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Oscillating Glucose Is More Deleterious to Endothelial Function and Oxidative Stress Than Mean Glucose in Normal and Type 2 Diabetic Patients

¹ Centre of Excellence in Diabetes and Endocrinology, University Hospital of Coventry and Warwickshire, Warwick Medical School, University of Warwick, Coventry, U.K
² Division of Metabolic Diseases, Center of Excellence for Cardiovascular Diseases, 2nd University of Naples SUN, Naples, Italy
³ Morpurgo-Hofman Research Laboratory on Aging, Udine, Italy
⁴ Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
⁵ Diabetology Unit, INRCA, Ancona, Italy

Corresponding author: Prof. Antonio Ceriello, Warwick Medical School, Clinical Science Research Institute, Clinical Science Building, University Hospital, Walsgrave Campus, Clifford Bridge Road, Coventry CV2 2DX, U.K. E-mail: antonio.ceriello{at}warwick.ac.uk

Abbreviations: FMD, flow-mediated dilatation; PGF2, prostaglandin F2

OBJECTIVE—To explore the possibility that oscillating glucose may outweigh A1C levels in determining the risk for cardiovascular diabetes complications.

RESEARCH DESIGN AND METHODS—A euinsulinemic hyperglycemic clamp at 5, 10, and 15 mmol/l glucose was given in increasing steps as a single "spike" or oscillating between basal and high levels over 24 h in normal subjects and type 2 diabetic patients. Flow-mediated dilatation, a marker of endothelial function, and plasma 3-nitrotyrosine and 24-h urinary excretion rates of free 8-iso PGF2, two markers of oxidative stress, were measured over 48 h postclamp.

RESULTS—Glucose at two different levels (10 and 15 mmol/l) 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/l every 6 h for 24 h resulted in further significant increases in endothelial dysfunction and oxidative stress compared with either continuous 10 or 15 mmol/l glucose.

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 favoring cardiovascular complications in diabetes. Concomitant vitamin C infusion can reverse this impairment.

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