Clinically Useful Estimates of Insulin Sensitivity During Pregnancy

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 ⅐ m Ϫ2 ⅐ min Ϫ1 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 ϭ 0.74, P Ͻ 0.0001), IS QUICKI (r 2 ϭ 0.64, P Ͻ 0.0001), and IS HOMA (r 2 ϭ 0.53, P Ͻ 0.0001). The IS OGTT provided a significantly better correlation (P Ͻ 0.0001) than either IS QUICKI or IS HOMA. Multivariate analysis showed a significant group effect (P Ͻ 0.0003) on the prediction model, and separate equations were developed for the NGT (r 2 ϭ 0.64, P Ͻ 0.0001) and GDM (r 2 ϭ 0.85, P Ͻ 0.0001) groups. When subdivided by period of pregnancy, the correlation between IS CLAMP and IS OGTT pregravid was r 2 ϭ 0.63 (P ϭ 0.0002), during early pregnancy was r 2 ϭ 0.80 (P Ͻ 0.0001), and during late pregnancy was r 2 ϭ 0.64 (P ϭ 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. Diabetes Care 24:1602-1607, 2001A number of standard clinical procedures are available for evaluating maternal insulin sensitivity during pregnancy, including the euglycemichyperinsulinemic clamp, the oral glucose tolerance test (OGTT), the intravenous glucose tolerance test, the Minimal Model, and various derivations of fasting glucose and insulin levels. The euglycemic-hyperinsulinemic clamp is considered by many the "gold standard" among these procedures (1). Although the clamp method can provide a precise measure of insulin sensitivity under physiological conditions, it is a relatively complicated and labor-intensive procedure and is not suitable for large-scale clinical or epidemiological studies. Therefore, a simple but valid estimate of insulin sensitivity is desirable to monitor and possibly reduce the potential adverse effects associated with hyperinsulinemia and/or hyperglycemia during pregnancy.In a recent report, Matsuda and DeFronzo (2) validated an index of insulin sensitivity estimated from glucose and insulin levels during an OGTT (IS OGTT ) against the clamp procedure. Katz et al. (3) have also validated an index of insul...

Overweight is associated with impaired β-cell function during pregnancy: a longitudinal study of 553 normal pregnancies

“…Also, high variability of insulin responses might influence the reliability of computed indices, as is known from the HOMA indices (26). Validation of indices of insulin sensitivity in pregnancy has been done in women with NGT (nZ10) and GDM (nZ5) using clamp studies and OGTT (15). Correlations between clamp results and IS ogtt were in the range of 0.6-0.8, depending on glucose tolerance and time in pregnancy, and correlations between these dynamic methods performed Former investigations with indices of b-cell function and insulin sensitivity are mostly from mid-pregnancy and are not prospective.…”

“…In recent years, a number of indices of insulin sensitivity and b-cell function based on OGTT data have been developed (reviewed in (14)). Validation of such insulin sensitivity indices with clamp studies in pregnancy has been performed (15), and to our knowledge, similar evaluations for b-cell function in pregnancy have not been reported.…”

Increased Skeletal Muscle Tumor Necrosis Factor-α and Impaired Insulin Signaling Persist in Obese Women With Gestational Diabetes Mellitus 1 Year Postpartum

“…Hyperinsulinemic-euglycemic clamps. A single-stage 2-h hyperinsulinemiceuglycemic clamp with [6,6-2 H]glucose kinetics (5 mmol/l glucose, 40 mU ⅐ m Ϫ2 ⅐ min Ϫ1 ) was performed during late pregnancy (30 -36 weeks) and was repeated ϳ1 year after delivery, as previously described (27). Insulin sensitivity (M) was computed from the glucose infusion rate that was required to maintain blood glucose at 90 mg/dl, plus residual endogenous glucose output based on [6,6-2 H]glucose kinetics.…”

Pre‐gravid physical activity and reduced risk of glucose intolerance in pregnancy: the role of insulin sensitivity

“…Insulin sensitivity was measured using the insulin sensitivity index (IS OGTT ) of Matsuda and DeFronzo (24). In pregnant women, IS OGTT has been shown to exhibit stronger correlation with insulin sensitivity measured by euglycemic-hyperinsulinemic clamp than either Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) or Quantitative Insulin Sensitivity Check Index (25). Beta-cell function was assessed by the insulinogenic index divided by HOMA-IR (26,27).…”