Low Birth Weight Is Associated with a Nongenetic Higher Incidence Rate of Type 2 Diabetes

Background: Low birth weight, indictive of a poor fetal environment, is a risk factor for type 2 diabetes (T2D) . Most previous studies were based on cross sectional prevalence data and not designed to study the timing of onset of T2D in relation to birth weight (BW) . Furthermore, earlier studies have not adjusted for common genetic variation influencing BW. We aimed to examine associations of BW with age-specific incidence of T2D using BW polygenetic risk scores (BWPRS) to adjust for genetic confounding. Methods: Adults (30-60 years) enrolled in the Inter99 cohort from 1999-20with information on BW from original birth records, and without diabetes at baseline were eligible. Birth records were linked with individual-level data on T2D incidence from the Danish Diabetes Register and key covariates from the Inter99 study. Incidence rates of T2D as a function of age, sex and BW were modelled using Poisson regression and adjusted for adult BMI, socioeconomic status, maternal history of diabetes and BWPRS. Results: Among 4584 participants there were 438 incident cases of T2D during a mean follow-up of 18 years. BW was inversely associated with T2D with a higher incidence in men. T2D incidence increased with age and the rate of increase was higher in persons with lower BW compared with higher BW in a dose-response manner. Conclusion: A lower birth weight is associated with a greater increase in incidence rate of T2D in a non-genetic manner. Disclosure R.Wibaek: Stock/Shareholder; Novo Nordisk A/S. G.S.Andersen: Stock/Shareholder; Novo Nordisk A/S. A.Linneberg: None. N.Grarup: None. T.Hansen: None. C.Brøns: Stock/Shareholder; Novo Nordisk. D.Vistisen: Research Support; Bayer AG, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi, Stock/Shareholder; Novo Nordisk A/S. A.A.Vaag: Stock/Shareholder; AstraZeneca. Funding Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation (NNF17SA0031406)