OBJECTIVE To longitudinally characterize changes in insulin sensitivity in obese women during and after pregnancy.

RESEARCH DESIGN AND METHODS Six glucose-tolerant obese women underwent a 4-h euglycemic-hyperinsulinemic (500–600 pmol/l) clamping during the second (22.5 ± 2 weeks [mean ± SD]) and third trimester (36.8 ± 0.9) of pregnancy and again 15.6 ± 1.4 weeks after delivery. Rates of total body glucose turnover (with [6.6⁻²H₂]glucose) and oxidation (with indirect calorimetry) were measured.

RESULTS There were no significant changes with respect to the action of insulin on rates of glucose disappearance (G_Rd), carbohydrate oxidation, or endogenous glucose production (EGP), comparing the second trimester of pregnancy with the nonpregnant (postpartum) state. The third trimester, however, was characterized 1) by reductions in insulin-stimulated GRd (−28%, P < 0.05, compared with the second trimester and −40%, P < 0.05, compared with postpartum); 2) by even larger reductions in insulin-stimulated carbohydrate oxidation (−46%, P < 0.05, compared with the second trimester and −54%, P < 0.02, compared with postpartum); and 3) by reduction of insulin suppression of EGP (−39% compared with −79% at the second trimester and −77% postpartum, P < 0.01).

CONCLUSIONS Glucose-tolerant obese women developed peripheral was well as hepatic insulin resistance during the third trimester of pregnancy. These alterationswere reversed after delivery and appeared to be adaptive mechanisms to copewith the increased demand for glucose of the growing fetus.