coenzyme-q10 and Diabetes-Mellitus--Type-2

A number of aging-related disorders (ARD) have been related to oxidative stress (OS) and mitochondrial dysfunction (MDF) in a well-established body of literature. Most studies focused on cardiovascular disorders (CVD), type 2 diabetes (T2D), and neurodegenerative disorders. Counteracting OS and MDF has been envisaged to improve the clinical management of ARD, and major roles have been assigned to three mitochondrial cofactors, also termed mitochondrial nutrients (MNs), i.e., α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and carnitine (CARN). These cofactors exert essential-and distinct-roles in mitochondrial machineries, along with strong antioxidant properties. Clinical trials have mostly relied on the use of only one MN to ARD-affected patients as, e.g., in the case of CoQ10 in CVD, or of ALA in T2D, possibly with the addition of other antioxidants. Only a few clinical and pre-clinical studies reported on the administration of two MNs, with beneficial outcomes, while no available studies reported on the combined administration of three MNs. Based on the literature also from pre-clinical studies, the present review is to recommend the design of clinical trials based on combinations of the three MNs.

Topics: Aging; Animals; Antioxidants; Cardiovascular Diseases; Carnitine; Cell Line; Diabetes Mellitus, Type 2; Humans; Mitochondria; Neurodegenerative Diseases; Oxidative Stress; Thioctic Acid; Ubiquinone

Several studies have investigated the effect of Co-Q10 on diabetes biomarkers, but findings are inconsistent. This systematic review and meta-analysis of clinical trials was conducted to summarize the effect of Co-Q10 supplementation on diabetes biomarkers.. We searched Pubmed, EMBASE, Science direct, ISI web of science, and Google Scholar for randomized controlled trials from 1989 until March 2016. We included randomized controlled trials reporting fasting blood glucose (FBG), fasting insulin and HbA1c. In total, we found 16 articles that examined the effect of Co-Q10 on fasting blood glucose, fasting insulin and HbA1c. Mean ± standard deviations (SD) of defined outcomes were used for calculating standardized mean differences (SMD) and its 95% confidence interval (95%CI) between intervention and control treatments based on Hedges' estimator.. Our preliminary meta-analysis on 14 eligible studies regarding the effect of Co-Q10 supplementation on FBG indicated a slightly significant decrement (SMD:-0.28 mg/d; 95% CI: -0.12, 0.04), with a substantial between-study heterogeneity (Cochrane Q test, I2 = 93.9%, P < 0.0001). After removal of three studies, heterogeneity was eliminated and a slightly significant decrease was found in FBG (SMD: -0.20 mg/dL, 95% CI: -0.38, -0.02). The effect of Co-Q10 on HbA1c and fasting insulin was not significant. SMDs for the effect of Co-Q10 on HbA1c and fasting insulin were -0.05% (95% CI: -0.22, 0.12) and 0.12 pmol/L (95% CI: -0.21, 0.44), respectively.. Co-Q10 supplementation slightly but significantly reduced fasting blood glucose, but not fasting insulin and HbA1c. More long-term studies are necessary to examine the association between Co-Q10 supplementation and diabetes biomarkers. This study was funded by the School of Nutrition and Food Science, Isfahan University of Medical Sciences.

Topics: Antioxidants; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Randomized Controlled Trials as Topic; Ubiquinone

There is growing evidence to suggest that statin therapy is associated with an increased risk of incident diabetes. The risk for statin-related diabetes depends upon many factors including age, pre-existing diabetic risk, type and potency of statin. Several mechanisms have been suggested for the diabetogenic effects of statins involving processes that alter islet ß-cell function, resulting in impaired glucose metabolism. Recent evidence suggests that the association of statin therapy with the development of diabetes may be partly mediated by a statin-induced decrease in circulating adiponectin and coenzyme Q10. The available evidence suggests the benefit of statins in reducing cardiovascular events outweigh the risk of developing diabetes. Moreover, statin therapy does not impair glycemic control in diabetic patients. Expert recommendations for the use of statins in people at risk of developing diabetes have recently been published. However, further research is required to elucidate both the association between statin use and incident diabetes as well as underlying mechanisms.

Topics: Adiponectin; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Disease Management; Global Health; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Risk Factors; Ubiquinone

Diabetes is a chronic metabolic disorder that continues to present as a major health problem worldwide. It is characterized by absolute or relative deficiencies in insulin secretion and/or insulin action and is associated with chronic hyperglycemia and disturbances of carbohydrate, lipid, and protein metabolism. Many studies suggest a central role for oxidative stress in the pathogenesis of this multi-faceted metabolic disorder. This has prompted investigations in the use of antioxidants as a complementary therapeutic approach. In this review we briefly summarize oxidative mechanisms implicated in diabetic complications and then focus on the findings resulting from human clinical trials where antioxidants were studied as an adjuvant to standard diabetes treatment during the last ten years. A literature search using PubMed (last ten years) was performed using the following terms: vitamin E, vitamin C, coenzyme Q10, alpha lipoic acid, L-carnitine, ruboxistaurin or LY 333531 and diabetes. This search was limited to human clinical trials. We concluded there is not any established benefit for antioxidants use in the management of diabetic complications. Therefore, routine vitamin or mineral supplementation is not generally recommended.

