Association between type 2 diabetes and prenatal exposure to the Ukraine famine of 1932-33: a retrospective cohort study

Abstract

Background: The effect of fetal and early childhood living conditions on adult health has long been debated, but empirical assessment in human beings remains a challenge. We used data from during the man-made Ukrainian famine of 1932-33 to examine the association between restricted nutrition in early gestation and type 2 diabetes in offspring in later life.

Methods: We included all patients with type 2 diabetes diagnosed at age 40 years or older in the Ukraine national diabetes register 2000-08, and used all individuals born between 1930 and 1938 from the 2001 Ukraine national census as the reference population. This study population includes individuals born before and after the famine period as controls, and those from regions that experienced extreme, severe, or no famine. We used prevalence odds ratios (ORs) as the measure of association between type 2 diabetes and early famine exposure, with stratification by region, date of birth, and sex for comparisons of diabetes prevalence in specific subgroups.

Findings: Using these two datasets, we compared the odds of type 2 diabetes by date and region of birth in 43,150 patients with diabetes and 1,421,024 individuals born between 1930 and 1938. With adjustment for season of birth, the OR for developing type 2 diabetes was 1·47 (95% CI 1·37-1·58) in individuals born in the first half of 1934 in regions with extreme famine, 1·26 (1·14-1·39) in individuals born in regions with severe famine, and there was no increase (OR 1·00, 0·91-1·09) in individuals born in regions with no famine, compared with births in other time periods. Multivariable analyses confirmed these results. The associations between type 2 diabetes and famine around the time of birth were similar in men and women.

Interpretation: These results show a dose-response relation between famine severity during prenatal development and odds of type 2 diabetes in later life. Our findings suggest that early gestation is a critical time window of development; therefore, further studies of biological mechanisms should include this period.

Funding: Ukraine State Diabetes Mellitus Program, US National Institutes of Health.