The main purpose of this study is to analyze the effects of the addition of sulfonylurea (gliclazide MR) or ,alternatively, basal insulin (insulin detemir) to life-style modification and metformin treatment as a second step treatment in type 2 diabetes mellitus on endothelial cell functions. The second goal is to identify the effects of these treatment alternatives on body-mass index, the changes in body fat mass, insulin resistance and on the insulin secretion capacity of beta cells. The third aim of this study is to determine the success rates of these treatment alternatives on glycemic control at 6 months follow-up.

The lack of enough number of randomized and controlled studies in the treatment of type 2 diabetes is the most important obstacle in recommending a single-drug or a combination treatment to the other.

The pleomorphic effects of the treatment choices other than the control of hyperglycemia in type 2 diabetes are equally important. There is yet a lack of the comparison of different treatment alternatives found in the treatment algorithms of American Diabetes Association (ADA) both in terms of the effects on hyperglycemia control as well as other pleomorphic effects. Some of these pleomorphic effects are the change in body-mass index, insulin resistance, insulin secretion capacity and the effects on endothelial functions and coagulation status.

This study is mainly prepared to analyze the effects of the addition of sulfonylurea (gliclazide MR) or alternatively basal insulin (insulin detemir) to life-style modification and metformin treatment as a second step treatment in type 2 diabetes mellitus treatment algorithm on endothelial cell functions. The second goal is to identify the effects of these treatment alternatives on body-mass index, the changes in body fat mass, insulin resistance and on the insulin secretion capacity of beta cells. The third aim of this study is to determine the success rates of these treatment alternatives on glycemic control at 6 months follow-up. This study in this sense is expected to shed the light on the decision of best treatment option as well as an essential contribution to the lacking literature in the field.

To reach these aims, 20-65 year-old patients applying to the endocrinology and the metabolism outpatient unit, having type 2 diabetes diagnoses with unregulated blood glucose levels after first step treatment (life-style modification and metformin) will be recruited and randomized either to the Gliclazide MR arm or the Insulin Detemir arm. As soon as patients in each arm reach to the target glycemic levels (0. week), basal tests showing endothelial function as well as inflammatory and coagulation status such as flow-mediated dilatation (FMD)and investigation of the peripheral blood levels of TNF-α, IL-6, MCP-1, sICAM-1, sVCAM-1, vWF, E-selectin, P-selectin, endothelin-1, PAI-1, tPA and HMW adiponectin will be performed. To investigate the insulin resistance and the changes in insulin secretory capacity of beta cells, mixed meal test will be performed and data obtained about glucose as well as insulin levels during mixed meal test will be evaluated. To identify the changes in body-fat mass, bioimpedance analyses will also be performed. All these basal tests will be repeated in each study subject, 12 weeks and 24 weeks after reaching the target glycemic levels. Patients randomized to insulin detemir arm in the beginning will only have gliclazide MR treatment after the 12.week tests are performed. The effects of continuous gliclazide MR treatment or early insulin detemir followed by gliclazide MR treatment on endothelial cell functions, inflammation and coagulation, insulin resistance, insulin secretory capacity of beta cells and body-fat mass will be evaluated by comparing the 0. week with 12. and 24. week values within each arm as well as 24. week values between arms.

Inclusion Criteria:

1. Type 2 diabetic patients using at least 1000 mg/day metformin at least for 3 months
2. 7\