Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects.
BACKGROUND
In type 2 diabetes, metformin reduces cardiovascular risk beyond the effect of glycaemic control. Since oxidative stress and the consequent enhanced platelet activation contribute to accelerated atherosclerosis in diabetes, we hypothesized that metformin could reduce oxidative stress in this condition.


METHODS
We randomized 26 newly diagnosed type 2 diabetic subjects to assume either metformin (M, n = 13) or gliclazide (G, n = 13) for 12 weeks. Drugs were titrated as needed to achieve good glycaemic control. Before and after treatment, we determined blood glucose, insulin, HbA(1c), vitamin A and E levels and 8-iso-PGF(2alpha) and 11-dehydro-thromboxane B(2) urinary excretion, an in vivo oxidative stress and a thromboxane-dependent platelet activation marker, respectively.


RESULTS
Notwithstanding a comparable improvement in metabolic control, 8-iso-PGF(2alpha) (M from 708 +/- 32 to 589 +/- 45 pg/mg cr, p < 0.001; G from 646 +/- 80 to 665 +/- 79, pg/mg cr, p = ns) and 11-dehydro-thromboxane B(2) (M from 2190 +/- 196 to 1753 +/- 150 pg/mg cr, p < 0.05; G from 2048 +/- 202 to 1923 +/- 223, pg/mg cr, p = ns) urinary excretion decreased after metformin but not after gliclazide treatment. After metformin, vitamin A and E levels significantly increased while they remained unchanged after gliclazide.


CONCLUSIONS
These data suggest that metformin could improve oxidative stress, preserve antioxidant function and restrain platelet activation in type 2 diabetes.
Formoso
Gloria
G
Department of Medicine and Aging Sciences, University -G. d'Annunzio, Chieti, Italy.
De Filippis
Elena A
EA
Michetti
Noemi
N
Di Fulvio
Patrizia
P
Pandolfi
Assunta
A
Bucciarelli
Tonino
T
Ciabattoni
Giovanni
G
Nicolucci
Antonio
A
Davì
Giovanni
G
Consoli
Agostino
A
D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005907:Gliclazide / Q000627:therapeutic use; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D015539:Platelet Activation / Q000187:drug effects*
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D005907:Gliclazide