ubiquinone and Diabetic-Angiopathies

Topics: Antioxidants; Coenzymes; Diabetic Angiopathies; DNA Damage; DNA, Mitochondrial; Drug Design; Electron Transport; Humans; Insulin Resistance; Mitochondria; Mitochondrial Diseases; Mutation; Oxidative Stress; Signal Transduction; Superoxides; Thiamine; Transcription Factors; Ubiquinone

Increased oxidative stress in diabetes mellitus may underlie the development of endothelial cell dysfunction by decreasing the availability of nitric oxide (NO) as well as by activating pro-inflammatory pathways. In the arterial wall, redox imbalance and oxidation of tetrahydrobiopterin (BH4) uncouples endothelial nitric oxide synthase (eNOS). This results in decreased production and increased consumption of NO, and generation of free radicals, such as superoxide and peroxynitrite. In the mitochondria, increased redox potential uncouples oxidative phosphorylation, resulting in inhibition of electron transport and increased transfer of electrons to molecular oxygen to form superoxide and other oxidant radicals. Coenzyme Q10 (CoQ), a potent antioxidant and a critical intermediate of the electron transport chain, may improve endothelial dysfunction by 'recoupling' eNOS and mitochondrial oxidative phosphorylation. CoQ supplementation may also act synergistically with anti-atherogenic agents, such as fibrates and statins, to improve endotheliopathy in diabetes.

Topics: Antioxidants; Coenzymes; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dietary Supplements; Drug Synergism; Endothelium, Vascular; Humans; Mitochondria; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Oxidative Stress; Phosphorylation; Receptors, Cytoplasmic and Nuclear; Transcription Factors; Ubiquinone

To investigate the effects of fenofibrate and coenzyme Q(10) (CoQ) on diastolic function, ambulatory blood pressure (ABP), and heart rate (HR) in type 2 diabetic subjects with left ventricular diastolic dysfunction (LVDD).. We randomized, double-blind, 74 subjects to fenofibrate 160 mg daily, CoQ 200 mg daily, fenofibrate 160 mg plus CoQ 200 mg daily, or matching placebo for 6 months. Echocardiography (including tissue Doppler imaging) and 24-h ABP and HR monitoring were performed pre- and postintervention.. Neither fenofibrate nor CoQ, alone or in combination, altered early diastolic mitral annular myocardial relaxation velocity (E'), early-to-late mitral inflow velocity ratio (E/A), deceleration time, isovolumic relaxation time, or the ratio of early mitral flow velocity to early diastolic mitral annular myocardial relaxation velocity (E/E') compared with placebo (P > 0.05). Fenofibrate and CoQ interactively (P = 0.001) lowered 24-h systolic blood pressure (-3.4 +/- 0.09 mmHg, P = 0.010), with a prominent nocturnal effect (-5.7 +/- 1.5 mmHg, P = 0.006). Fenofibrate (-1.3 +/- 0.5 mmHg, P = 0.013) and CoQ (-2.2 +/- 0.5 mmHg, P < 0.001) independently lowered 24-h diastolic blood pressure. Fenofibrate reduced 24-h HR (-3.3 +/- 0.5 beats/min, P < 0.001), but CoQ had no effect on HR.. In type 2 diabetic subjects with LVDD, neither fenofibrate nor CoQ, alone or in combination, improved diastolic function significantly. However, fenofibrate and CoQ independently and interactively lowered 24-h blood pressure, and fenofibrate alone reduced 24-h HR.

Topics: Adult; Aged; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diastole; Double-Blind Method; Echocardiography; Female; Fenofibrate; Heart Rate; Humans; Hypolipidemic Agents; Male; Middle Aged; Placebos; Ubiquinone; Ventricular Dysfunction, Left

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.. 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 flow-mediated 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.. 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.. 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.

