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Persistent Elevation and Metabolic Dependence of Circulating E-Selectin after Delivery in Women with Gestational Diabetes Mellitus

Department of Medicine III, Division of Endocrinology and Metabolism (A.K-W., P.F., W.W.), Department of Clinical Pharmacology (B.J.) and Department of Medical and Chemical Laboratory Diagnostics (O.F.W.), University of Vienna, Austria

Address all correspondence and requests for reprints to: Oswald F Wagner, Department of Clinical and Chemical Laboratory Diagnostics, University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria.

The increased risk of premature atherosclerosis in noninsulin-dependent diabetes mellitus (NIDDM) might be related in part to augmented expression of endothelial adhesion molecules (AMs). So far it is, however, unknown whether increased circulating (c) AMs in NIDDM are only a consequence of this disease or also involved in its sequelae.

To determine the presence of cAMs in a population at increased risk for subsequent development of NIDDM, we analyzed fasting and postprandial [oral glucose tolerance test (OGTT): 100 g] serum concentrations of circulating E-selectin, vascular cell adhesion molecule-1 (cVCAM-1), and intercellular adhesion molecule-1 (cICAM-1) in pregnant women with either gestational diabetes (GDM) or normal glucose tolerance (NT) before and after delivery vs. nonpregnant healthy women (C). During pregnancy cE-selectin and cVCAM-1 were elevated in both GDM and NT vs. nonpregnant females (P < 0.01 vs. C). Following delivery, all GDM females regained normal glucose tolerance according to OGTT criteria, but showed slightly higher postprandial [area under the curve (AUC)_{180 min}] glycemia and HbA1c values than nonpregnant healthy women (P < 0.05), indicating persisting subtle abnormalities in carbohydrate metabolism. cE-selectin and cVCAM-1 remained increased in GDM (P < 0.01 vs.C) after delivery, but fell to normal in NT (P < 0.05 before vs. after delivery). Furthermore, a correlation was seen in GDM females between cE-selectin and HbA1c (P < 0.005), fasting glucose (P < 0.01), and insulin (P < 0.05) as well as postprandial (AUC_{180 min}) glucose and insulin concentrations (P < 0.05) during OGTTs, both before and after delivery. ICAM-1, however, did not differ significantly between groups.

In summary, GDM is characterized by persistently raised levels of cE-selectin and cVCAM-1 12 weeks after delivery. Whether these persistent elevations of cE-selectin and cVCAM-1 reflect early vascular injury or represent a risk factor for atherosclerosis in women at increased risk for NIDDM remains to be determined.

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