Metformin Improves Peripheral Vascular Flow in Nonhyperlipidemic Patients with Arterial Disease

Sirtori, Cesare R.; Franceschini, G.; Gianfranceschi, G.; Sirtori, M; Montanari, G; Bosisio, E.; Mantero, Emanuela; Bondioli, A

doi:10.1097/00005344-198409000-00027

Cited by 61 publications

(20 citation statements)

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“…Metformin has multiple biological effects, among which are less recognized vascular actions. The 40% reduction in cardiovascular risk observed in metformin-treated type 2 diabetic patients in the UKPDS (13) confirmed previous evidence (23) that this drug has vasculoprotective actions that are largely independent of its known antihyperglycemic effects.…”

Section: Vascular Changessupporting

confidence: 80%

Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance

et al. 2006

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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 Ϯ 7.6 years and BMI 36.3 Ϯ 5.2 kg/m 2 ), 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 ϭ 15) or metformin (n ϭ 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 g/min) and independent (sodium nitroprusside 2, 4, and 8 g/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. Diabetes Care 29:1083-1089, 2006T he precocious and accelerated atherosclerosis seen in type 2 diabetes raised the question about pathogenetic factors that initiate the development of vascular derangements in the prediabetic population. Metabolic syndrome, a pre-diabetic state, comprises an array of cardiovascular risk factors such as abdominal obesity, dyslipidemia, hypertension, impaired glucose tolerance, and insulin resistance. Insulin resistance, the central abnormality for the pathogenesis of metabolic syndrome, is considered an independent risk factor for cardiovascular mortality in general (1) and in the diabetic population (2) in particular.The endothelium is an important locus for the control of vascular function. It actively regulates vascular tone, permeability to leukocytes and macromolecules, the balance between coagulation and fibrinolysis, composition of the subendothelial matrix, and proliferation of vascular smooth muscle cells. The great variety of beneficial functions attributed to the endothelium is mainly associated with nitric oxide (NO) bioavailability. In experimental studies of atherogenesis,...

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Section: Vascular Changessupporting

confidence: 80%

Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance

et al. 2006

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“…Among earlier observations, an interesting crossover study (6-months each period) in 15 non-diabetic patients with peripheral vascular disease found that metformin increased lower limb arterial flow as measured by plethysmography [35]. During a 6 months 'before-after' observation study of 42 hyperlipidaemic individuals with nitroglycerine (NG)-treated angina, 35 reported discontinuation of NG after receiving metformin [36].…”

Section: Additional Evidence Of Anti-atherogenic Effectsmentioning

confidence: 99%

Metformin: Effects on Micro and Macrovascular Complications in Type 2 Diabetes

Bailey

2008

Cardiovasc Drugs Ther

108

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Metformin has long been known to reduce the development of atherosclerotic lesions in animal models, and clinical studies have shown the drug to reduce surrogate measures such as carotid intima-media thickness. The anti-atherogenic effects of metformin include reductions in insulin resistance, hyperinsulinaemia and obesity. There may be modest favourable effects against dyslipidaemia, reductions in pro-inflammatory cytokines and monocyte adhesion molecules, and improved glycation status, benefiting endothelial function in the macro- and micro-vasculature. Additionally metformin exerts anti-thrombotic effects, contributing to overall reductions in athero-thrombotic risk in type 2 diabetic patients.

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“…Metformin has also been shown to have some beneficial haemovascular effects, i.e. antiatherogenicity, increased fibrinolytic activity, decreased neovascularisation, decreased platelet aggregation, Drugs & Aging 4 (6) 1994 and decreased blood pressure (Bailey 1992;Campbell et al 1988;Chakrabarti et al 1965;Feruglio et al 1979;Hocking et al 1967;Koschinsky et al 1988;Sirtori et al 1984;Vague et al 1987).…”

Section: Biguanidesmentioning

confidence: 99%

Treatment of Non-Insulin-Dependent Diabetes Mellitus and its Complications

Ilarde¹,

Tuck

1994

Drugs & Aging

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Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem which occurs predominantly in the older population; 16.8% of persons over age 65 years have NIDDM. The total health costs of NIDDM are in excess of $US20 billion annually. The primary objective in the treatment of NIDDM is to achieve normoglycaemia, without aggravating coexisting abnormalities. Common abnormalities include obesity, hypertension, retinopathy, nephropathy and neuropathies. Diet, and consequent bodyweight reduction, is the cornerstone of therapy for NIDDM. Total calorie intake should be limited, while the percentage of calories from carbohydrates should be increased and that from fats and cholesterol should be decreased. Exercise may also help to reduce bodyweight. Sulphonylurea drugs stimulate insulin secretion from beta-cells, and may be a useful adjunct to nonpharmacological therapy. Failure to respond to sulphonylurea drugs may be primary (25 to 30% of initially treated patients) or secondary (5 to 10% per year). It is not clear which is the most effective pharmacological intervention in such cases. Options include switching to or combining therapy with insulin, a biguanide, or other insulin-sparing antihyperglycaemic agents, e.g. alpha-glucosidase inhibitors, thiazolidinediones, chloroquine or hydroxychloroquine, or fibric acid derivatives such as clofibrate. Other experimental agents include the fatty acid oxidation inhibitors and dichloroacetate. Specific agents, such as antihypertensives, lipid lowering agents and sorbitol inhibitors, may be needed to prevent the complications arising from the spectrum of clinical and metabolic abnormalities which arise from insulin resistance.

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Metformin Improves Peripheral Vascular Flow in Nonhyperlipidemic Patients with Arterial Disease

Cited by 61 publications

References 0 publications

Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance

Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance

Metformin: Effects on Micro and Macrovascular Complications in Type 2 Diabetes

Treatment of Non-Insulin-Dependent Diabetes Mellitus and its Complications

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