Birthweight and early-onset type 2 diabetes in American Indians: differential effects in adolescents and young adults and additive effects of genotype, BMI and maternal diabetes.

Abstract

The aim of this work was to estimate the impact of birthweight on early-onset (age <40years) type 2 diabetes. A longitudinal study of American Indians, aged ≥5years, was conducted from 1965 to 2007. Participants who had a recorded birthweight were followed until they developed diabetes or their last examination before the age of 40years, whichever came first. Age- and sex-adjusted diabetes incidence rates were computed and Poisson regression was used to model the effect of birthweight on diabetes incidence, adjusted for sex, BMI, a type 2 diabetes susceptibility genetic risk score (GRS) and maternal covariates. Among 3039 participants, there were 652 incident diabetes cases over a median follow-up of 14.3years. Diabetes incidence increased with age and was greater in the lowest and highest quintiles of birthweight. Adjusted for covariates, the effect of birthweight on diabetes varied over time, with a non-linear effect at 10-19years (p < 0.001) and a negative linear effect at older age intervals (20-29years, p < 0.001; 30-39years, p = 0.003). Higher GRS, greater BMI and maternal diabetes had additive but not interactive effects on the association between birthweight and diabetes incidence. In this high-risk population, both low and high birthweights were associated with increased type 2 diabetes risk in adolescence (age 10-19years) but only low birthweight was associated with increased risk in young adulthood (20-39years). Higher type 2 diabetes GRS, greater BMI and maternal diabetes added to the risk of early-onset diabetes.