*note that this article is published in Diabetologia at the same time as it is presented at the annual meeting of the American Diabetes Association in New Orleans, Louisiana, USA*
A new study published in Diabetologia and presented this year at the American Diabetes Association annual meeting in New Orleans, Louisiana, USA, shows that an excessively high body mass index (BMI) in adolescents is linked to the development of type 1 diabetes (the form of the condition most associated with autoimmune complications), not just the type 2 form usually associated with excess weight. The study is carried out by Professor Gilad Twig, Sheba Medical Center, Israel and his colleagues.
Type 1 diabetes is traditionally called childhood diabetes, occurring in children of any age and weight, although it can also develop in adolescence and into adulthood. However, the rapidly growing epidemic of diabetes in almost all countries today consists mainly of cases of type 2 diabetes, linked to risk factors such as obesity/overweight, low activity physique and increased sedentary behavior.
More recently, studies in younger children have reported an association between increased BMI and the risk of developing type 1 diabetes, but the evidence in late adolescence is limited. This is interesting because about 50% of type 1 diabetes cases developed after late adolescence (from age 18). In this new study, the authors analyzed the association between BMI in late adolescence and incident type 1 diabetes in young adults.
In this nationwide study, all Israeli adolescents, ages 16-19, undergoing medical evaluation for mandatory military conscription between January 1996 and December 2016 were included for analysis, unless they had a history of blood sugar abnormal. A total of 1.46 million adolescents were included. The data was linked to information on the onset of type 1 diabetes in adults in Israel’s National Diabetes Registry. Weight and height were measured at the start of the study, and statistical modeling was used to calculate any excess risk of type 1 diabetes associated with overweight or obesity.
There were 777 new cases of type 1 diabetes during 15,819,750 person-years of follow-up (mean age at diagnosis 25 years). BMI was found to be associated with the incidence of type 1 diabetes. In a model adjusted for age, sex, and sociodemographic variables, the increased risk of type 1 diabetes increased with increasing blood pressure. ‘BMI.
Compared to adolescents classified as optimal BMI (5e-49e BMI percentiles corresponding to age and sex according to the United States Centers for Diseases Control and Prevention [CDC]), obese adolescents (≥95e percentile) had double the risk of developing type 1 diabetes, while overweight people (85e-94e BMI percentile) had a 54% increased risk of type 1 diabetes. A slight increased risk (41%) was evident for BMI values in the upper normal range (75e-84e BMI percentiles). For the entire BMI range, the authors reported that every 5 kg/m2 the adjusted risk of developing type 1 diabetes increases by 35%.
The authors discuss that there is growing evidence of a link between obesity and various autoimmune diseases. One possible explanation they provide is that the elevated levels of adipokines and inflammatory cytokines associated with obesity decrease self-tolerance by promoting pro-inflammatory processes that lead to diabetes.
They add, “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. Given that in our cohort there was an association between adolescent obesity and type 1 diabetes, even excluding those with pre-existing autoimmune diseases, additional factors may specifically link obesity to type 1 diabetes.”
They explain that several biological mechanisms have been suggested to explain the association between obesity and type 1 diabetes. The “accelerator” hypothesis suggests that both type 1 and type 2 diabetes are caused by resistance to insulin in various genetic backgrounds that affect the rate of loss of insulin-producing beta cells in the pancreas and thus ultimately lead to the clinical presentation of diabetes. According to this hypothesis, the increasing demand for insulin makes beta cells more “antigenic” (prone to self-destruction) and thus accelerates their loss by autoimmune injury.
The authors conclude: “Our findings have public health implications. The prevalence of adolescent obesity is increasing worldwide at an alarming rate, with dire projections for the near future. Currently, it is estimated that nearly 60% of young Americans today (age range, 2-19) will develop obesity by the age of 35, with most in adolescence, half progressing to severe obesity. The current study predicts that approximately 1 in 8 (12.8%) of newly diagnosed type 1 cases in the study can be attributed to abnormally excessive weight in adolescence. Thus, with the increase in obesity levels, in particular that of the severe form, it can be expected that the current annual increase in type 1 cases (which varies between +2% and +4% in most high-income countries) is even more pronounced.”
“Our study adds to the growing evidence regarding the health risks associated with adolescent obesity. Not only is adolescent obesity correlated with the onset of type 2 diabetes in adulthood, as noted earlier, but also with type 1 diabetes. More work needs to be done to untangle this association so that we we can better address the full range of risks posed by the obesity epidemic or identify common environmental factors affecting both weight and type 1 diabetes.”