Adiponectin (Acrp30), an adipocyte-derived protein, exists in serum as a trimer, a hexamer, and a high-molecular weight (HMW) form, including 12-18 subunits. Because HMW adiponectin may be biologically active, we measured it in serum using a novel enzyme-linked immunosorbent assay (ELISA) confirmed by gel filtration chromatography that the ELISA detected mainly adiponectin with 12-18 subunits, and we compared HMW with total adiponectin concentration in patients with type 2 diabetes. We next investigated the relationship between serum HMW and coronary artery disease (CAD) in 280 consecutive type 2 diabetic patients, including 59 patients with angiographically confirmed CAD. Total adiponectin was measured in serum by a commercially available ELISA. Like serum total adiponectin, HMW adiponectin correlated positively with HDL cholesterol and negatively with triglyceride, insulin sensitivity, creatinine clearance, and circulating inflammatory markers. Total and HMW adiponectin were significantly higher in women than in men, as was the HMW-tototal adiponectin ratio. Serum HMW and the HMW-to-total adiponectin ratio were significantly lower in men with than without CAD (P < 0.05, respectively). In women, the ratio, but neither total nor HMW adiponectin, tended to be lower when CAD was present. In conclusion, determination of HMW adiponectin, especially relative to total serum adiponectin, is useful for evaluating CAD in type 2 diabetic patients. Diabetes

The current study shows that RBP4 is associated with variables related to insulin resistance and diabetic complications. The addition of pioglitazone for 12 wk to other diabetic medications the patients were already taking did not affect serum RBP4 levels.

No abstract

OBJECTIVE -We compared plasma interleukin (IL)-18 concentrations in patients with type 2 diabetes with those in age-matched control subjects and investigated whether plasma IL-18 was associated with plasma total homocysteine (tHcy) concentration or carotid intimalmedia wall thickness (IMT), an early marker of atherosclerosis, in these patients.RESEARCH DESIGN AND METHODS -We measured plasma IL-18 in 103 type 2 diabetic patients and 45 age-matched control subjects. We also measured patients' plasma tHcy and serum high-sensitivity C-reactive protein (hs-CRP). IMT was evaluated for both common carotid arteries.RESULTS -Plasma IL-18 was significantly higher in diabetic patients than in control subjects (203 Ϯ 153 vs. 118 Ϯ 37 pg/ml, P Ͻ 0.001). High IL-18 was defined as equaling or exceeding the mean ϩ 2 SD of plasma IL-18 in control subjects (192 pg/ml). Patients with high IL-18 showed a greater carotid IMT than those with normal IL-18. Carotid plaques were more numerous in diabetic patients with high IL-18 than in those with normal IL-18. Plasma tHcy concentrations were significantly higher in patients with high IL-18 than in those with normal IL-18. Univariate and multivariate analyses showed a strong independent association between tHcy and IL-18. Plasma IL-18 also correlated positively with serum hs-CRP.CONCLUSIONS -In patients with type 2 diabetes, plasma IL-18 concentrations are greater than in nondiabetic subjects. Plasma IL-18 is an independent determinant of plasma tHcy, which is linked independently with atherosclerotic carotid wall thickening. Diabetes Care 26:2622-2627, 2003P atients with type 2 diabetes have a high incidence of atherosclerosis, which leads to increased morbidity and mortality from coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease (PVD) (1-3). Atherosclerosis is a chronic low-grade inflammatory disease (4 -6). Plasma concentrations of several inflammatory markers such as C-reactive protein (CRP) and interleukin (IL)-6 have been linked with future cardiovascular disease (CVD) in a variety of clinical settings (7,8). IL-18 stimulates release of interferon-␥, shows potent activities on inflammatory and vascular cells, and is considered a proinflammatory cytokine (9). Recently, increased expression of IL-18 has been reported in carotid ulcerated atherosclerotic plaques (10), suggesting that IL-18 also plays a role in plaque destabilization. A recent study (11) identified high serum IL-18 concentrations as a strong predictor of death from cardiovascular causes in patients with CAD.Hyperhomocysteinemia has been associated with atherothrombotic vascular diseases such as CAD, stroke, and PVD (12-14). A previous study (15) demonstrated that moderate hyperhomocysteinemia is a stronger risk factor for CVD in patients with type 2 diabetes than in nondiabetic subjects, suggesting a synergistic effect of diabetes with hyperhomocysteinemia that accelerates the development of atherosclerosis. Although homocysteine can exert vascular toxicity via several mechanis...