Clinically Useful Estimates of Insulin Sensitivity During Pregnancy

Clinically Useful Estimates of Insulin Sensitivity During Pregnancy Validation studies in women with normal glucose tolerance and gestational diabetes mellitus John P. Kirwan , PHD 1 2 , Larraine Huston-Presley , MS 1 , Satish C. Kalhan , MD 3 and Patrick M. Catalano , MD 1 3 1 Reproductive Biology and 2 Nutrition and the 3 Schwartz Center for Metabolism & Nutrition, Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio Abstract OBJECTIVE —We examined whether selected indexes of insulin sensitivity derived from an oral glucose tolerance test (IS OGTT ) or fasting glucose/insulin levels (IS QUICKI and IS HOMA ) can be used to predict insulin sensitivity in women before and during pregnancy. RESEARCH DESIGN AND METHODS —A 2-h euglycemic-hyperinsulinemic clamp (5 mmol/l glucose, 40 mU · m −2 · min −1 insulin) and a 120-min oral glucose tolerance test (75 g load pregravid, 100 g pregnant) were repeated on 15 women (10 with normal glucose tolerance [NGT] and 5 with gestational diabetes mellitus [GDM]) pregravid and during both early (12–14 weeks) and late (34–36 weeks) pregnancy. An index of insulin sensitivity derived from the clamp (IS CLAMP ) was obtained from glucose infusion rates adjusted for change in fat-free mass and endogenous glucose production measured using [6,6- 2 H 2 ]glucose. RESULTS —Univariate analysis using combined groups and periods of pregnancy resulted in significant correlations between IS CLAMP and IS OGTT ( r 2 = 0.74, P < 0.0001), IS QUICKI ( r 2 = 0.64, P < 0.0001), and IS HOMA ( r 2 = 0.53, P < 0.0001). The IS OGTT provided a significantly better correlation ( P < 0.0001) than either IS QUICKI or IS HOMA. Multivariate analysis showed a significant group effect ( P < 0.0003) on the prediction model, and separate equations were developed for the NGT ( r 2 = 0.64, P < 0.0001) and GDM ( r 2 = 0.85, P < 0.0001) groups. When subdivided by period of pregnancy, the correlation between IS CLAMP and IS OGTT pregravid was r 2 = 0.63 ( P = 0.0002), during early pregnancy was r 2 = 0.80 ( P < 0.0001), and during late pregnancy was r 2 = 0.64 ( P = 0.0002). CONCLUSIONS —Estimates of insulin sensitivity from the IS OGTT during pregnancy were significantly better than from fasting glucose and insulin values. However, separate prediction equations are necessary for pregnant women with NGT and women with GDM. FFM, fat-free mass FPG, fasting plasma glucose FPI, fasting plasma insulin GDM, gestational diabete