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 -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 -cell function than ND. During the late visit, GDM2 also showed impaired -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. -Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance. (J Clin Endocrinol Metab 93: 876 -880, 2008) N ormal pregnancy can be considered a state of insulin resistance because insulin sensitivity decreases in pregnancy, reaching its nadir in the third trimester and rapidly returning to prepregnancy levels after delivery (1-4). Although the specific mechanisms behind the progressive insulin resistance during pregnancy have not been completely clarified, an important contribution seems to come from the endocrine modifications characteristic of pregnancy, including the increase in estrogens, progesterone, human placental lactogen, cortisol, and TNF-␣ (5, 6). Both insulin resistance (7) and a defective insulin secretion and action (8, 9) also characterize gestational diabetes mellitus (GDM).The euglycemic glucose clamp, the "gold standard" for assessing insulin sensitivity, has been used in pregnancy, but the test is complex, so most of the studies were performed on a small number of patients (1-3). Studies on insulin secretion, which usually simply evaluated the area under the concentration curve (1, 2), only rarely also using the glucose clamp (9), have involved a small number of patients, who were obese in most cases (1, 9). Evaluation of insulin sensitivity and secretion in large numbers Abbreviations: AUC, Area under the curve; AUC glu , area under the glucose concentration curve; AUC ins , area under the insulin concentration curve; AUCR, area under the curv...
