Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance
- Luiz Guilherme Kraemer de Aguiar, MD,
- Luciana R. Bahia, MD,
- Nivaldo Villela, MD, PHD,
- Camila Laflor, MSC,
- Fernando Sicuro, MSC,
- Nicolas Wiernsperger, PHD,
- Daniel Bottino, MD, PHD and
- Eliete Bouskela, MD, PHD
- Department of Physiological Sciences, Laboratório de Pesquisas em Microcirculação, State University of Rio de Janeiro, Rio de Janeiro, Brazil
- Address correspondence and reprint requests to L.G. Kraemer de Aguiar, Av. Sete de Setembro, 332 apto 601, CEP 24230-253, Niterói, RJ, Brazil. E-mail: gkraemer{at}ig.com.br
Abstract
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.
RESEARCH DESIGN AND 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 μg/min) and independent (sodium nitroprusside 2, 4, and 8 μg/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.
- ACh, acetylcholine
- FBF, forearm blood flow
- FFA, free fatty acid
- FPG, fasting plasma glucose
- SNP, sodium nitroprusside
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted January 28, 2006.
- Received November 4, 2005.
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