Early-life exposure to the Chinese famine, genetic susceptibility and the risk of type 2 diabetes in adulthood

Aims/hypothesis: Early famine exposure has been related to the development of type 2 diabetes; however, little is known about whether the genetic background modifies this association. We aimed to investigate the joint effects of famine exposure at different stages of early life and genetic susceptibility on diabetes risk in adulthood. Methods: The study included 8350 participants from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) who were born around the time of the Chinese Great Famine. We determined famine exposure subgroups according to the birth year as nonexposed (1963–1974), fetal-exposed (1959–1962), childhood-exposed (1949–1958), and adolescence-exposed (1941–1948). We developed a genetic risk score of 21 variants previously associated with type 2 diabetes in East Asians. Hierarchical logistic models were used to examine the association of famine exposure and genetic risk with diabetes. Results: The age-standardised prevalence of diabetes in nonexposed, fetal-exposed, childhood-exposed and adolescence-exposed subgroups was 13.0%, 18.2%, 15.1% and 13.2%, respectively. Compared with nonexposed participants, fetal-exposed participants showed an increased risk of diabetes in adulthood (OR 1.47; 95% CI 1.13, 1.93). A higher genetic risk score was associated with an increased risk of diabetes (OR 1.23; 95% CI 1.15, 1.31 per SD increment). The association between famine exposure and diabetes was consistent across genetic risk strata (all p for interaction >0.05). When considered jointly, fetal- or childhood-exposed participants at high genetic risk (highest tertile of genetic risk score) had 2.60-fold (95% CI 1.71, 3.93) and 1.95-fold (95% CI 1.24, 3.05) higher risks of diabetes, respectively, compared with nonexposed participants at low genetic risk (lowest tertile). Conclusions/interpretations: Prenatal exposure to famine was associated with an increased risk of type 2 diabetes in Chinese adults independent of genetic risk score using 21 variants common in the East Asian population. Famine exposure and genetic susceptibility may exhibit an additive effect on diabetes development. Graphical abstract: [Figure not available: see fulltext.].