Differential Effects of Birth Weight on Early-Onset Type 2 Diabetes in Adolescents and Young Adults

Abstract

Background: Type 2 diabetes mellitus (T2DM) is increasingly diagnosed in adolescents and young adults. However, the impact of birth weight (BW) on this early onset T2DM is not well quantified. Methods: A longitudinal study of Southwestern American Indians, aged ≥ 5 years, was conducted from 1965-2007. Subjects who had a recorded BW and at least one research exam that included an OGTT were followed until they developed T2DM or their last exam before the age of 40 years, whichever came first. Age-sex-adjusted incidence rate of T2DM was computed and Poisson regression models were used to estimate the effect of BW on the incidence of T2DM, adjusted for sex, BMI z-score (fitted as time-varying), and maternal variables, such as the presence of diabetes during pregnancy. The effect of BW on T2DM was non-proportional over time, and in some regression models, the effect was non-linear (quadratic). Therefore, all analyses were stratified by decade of age at follow-up and BW was analyzed as quintiles. Results: Among 4,275 subjects (52% females, median BW 3.45 kg), there were 728 incident cases of T2DM over a median follow-up of 20.6 years (7.5 cases per 1000 person-years). Incidence rates, stratified by decade of age at follow-up, were greater in females and in older age groups. In multivariable regression analyses, the effect of BW on T2DM risk varied by age group, showing a quadratic (U-shaped) effect at 10-19 years (P<0.05) and a negative linear effect at older age intervals (20-29 years, P=0.015; 30-39 years, P<0.001). We could not reliably estimate risk at 0-9 years because of few cases. Female sex, greater BMI z-score, and the presence of maternal diabetes in pregnancy added to the effect of BW on T2DM risk in all age groups. Conclusions: Both low and high BWs increased the risk of T2DM in adolescence, but only the effect of low BW persisted into young adulthood. Effects of female sex, accelerated growth, or being the offspring of a diabetic pregnancy added to the effect of BW on the risk of early onset T2DM. Disclosure M.T. Olaiya: None. M. Sinha: None. R.L. Hanson: None. S. Kobes: None. R. Nelson: None. W.C. Knowler: None.