Hormonal and metabolic factors associated with variations in insulin sensitivity in human pregnancy

Abstract

Objective: To determine maternal hormonal and metabolic factors associated with insulin sensitivity in human pregnancy

Research Design and Methods: Prospective observational cross sectional study of one hundred and eighty normal pregnant women, using samples collected at the time of blinded oral glucose tolerance testing between 24 and 32 weeks gestation as an ancillary to the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Setting - two public university teaching hospitals — Cleveland, Ohio, USA and Brisbane, Australia. Methods of assessment - Fasting maternal serum cholesterol, triglycerides, free fatty acids, insulin, leptin, tumour necrosis factor alpha, 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 estimated using both OGTT derived (IS _OGTT) and fasting (IS _HOMA) insulin and glucose concentrations.

Results: Insulin sensitivity correlated (r = x, y for IS _OGTT, IS _HOMA respectively) with fasting maternal serum leptin (−0.44, −0.52 ), IGFBP1 ( 0.42, 0.39) and triglycerides (−0.31, −0.27 ). These factors were significantly associated with insulin sensitivity in multiple regression analyses (adjusted R² 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.