Obesity in late adolescence and incident type 1 diabetes in young adulthood

Abstract

Aims/hypothesis Studies in children have reported an association between increased BMI and risk for developing type 1 diabetes, but evidence in late adolescence is limited. We studied the association between BMI in late adolescence and incident type 1 diabetes in young adulthood. Methods All Israeli adolescents, ages 16-19 years, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycaemia. Data were linked with information about adult onset of type 1 diabetes in the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied, with BMI being analysed both as a categorical and as a continuous variable. Results There were 777 incident cases of type 1 diabetes during 15,819,750 person-years (mean age at diagnosis 25.2 ±3.9 years). BMI was associated with incident type 1 diabetes. In a multivariable model adjusted for age, sex and sociodemographic variables, the HRs for type 1 diabetes were 1.05 (95% CI 0.87, 1.27) for the 50th-74th BMI percentiles, 1.41 (95% CI 1.11, 1.78) for the 75th-84th BMI percentiles, 1.54 (95% CI 1.23, 1.94) for adolescents who were overweight (85th-94th percentiles), and 2.05 (95% CI 1.58, 2.66) for adolescents with obesity (≥95th percentile) (reference group: 5th-49th BMI percentiles). One increment in BMI SD was associated with a 25% greater risk for incidence of type 1 diabetes (HR 1.25, 95% CI 1.17, 1.32). Conclusions Excessively high BMI in otherwise healthy adolescents is associated with increased risk for incident type 1 diabetes in early adulthood.

Cardiovascular outcomes in type 1 and type 2 diabetes

“…Recent data suggest a marked variation across countries and regions worldwide, potentially in response to heterogeneity in external factors [ 17 ]. Among factors postulated to be of interest are perinatal factors [ 18 ], and some hygienic factors that might indicate lack of microbial exposure in early life [ 19 ], while findings with respect to body weight and incident type 1 diabetes have been divergent [ 20 , 21 ]. Data obtained from the Global Burden of Disease study described temporal trends in the incidence of different types of diabetes mellitus from 1990 to 2017 at global, regional and national levels [ 22 ], with a higher increase in estimated annual percentage change in type 2 diabetes compared with type 1 diabetes.…”

Development of Type 1 Diabetes may occur through a Type 2 Diabetes mechanism

“…We did see changes in insulin-and insulin-like growth factor 2-receptor expression in tissue from T1D patients (and not in tissue from T2D patients, as was also found by western blotting (39)), but it is not currently clear what the implication of the finding is, since it has been found that a lack of insulin stimulation on beta cells can both decrease (40) and increase (41) insulin stimulation. Interestingly, we and others have found that overweight adolescents, predisposed to T2D, also have a higher risk of developing T1D (42,43). Furthermore, presence of insulin resistance can actually predict progression to T1D (44).…”

ER stress promotes mitochondrial DNA mediated type-1 interferon response in beta-cells and interleukin-8 driven neutrophil chemotaxis

“…In T1D, the induction of the UPR response to stress has been mostly described as an adaptive response of beta-cell to inflammatory environment. Yet, the recent association between obesity and T1D supporting the “accelerator hypothesis” that the rising demand for insulin during obesity could lead to autoimmunity may position the ER stress as possible cause for immune cell infiltration ( 49 ).…”