Metformin improves endothelial vascular reactivity in first-degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance.
OBJECTIVE
Endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2 diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We aimed to investigate the vascular effects of metformin in first-degree relatives with metabolic syndrome of type 2 diabetic patients.


METHODS
The study included 31 subjects (age 38.3 +/- 7.6 years and BMI 36.3 +/- 5.2 kg/m2), who were first-degree relatives of type 2 diabetic patients and who had metabolic syndrome and normal glucose tolerance. The subjects were randomly assigned 1:1 in a double-blind fashion to receive placebo (n = 15) or metformin (n = 16). Endothelial function was assessed by venous occlusion plethysmography, measuring forearm blood flow (FBF) and vascular resistance responses to three intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30 microg/min) and independent (sodium nitroprusside 2, 4, and 8 microg/min) vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were assessed at baseline and after treatment.


RESULTS
The metformin and placebo groups did not differ in anthropometric, clinical, laboratory, and vascular measurements at baseline. The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses. There was no correlation between the improvement on FBF responses and the observed changes on anthropometric, clinical, and laboratory parameters.


CONCLUSIONS
We concluded that metformin improved vascular endothelial reactivity in first-degree relatives with metabolic syndrome of type 2 diabetic patients, independently of its known antihyperglycemic effects.
de Aguiar
Luiz Guilherme Kraemer
LG
Department of Physiological Sciences, Laboratório de Pesquisas em Microcirculação, State University of Rio de Janeiro, Rio de Janeiro, Brazil. gkraemer@ig.com.br
Bahia
Luciana R
LR
Villela
Nivaldo
N
Laflor
Camila
C
Sicuro
Fernando
F
Wiernsperger
Nicolas
N
Bottino
Daniel
D
Bouskela
Eliete
E
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010919:Placebos; D014665:Vasodilator Agents / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010919:Placebos; D014665:Vasodilator Agents; D009599:Nitroprusside; D008687:Metformin