Subclinical Inflammation and Vascular Dysfunction in Women with Previous Gestational Diabetes Mellitus

Abstract

Context: A history of gestational diabetes (GDM) significantly increases the risk of developing type 2 diabetes, an independent risk factor for cardiovascular disease (CVD). It is not known whether nondiabetic women with prior GDM are also at increased risk of CVD. Objective: The aim of this study was to compare biochemical and hemodynamic surrogate markers of CVD in nondiabetic women with and without a history of GDM who were at least 1 yr post delivery. Design: This was a single center cross-sectional study. Setting: The study was performed in an academic referral center. Subjects: Forty-eight premenopausal healthy women with a history of GDM (n = 25) or a history of normal pregnancy (n = 23) were studied in the follicular phase of the menstrual cycle. Main Outcome Measures: The main outcome measures were: 1) inflammatory markers associated with CVD including C-reactive protein, IL-6, and plasminogen activator inhibitor-1; 2) the adipokine adiponectin; and 3) conduit vessel stiffness. Results: When compared to normal controls, women with prior GDM had higher mean levels of C-reactive protein (3.58 ± 3.86 vs. 0.52 ± 0.16 mg/liter; P < 0.001), IL-6 (1.81 ± 1.04 vs. 0.99 ± 0.52 pg/ml; P = 0.001), plasminogen activator inhibitor-1 (29.6 ± 17.6 vs. 16.5 ± 14.0 ng/ml; P = 0.001), and lower levels of adiponectin (8.9 ± 3.9 vs. 15.9 ± 7.3 μg/ml; P = 0.001). Women with prior GDM also had significantly (P ≤ 0.04) increased peripheral vascular resistance (1658 ± 290 vs. 1462 ± 340 dyne·sec/cm⁵), decreased stroke volume (65 ± 13 vs. 75 ± 14 ml/beat), and decreased cardiac output (70 ± 12 vs. 74 ± 13 ml/sec) when compared to controls, after adjusting for body mass index. Conclusions: Nondiabetic women with prior GDM have evidence of subclinical inflammation, hypoadiponectinemia, and early vascular dysfunction; this population may be at increased risk of developing CVD.