agents, and optimal management strategies will allow clinicians to better prepare for the upcoming surge in T1D patients and improve the quality of life for all patients of this chronic condition.

About the study

The present review aims to elucidate current knowledge on the relationship between T1D and obesity, summarise the drivers of both conditions and discuss the best evidence-backed management strategies for treating T1D. The PubMed (MEDLINE) online scientific repository was searched for all publications researching obesity, T1D, their known contributors and risk determinants, and interventions against both conditions from database initiation till June 2023. More than 120 papers were identified for descriptive summarization and discussion following title, abstract, and full-text screening.

The reviewed literature was summarized under four main subheadings – 1. Multinational patterns of obesity with type 1 diabetes, 2. The distinctive biopsychosocial factors contributing to increased obesity in type 1 diabetes, 3. Treatments for obesity in patients with type 1 diabetes, and 4. Future directions for obesity management in type 1 diabetes.

Study findings

Unlike previously thought, overweight and obesity are significantly positively associated with T1D. Research has revealed that in adolescents between the ages of 16 and 19, every incremental standard deviation (SD) from mean body mass index (BMI) was associated with a 25% increased risk of developing T1D. These findings have been validated by Mendelian randomization studies and genome-wide association studies (GWAS).

Encouragingly, these GWAS also elucidated an unexpected finding – children with severe obesity (and, therefore, high T1D risk) could drastically reduce their T1D risk by up to 22% for every 10% weight loss. This suggests the existence of a critical window of opportunity wherein weight management interventions before the onset of T1D could potentially prevent the development of the condition, directly improving the futures of thousands or even millions of would-be diabetic patients.

This review highlights significant confound between metrics and methodologies used to measure overweight/obesity and T1D globally, as noted from the SEARCH (US-based), Diabetes Patienten Verlaufsdokumentation (Europe-based), Type 1 Diabetes Exchange (US-based), all of which found positive associations between obesity and T1D, but with prevalence ranging for just 15.3% to 36% or more. Similarly, the SWEET cohort (Europe, India, and Canada) documented a 10-trend of reduced childhood and adolescent obesity, whereas the Diabetes Control and Complications Trial (DCCT) found no such reductions. Finally, UK-based studies have found no association between obesity and T1D, contradicting the previously mentioned cohorts.

"Future comparative studies should assess the applicability of different obesity measurements in phenotyping obesity in T1D to ensure reliable epidemiological data."

The last few decades have seen unprecedented increases in poor health behaviors, most notably in the consumption of energy-dense foods (e.g., the Western diet) and shifts to highly sedentary lifestyles, especially following the COVID-19 pandemic and its associated 'work-from-home.' These trends have defined the obesogenic (obesity-inducing) landscape, which is now known to arise from a combination of genetic, political, socioeconomic, and cultural factors. Unfortunately, despite new risk contributors being discovered almost every day, most have not received adequate attention, both from clinicians and policymakers.

"First, there remains an inadequate comprehension of obesity in the pathogenesis of T1D, which may impede effective prevention and treatment strategies. Second, treating obesity is complicated by intensive insulin therapy, the standard of care for T1D, which paradoxically causes weight gain, creating a challenging dilemma for achieving weight management goals. Third, health disparities in T1D lead to a wide variation in disability-adjusted life years (DALY), with unaddressed gaps."

Notably, T1D is characterized by the induction of β-cell inflammation. This condition is exacerbated by obesity due to the latter's comorbidities, including lipotoxicity, mitochondrial dysfunction, glucotoxicity, adipose tissue damage, endocrine alterations, and the recently described imbalances in gut microbial communities. The interplay between these factors induces synergistic effects much more pronounced than any taken in isolation. Current research fails to incorporate these effects in its predictions and intervention recommendations, often resulting in suboptimal outcomes. Future clinical research should account for the holistic effects of T1D and diabetes and aim to treat body conditions rather than focus on one at the cost of the other.

An ideal example of this is exercise, the primary non-clinical intervention in obesity treatment. While high-intensity exercise significantly promotes weight loss, subjecting a T1D patient to vigorous physical activity can sometimes cause more harm than good because it increases hyperglycemia (high blood sugar), the main T1D complication. If used as an intervention, exercise must be tailored to account for both obesity and T1D (e.g., low-intensity walking as opposed to high-intensity running).

"Breakthroughs in insulin pumps, continuous glucose monitoring, and sensor-automated insulin devices help control glycaemic levels around most forms of exercise and hold the most optimistic hope in exercise safety."

Similarly, dietary and nutritional interventions tailored toward treating obesity may sometimes aggravate T1D, resulting in increases in pharmacotherapeutic interventions (insulin injections). Dietary interventions must be fine-tuned on a per-patient basis rather than a 'one-size-fits-all' medical nutrition therapy (MNT) approach.

The use of pharmacological interventions should similarly be extensively tested before use. Incretin mimetics (receptor agonists that increase insulin release from the pancreas) should be used with care lest they cause unexpected weight loss outcomes. The importance of patient education and adaptable care as a growing body of evidence suggests that patient-reported symptoms can closely resemble clinically diagnosed medical profiles and might be used as preliminary proxies for the latter.

"Finally, attention to healthcare inequality should intensify. The evolving technological innovations and limited availability of off-label medications are progressively tilting towards a first-world-centric resolution."

A growing body of research highlights that socioeconomically backward communities and racial minorities are the worst affected by T1D and obesity, a phenomenon aggravated by their being at increased risk of both conditions. Policymakers and pharmaceutical companies should ensure fair and cost-effective healthcare administration to all patients, irrespective of the size of their wallets.

Conclusions

T1D has historically received far less clinical and scientific interest than its much more prevalent T2D counterpart, resulting in numerous myths and misinformation about its prevalence, associated risk factors, and optimal treatment. Recent research has begun debunking these myths, revealing that the prevalence of T1D is higher than previously thought, and its incidence is expected to surge in the coming years. Unlike previously assumed, T1D is not restricted to lean individuals. Instead, its associations with weight abnormalities are synergistic and profound. Future research, policy, and interventions must be patient-specific and tailored to address T1D, obesity, and their comorbidities simultaneously.

"On a systemic level, an aligned multistakeholder initiative is needed to ensure the true value of the global action plan on this T1D-obesity burden."

Written by

Hugo Francisco de Souza

Hugo Francisco de Souza is a scientific writer based in Bangalore, Karnataka, India. His academic passions lie in biogeography, evolutionary biology, and herpetology. He is currently pursuing his Ph.D. from the Centre for Ecological Sciences, Indian Institute of Science, where he studies the origins, dispersal, and speciation of wetland-associated snakes. Hugo has received, amongst others, the DST-INSPIRE fellowship for his doctoral research and the Gold Medal from Pondicherry University for academic excellence during his Masters. His research has been published in high-impact peer-reviewed journals, including PLOS Neglected Tropical Diseases and Systematic Biology. When not working or writing, Hugo can be found consuming copious amounts of anime and manga, composing and making music with his bass guitar, shredding trails on his MTB, playing video games (he prefers the term ‘gaming’), or tinkering with all things tech.