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Elevated Homocysteine as a Risk Factor for the Development of Diabetes in Women With a Previous History of Gestational Diabetes Mellitus

A 4-year prospective study

¹ Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea
² Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
³ Department of Internal Medicine, Ilsin Christian Hospital, Pusan, Korea
⁴ Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois

Address correspondence and reprint requests to Nam H. Cho, MD, PhD, Department of Preventive Medicine, Ajou University School of Medicine, #5, Wonchon-Dong, Youngtong-Gu, Suwon, Korea. E-mail: chnaha{at}ajou.ac.kr

OBJECTIVE—To investigate the potential use of the plasma homocysteine level as a predictor of diabetes in women with a previous history of gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS—At 6 weeks’ postpartum, baseline examination was performed in 177 GAD-negative subjects. Of these subjects, 7 who were diagnosed with diabetes at baseline were excluded from further evaluation, and 170 with normal or impaired glucose tolerance (IGT) at baseline were followed annually over 4 years. The follow-up examinations included 2-h 75-g oral glucose tolerance tests (OGTTs), lipid profiles, homocysteine levels, anthropometric measurements, history taking, diet, and lifestyle. During the OGTTs, insulin and glucose levels were assayed every 30 min. Plasma homocysteine levels were determined by ion-exchange chromatography.

RESULTS—Of the 170 women, 18 (10.6%) converted to diabetes during the 4-year follow-up period. Mean age, BMI, fasting insulin, and total cholesterol at baseline (6 weeks’ postpartum test) were similar in the three study groups (i.e., normal, IGT, and diabetes). Fasting glucose levels, insulin-to-glucose ratios, and homocysteine levels were significantly higher in the diabetic group (P < 0.05). Higher glucose at the time of the diagnosis of GDM and higher homocysteine levels at baseline were independently associated with the onset of postpartum diabetes. These relationships were independent of age, BMI, and family history of diabetes.

CONCLUSIONS—This prospective study identified homocysteine level as a significant risk factor for development of diabetes in women with previous GDM.

Abbreviations: AUC, area under the curve • GDM, gestational diabetes mellitus • HOMA, homeostasis model assessment • IGT, impaired glucose tolerance • NGT, normal glucose tolerance • OGTT, oral glucose tolerance test • ROC, receiver operating characteristic

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