2 Aetiology of gestational diabetes

Abstract

Glucose tolerance deteriorates in human pregnancy, but about 97-98% of all pregnant women retain a normal glucose tolerance and only 2-3% develop gestational diabetes. The data reviewed show that the diabetogenicity of pregnancy is not due to diminished secretion of insulin or disproportional secretion of proinsulin or glucagon, nor is an increased insulin degradation involved. Only quantitative differences in insulin secretion have been observed between normal pregnant women and women with gestational diabetes. The insulin responses to an oral glucose load or a test meal are thus lower in gestational diabetic women than in normal pregnant women, despite significantly higher plasma glucose concentrations in the gestational diabetics. Also the insulin responses to intravenous glucose injections or infusions are abnormal in gestational diabetics when compared with normal pregnant women, a difference which is still detectable for some time after the completion of pregnancy in at least a fraction of gestational diabetic women. There is thus ample evidence that the diabetogenicity of pregnancy is related to a pronounced peripheral resistance to insulin. The resistance is of a similar magnitude in normal pregnant women and women with gestational diabetes, and it does not seem to be caused by significant alterations in insulin receptor binding to target tissues. The insulin resistance of the whole body is increased to about three times that seen in the non-pregnant state. The increased resistance is caused by post-insulin receptor events and is probably brought about by the cellular effects of the increased plasma levels of one or more of the pregnancy-associated hormones and free cortisol. There is evidence that the resistance is predominantly located to the muscle tissue, where significant reductions in certain key enzymes in glucose and lipid metabolism have been demonstrated. Published evidence points to a similar degree of insulin resistance in normal pregnant women and normal weight women with gestational diabetes. Most normal pregnant women are able to counteract the peripheral resistance by a significant augmentation of their basal and nutrient-stimulated insulin secretion. However, a few (2-3%) of the women do not appear to have the capability to produce a sufficiently large increase in insulin secretion and hence cannot overcome the peripheral resistance. These are the women who become glucose intolerant to such an extent that the diagnostic criteria for gestational diabetes are fulfilled.