Hormonal and Metabolic Factors Associated With Variations in Insulin Sensitivity in Human Pregnancy

OBJECTIVE: The objective of this study was to determine maternal hormonal and metabolic factors associated with insulin sensitivity in human pregnancy. RESEARCH DESIGN AND METHODS: This was a prospective observational cross-sectional study of 180 normal pregnant women, using samples collected at the time of a blinded oral glucose tolerance test (OGTT) between 24 and 32 weeks' gestation as an ancillary to the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The study was conducted at two public university teaching hospitals, Cleveland, Ohio, and Brisbane, Australia. Fasting maternal serum cholesterol, triglycerides, free fatty acids, insulin, leptin, tumor necrosis factor-α, placental growth hormone (PGH), insulin-like growth factors (IGFs) 1 and 2, and insulin-like growth factor binding proteins (IGFBPs) 1 and 3 were assayed. Correlation and multiple regression analyses were used to determine factors associated with maternal insulin sensitivity (IS) estimated using both OGTT-derived (IS(OGTT)) and fasting (using the homeostasis model assessment [HOMA]; IS(HOMA)) insulin and glucose concentrations. RESULTS: Insulin sensitivity correlated (r = x and y for IS(OGTT) and IS(HOMA,) respectively) with fasting maternal serum leptin (−0.44 and −0.52), IGFBP1 (0.42 and 0.39), and triglycerides (−0.31 and −0.27). These factors were significantly associated with insulin sensitivity in multiple regression analyses (adjusted R(2) 0.44 for IS(OGTT) and IS(HOMA)). These variables explained more than 40% of the variance in estimates of insulin sensitivity. CONCLUSIONS: Maternal hormonal and metabolic factors related to the placenta, adipose tissue, and the growth hormone axis are associated with the variation in insulin sensitivity seen during normal human pregnancy.