Therapeutic regulation of endothelial dysfunction in type 2 diabetes mellitus

Hamilton, Sandra J.; Chew, Gerard T.; Watts, Gerald F.

doi:10.3132/dvdr.2007.026

Cited by 82 publications

(61 citation statements)

References 193 publications

(317 reference statements)

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“…Indeed FMD correlates with coronary endothelial function [8], reflecting endothelium-dependent vasodilator function in response to endothelium-dependent nitric oxide (NO) release and its reduction may predict cardiovascular events [9].…”

Section: Introductionmentioning

confidence: 99%

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Sahebkar

Giua

Pedone

et al. 2016

Pharmacological Research

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Flow-mediated dilation (FMD) of the brachial artery reflects endothelium-dependent vasodilator function; since it correlates with coronary endothelial function, its reduction could predict cardiovascular events. Several studies have investigated the potential impact of fibrates therapy on endothelial function, but clinical findings have not been fully consistent. We aimed to conduct a meta-analysis of randomized placebo-controlled trials in order to clarify whether fibrate therapy could improve endothelial function. A systematic search in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases was performed to identify randomized placebo-controlled trials investigating the effect of fibrates on endothelial function as estimated by FMD. A randomeffects model and generic inverse variance method were used for meta-analysis. Sensitivity analysis, risk of bias evaluation, and publication bias assessment were carried out using standard methods. Random-effects meta-regression was used to evaluate the impact of treatment duration on the estimated effect size. Fifteen trials with a total of 556 subjects met the eligibility criteria. Fibrate 3 therapy significantly improves FMD (weighted mean difference [WMD]: 1.64%, 95% CI: 1.15, 2.13, p < 0.001) and the result was confirmed in both subgroups with treatment durations ≤8 weeks (WMD: 1.35%, 95% CI: 0.85, 1.86, p < 0.001) and >8 weeks (WMD: 2.55%, 95% CI: 1.21, 3.89, p < 0.001). When the analysis was stratified according to the fibrate type, a significant effect was observed with fenofibrate but not with gemfibrozil, though difference between the two subgroups was not significant. Meta-analysis of data from trials where nitrate mediated dilation (NMD) was available did not suggest a significant change in NMD following treatment with fibrates. The results of this meta-analysis suggest that fibrates may exert beneficial effects on endothelial function, even over a short-term treatment course.

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Section: Introductionmentioning

confidence: 99%

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Sahebkar

Giua

Pedone

et al. 2016

Pharmacological Research

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“…At inception, they probably involve uncoupling of both eNOS activity (Figure 1B) and mitochondrial oxidative phosphorylation (Figure 2), as well as the activation of vascular NADPH oxidase [12,39,66]. These three mechanisms essentially result in the uncoupling of eNOS production, increased generation of superoxide ( Evidence suggests a reciprocal relationship between insulin resistance and ED [6].…”

Section: Endothelial Dysfunction In Type 2 Diabetesmentioning

confidence: 99%

“…Both invasive and non-invasive methods for assessing endothelial function have generated a wealth of knowledge concerning the pathogenesis and therapeutic regulation of ED in T2D [4, 11,12]. Treatment strategies necessarily target the pathophysiological factors that underlie ED and range from lifestyle interventions to nutritional supplements and specific pharmacological therapies [12]. We review these areas with a focus on dyslipoproteinemia.…”

Section: Introductionmentioning

confidence: 99%

“…Although important, dysglycemia, hypertension and insulin resistance chiefly operate through oxidative stress and pro-inflammatory pathways [6,9,10]. Both invasive and non-invasive methods for assessing endothelial function have generated a wealth of knowledge concerning the pathogenesis and therapeutic regulation of ED in T2D [4, 11,12]. Treatment strategies necessarily target the pathophysiological factors that underlie ED and range from lifestyle interventions to nutritional supplements and specific pharmacological therapies [12].…”

Section: Introductionmentioning

confidence: 99%

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Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

