Dyslipoproteinaemia and hyperoxidative stress in the pathogenesis of endothelial dysfunction in non-insulin dependent diabetes mellitus: an hypothesis

Watts, Gerald F.; Playford, David

doi:10.1016/s0021-9150(98)00170-1

Cited by 96 publications

(74 citation statements)

References 185 publications

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“…A dissociation between changes in endothelial function and plasma F 2 -isoprostane concentrations was found using antioxidant vitamin supplementation in non-diabetic subjects [33]. Our patients were dyslipidaemic and it is possible that increased plasma concentrations of lipoprotein remnants, small-dense LDL and low HDL cholesterol might have contributed to endothelial dysfunction in the absence of a systemic increase in oxidative stress [6].…”

Section: Discussionmentioning

confidence: 59%

“…The improvement in endothelial function also occurred in the presence of dyslipidaemia and was not related to changes in plasma F 2 -isoprostanes, glycated haemoglobin or blood pressure. That oxidative stress is increased in diabetes is well supported by experimental and clinical observations [5,6,11,29,30]. Oxidative stress occurs in diabetes as a consequence of several mechanisms related to hyperglycaemia [5,6].…”

Section: Discussionmentioning

confidence: 82%

“…These include accumulation of AGE, activation of the polyol pathway and stimulation of protein kinase C activity. Diabetes-induced generation of reactive oxygen species, in particular superoxide, decreases the expression of nitric oxide synthase and inactivates nitric oxide [6,31]. Vascular oxidative stress could explain why our patients had impaired FMD of the brachial artery with preserved vasodilation to glyceryl trinitrate.…”

Section: Discussionmentioning

confidence: 82%

“…That oxidative stress is increased in diabetes is well supported by experimental and clinical observations [5,6,11,29,30]. Oxidative stress occurs in diabetes as a consequence of several mechanisms related to hyperglycaemia [5,6]. These include accumulation of AGE, activation of the polyol pathway and stimulation of protein kinase C activity.…”

Section: Discussionmentioning

confidence: 84%

“…CoQ is a more powerful antioxidant than vitamin E, inhibiting its pro-oxidant activity [15,16]. Its deficiency can occur in diabetes in relation to impaired mitochondrial substrate metabolism [17] and increased oxidative stress [6]. Mitochondrial CoQ deficiency could be involved in the pathogenesis of Type II diabetes by impairing beta-cell function [18].…”

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confidence: 99%

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Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus

et al. 2002

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In Type II (non-insulin-dependent) diabetes mellitus the pathogenesis of vascular disease, its most common complication, remains unclear [1]. Endothelial dysfunction reflects the disordered physiology of several endothelium-derived vasoactive factors, in particular nitric oxide [2]. Endothelial dysfunction occurs commonly in diabetes and is an early feature of vasculopathy [3,4]. Increased oxidative stress due to the effects of hyperglycaemia and its sequelae is a recognized feature of diabetes [5]. It might cause endothelial dysfunction through the inactivation and Abstract Aim/hypothesis. We assessed whether dietary supplementation with coenzyme Q 10 improves endothelial function of the brachial artery in patients with Type II (non-insulin-dependent) diabetes mellitus and dyslipidaemia. Methods. A total of 40 patients with Type II diabetes and dyslipidaemia were randomized to receive 200 mg of coenzyme Q 10 or placebo orally for 12 weeks. Endothelium-dependent and independent function of the brachial artery was measured as flowmediated dilatation and glyceryl-trinitrate-mediated dilatation, respectively. A computerized system was used to quantitate vessel diameter changes before and after intervention. Arterial function was compared with 18 non-diabetic subjects. Oxidative stress was assessed by measuring plasma F 2 -isoprostane concentrations, and plasma antioxidant status by oxygen radical absorbance capacity. Results. The diabetic patients had impaired flow-mediated dilation [3.8 % (SEM 0.5) vs 6.4 % (SEM 1.0), p = 0.016], but preserved glyceryl-trinitrate-mediated dilation, of the brachial artery compared with non-diabetic subjects. Flow-mediated dilation of the brachial artery increased by 1.6 % (SEM 0.3) with coenzyme Q 10 and decreased by ±0.4 % (SEM 0.5) with placebo (p = 0.005); there were no group differences in the changes in pre-stimulatory arterial diameter, post-ischaemic hyperaemia or glyceryl-trinitrate-mediated dilation response. Coenzyme Q 10 treatment resulted in a threefold increase in plasma coenzyme Q 10 (p < 0.001) but did not alter plasma F 2 -isoprostanes, oxygen radical absorbance capacity, lipid concentrations, glycaemic control or blood pressure. Conclusion/interpretation. Coenzyme Q 10 supplementation improves endothelial function of conduit arteries of the peripheral circulation in dyslipidaemic patients with Type II diabetes. The mechanism could involve increased endothelial release and/or activity of nitric oxide due to improvement in vascular oxidative stress, an effect that might not be reflected by changes in plasma F 2 -isoprostane concentrations. [Diabetologia (2002) 45: 420±426]

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 84%

mentioning

confidence: 99%

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Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus

et al. 2002

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Coronary disease, dyslipidaemia and clinical trials in type 2 diabetes mellitus

Watts

2000

Pract Diab Int

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Coronary disease, dyslipidaemia and clinical trials in type 2 diabetes mellitus

Watts

2000

Pract Diab Int

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Epidemiological data testify that dyslipidaemia is a major risk factor for coronary disease in type 2 diabetes mellitus. Post hoc analyses of the subgroup of diabetic patients in the large lipid-regulating trials suggest that increasing plasma HDL-cholesterol in association with a major fall in LDL-cholesterol with a statin, or increasing HDL-cholesterol together with a major fall in triglyceride with a ®brate, decreases the incidence of coronary events. The absolute risk reduction appears to be suf®ciently high to make lipid-regulating therapy in these patients cost-effective. Correction of dyslipidaemia is therefore likely to play a major role in preventing and reversing macrovascular disease in diabetes, but this needs to be tested prospectively. This demand is being met by on-going trials of lipid-regulating therapy in type 2 diabetes and these are accordingly reviewed. Their results should establish a more rigorous approach to the detection and treatment of diabetic dyslipidaemia, which at present should, in general, follow guidelines recommended by the ADA and other expert bodies. The management of diabetic dyslipidaemia in particular needs to be considered within the context of modi®cation of multiple co-existent cardiovascular risk factors. Besides lipid-regulation, there are several new therapies that warrant testing in future clinical trials of the prevention and reversal of coronary disease in diabetes.

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Dyslipoproteinaemia and hyperoxidative stress in the pathogenesis of endothelial dysfunction in non-insulin dependent diabetes mellitus: an hypothesis

Cited by 96 publications

References 185 publications

Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus

Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus

Coronary disease, dyslipidaemia and clinical trials in type 2 diabetes mellitus

Coronary disease, dyslipidaemia and clinical trials in type 2 diabetes mellitus

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