 The investigators intend to recruit fifty type 2 diabetic patients treated with diet alone or diet plus sulfonylureas or meglitinides and add Pioglitazone 45 mg, an insulin sensitizer, for 6 months. In addition to assessment of clinical and metabolic parameters, insulin sensitivity and brachial artery and skin microcirculatory responses to acetylcholine and nitroprusside in combination with simultaneous determination of nitric oxide release will be documented before, 3 and 6 months after Pioglitazone therapy is initiated. Circulating levels of markers of endothelial damage VCAM, ICAM, selectins, inflammation C-reactive protein and interleukins, increased coagulability PAI-1 as well as lipids and apolipoproteins will measured during the study. Skeletal muscle biopsies will be performed during the euglycemic insulin clamp before and 6 months after therapy for measurements of NO synthase activity and key elements of the insulin signal transduction pathway involved in the regulation of glucose metabolism IRS-1, PI-3 kinase, PI-3 kinase associated with IRS-1 and the mitogenesis MAP-kinase. 