To assess the mechanisms esponsible for the insulin resistance associated with both normal human pregnancy and gestational-onset diabetes, we have measured exogenus glucose disposal using sequential insulin infusions with the euglycemic glucose clamp technique and erythrocyte insulin binding. Three groups of women were studied: nonpregnant women with normal glucose tolerance (N=7, mean age 32.9 ± 2.1 yr), pregnant women with normal glucose tolerance (N=5, mean age 24.8 ± 3.5 Yr), and pregnant women with gestational-onset diabetes (N=5, mean age 34.6 ± 2.6 yr). Despite normal plasma glucose levels obtained during a 100-g oral glucose tolerance test, plasma insulin levels were significantly elevated in pregnant women compared with the nonpregnant control subjects, suggesting a state of insulin resistance. Insulin binding to erythrocytes was similar in all three groups (maximum specific binding being 5.0 ± 0.6%, 5.5 ± 1.1%, and 6.0 ± 0.7% in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively). In vivo peripheral insulin action was measured using the euglycemic glucose clamp technique during an insulin infusion of 40 mU/m2.min, with bolld glucose slamped at a concentration of 75 mg/dl using a variable glucose infusion. Glucose infusion rates were 213 ± 11 mg/ml2.min, 143 ± 23 mg/m2.min, and 57 +18 mg/m2.min in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively. This demonstrates that pregnant subjects display a state of insulin resistance, and that this appears to be more marked in gestational-onset diabetic subjects. To further define the possible mechanism of insulin resistance during pregnancy, the insulin infusion rate was increased to 240 mU/m2.min and further euglycemic clamp measurements performed. Glucose infusion rates were 372 ± 11 mg/m2.min, 270 ± 31 mg/m2.min, and 157 ± 26 mg/m2.min, in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively. This demonstrates a shift to the right of dose-response curve of insulin action and suggests that the insulin resistance of pregnancy may include a decrease in presumed 'maximum' insulin responsivity. In four subjects, studies were repeated in post-partum period, and these demonstrated that the insulin resistance of pregnancy is ameliorated shortly after delivery. These studies suggest that the insulin resistance of pregnancy results from a target cell defect in insulin action beyond the initial step of insulin binding to cellular receptors, a postreceptor (or postbinding) defect in insulin action.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism