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Inflammation and Glucose Intolerance

A prospective study of gestational diabetes mellitus

¹ Renal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
² Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Myles Wolf, MD, MMSc, Bartlet, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114. E-mail: mswolf{at}partners.org

OBJECTIVE—Increased leukocyte count is a marker of inflammation that has been associated with the development of type 2 diabetes in prospective studies. Although gestational diabetes mellitus (GDM) and type 2 diabetes share certain pathophysiological mechanisms, few studies have examined inflammation and risk of GDM.

RESEARCH DESIGN AND METHODS—We prospectively examined routine leukocyte counts collected at the first prenatal visit in a cohort of 2,753 nulliparous euglycemic women, 98 (3.6%) of whom were later diagnosed with GDM. Subjects were divided into quartiles of leukocyte count, and the results of third-trimester glucose screening tests and the incidence of GDM among these quartiles were compared. Logistic regression was used to calculate univariate and multivariable-adjusted relative risks (RRs) of GDM according to leukocyte quartiles.

RESULTS—Leukocyte counts were increased among women who subsequently developed GDM compared with those who remained free of GDM (10.5 ± 2.2 vs. 9.2 ± 2.2 x 10³ cells/ml; P < 0.01). There was a linear increase in postloading mean glucose levels (P for trend <0.01), the area under the glucose tolerance test curves (P for trend <0.01), and the incidence of GDM (quartile 1, 1.1; quartile 2, 2.5; quartile 3, 4.2; and quartile 4, 6.4%; P for trend <0.01) with increasing leukocyte quartiles. In the multivariable-adjusted analysis, the linear trend in the RR of GDM with increasing leukocyte quartiles remained statistically significant (quartile 1, reference; quartile 2, RR 2.3 [95% CI 0.9–5.7]; quartile 3, 3.3 [1.4–7.8]; quartile 4, 4.9 [2.1–11.2]; P for trend <0.01).

CONCLUSIONS—Increased leukocyte count early in pregnancy is independently and linearly associated with the results of GDM screening tests and the risk of GDM. Although overlap in the leukocyte count distributions precludes it from being a clinically useful biomarker, these data suggest that inflammation is associated with the development of GDM and may be another pathophysiological link between GDM and future type 2 diabetes.

Abbreviations: CRP, C-reactive protein • GDM, gestational diabetes mellitus • GLT, glucose-loading test • GTT, glucose tolerance test • IL, interleukin • MGH, Massachusetts General Hospital • MOMS, Massachusetts General Hospital Obstetric Maternal Study • TNF, tumor necrosis factor

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