Topics: Antioxidants; Ascorbic Acid; Carnitine; Clinical Trials as Topic; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Indoles; Male; Maleimides; Oxidative Stress; Thioctic Acid; Treatment Outcome; Ubiquinone; Vitamins

Topics: Coenzymes; Deafness; Diabetes Mellitus, Type 2; Diagnosis, Differential; DNA, Mitochondrial; Hypoglycemic Agents; Insulin; Insulin Secretion; MELAS Syndrome; Mitochondria; Mutation; Prognosis; 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

A growing body of evidence has demonstrated a link between various disturbances in mitochondrial functioning and type 2 diabetes. This review focuses on a range of mitochondrial factors important in the pathogenesis of this disease. The mitochondrion is an integral part of the insulin system found in the islet cells of the pancreas. Because of the systemic complexity of mitochondrial functioning in terms of tissue and energetic thresholds, details of structure and function are reviewed. The expression of type 2 diabetes can be ascribed to a number of qualitative or quantitative changes in the mitochondria. Qualitative changes refer to genetic disturbances in mitochondrial DNA (mtDNA). Heteroplasmic as well as homoplasmic mutations of mtDNA can lead to the development of a number of genetic disorders that express the phenotype of type 2 diabetes. Quantitative decreases in mtDNA copy number have also been linked to the pathogenesis of diabetes. The study of the relationship of mtDNA to type 2 diabetes has revealed the influence of the mitochondria on nuclear-encoded glucose transporters and the influence of nuclear encoded uncoupling proteins on the mitochondria. This basic research into the pathogenesis of diabetes has led to the awareness of natural therapeutics (such as coenzyme Q10) that increase mitochondrial functioning and avoidance of trans-fatty acids that decrease mitochondrial functioning.

Topics: Adenosine Triphosphate; Animals; Carrier Proteins; Coenzymes; Diabetes Mellitus, Type 2; Dietary Fats; DNA, Mitochondrial; Glucose; Humans; Insulin; Ion Channels; Membrane Proteins; Mitochondria; Mitochondrial Proteins; Mutation; Rats; Ubiquinone; Uncoupling Protein 1

Diabetes mellitus associated with mitochondrial tRNA mutation at position 3243(DM-Mt3243) is a new disease. Patients have a distinctly different picture from MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). During observations at the Saiseikai Central Hospital, the following findings were noted in DM-Mt3243 patients: DM-Mt3243 patients are diagnosed earlier with diabetes, compared to NIDDM (non-insulin dependent diabetes mellitus) controls without family history. DM-Mt3243 patients often need insulin more often than NIDDM controls without family history. Post-treatment neuropathy and insulin edema are often found in DM-Mt3243, and the two phenomena possibly have a similar pathophysiology related to mitochondrial dysfunction. Ambiguous psychiatric disorders of functional psychosis are observed frequently in DM-Mt3243. Mild headache is common in DM-Mt3243 cases. Ambiguous neuromuscular abnormalities such as sleep disturbance, paresthesia of the legs, edema of the legs, and palpitation may be symptoms associated with mitochondrial dysfunction in DM-Mt3243. Coenzyme Q may be effective in the relief of these neuromuscular symptoms.

Topics: Adult; Aged; Clinical Trials as Topic; Coenzymes; Depression; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diagnosis, Differential; DNA, Mitochondrial; Edema; Female; Humans; Insulin; Male; Middle Aged; Mitochondrial Encephalomyopathies; Peripheral Nervous System Diseases; Point Mutation; Psychotic Disorders; RNA, Transfer, Leu; Ubiquinone

Metabolic syndrome (MetS) as a cluster of conditions including hyperlipidemia, hypertension, hyperglycemia, insulin resistance, and abdominal obesity is linked to cardiovascular diseases and type 2 diabetes. Evidence suggested that intake of curcumin and coenzyme Q10 may have therapeutic effects in the management of MetS.. We investigated the effects of curcumin and/or coenzyme Q10 supplementation on metabolic syndrome components including systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference (WC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c) and fasting plasma glucose (FPG) as primary outcomes, and total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and body mass index (BMI) as secondary outcomes in subjects with MetS.. In this 2 × 2 factorial, randomized, double-blinded, placebo-controlled study, 88 subjects with MetS were randomly assigned into four groups including curcumin plus placebo (CP), or coenzyme Q10 plus placebo (QP), or curcumin plus coenzyme Q10 (CQ), or double placebo (DP) for 12 weeks.. The CP group compared with the three other groups showed a significant reduction in HDL-c (P = 0.001), TG (P <  0.001), TC (P <  0.001), and LDL-c (P <  0.001). No significant differences were seen between the four groups in terms of SBP, DBP, FPG, WC, BMI and weight.. Curcumin improved dyslipidemia, but had no effect on body composition, hypertension and glycemic control. Furthermore, coenzyme Q10 as well as the combination of curcumin and coenzyme Q10 showed no therapeutic effects in subjects with MetS. The trial was registered on 09/21/2018 at the Iranian clinical trials website (IRCT20180201038585N2), URL: https://www.irct.ir/trial/32518 .

