Long-term impact of pre-natal exposure to the Ukraine famine of 1932-1933 on adult type 2 diabetes mellitus

Abstract

AbstractImportanceThe long-term impacts of early-life famine exposure on Type 2 Diabetes Mellitus (T2DM) have been widely documented across countries, but it remains less clear what is the critical time window and if there is a dose-response between famine intensity and risk of T2DM.ObjectiveTo establish the relation between prenatal famine exposure and adult Type 2 diabetes mellitus (T2DM).DesignA national cross-sectional study.SettingThe man-made Ukrainian Holodomor famine of 1932-1933.ParticipantsA total number of 128,225 T2DM cases diagnosed at age 40 or over from the national diabetes register 2000-2008 in Ukraine. The population at risk includes 10,186,016 Soviet Ukraine births (excepting one oblast/province) between 1930-1938 classified by month and year and oblast of birth.ExposureBirths born in January-June 1934 from oblasts that experienced extreme, severe, or significant famine in 1932-1933. Famine intensity was measured based on the excess mortality during the famine.Main Outcomes and MeasuresT2DM diagnosis was based on WHO (1999) criteria.ResultsWe observed in univariate analysis a 1.8-fold increase in T2DM (OR 1.80; 95% CI 1.74-1.85) among individuals born in the first half-year of 1934 in regions with extreme, severe, or significant famine. We observed no increase among individuals born in regions with no famine. In multivariate analysis across regions and adjusting for season of birth we observed a larger than 2-fold increase (OR 2.21; 95% CI 2.00-2.45). There was a dose-response by famine intensity, with ORs increasing from 1.94 to 2.39 across regions. The pattern was similar in men and women.Conclusions and RelevanceBirths in the first half-year of 1934 were conceived at the height of the Ukraine famine in 1933. This relation for T2DM outcomes points to early gestation as a critical time window relating maternal nutrition in pregnancy to offspring health in later life. Further studies of biological mechanisms should focus on this time window for which changes in DNA methylation and later body size have also been observed.Key PointsQuestionWhat is the critical time window for early-life famine exposure on Type 2 Diabetes Mellitus (T2DM)? Is there any dose-response relationship between early-life famine exposure and T2DM?FindingsWe found an increased risk of T2DM (Odds Ratio 2.21; 95% CI 2.00-2.45) among individuals born during the first half-year of 1934. A clear dose-response relationship was observed using excess mortality as a measure of famine intensity.MeaningEarly gestation is a critical time window relating maternal undernutrition in pregnancy to offspring health in later life.