Mechanism of Insulin Resistance in Normal Pregnancy

Normal pregnancy is associated with insulin resistance although the mechanism is not understood. Increased intramyocellular lipid is closely associated with the insulin resistance of type 2 diabetes and obesity, and the aim of this study was to determine whether this was so for the physiological insulin resistance of pregnancy. Eleven primiparous healthy pregnant women (age: 27-39 years, body mass index 24.0 +/- 3.1 kg/m(2)) and no personal or family history of diabetes underwent magnetic resonance studies to quantify intramyocellular lipid, plasma lipid fractions, and insulin sensitivity. The meal-related insulin sensitivity index was considerably lower in pregnancy (45.6 +/- 9.9 vs. 193.0 +/- 26.1; 10(-4) dl/kg/min per pmol/l, p = 0.0002). Fasting plasma triglyceride levels were elevated 3-fold during pregnancy (2.3 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, p < 0.01) and the low-density density lipoprotein fraction, responsible for fatty acid delivery to muscle and other tissues, was 6-fold elevated (0.75 +/- 0.43 vs. 0.12 +/- 0.09 mmol/l; p = 0.001). However, mean intramyocellular lipid concentrations of the soleus muscle were not different during pregnancy (20.0 +/- 2.3 vs. 19.1 +/- 3.2 mmol/l, p = 0.64). The pregnancy effect on muscle insulin resistance is distinct from that underlying type 2 diabetes.