2013

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■ AbstractType 2 diabetes (T2D) markedly increases the risk of cardiovascular disease. Endothelial dysfunction (ED), an early indicator of diabetic vascular disease, is common in T2D and independently predicts cardiovascular risk. Although the precise pathogenic mechanisms for ED in T2D remain unclear, at inception they probably involve uncoupling of both endothelial nitric oxide synthase activity and mitochondrial oxidative phosphorylation, as well as the activation of vascular nicotinamide adenine dinucleotide phosphate oxidase. The major contributing factors include dyslipoproteinemia, oxidative stress, and inflammation. Therapeutic interventions are designed to target these pathophysiological factors that underlie ED. Therapeutic interventions, including lifestyle changes, antiglycemic agents and lipid-regulating therapies, aim to correct hyperglycemia and atherogenic dyslipidemia and to improve ED. However, high residual cardiovascular risk is seen in both research and clinical practice settings. Well-designed studies of endothelial function in appropriately selected volunteers afford a good opportunity to test new therapeutic interventions, paving the way for clinical trials and utilization in the care of the diabetic patient. However, based on the results from a recent clinical trial, niacin should not be added to a statin in individuals with low high-density lipoprotein cholesterol and very well controlled low-density lipoprotein cholesterol.

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“…Diabetic nephropathy is another kidney disease where oxidative stress is increased and NO production is altered. Dietary supplementation with antioxidants has been shown in several studies to have a positive effect on kidney function in diabetic nephropathy and these effects have been associated with changes in renal NO production and NOS activity [26][27][28][29][30][31] Because of the role of oxidative damage and free radicals in I/R injury as well, pretreatment of scheduled donors with a diet fortified in antioxidants might help ameliorate free radical over-production and decrease I/R damage. Accordingly, the hypothesis of this study is that an antioxidant therapeutic treatment given to rats for a defined time both prior to and following renal I/R injury will reduce the kidney damage that results from I/R injury and improve renal function.…”

Section: Introductionmentioning

confidence: 99%

Short-term antioxidant diet prevents hyperfiltration in young male rat kidney subjected to ischemia/reperfusion injury

Slyvka¹,

Nowak²,

Hayes³

et al. 2013

OJMIP

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Objectives: The process of transplantation is associated with exposure to both long and short cold and warm ischemic times that result in ischemia/reperfusion injury. Oxidative stress contributes to tissue fibrosis, renal dysfunction, and/or rejection. Treatments that scavenge oxygen free radicals and have antioxidant properties can ameliorate the damaging results in renal grafts following ischemia/reperfusion injury. The present study tests the hypothesis that an antioxidant-fortified diet given to rats before and after renal ischemia/reperfusion injury will reduce the kidney damage that results and improve renal function. Endothelial and inducible nitric oxide synthases may change with tissue injury, including ischemia/ reperfusion. Materials and Methods: Male Wistar rats were subjected to ischemia/reperfusion injury at 7 or 19 weeks of age with or without dietary antioxidant supplementation. One week later, glomerular filtration rate, mean arterial pressure and urinary nitric oxide were measured, and renal endothelial and inducible nitric oxide synthases examined. Results: The glomerular filtration rate was elevated more than two-fold above the normal range at 8 weeks in animals on the regular diet exposed to ischemia/reperfusion, while in the 8 week antioxidant-fortified diet group the glomerular filtration rate was normal. Also, in 8 week rats, levels of endothelial nitric oxide synthase protein in cortex were higher on the regular than on the antioxidant-fortified diet. Conclusion: Early after ischemia/reper-fusion injury renal endothelial nitric oxide synthase levels rise, possibly contributing to vascular dilation and hyperperfusion, and an antioxidant-fortified diet can ameliorate these changes in the younger age group.

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Therapeutic regulation of endothelial dysfunction in type 2 diabetes mellitus

Cited by 82 publications

References 193 publications

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

Short-term antioxidant diet prevents hyperfiltration in young male rat kidney subjected to ischemia/reperfusion injury

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