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Free Fatty Acids and Insulin Resistance during Pregnancy¹

Departments of Obstetrics/Gynecology (E.S., C.J.H., P.G.W., E.A.R.) and Medicine (X.C., G.B.), Temple University Hospital, Philadelphia, Pennsylvania 19140

Address all correspondence and requests for reprints to: Guenther Boden, M.D., Temple University Hospital, 3401 North Broad Street, Philadelphia, Pennsylvania 19140.

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 hyperinsulinemic (1 mU/kg·min) clamping during the early second trimester of pregnancy (14–17 weeks) on 2 consecutive days, receiving either lipid (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 disposal (6,6-²H₂ glucose) and of carbohydrate and fat oxidation (indirect calorimetry) were determined at hourly intervals. Blood glucose was clamped at about 85 mg/dL. Plasma FFA increased from 290 ± 50 to 1000 ± 139 µmol/L during L/H infusion and decreased from 351 ± 60 to 35 ± 11 µmol/L during S/G infusion. L/H infusion inhibited insulin 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 infusion 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 decreased equally by approximately 70% during L/H and S/G infusions. These data showed that elevating plasma FFA levels during early pregnancy inhibits total body glucose uptake and oxidation. We conclude that elevation of plasma FFA can contribute to the peripheral insulin resistance commonly observed during late pregnancy.

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