Inflammation and glucose intolerance: a prospective study of gestational diabetes mellitus.
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.


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 10(3) 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.
Wolf
Myles
M
Renal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. mswolf@partners.org
Sauk
Jenny
J
Shah
Anand
A
Vossen Smirnakis
Karen
K
Jimenez-Kimble
Ricardo
R
Ecker
Jeffrey L
JL
Thadhani
Ravi
R
D000328:Adult; D001724:Birth Weight; D001794:Blood Pressure; D001900:Boston; D002585:Cesarean Section; D036861:Delivery, Obstetric; D016640:Diabetes, Gestational / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D005865:Gestational Age; D018149:Glucose Intolerance / Q000503:physiopathology*; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000503:physiopathology*; D011247:Pregnancy; D011446:Prospective Studies