Excessively high body mass index (BMI) in late adolescence has been linked to development of type 1 diabetes (T1D), not just type 2 diabetes (T2D), according to research presented at the American Diabetes Association 82nd Scientific Sessions in New Orleans, LA.
“Our study adds to the growing evidence regarding the health hazards associated with adolescent obesity. Not only is adolescent obesity correlated with adult onset of type 2 diabetes as previously reported, but also with type 1 diabetes,” reported senior author Professor Gilad Twig, MD, PhD, of the Division of Endocrinology, Diabetes, and Metabolism at Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. The findings were also published in Diabetologia.
The rise in adolescent obesity has mirrored the increase in T1D, wrote the authors. To study whether excessively high BMI in adolescence is associated with T1D, the researcher studied all Israeli teenagers aged 16 to 19 years who were undergoing medical examination ahead of mandatory military service between January 1996 and December 2016. Data collected included height, weight, BMI, and blood work and were linked with information about adult-onset T1D in the Israeli National Diabetes Registry.
A total of 1.46 million adolescents were included in the study. The researchers identified 777 incident cases of T1D during 11.2 years of follow-up (mean age at diagnosis, 25 years). The incidence of T1D increased with BMI groups from underweight to obesity “from 3.6 to 8.4 cases per 100,000 person years, respectively,” reported the authors.
Compared with adolescents classified as having optimal BMI, adolescents with obesity (≥95th percentile in weight based on Centers for Disease Control and Prevention criteria) had double the risk of developing T1D, while those with overweight (85th-95th percentile) had a 54% increased risk of developing T1D. A mildly increased risk (41%) was evident among adolescents with BMIs in the higher end of normal range (75th-84th percentile). For the entire BMI range, the authors reported that for “every 5 kg/m2 increase in weight, the adjusted risk to develop type 1 diabetes increases by 35%.”
“Additional factors associated with obesity may contribute to the development of autoimmunity, including vitamin D deficiency, consumption of a high-fat diet, and modulation of the gut microbiota,” the authors wrote. “Given that, in our cohort, there was an association between adolescent obesity and type 1 diabetes even when excluding those with pre-existing autoimmune conditions, additional factors may link obesity specifically to type 1 diabetes.”
Several biological mechanisms have been suggested to explain the association between obesity and T1D, the authors noted. “The ‘accelerator’ hypothesis suggests that both type 1 and type 2 diabetes are caused by insulin resistance set against various genetic backgrounds that affect the rate of loss of beta cells” in the pancreas and thereby ultimately resulting in clinical presentation of diabetes. “According to this hypothesis, the increasing demand for insulin renders the beta cells more antigenic and thus accelerates their loss through autoimmune injury,” they said.
Genetic Link Between Obesity and Type 1 Diabetes
In addition, the researchers noted increasing evidence of a shared genetic basis for T1D, T2D, and obesity. The single nucleotide polymorphism (SNP) in “TCF7L2 is considered to be a strong risk factor for T2D and was recently also linked to increased risk for T1D, primarily in adolescents,” they wrote.
“Our findings have public health implications. The prevalence of adolescent obesity is rising worldwide at an alarming rate, with dire projections for the near future,” wrote the authors. “Currently it is estimated that nearly 60% of today’s US youth [ages 2-19 years] will develop obesity by age 35 years, most of them by adolescence, with half progressing to severe obesity. The current study projects that around 1 in 8 (12.8%) of the newly diagnosed cases of type 1 in the study can be attributed to abnormally excessive weight at adolescence.”
Zucker I, Zloof V, Bardugo A, et al. Obesity in late adolescence and incident type 1 diabetes in young adulthood. Diabetologia. 2022, June 4. [Published online ahead of print]. doi:10.1007/s00125-022-05722-5