Oscillating glucose is more deleterious on endothelial function and oxidative stress than mean glucose in normals and type 2 diabetic patients.

  1. Antonio Ceriello, MD (antonio.ceriello{at}warwick.ac.uk)1,
  2. Katherine Esposito, MD2,
  3. Ludovica Piconi, PhD3,
  4. Michael A. Ihnat, PhD4,
  5. Jessica E. Thorpe, PhD4,
  6. Roberto Testa, MD5,
  7. Massimo Boemi, MD5 and
  8. Dario Giugliano, MD2
  1. 1Centre of Excellence in Diabetes and Endocrinology, University Hospital of Coventry and Warwickshire, Warwick Medical School, University of Warwick, Coventry, U.K.
  2. 2Division of Metabolic Diseases, Center of Excellence for Cardiovascular Diseases, 2ndUniversity of Naples SUN, Italy
  3. 3Morpurgo-Hofman Research Laboratory on Aging, Udine, Italy
  4. 4Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, U.S.A.
  5. 5Diabetology Unit, INRCA, Ancona, Italy

    Abstract

    Background: Much attention has been recently paid to the possibility that oscillating glucose may super impose to HbA1c levels in determining the risk for cardiovascular diabetic complications.

    Methods and Results: A euinsulinemic hyperglycemic clamp at 5, 10 and 15 mmol/liter glucose was given in increasing steps; as a single “spike;” or oscillating between basal and high levels over 24 hr in normal subjects and type 2 diabetic patients; flow mediated dilation, a marker of endothelial function; and plasma 3-nitrotyrosine and 24-hour urinary excretion rates of free 8-iso prostaglandin F2alpha, two markers of oxidative stress, were measured over 48 hr post-clamp. Glucose at two different levels (10 and 15 mmol/liter) resulted in a concentration-dependent fasting blood glucose-independent induction of both endothelial dysfunction and oxidative stress in both normal and type 2 diabetic patients. Oscillating glucose between 5 and 15 mmol/liter every 6 hr for 24 hr resulted in further significant increases in endothelial dysfunction and oxidative stress as compared to either continuous 10 or 15 mmol/liter glucose and that concomitant vitamin C infusion can reverse this impairment.

    Conclusions: These data suggest that oscillating glucose can have more deleterious effects than constant high glucose on endothelial function and oxidative stress, two key players in favouring cardiovascular complications in diabetes.

    Footnotes

      • Received January 16, 2008.
      • Accepted February 19, 2008.
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