OBJECTIVE-To examine associations of fasting C-peptide, BMI, and maternal glucose with risk of preeclampsia, in a multicenter multinational study.STUDY DESIGN-Secondary analysis of blinded observational cohort study. Subjects underwent a 75-g OGTT at 24-32 weeks gestation. Associations of preeclampsia with fasting C-peptide, BMI, and maternal glucose were assessed using multiple logistic regression analyses, adjusting for potential confounders.RESULTS-Of 21,364 women included in analyses, 5.2% developed preeclampsia. Adjusted odds ratios (OR) for preeclampsia for 1 SD higher fasting C-peptide (0.87 ug/L), BMI (5.1 kg/m 2 ), fasting (6.9 mg/dl), 1-hour (30.9 mg/dl), and 2-hour plasma glucose (23.5 mg/dl) were 1.28 (1.20, 1.36), 1.60 (95% CI 1.60-1.71), 1.08 (95% CI 1.00-1.16), 1.19 (95% CI 1.11-1.28), and 1.21 (1.13-1.30), respectively. CONCLUSION-Resultsindicate strong, independent associations of fasting C-peptide and BMI with preeclampsia. Maternal glucose levels (below diabetes) had weaker associations with preeclampsia, particularly after adjustment for fasting C-peptide and BMI.Keywords preeclampsia associations; BMI; C-peptide; glucose INTRODUCTIONPreeclampsia complicates 2-8% of pregnancies worldwide and is associated with increased risk of adverse outcomes for mother and baby (1). It is a systemic disease characterized by increased vascular resistance, endothelial dysfunction, proteinuria and coagulopathy, in addition to hypertension (2). The pathophysiology is not completely defined but probably includes immune, genetic, and placental abnormalities. Insulin resistance and secretion rise during normal pregnancy; there is growing evidence that preeclampsia is related to increased insulin resistance during pregnancy (3-9). There is also strong evidence that women with Corresponding Author and Reprint Requests: Boyd E. Metzger, MD, Northwestern University Feinberg School of Medicine, Endocrinology, 645 N Michigan Ave, Chicago, IL 60611, bem@northwestern.edu NIH Public Access Author ManuscriptAm J Obstet Gynecol. Author manuscript; available in PMC 2011 March 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript higher pre-pregnancy body mass index (BMI) are more likely to develop preeclampsia (10-13).Most observational studies of GDM and preeclampsia included adjustment for maternal BMI (14-16), but none included adjustment for insulin resistance. Nordin, et al (17) showed that lesser degrees of glucose intolerance are associated with risk of preeclampsia; however, it is not clear if there was an independent association as this study did not include adjustment for BMI or other potential confounders. Another study looked at the association with preeclampsia across quartiles of glucose values below those diagnostic of GDM and found a positive association that became non-significant after adjustment for confounders (18). Thus, the nature of the association between lesser degrees of hyperglycemia and preeclampsia remains uncertain.The objective of the Hyperglycemia and Advers...

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