Topics: Antioxidants; Blood Pressure; Brachial Artery; Cholesterol; Coenzymes; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Female; Humans; Hyperemia; Lipoproteins; Male; Middle Aged; Placebos; Regional Blood Flow; Triglycerides; Ubiquinone; Vasodilation

The study included 39 patients with DM1, symptoms of peripheral diabetic angiopathy and metabolic disorders either compensated, subcompensated or decompensated 20 subjects served as controls. All the patients were given basal therapy with short-acting and intermediate-acting insulins, Some subcompensated patients were treated with hypoglycemic agents in combination with coenzyme Q10. The following parameters were measured: lipid peroxidation, activity of antioxidative enzymes, total nitric oxide (NO) metabolites, cholesterol (CH) metabolism, ALT AST GGT blood flow in the lower extremities was evaluated from rheovasograms. It was shown that patients with decompensated or subcompensated DM1 experienced oxidative stress accompanied by reduced NO levels and bioavailability. Elevated concentration of total CH and LDLP and decreased HDLP levels promoted endothelial dysfunction and were risk factors of atherosclerosis. Traditional therapy relieved disorders of carbohydrate and lipid metabolism but failed to correct hemodynamic disturbances in the lower extremities. Combined treatment with coenzyme Q10 reduced lipid peroxidation, increased activity of antioxidant enzymes, total NO metabolites and bioavailability, decreased the level of atherogenic LDLP. Improvement of metabolism was associated with normalization of elasticity of microvessels and pulse blood filling of the lower limb vessels, reduced tone and modulus of elasticity of arterioles and capillaries, correction of venous hyperemia. Reduced resistance of the microcirculatory bed resulted in normalization of arterial pressure.

Topics: Adolescent; Adult; Combined Modality Therapy; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin; Male; Oxidative Stress; Risk; Treatment Outcome; Ubiquinone; Vascular Resistance; Young Adult

Individuals with diabetes and prediabetes are at risk of vascular injury. However, the exact mechanisms are unclear. The mitochondria mobile electron carrier coenzyme Q(10) (CoQ(10)) is a potent lipophilic antioxidant. We hypothesize that oxidative stress, detectable as changes in plasma CoQ(10) concentrations and composition, plays an important role in vascular disease in diabetes.. We measured plasma CoQ(10) concentrations (including reduced ubiquinol and oxidized ubiquinone subfractions) in 60 subjects with normal glucose tolerance [NGT; fasting plasma glucose (FPG) < 5.5 mmol/l], 63 with impaired fasting glucose (IFG; FPG 5.6-6.9 mmol/l) and 69 with Type 2 diabetes (DM; FPG > 6.9 mmol/l).. In men and women, the total CoQ(10)/total cholesterol ratio was reduced in DM (mean +/-sd) [male (M) 0.09 +/- 0.04; female (F) 0.07 +/- 0.04] compared with NGT (0.29 +/- 0.08; 0.21 +/- 0.07) and IFG (0.27 +/- 0.07; 0.23 +/- 0.07) (DM vs. NGT and IFG P = 0.001). A stepwise reduction in the plasma ubiquinol fraction (ubiquinol/total CoQ10) was observed from NGT (M 0.93 +/- 0.06; F 0.95 +/- 0.06) compared with IFG (0.43 +/- 0.25; 0.41 +/- 0.15) and DM (0.24 +/- 0.11; F 0.29 +/- 0.16) (DM vs. IFG vs. NGT P = 0.001). In contrast, the plasma ubiquinone/ubiquinol ratio increased from NGT (M 0.08 +/- 0.07, F 0.06 +/- 0.08) to IFG (2.14 +/- 1.84, 1.75 +/- 1.04) to DM (4.77 +/- 4.88, 3.81 +/- 3.71) (DM vs. IFG vs. NGT P = 0.001). These differences remained after adjusting for age, body mass index and FPG.. The change in CoQ(10) with increasing FPG concentration suggests an increase in oxidative burden, already evident in the prediabetic IFG individuals. This increase in oxidative stress might contribute to the increased risk of vascular disease.

Topics: Adult; Blood Glucose; Case-Control Studies; Coenzymes; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Ubiquinone