The Effects of Insulin Detemir and Gliclazide-MR Treatments on Endothelial Functions in Patients With Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Gliclazide MR; Insulin Detemir
Intervention type(s): Drug; Drug
Intervention description(s): Doses between 30 mg to 120 mg/day p.o. Gliclazide MR will be arranged according to the target glycemic levels.; Early initiation of s.c. insulin detemir in contrast to Gliclazide MR. Insulin detemir treatment will be exchanged to Gliclazide MR after 12 weeks.
Other intervention name(s): Diamicron MR; Levemir Flexpen
Intervention MeSH terms: Insulin Detemir; Gliclazide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tip 2 DM; Endothelium; Gliclazide; Insulin detemir