Elsevier

The Lancet

Volume 351, Issue 9097, 17 January 1998, Pages 173-177
The Lancet

Articles
Glucose tolerance in adults after prenatal exposure to famine

https://doi.org/10.1016/S0140-6736(97)07244-9Get rights and content

Summary

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.

Introduction

Decreased fetal growth is related to the occurrence of type 2 (non-insulin-dependent) diabetes in later life. In various populations and in different countries, decreased glucose tolerance in adults has been associated with low birthweight and thinness at birth.1, 2, 3, 4, 5, 6, 7, 8 Associations between decreased rates of fetal growth and impaired insulin-glucose metabolism have also been found in children and adolescents.9, 10, 11, 12, 13, 14

Retarded growth in utero during sensitive periods of development leads to permanent long-term changes in the body's structure, physiology, and metabolism. The “fetal origins hypothesis” proposes that impaired glucose tolerance and type 2 diabetes, together with the related disorders coronary heart disease and hypertension, are initiated by impaired fetal growth in mid to late gestation, which leads to disproportionate body size at birth.15 Nutrient supply to the fetus is thought to have strong influences on the fetus.15 Nutrient supply is determined by the mother's own fetal and childhood growth, her nutrition before and during pregnancy, and transfer capacity across the placenta. The fetal origins hypothesis is supported by studies on animals. If rats are undernourished during pregnancy, the offspring show persistent changes in insulin secretion and in responsiveness to the hormone.16, 17, 18, 19, 20

No studies directly link human maternal nutrition during specific periods of gestation with glucose tolerance later in life. The Dutch famine, which occurred in the western part of the Netherlands at the end of World War II, provides a unique opportunity to study such an effect.21, 22 The famine is clearly delineated in time (late November, 1944, to early May, 1945). The official rations varied from 400 calories to 800 calories per day in the first months of 1945. We investigated glucose and insulin responses in people who had been exposed to famine at any point during gestation (exposed participants) and in those who were born in the year before or conceived in the year after famine (non-exposed).

Section snippets

Methods

We traced 5425 people born between November, 1943, and February, 1947 in the Wilhelmina Gasthuis, one of the principal hospitals in Amsterdam at that time, for whom we obtained detailed records of the course of gestation and birth. Most patients were in the lower and middle social classes, but little is known about the referral pattern during that period. We retrieved from the Gemeentearchief (city archive) of Amsterdam the medical records of the 1380 liveborn singletons who were born between

Results

202 (28·8%) of the 702 people were born before the famine, 279 (39·7%) were exposed to famine during gestation, and 221 (31·4%) were conceived after the famine. Characteristics of mothers and babies (table 1) have been described in a detailed analysis of all 2414 births in the hospital (unpublished). Mothers exposed to famine during mid or late pregnancy weighed less than those not exposed. Babies born after famine exposure during mid or late gestation had lower birthweights, lengths, head

Discussion

We found an association between exposure to famine during gestation and decreased glucose tolerance in adults aged about 50 years. Glucose tolerance was decreased most among participants who were exposed to famine during mid or late gestation. Previous studies in human beings of the long-term effects of maternal malnutrition have used body size at birth as an indirect measure of fetal nutrition.26 We found links between decreased glucose tolerance and decreased fetal growth (low birthweight,

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