Plasma adiponectin, insulin sensitivity, and subclinical inflammation in women with prior gestational diabetes mellitus

OBJECTIVE - Women with prior gestational diabetes mellitus (pGDM) are at increased risk of developing type 2 diabetes and associated vasculopathy. Because increased fat mass and inflammatory processes are angiopathic risk factors, the relationship between insulin sensitivity, parameters of subclinical inflammation, and plasma concentrations of adipocytokines was investigated in pGDM both at 3 months and 12 months after delivery. RESEARCH DESIGN AND METHODS - insulin sensitivity (through a frequently sampled intravenous glucose tolerance test) and plasma concentrations of ultrasensitive C-reactive protein (CRP), adiponectin, plasminogen activator inhibitor (PAI)-1, tumor necrosis factor-alpha., leptin, and interleukin-6 were measured in 89 pGDM (BMI 26.9 +/- 0.5 kg/m(2), age 32 +/- 0.5 years) and in 19 women with normal glucose tolerance during pregnancy (NGT) (23.7 +/- 0.9 kg/m(2), 31 +/- 1.3 years). RESULTS - pGDM showed lower (P < 0.0001) plasma adiponectin (6.7 - 0.2 mug/ml) than NGT (9.8 +/- 0.6 mug/ml) and a decreased (P < 0.003) insulin sensitivity index (S-i) and disposition index (P < 0.03), but increased plasma leptin (P < 0.003), PAI-1 (P < 0.002), and CRP (P < 0.03). After adjustment for body fat mass, plasma adiponectin remained lower in pGDM (P < 0.004) and correlated positively with S-i (P < 0.003) and HDL cholesterol (P < 0.0001) but negatively with plasma glucose (2-h oral glucose tolerance test [OGTT]) (P < 0.0001), leptin (P < 0.01), CRP (P < 0.007), and PAI-1 (P < 0.0001). On regression analysis, only HDL cholesterol, postload (2-h OGTT) plasma glucose, and S-i remained significant predictors of. plasma adiponectin, explaining 42% of its variability. Of note, adiponectin further decreased (P < 0.05) only in insulin-resistant, pGDM despite unchanged body fat content and distribution after a 1-year follow-up. CONCLUSIONS - Lower plasma adiponectin concentrations characterize women with previous GDM independently of the prevailing insulin sensitivity or the degree of obesity and are associated with subclinical inflammation and atherogenic parameters.