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First-Trimester C-Reactive Protein and Subsequent Gestational Diabetes

From the Renal Unit, Department of Medicine and Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

OBJECTIVE—Systemic inflammation is associated with the development of type 2 diabetes. We tested the hypothesis that increased inflammation, measured early in pregnancy, is associated with the subsequent development of gestational diabetes mellitus (GDM), a precursor of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We conducted a prospective nested case-control study in a pregnancy cohort. First-trimester C-reactive protein (CRP) levels were measured using a high-resolution assay in 43 women who subsequently developed GDM and in a random sample of 94 women who remained euglycemic throughout pregnancy. Median CRP levels were compared using Wilcoxon’s rank-sum test. Logistic regression was used to compute unadjusted and multivariable-adjusted odds ratios for developing GDM among CRP tertiles.

RESULTS—First-trimester CRP levels were significantly increased among women who subsequently developed GDM compared with control subjects (3.1 vs. 2.1 mg/l, P < 0.01). The risk of developing GDM among women in the highest CRP tertile compared with the lowest tertile was 3.2 (95% CI 1.2–8.8). After adjusting for age, race/ethnicity, smoking, parity, blood pressure, and gestational age at CRP sampling, the risk of developing GDM among women in the highest compared with the lowest tertile was 3.6 (95% CI 1.2–11.4). When BMI was included in the model, however, the association between increased CRP and GDM was attenuated (odds ratio for the highest compared with lowest tertile 1.5 [95% CI 0.4–5.5]).

CONCLUSIONS—In women who develop GDM, there is evidence of increased inflammation during the first trimester. This association is mediated in part by increased BMI. Larger studies are needed to verify these results.

Abbreviations: CRP, C-reactive protein • CV, coefficient of variation • GDM, gestational diabetes mellitus • GLT, glucose-loading test • GTT, glucose tolerance test • IL-6, interleukin-6 • MOMS, Massachusetts General Hospital Obstetric Maternal Study • OR, odds ratio • TNF, tumor necrosis factor.

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