LONGITUDINAL-STUDY OF CARBOHYDRATE-METABOLISM IN HEALTHY OBESE PREGNANT-WOMEN

OBJECTIVE - To longitudinally characterize changes in insulin sensitiv ity in obese women during and after pregnancy. RESEARCH DESIGN AND MET HODS - Six glucose-tolerant obese women underwent a 4-h euglycemic-hyp erinsulinemic (500-600 pmol/l) clamping during the second (22.5 +/- 2 weeks [mean +/- SD]) and third trimester (36.8 +/- 0.9) of pregnancy a nd again 15.6 +/- 1.4 weeks after delivery. Rates of total body glucos e turnover (with [6,6-H-2(2)]glucose) and oxidation (with indirect cal orimetry) were measured. RESULTS - There were no significant changes w ith respect to the action of insulin on rates of glucose disappearance (G(Rd)), carbohydrate oxidation, or endogenous glucose production (EG P), comparing the second trimester of pregnancy with the nonpregnant ( postpartum) state. The third trimester, however, was characterized 1) by reductions in insulin-stimulated G(Rd) (-28%, P < 0.05, compared wi th the second trimester and -40%, P < 0.05, compared with postpartum); 2) by even larger reductions in insulin-stimulated carbohydrate oxida tion (-46%, P < 0.05, compared with the second trimester and -54%, P < 0.02, compared with postpartum); and 3) by reduction of insulin suppr ession of EGP (-39% compared with -79% at the second trimester and -77 % postpartum, P < 0.01). CONCLUSIONS - Glucose-tolerant obese women de veloped peripheral as well as hepatic insulin resistance during the th ird trimester of pregnancy. These alterations were reversed after deli very and appeared to be adaptive mechanisms to cope with the increased demand for glucose of the growing fetus.