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

Division of Endocrinology, Diabetes, and Hypertension (S.M.H., N.S.-O, E.W.S.), Divisions of General Internal Medicine and Women’s Health (C.G.S.), Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts 02115; and Cardiovascular Engineering, Inc. (G.F.M.), Holliston, Massachusetts 01746

Address all correspondence and requests for reprints to: Shannon Heitritter, M.D., Division of Endocrinology, Diabetes, and Hypertension, 221 Longwood Avenue, Boston, Massachusetts 02115. E-mail: sheitritter{at}partners.org.

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.

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