Clinically useful estimates of insulin sensitivity during pregnancy: validation studies in women with normal glucose tolerance and gestational diabetes mellitus.
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.


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.
Kirwan
J P
JP
Department of Reproductive Biology, Case Western Reserve University School of Medicine at MetroHealth Medical Center, Bell Greve Building, 2500 MetroHealth Dr., Cleveland, OH 44109-1998, USA. jkirwan@metrohealth.org
Huston-Presley
L
L
Kalhan
S C
SC
Catalano
P M
PM
D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition; D016640:Diabetes, Gestational / Q000097:blood*; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D011247:Pregnancy / Q000097:blood* / Q000502:physiology; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D012016:Reference Values; D012044:Regression Analysis; D015203:Reproducibility of Results
D001786:Blood Glucose; D007328:Insulin