Physiologic and molecular alterations in carbohydrate metabolism during pregnancy and gestational diabetes mellitus.

Recent progress suggests that postreceptor mechanisms that contribute to insulin resistance of pregnancy appear to be multifactorial, but are exerted at the beta-subunit of the insulin receptor and at the level of IRS-1. Gestational diabetes mellitus represents the combination of acquired and intrinsic abnormalities of insulin action. The resistance to insulin-mediated glucose transport appears to be greater in skeletal muscle from GDM subjects than from pregnancy alone. There is also a modest but significant decrease in maximal insulin receptor tyrosine phosphorylation in muscle from obese GDM subjects. Results also suggest that increased insulin receptor serine/threonine phosphorylation and PC-1 could underlie the insulin resistance of pregnancy and pathogenesis of GDM. Whether additional defects are exerted further downstream from IRS-1 remains to be investigated.