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Impaired Glucose Tolerance of Pregnancy Is a Heterogeneous Metabolic Disorder as Defined by the Glycemic Response to the Oral Glucose Tolerance Test

¹ Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada
² Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada
³ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
⁴ Division of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, Ontario, Canada

Address correspondence and reprint requests to Dr. Anthony Hanley, Mount Sinai Hospital, Lebovic Building, Room-L5-210, 600 University Ave., Toronto, Ontario, Canada M5G1X5. E-mail: hanley{at}mshri.on.ca

OBJECTIVE—Gestational diabetes mellitus (GDM), defined by two abnormal glucose values on a 3-h oral glucose tolerance test (OGTT), is associated with insulin resistance and a low serum concentration of adiponectin. The metabolic implications of impaired glucose tolerance (IGT) of pregnancy (i.e., a single abnormal value on an OGTT), however, are not well established. We sought to evaluate the metabolic phenotype of pregnant women with IGT in relation to the timing of their isolated hyperglycemia.

RESEARCH DESIGN AND METHODS—A cross-sectional study was performed in pregnant women undergoing a 3-h, 100-g OGTT. The OGTT stratified participants into four groups: 1) GDM (n = 48), 2) 1-h IGT (single elevated value at 1 h) (n = 15), 3) 2-h/3-h IGT (single elevated value at either 2 or 3 h) (n = 23), and 4) normal glucose tolerance (NGT) (n = 93). Insulin sensitivity was measured by the validated insulin sensitivity index (IS_OGTT) of Matsuda and DeFronzo.

RESULTS—Measures of severity of glycemia (fasting glucose, area under the glucose curve from the OGTT, and glucose challenge test result) were highest in the GDM group, followed by the 1-h IGT, 2-h/3-h IGT, and NGT groups, respectively (each trend P < 0.0001). Consistent with this finding, IS_OGTT was highest in the NGT group (5.1), followed by the 2-h/3-h IGT (4.6), 1-h IGT (3.8), and GDM (3.2) groups (trend P < 0.0001). Furthermore, on multiple linear regression analysis of IS_OGTT, both GDM and 1-h IGT were independently associated with reduced insulin sensitivity (whereas 2-h/3-h IGT was not). Mean adjusted adiponectin was highest in the NGT group (15.7 µg/ml), followed by the 2-h/3-h IGT (15.6 µg/ml), 1-h IGT (13.7 µg/ml), and GDM (12.0 µg/ml) groups (trend P = 0.0024).

CONCLUSIONS—The metabolic implications of IGT in pregnancy vary in relation to the timing of the abnormal glucose value from the diagnostic OGTT. The metabolic phenotype associated with 1-h IGT resembles that of GDM, whereas the phenotype associated with 2-h/3-h IGT exhibits similarity to that of NGT.

Abbreviations: AUC_glucose, area under the glucose curve • GCT, glucose challenge test • GDM, gestational diabetes mellitus • IGT, impaired glucose tolerance • NDDG, National Diabetes Data Group • NGT, normal glucose tolerance • OGTT, oral glucose tolerance test

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