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 Ϯ 2.2 vs. 9.2 Ϯ 2.2 ϫ 10 3 cells/ml; P Ͻ 0.01). There was a linear increase in postloading mean glucose levels (P for trend Ͻ0.01), the area under the glucose tolerance test curves (P for trend Ͻ0.01), 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 Ͻ0.01) 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 Ͻ0.01).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. Diabetes Care 27:21-27, 2004G estational diabetes mellitus (GDM) complicates roughly 4% of pregnancies (1,2). After delivery, women with GDM are at substantially increased risk of developing type 2 diabetes, and they are more likely to display features of the insulin resistance syndrome that are linked to cardiovascular disease, such as hypertension, dyslipidemia, microalbuminuria, and endothelial dysfunction (3-6). Women with GDM, therefore, represent a high-risk group for cardiovascular disease that can be identified years before the development of adverse events. With the incidence of type 2 diabetes increasing at epidemic proportions (7), further understanding of the mechanisms of GDM that might also contribute to the progression to type 2 diabetes, and more distantly to future cardiovascular disease, is needed so that additional pathophysiological pathways may be targeted for primary prevention.Insulin resistance and obesity are important pathophysiological contributors to both GDM and ...

Abstract. Preeclampsia and gestational hypertension are leading complications of pregnancy that also portend increased risk of future chronic hypertension. Although rates of chronic hypertension differ between non-Hispanic Caucasian and Hispanic women, few studies examined their relative rates of hypertensive disorders of pregnancy. The purpose of this study was to compare the risk of preeclampsia and gestational hypertension in a prospective cohort of normotensive, nulliparous Hispanic (n ϭ 863) and non-Hispanic Caucasian women (n ϭ 2,381). Compared with non-Hispanic Caucasian women, Hispanic women demonstrated a significantly decreased incidence of gestational hypertension (1.6% versus 8.5%; P Ͻ 0.01), but a similar incidence of preeclampsia (3.8% versus 3.7%; P ϭ 0.9). Adjusting for age, smoking, diabetes, BP, body mass index (BMI), and multiple gestation uncovered an increased relative risk (RR) for preeclampsia among Hispanic women (RR 1.9; 95% CI, 1.1 to 3.3; P ϭ 0.01), while their relative risk for gestational hypertension remained significantly decreased (RR 0.39; 95% CI, 0.22 to 0.72; P Ͻ 0.01). Among women who initially presented with hypertension during pregnancy, Hispanic women were over threefold (hazard ratio 3.3; 95% CI, 1.9 to 6.0; P Ͻ 0.01) more likely to develop preeclampsia than non-Hispanic Caucasian women. Besides Hispanic ethnicity, baseline BP, BMI, diabetes, and multiple gestation were independent risk factors for preeclampsia, whereas only baseline BP and BMI were associated with gestational hypertension. Socioeconomic status and access to prenatal care were not associated with either disorder. Hispanic ethnicity is independently associated with increased risk for preeclampsia and decreased risk for gestational hypertension. The initial presentation of hypertension during pregnancy in Hispanic women most likely represents early preeclampsia.The hypertensive disorders of pregnancy, preeclampsia, and gestational hypertension, which complicate 6 to 8% of pregnancies (1), are leading causes of maternal and fetal morbidity and mortality, and are associated with increased risk of future chronic hypertension (2). Although the characteristic placental pathology of preeclampsia is established during early pregnancy (3), there are no reliable tools for early clinical diagnosis and no effective therapies to prevent disease or improve maternal and fetal outcomes. Importantly, there are also no means to differentiate whether the new onset of hypertension during pregnancy represents gestational hypertension or preeclampsia in which proteinuria has yet to develop. More fundamentally, it remains unclear if preeclampsia and gestational hypertension represent ends of a single pathophysiological spectrum of pregnancy-induced hypertension or distinct disorders with unique biological pathways and differential risk factor profiles.Risk factors for preeclampsia have been studied extensively as preeclampsia is the hypertensive disorder of pregnancy most commonly associated with devastating complications. Nullip...

Abstract-Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are leading causes of pregnancy-associated morbidity. Although insulin resistance and inflammation contribute to preeclampsia, prospective data regarding mechanisms of gestational hypertension are sparse. We conducted a prospective, nested case-control study to test the hypotheses that insulin resistance, marked by reduced sex hormone-binding globulin (SHBG) levels, and inflammation, marked by increased C-reactive protein levels, are similarly associated with gestational hypertension. We measured first-trimester C-reactive protein and SHBG levels in 51 women who subsequently developed gestational hypertension and 102 randomly selected normotensive pregnant controls. Compared with controls, first-trimester SHBG levels were significantly reduced among women who later developed gestational hypertension (176Ϯ73 versus 203Ϯ79 nmol/L; Pϭ0.03), but there was no difference in C-reactive protein levels. There was statistically significant interaction among nulliparity, first-trimester SHBG levels, and risk of gestational hypertension, such that increasing SHBG levels were associated with significantly reduced risk of gestational hypertension among nulliparous women (odds ratio, 0.64 per 50-nmol/L increase; 95% confidence interval, 0.46, 0.90; PϽ0.01) but not among multiparous women. This association remained significant after adjusting for potential confounders (odds ratio, 0.55; 95% confidence interval, 0.31, 0.98; Pϭ0.04). We conclude that insulin resistance, but not inflammation, is an independent risk factor for gestational hypertension among nulliparous women. Furthermore, important mechanistic differences exist in the pathogenesis of gestational hypertension comparing nulliparous and multiparous women. Key Words: hypertension, gestational Ⅲ insulin resistance Ⅲ prospective studies H ypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, complicate 5% to 10% of pregnancies. 1 Gestational hypertension refers to transient, pregnancy-induced hypertension, whereas preeclampsia is defined as similar new onset hypertension in association with proteinuria. 1 Although preeclampsia is widely recognized as a leading cause of maternal and fetal morbidity and mortality, gestational hypertension is often considered a benign condition. However, although maternal end-organ damage is more common in preeclampsia, gestational hypertension is also associated with increased rates of cesarean section, preterm delivery, and small-for-gestationalage babies. 2-4 Furthermore, like preeclampsia, gestational hypertension is often the harbinger of future chronic hypertension. 5,6 Nonetheless, most studies that examined hypertensive disorders of pregnancy focused primarily on preeclampsia, and as a result, little is known about mechanisms of gestational hypertension. Moreover, whether gestational hypertension and preeclampsia represent different ends of a single pathophysiological spectrum or 2 distinct processes ...

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