FREE FATTY-ACIDS AND INSULIN-RESISTANCE DURING PREGNANCY

The purpose of this study was to determine whether elevation of plasma free fatty acids (FFA) in early pregnancy would cause alterations in insulin-stimulated glucose disposal similar to those occurring in late gestation. Seven glucose-tolerant women underwent 4-h euglycemic hype rinsulinemic (1 mU/kg.min) clamping during the early second trimester of pregnancy (14-17 weeks) on 2 consecutive days, receiving either lip id (Liposyn II; 1.5 ml/min) and heparin (0.4 U/kg.min; L/H) or saline/ glycerol (2.25 g/h; S/G) infusions. Rates of total body glucose dispos al (6,6-H-2(2) glucose) and of carbohydrate and fat oxidation (indirec t calorimetry) were determined at hourly intervals. Blood glucose was clamped at about 85 mg/dL. Plasma FFA increased from 290 +/- 50 to 100 0 +/- 139 mu mol/L during L/H infusion and decreased from 351 +/- 60 t o 35 +/- 11 mu mol/L during S/G infusion. L/H infusion inhibited insul in stimulation of total body glucose disposal by 28% compared with S/G infusion (from 6.7 +/- 0.7 to 4.9 +/- 0.6 mg/kg min; P < 0.01). L/H i nfusion increased fat oxidation from 0.73 +/- 0.04 to 1.26 +/- 0.2 mg/ kg.min (P < 0.05) and decreased carbohydrate oxidation from 2.0 +/- 0. 2 to 1.6 +/- 0.2 mg/kg min (P < 0.05). Endogenous glucose production d ecreased equally by approximately 70% during L/H and S/G infusions. Th ose data showed that elevating plasma FFA levels during early pregnanc y inhibits total body glucose uptake and oxidation. We conclude that e levation of plasma FFA can contribute to the peripheral insulin resist ance commonly observed during late pregnancy.