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Early Detection of Insulin Sensitivity and β-Cell Function with Simple Tests Indicates Future Derangements in Late Pregnancy

Department of Medical and Surgical Sciences (A.L., M.G.D., M.M., D.F.), University of Padova, 35100 Padova, Italy; Department of Gynecology, Perinatology and Human Reproduction (G.Mel., E.P., R.C.), and Laboratory (A.O., G.Mes.), Careggi Hospital, University of Florence, 4–50121 Florence, Italy; and Metabolic Modeling Unit, Institute of Biomedical Engineering (A.M., G.P.), and Aging Branch Institute of Neuroscience (C.M.), National Research Council, I-35127 Padova, Italy

Address all correspondence and requests for reprints to: Annunziata Lapolla, M.D., Department of Medical and Surgical Sciences, Via Giustiniani n 2, 35100 Padova, Italy. E-mail: annunziata.lapolla{at}unipd.it.

Objective: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM).

Research Design and Methods: The oral glucose tolerance test (OGTT) was performed in 903 women at 16–20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26–30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and β-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests.

Results: In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower β-cell function than ND. During the late visit, GDM2 also showed impaired β-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2.

Conclusions: In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. β-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.