Serum apoA1 (Apolipoprotein A-1), Insulin Resistance, and the Risk of Gestational Diabetes Mellitus in Human Pregnancy.

OBJECTIVE apoA1 (apolipoprotein A-1) is the main lipoprotein associated with HDL (high-density lipoprotein) cholesterol. It was recently reported that intravenous infusion of apoA1 could lower insulin resistance in pregnant rats, leading to the suggestion that apoA1 could provide a target for reducing pregnancy-induced insulin resistance and the risk of gestational diabetes mellitus (GDM) in humans. However, the effects of apoA1 on insulin resistance and risk of GDM in human pregnancy are not known. Thus, we sought to systematically evaluate the relationships of apoA1 with glucose homeostasis and metabolic function in pregnant women. Approach and Results: In this study, 870 pregnant women were recruited in late second trimester and underwent metabolic characterization, including an oral glucose tolerance test on which 214 were diagnosed with GDM. Metabolic characterization included assessment of glucose tolerance, insulin sensitivity/resistance (Matsuda index, homeostasis model assessment of insulin resistance), pancreatic β-cell function, lipids (LDL [low-density lipoprotein] cholesterol, HDL cholesterol, triglycerides, apoB [apolipoprotein B], and apoA1), CRP (C-reactive protein), and adiponectin. Serum apoA1 was strongly correlated with HDL (r=0.79, P<0.0001) and weakly so with adiponectin (r=0.12, P=0.0004) but showed no association with measures of insulin sensitivity/resistance, β-cell function, glycemia, or CRP. There were no significant differences across apoA1 tertiles in mean adjusted Matsuda index (P=0.24), homeostasis model assessment of insulin resistance (P=0.08), or area under the glucose curve on the oral glucose tolerance test (P=0.96). Moreover, there were no differences in risk of GDM across tertiles of apoA1, both before (P=0.67) and after covariate adjustment (P=0.78). CONCLUSIONS Serum apoA1 is not associated with insulin resistance or the risk of GDM in human pregnancy.