Effect of Sitagliptin on Endothelial Progenitor Cells
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      Endothelial progenitor cells (EPCs) are involved in cardiovascular homeostasis, through
      angiogenesis and endothelial healing. Diabetic patients have a high risk of cardiovascular
      events and low levels of circulating EPCs.

      Sitagliptin is an oral DPP-IV antagonist, approved for the treatment of type 2 diabetes. It
      increases the bioavailability of endogenous incretins, thus improving insulin and glucagon
      secretion. SDF-1, one of the major EPC regulators, is also a substrate of DPP-IV. This study
      tests the hypothesis that sitagliptin increases the levels of circulating EPCs in type 2
      diabetic patients.
    

Detailed description: 
      Diabetic patients suffer an elevated wirk of cardiovascular events, which strongly impact on
      morbidity and mortality. The mechanisms that lead to cardiovascular disease in diabetes
      include alterations in the endothelial layer, due to hyperglycemia, oxidative stress and
      other associated abnormalities. Endothelial progenitor cells (EPCs) are bone marrow-derived
      cells involved in endothelial repair after injury, and they have been found to be reduced in
      diabetic patients. Thus, reduced EPCs in diabetes may be another mechanism of vascular
      disease induction. Reduction of EPCs in diabetes is attributable at least in part to the
      impairment of bone marrow mobilization, which is regulated by the chemokine SDF-1alpha, among
      others.

      The oral hypoglycemia agent sitagliptin is a dipeptidyl dipeptidase-IV inhibitor, which
      prevents degradation of endogenous incretins (GIP and GLP-1), thus re-equilibrating insulin
      and glucagon secretion. Sitagliptin may also increase the concentrations of SDF-1alpha, which
      is another substrate of DPP-IV. The hypothesis is that sitagliptin may increase circulating
      EPC levels, through SDF-alpha.

      This is going to be a pilot, non-randomized controlled 4-week trial of 100 mg oral
      sitagliptin therapy added to metformin/sulphonylureas in poorly controlled type 2 diabetic
      patients. At baseline and 4 weeks after the initiation of therapy blood samples will be drawn
      for the determination of circulating EPC levels, and concentrations of SDF-1alpha. EPCs will
      be defined as CD34+KDR+ cells and measured by flow cytometry as previously described in
      detail. SDF-1alpha will be measured using ELISA kits according to the manufacturer's
      instructions.

      Changes between baseline and 4 weeks will be evaluated using two-tailed paired Student's t
      test and statistical significance accepted at p<0.05.
    

Intervention name(s): Sitagliptin
Intervention type(s): Drug
Intervention description(s): 100 mg once daily for 4 weeks
Other intervention name(s): Januvia; Xelevia; Tesavel
Intervention MeSH terms: Sitagliptin Phosphate
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: diabetes; endothelium; stem cells