Glucose tolerance in adults after prenatal exposure to famine

Abstract

Background: Reduced growth in utero is associated with type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance in adult life. There is no direct evidence in human beings that maternal nutrition during gestation affects insulin-glucose metabolism. We investigated glucose tolerance in people born around the time of famine in the Netherlands during 1944-45.

Methods: We included 702 people born between Nov 1, 1943, and Feb 28, 1947, in Amsterdam, for whom we had detailed prenatal and birth records. We compared glucose and insulin responses to a standard oral glucose load in participants exposed to famine at any stage during gestation (exposed participants) with those who were born in the year before or conceived in the year after the famine (non-exposed participants).

Findings: Glucose concentrations were increased 2 h after a standard glucose load among exposed participants (p = 0.006), and were highest in men and women exposed during mid and late gestation. Mean 2 h glucose concentration among non-exposed participants was 5.8 mmol/L; concentrations were 0.5 mmol/L (95% CI 0.1-0.9) higher among participants exposed during late gestation, 0.4 mmol/L (0-0.8) higher among those exposed during mid gestation, and 0.1 mmol/L (-0.4 to 0.6) among those exposed during early gestation. Participants born as thin babies to mothers with low bodyweights had the highest concentrations and concentrations were especially high among people exposed to famine who became obese as adults. Prenatal exposure to famine was related to increased fasting proinsulin (p = 0.05) and 2 h insulin concentrations (p = 0.04), which suggests an association with insulin resistance.

Interpretation: Prenatal exposure to famine, especially during late gestation, is linked to decreased glucose tolerance in adults. Poor nutrition in utero may lead to permanent changes in insulin-glucose metabolism, even if the effect on fetal growth is small. This effect of famine on glucose tolerance is especially important in people who become obese.