Metformin improves endothelial function in patients with metabolic syndrome.
BACKGROUND
Metabolic Syndrome (MS) is associated with impaired endothelial function and increased cardiovascular risk. Insulin resistance is a key feature of MS and plays an important role in the pathogenesis of endothelial dysfunction. Aim of the present study was to evaluate the effect of metformin on endothelial function and insulin resistance, assessed by the homeostasis model (HOMA-IR, homeostasis model assessment-insulin resistance), in patients with MS.


METHODS
Sixty-five subjects (37 men and 28 women, mean age 54 +/- 6 years) with MS were allocated to receive metformin 500 mg twice daily (n = 32) or placebo (n = 33) for 3 months. Before and after treatment we assessed endothelial function, using flow-mediated dilatation of the brachial artery, and HOMA-IR.


RESULTS
Patients who received metformin demonstrated statistically significant improvement in endothelium-dependent vasodilation compared with those treated with placebo (from 7.4 +/- 2.1% to 12.4 +/- 1.9% vs. 7.3 +/- 2.5% to 6.9 +/- 2.7%, P = 0.0016, metformin vs. placebo respectively), without significant effect on endothelium-independent response to sublingual glyceryl trinitrate (P =0.32). Metformin improved insulin resistance compared with placebo group (HOMA-IR from 3.39 to 2.5 vs. 3.42 to 3.37; 26% reduction in HOMA-IR, P = 0.01). An association between the improvement in insulin resistance and the improvement in endothelial function (r = -0.58, P = 0.0016) was found.


CONCLUSIONS
Metformin improves both endothelial function and insulin resistance in patients with MS. These findings support the central role of insulin resistance in the development of endothelial dysfunction and the role of metformin for the treatment of patients with MS.
Vitale
C
C
Department of Medical Sciences, Cardiovascular Research Unit, IRCCS San Raffaele, Roma, Tosinvest Sanita, Rome, Italy.
Mercuro
G
G
Cornoldi
A
A
Fini
M
M
Volterrani
M
M
Rosano
G M C
GM
D001916:Brachial Artery; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007091:Image Processing, Computer-Assisted; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D005996:Nitroglycerin; D014463:Ultrasonography; D014665:Vasodilator Agents
D007004:Hypoglycemic Agents; D014665:Vasodilator Agents; D008687:Metformin; D005996:Nitroglycerin