Effects of rosiglitazone/metformin fixed-dose combination therapy and metformin monotherapy on serum vaspin, adiponectin and IL-6 levels in drug-naïve patients with type 2 diabetes.

OBJECTIVE: Vaspin, adiponectin and interleukin-6 (IL-6) constitute novel adipose-tissue derivatives, known as adipokines, which mediate insulin resistance. The aim of the present study was to evaluate the effects of metformin and rosiglitazone on serum levels of those novel adipokines in drug-naïve patients with type 2 diabetes mellitus (T2DM). METHODS: 140 patients with T2DM, already treated with diet, but without adequate glycemic control (HbA1c > 7%), were randomly assigned to: RSG+MET group, (n = 70): Combination therapy with fixed dose of 4 mg rosiglitazone plus 500 mg metformin. MET group, (n = 70): Half-maximum dose of metformin monotherapy (1 700 mg/day). Before and after 6-month treatment, body-mass index (BMI), blood pressure (BP), fat-mass, fasting plasma glucose (FPG), HbA1c, insulin resistance indexes (HOMA-IR, insulin), lipids, high-sensitivity CRP (hsCRP), vaspin, adiponectin, and interleukin-6 (IL-6) were measured. RESULTS: Glucose regulation and insulin resistance were equivalently improved from baseline within both groups (p < 0.05). There was a considerable amelioration of hsCRP, WBC, adiponectin, IL-6, systolic and diastolic BP with rosiglitazone/metformin combined treatment as compared to baseline (p < 0.05) and MET group (p < 0.05). In contrast, metformin monotherapy significantly reduced BMI (p < 0.001), total-cholesterol (p = 0.012) and LDL (p = 0.020) levels compared to RSG+MET group. Importantly, serum vaspin concentration was equivalently decreased from baseline in both RSG+MET (-0.96 ± 0.75 ng/ml, p < 0.001) and MET (-0.92 ± 0.57 ng/ml, p=0.001) group. The aforementioned vaspin changes correlated with changes in WHR, HbA1c, FPG, HOMA-IR, insulin, IL-6 (only in the RSG+MET group) and fat-mass. In standard multiple regression analysis, FPG, HbA1c, HOMA-IR and insulin remained independent determinants of serum vaspin levels changes (R² = 0.836, p = 0.004). CONCLUSIONS: Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naïve patients with T2DM.

Visfatin (nampt) and ghrelin as novel markers of carotid atherosclerosis in patients with type 2 diabetes.

OBJECTIVE: Visfatin (nampt) and ghrelin are the most recently identified adipocytokines, but their role in atherosclerosis is poorly clarified. In our study we investigated their association with advanced carotid atherosclerosis and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM). METHODS: 122 patients (50 males) with T2DM, aged 55-70 were enrolled. Sixty-four age- and sex-matched healthy individuals served as controls (group A). CIMT was assayed in all participants by ultrasound. Among diabetic patients, 47 appeared with carotid plaques (group B), while 75 without plaques (group C). Anthropometric parameters, blood pressure, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), fibrinogen, nampt and ghrelin were measured. RESULTS: Diabetic patients had a higher mean-CIMT, increased body-mass index, worse lipid profile, elevated blood pressure and higher levels of white blood cells count, nampt and hsCRP with respect to controls (p<0.01). Among diabetic patients, groups B and C were comparable in anthropometric, glycemic and lipid parameters. Serum nampt was significantly higher in group B rather than in groups A and C (p<0.05). On the other hand, ghrelin levels were considerably lower only in diabetic patients with carotid atherosclerosis compared with healthy individuals. In univariate analysis, mean-CIMT correlated with age (r=0.312; p=0.003), nampt (r=0.341; p<0.001) and ghrelin (r=-0.421; p=0.002) and the latter associations remained significant in multiple regression analysis. CONCLUSIONS: High nampt and low ghrelin serum levels are significantly associated with advanced carotid atherosclerosis in patients with T2DM. Moreover these adipocytokines are independently associated with CIMT, implicating their role as novel atherosclerotic biomarkers and providing another important link between adiposity and atherosclerosis.

Intensive lipid-lowering therapy ameliorates novel calcification markers and GSM score in patients with carotid stenosis.

OBJECTIVES/DESIGN: Carotid plaque echogenicity quantified by the Gray-Scale Median (GSM) score has been associated with plaque vulnerability. The aim of this study was to assess whether intensive lipid-lowering treatment with atorvastatin in patients with carotid artery stenosis ameliorates novel vascular calcification inhibitors, such as osteopontin (OPN) and osteoprotegerin (OPG), and improves GSM score. METHODS: Ninety-seven patients with carotid stenosis (>40%), but without indication for intervention, were treated for 6 months with atorvastatin (10mg-80mg) to target LDL<100mg/dl. Fifty-two age-and sex-matched healthy individuals served as the control group. Blood samples and GSM were obtained at the beginning and after 6 months. RESULTS: Systolic blood pressure, hsCRP, fibrinogen, OPN and OPG levels differed significantly between patients with carotid stenosis and healthy controls at baseline (p<0.05). Atorvastatin treatment improved lipid profile and significantly reduced hsCRP (p=0.002), WBC count (p=0.041), OPN (p<0.001) and OPG levels (p<0.001). GSM score increased considerably after atorvastatin therapy (from 58.33+/-24.38 to 79.33+/-22.3; p<0.001) and that effect appeared related to OPN (p=0.001), OPG (p=0.013) and LDL (p=0.01) reduction. CONCLUSIONS: In patients with carotid stenosis, intensive lipid-lowering therapy with statins attenuates serum OPN and OPG levels and enhances carotid plaque echogenicity, outlining their beneficial effects on plaque stability.