Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes.
BACKGROUND
Glycemic disorders, one of the main risk factors for cardiovascular disease, are associated with activation of oxidative stress.


OBJECTIVE
To assess the respective contributions of sustained chronic hyperglycemia and of acute glucose fluctuations to oxidative stress in type 2 diabetes.


METHODS
Case-control study of 21 patients with type 2 diabetes (studied 2003-2005) compared with 21 age- and sex-matched controls (studied in 2001) in Montpellier, France.


METHODS
Oxidative stress, estimated from 24-hour urinary excretion rates of free 8-iso prostaglandin F2alpha (8-iso PGF2alpha). Assessment of glucose fluctuations was obtained from continuous glucose monitoring system data by calculating the mean amplitude of glycemic excursions (MAGE). Postprandial contribution to glycemic instability was assessed by determining the postprandial increment of glucose level above preprandial values (mean postprandial incremental area under the curve [AUCpp]). Long-term exposure to glucose was estimated from hemoglobin A1c, from fasting glucose levels, and from mean glucose concentrations over a 24-hour period.


RESULTS
Mean (SD) urinary 8-iso PGF2alpha excretion rates were higher in the 21 patients with diabetes (482 [206] pg/mg of creatinine) compared with controls (275 [85] pg/mg of creatinine). In univariate analysis, only MAGE (r = 0.86; P<.001) and AUCpp (r = 0.55; P = .009) showed significant correlations with urinary 8-iso PGF2alpha excretion rates. Relationships between 8-iso PGF2alpha excretion rates and either MAGE or AUCpp remained significant after adjustment for the other markers of diabetic control in multiple linear regression analysis (multiple R2 = 0.72 for the model including MAGE and multiple R2 = 0.41 for the model including AUCpp). Standardized regression coefficients were 0.830 (P<.001) for MAGE and 0.700 (P = .003) for AUCpp.


CONCLUSIONS
Glucose fluctuations during postprandial periods and, more generally, during glucose swings exhibited a more specific triggering effect on oxidative stress than chronic sustained hyperglycemia. The present data suggest that interventional trials in type 2 diabetes should target not only hemoglobin A1c and mean glucose concentrations but also acute glucose swings.
Monnier
Louis
L
Department of Metabolic Diseases, Lapeyronie Hospital, University of Montpellier, Montpellier, France. l-monnier@chu-montpellier.fr
Mas
Emilie
E
Ginet
Christine
C
Michel
Françoise
F
Villon
Laetitia
L
Cristol
Jean-Paul
JP
Colette
Claude
C
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
D001786:Blood Glucose; D015237:Dinoprost; D006442:Glycated Hemoglobin; C075750:8-epi-prostaglandin F2alpha