Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients.
OBJECTIVE
To explore the possibility that oscillating glucose may outweigh A1C levels in determining the risk for cardiovascular diabetes complications.


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 alpha, 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.
Ceriello
Antonio
A
Centre of Excellence in Diabetes and Endocrinology, University Hospital of Coventry and Warwickshire, Warwick Medical School, University of Warwick, Coventry, UK. antonio.ceriello@warwick.ac.uk
Esposito
Katherine
K
Piconi
Ludovica
L
Ihnat
Michael A
MA
Thorpe
Jessica E
JE
Testa
Roberto
R
Boemi
Massimo
M
Giugliano
Dario
D
D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology* / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009991:Oscillometry; D018384:Oxidative Stress; D012016:Reference Values; D013004:Somatostatin / Q000097:blood; D014664:Vasodilation / Q000502:physiology*
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D013004:Somatostatin