Adiponectin isoforms are not associated with the severity of coronary atherosclerosis but with undiagnosed diabetes in patients affected by stable CAD.

BACKGROUND AND AIMS: Total adiponectin is emerging as an independent risk factor for cardiovascular diseases, but the role of adiponectin isoforms in coronary artery disease (CAD) is still unknown. We investigated the role of adiponectin isoforms with respect to the severity of coronary disease and to the presence of undiagnosed diabetes in patients with CAD. METHODS AND RESULTS: We recruited 205 CAD patients, all living in the central area of Italy, with a history of a previous myocardial infarction but apparently not affected by type 2 diabetes (DM2). We compared the CAD patients to a control population (n=100) matched for age, sex, BMI and cardiovascular risk factors, but without overt diabetes and cardiovascular disease. In all patients we measured Total Adiponectin (Tot-Ad) and its isoforms, metabolic, pro- and anti-inflammatory markers and we performed an oral glucose tolerance test (OGTT). CAD patients underwent a coronary angiography and/or coronary multi-slice computed tomography. Based on the severity of CAD they were divided into mono-vessel versus multi-vessel patients. Tot-Ad levels and its isoforms were comparable in patients with mono-vessel versus multi-vessel CAD. After the OGTT, in CAD patients, the results showed that 19% of patients were affected by unknown DM2, 36.1% by unknown impaired glucose tolerance (IGT), and only 43.9% were truly normoglycemic (NGT). Low levels of high molecular weight-adiponectin (HMW-Ad) were significantly associated with undiagnosed IGT or DM2 status (p<0.01). CONCLUSIONS: In our cohort of CAD patients, Tot-Ad and its isoforms do not correlate with severity of CAD, but with undiagnosed defects of glucose metabolism.

Pioglitazone improves endothelial and adipose tissue dysfunction in pre-diabetic CAD subjects.

OBJECTIVE: To investigate the effect of pioglitazone on endothelial and adipose tissue dysfunction in newly detected IGT patients with CAD. METHODS AND DESIGN: Participants (n=25) were randomized to treatment with either placebo or pioglitazone (30 mg/day) for 12 weeks. Before and after treatment we evaluated endothelial function (flow-mediated dilation--FMD--of the brachial artery), circulating adipose and inflammatory markers (adiponectin isoforms, TNF-alpha, and high sensitivity-CRP), and insulin sensitivity (euglycemic hyperinsulinemic clamp). RESULTS: No significant changes were observed in subjects (n=12) treated with placebo. By contrast, subjects (n=13) treated with pioglitazone had significant improvement in FMD (10.8±5.3 vs 13.3±3.6%, p<0.01), accompanied by increased high molecular weight adiponectin (HMW-Ad) (1.7±1.2 vs 4.8±3.6 µg/ml, p<0.05) and decreased TNF-alpha (4.3±1.9 vs 3.2±1.2 pg/ml, p<0.05) associated to an increased glucose disposal (4.8±1.9 vs 5.4±2.0 mg kg(-1) min(-1), p<0.05). A multiple regression analysis indicated that increasing of HMW-Ad after pioglitazone predicted increased FMD. CONCLUSION: Pioglitazone significantly improves endothelial and adipose tissue dysfunction in pre-diabetic patients with CAD.