Metformin improves endothelial function in patients with metabolic syndrome

Vitale, Cristiana; Mercuro, Giuseppe; Cornoldi, Alessandra; Fini, Massimo; Volterrani, Maurizio; Rosano, Giuseppe

doi:10.1111/j.1365-2796.2005.01531.x

Cited by 155 publications

(131 citation statements)

References 44 publications

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“…17,[23][24][25][26] In the current study, a 1-year combined program of intensive lifestyle Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure. During salt-sensitivity testing, subjects were first exposed to 1 week of a high-salt diet followed by a week of a low-salt diet.…”

Section: Discussionmentioning

confidence: 99%

“…As indicated above caloric restriction, increase physical activity and metformin have been shown independently to reduce cardiovascular risk factors and the development of type II diabetes. 17,[23][24][25][26] However, the lifestyle interventions have been shown to be more effective than metformin in preventing development of type II diabetes mellitus. 26 A substantial body of evidence supports the concept that pre-hypertension and hypertension are associated with obesity; however, the reason for this association in still controversial, and may be multifactorial.…”

Section: Discussionmentioning

confidence: 99%

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Effects of lifestyle changes and metformin on salt sensitivity and nitric oxide metabolism in obese salt-sensitive Hispanics

2007

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Salt sensitivity is associated with obesity, and increased cardiovascular morbidity and mortality. We investigated whether treatment of obesity and its associated metabolic abnormalities corrects salt sensitivity and restores impaired nitric oxide (NO) metabolism characteristic of salt sensitivity. Twenty, otherwise, healthy obese saltsensitive subjects completed a 12-month program of caloric restriction, aerobic exercise and metformin. Two salt sensitivity tests were performed, that is at baseline and end of program. Lifestyle-metformin treatment decreased weight (9.870.3 kg), body mass index (3.970.2 kg/m 2 ), waist (11.570.5 cm), systolic blood pressure (SBP) (8.670.4 mm Hg), diastolic blood pressure (DBP) (5.570.4 mm Hg), triglyceride (4075 mg/dl), fasting (8.371 lIU/ml) and post-load (2074 lIU/ml) insulin levels, and salt sensitivity. Going from a highsodium (B300 mmol) to a low-sodium diet (B30 mmol of sodium/day) lowered SBP/DBP by 14.771.7/7.470.9 mm Hg at baseline and by 8.671.9/3.271.2 mm Hg after treatment (Po0.001). More importantly, blood pressure (BP) sensitivity to customary levels of dietary salt (B150 mmol of sodium/day) was abolished by the lifestyle-metformin treatment. Differences in SBP/DBP between usual and low salt averaged 1171/871 mm Hg before treatment, and 371/170.5 mm Hg after treatment (Po0.001). At baseline, NO-metabolite excretion was inhibited during high salt; this impairment was corrected by the lifestyle-metformin treatment. In conclusion, acquired correctable factors play an important role in the pathogenesis of salt sensitivity associated with obesity. Correction of salt sensitivity may account for the BP lowering induced by weight reduction. Restoration of the inability to increase or sustain NO production in response to high salt could account for the correction of salt sensitivity induced by the lifestylemetformin treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of lifestyle changes and metformin on salt sensitivity and nitric oxide metabolism in obese salt-sensitive Hispanics

2007

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“…Metformin has been also shown to improve endotheliumdependent vasodilation in rats (27) and in patients with type 2 diabetes (28). Additionally, it has been recently shown that in subjects with metabolic syndrome, metformin improved flow-mediated vasodilation of the brachial artery (29).…”

Section: Vascular Changesmentioning

confidence: 99%

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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“…It also decreases hepatic output of glucose [36]. Moreover, metformin decreases β-cells apoptosis and slows diabetes disease progression [37][38][39]. Many of these effects are mediated through AMP-kinase pathway [22,23,30].…”

Section: Discussionmentioning

confidence: 99%

Effects of metformin on middle cerebral artery flow velocity in newly diagnosed type 2 Diabetic patients

2016

AJBM

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Type 2 diabetes mellitus is a major cause of cerebrovascular disease. Risk of ischemic stroke is higher in diabetic patients and it is about 2-6 times that in normal population. Atherosclerotic lesions happen early in the disease and patients with type 2 diabetes mellitus. Transcranial Doppler can be used for examination of cerebral arteries and it can detect early atherosclerotic changes. Metformin an old oral anti-diabetic drug but still cornerstone in the treatment guidelines of type 2 diabetes mellitus. It improves endothelial function with preferable cardiovascular effects. Twenty patients were recruited for the study. Transcranial Doppler examination done for all patients before initiation of treatment. Patients received metformin for twelve weeks and they were re-examined with transcranial Doppler. The data of present study showed that a highly significant increase in diastolic velocity and mean flow velocity after treatment with significant reduction in pulsatility index and resistive index. In conclusion, metformin treatment increases cerebral diastolic flow velocity with reduction in vascular resistance in patients with type 2 diabetes.

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Metformin improves endothelial function in patients with metabolic syndrome

Cited by 155 publications

References 44 publications

Effects of lifestyle changes and metformin on salt sensitivity and nitric oxide metabolism in obese salt-sensitive Hispanics

Effects of lifestyle changes and metformin on salt sensitivity and nitric oxide metabolism in obese salt-sensitive Hispanics

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

Effects of metformin on middle cerebral artery flow velocity in newly diagnosed type 2 Diabetic patients

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