Decreased carotid atherosclerotic process by control of daily acute glucose fluctuations in diabetic patients treated by DPP-IV inhibitors

Atherosclerosis. 2013 Apr;227(2):349-54. doi: 10.1016/j.atherosclerosis.2012.12.018. Epub 2013 Jan 17.

Abstract

Objective: Blood glucose fluctuations have been found to be relevant to the progression of atherosclerosis in patients with type 2 diabetes and to be more detrimental for the development of atherosclerosis than the sustained hyperglycemia. We aim at evaluating the effect of blunted daily acute glucose fluctuations by DPP-IV inhibitors on intima-media thickness (IMT), a surrogate marker for early atherosclerosis.

Methods: Data from a 12-week prospective, randomized, open-label parallel group trial with a blinded-endopoint study on 90 patients with DMT2, assessing the role of Dipeptidyl Peptidase-4 inhibition in lowering oxidative stress and inflammation by reducing daily acute glucose fluctuations (MAGE), were included in the present analysis.

Results: Administration of both sitagliptin and vildagliptin treatment resulted in a significant decline in IMT. Indeed, vs baseline data Vildagliptin vs Sitagliptin resulted in a greater IMT reduction. After 3 months therapy changes in IMT significantly correlated with changes in MAGE but not with change in HbA1c in the whole population. Only change in MAGE and LDL plasma levels resulted to be independent predictors of the reduced carotid intima-media thickness after adjusting for conventional cardiovascular risk factors in patients with type 2 diabetes. Significant correlations between change in MAGE, change in IMT and change in fasting and interprandial inflammation score and nitrotyrosine plasma levels were found.

Conclusion: Reduction of glucose excursion due to DPP-IV inhibitors administration, may prevent atherosclerosis progression in patients with type 2 diabetes probably through the reduction of daily inflammation and oxidative stress.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / therapeutic use
  • Atherosclerosis / diagnosis
  • Atherosclerosis / pathology
  • Blood Glucose / analysis*
  • Blood Glucose / metabolism
  • Carotid Arteries / drug effects*
  • Carotid Artery Diseases / blood
  • Carotid Artery Diseases / prevention & control*
  • Carotid Intima-Media Thickness
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / pathology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glycated Hemoglobin / analysis
  • Humans
  • Inflammation
  • Nitriles / therapeutic use
  • Oxidative Stress
  • Prospective Studies
  • Pyrazines / therapeutic use
  • Pyrrolidines / therapeutic use
  • Sitagliptin Phosphate
  • Triazoles / therapeutic use
  • Tyrosine / analogs & derivatives
  • Tyrosine / blood
  • Vildagliptin

Substances

  • Blood Glucose
  • Cytokines
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Nitriles
  • Pyrazines
  • Pyrrolidines
  • Triazoles
  • hemoglobin A1c protein, human
  • 3-nitrotyrosine
  • Tyrosine
  • Vildagliptin
  • Adamantane
  • Sitagliptin Phosphate