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C-Reactive Protein and Gestational Diabetes: The Central Role of Maternal Obesity

Division of Endocrinology (R.R., A.J.G.H., B.Z.), University of Toronto, Toronto M5G 1X5, Ontario, Canada; Leadership Sinai Centre for Diabetes (A.J.G.H., N.R., B.Z.), and Division of Obstetrics and Gynecology (M.S.), Mount Sinai Hospital, Toronto M5G 1X5, Ontario, Canada; and Department of Laboratory Medicine and Pathobiology, Univeristy of Toronto, Toronto M5G 1X5, Ontario, Canada

Address all correspondence and requests for reprints to: Dr. Bernard Zinman, Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, 60 Murray Street, Suite 5024, Toronto, Ontario, Canada M5G 1X5. E-mail: zinman{at}mshri.on.ca.

Acute-phase biomarkers such as C-reactive protein (CRP) and IL-6 have emerged as predictors of incident type 2 diabetes mellitus, implicating chronic subclinical inflammation as a factor in the pathophysiology of diabetes. Gestational diabetes (GDM) identifies a population of women at high risk of subsequent type 2 diabetes mellitus, representing an early stage in the natural history of the disease. In this context, we performed a cross-sectional study to determine whether markers of subclinical inflammation are elevated in patients with GDM. We studied 180 healthy pregnant women undergoing oral glucose tolerance testing in the late second or early third trimester. Based on oral glucose tolerance testing and prepregnancy body mass index (BMI), participants were stratified into four groups: 1) normal glucose tolerance (NGT) lean (BMI, <25 kg/m²) (n = 65); 2) NGT overweight (n = 28); 3) impaired glucose tolerance (n = 39); and 4) GDM (n = 48). Median CRP level was highest in overweight NGT subjects (8.8 mg/liter), followed by GDM (5.5 mg/liter), impaired glucose tolerance (4.4 mg/liter), and lean NGT (4.4 mg/liter) (overall P = 0.0297). CRP was significantly correlated with prepregnancy BMI (r = 0.38, P < 0.0001), followed by fasting insulin (r = 0.27, P = 0.0002) and fasting blood glucose (r = 0.18, P = 0.016). In multivariate linear regression analysis, prepregnancy BMI emerged as the most important determinant of CRP concentration, whereas glycemic tolerance status was not a significant factor. Furthermore, the observed stepwise increase in CRP per tertile of prepregnancy BMI was not significantly attenuated by glycemic tolerance status or factors known to be associated with GDM. In summary, we demonstrate that maternal serum levels of CRP are not related to GDM but rather correlate significantly with prepregnancy obesity. An independent contribution of CRP to risk of GDM could not be confirmed. These data suggest a model in which obesity mediates a systemic inflammatory response, with possible downstream metabolic sequelae, including insulin resistance and glucose dysregulation.

Abbreviations: BMI, Body mass index; CRP, C-reactive protein; DM, diabetes mellitus; GDM, gestational diabetes mellitus; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; pc, after meals.

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