Topics: Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Hypertension; Iran; Metabolic Syndrome; Triglycerides; Ubiquinone

Type 2 diabetes mellitus (T2DM) is a disease associated with increased oxidative stress which results from mitochondrial dysfunction. Coenzyme Q. Eighty women with T2DM enrolled in this study. Thirty six of them were randomized in the drug group (receiving 100 mg/day of CoQ. Serum values of FBS (P=0.039), HOMA-IR (P=0.01), ferritin (P<0.001), total cholesterol (TC) (P=0.006), LDL-C (P=0.007) decreased and HDL-C (P=0.02) increased significantly in the drug group after intervention. Serum levels of triglyceride (P=0.09) decreased marginally in CoQ. The results of the current study had shown that after supplementation with 100 mg/day of CoQ

Topics: Adult; Bilirubin; Blood Glucose; Butyrylcholinesterase; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Ferritins; gamma-Glutamyltransferase; Humans; Middle Aged; Treatment Outcome; Ubiquinone

Patients with type 2 diabetes mellitus (T2DM) have been known to be suffering from coenzyme Q10 (CoQ10) deficiency which results in some complications in them. The purpose of this clinical trial study was to evaluate the effects of CoQ10 supplementation on serum values of adiponectin (A), leptin (L), 8-isoprostane, malondialdehyde (MDA), the A/L ratio in women with T2DM. Sixty-eight women with T2DM were enrolled in the current study and were randomly divided into drug (n = 34) and placebo (n = 34) groups who were consuming 100 mg CoQ10 and 100 mg cellulose acetate per day for 12 weeks, respectively. Measurements were performed at the beginning and after the intervention. Serum values of adiponectin (p = .001) and the A/L ratio (p = .001) were increased while values of leptin (p = .041), MDA (p = .023), 8-isoprostane (p = .004) were decreased significantly in drug group after intervention. This study had shown that CoQ10 supplementation in women with T2DM was effective in elevation of adiponectin and the A/L ratio and reduction of leptin, MDA and 8-isoprostane which could result in improving insulin resistance and modulating oxidative stress situation.. 摘要 患有2型糖尿病（T2DM）的患者伴有辅酶Q10（CoQ10）缺乏, 这将导致一系列并发症。该临床试验研究的目的是评估补充CoQ10对2型糖尿病（T2DM）女性患者的脂联素（A）, 瘦素（L）, 8-异前列烷, 丙二醛（MDA）, A/L比值的影响。本研究纳入了68名T2DM女性, 随机分为药物组（n = 34）和安慰剂组（n = 34）, 每天服用100mg辅酶Q10和100mg醋酸纤维素, 共12周。在开始时和干预后对观察指标进行测量。干预后药物组患者的脂联素（p = .001）和A/L比（p = .001）的血清值增加, 瘦素（p = .041）, MDA（p = .023）, 8-异前列烷（p = .004）显著下降。本研究表明补充CoQ10对T2DM女性有效, 可提高脂联素和A/L比值, 减少瘦素, MDA和8-异前列烷, 从而改善胰岛素抵抗, 调节氧化应激状态。.

Topics: Adiponectin; Diabetes Mellitus, Type 2; Dietary Supplements; Dinoprost; Double-Blind Method; Female; Humans; Leptin; Malondialdehyde; Middle Aged; Ubiquinone; Vitamins

Ubiquinone is a lipid antioxidant, and a novel liquid ubiquinol (a hydro-soluble, reduced form of coenzyme Q10) supplement was recently developed. The purpose of this study was to examine the levels of glucose, lipids and antioxidant capacity of type 2 diabetes patients after liquid ubiquinol supplementation. This study was designed as a randomised, double-blind, placebo-controlled trial. In all, fifty participants were randomly assigned to a placebo (n 25) or liquid ubiquinol (100 mg/d, n 25) group, and the intervention lasted for 12 weeks. Plasma coenzyme Q10, glucose homoeostasis parameters, lipid profiles, oxidative stress and antioxidative enzyme activities were measured during the study. After 12 weeks of supplementation, glyco Hb (HbA1c) value was significantly decreased in the liquid ubiquinol group (P=0·03), and subjects in the liquid ubiquinol group had significantly lower anti-glycaemic medication effect scores (MES) compared with those in the placebo group (P=0·03). The catalase (P<0·01) and glutathione peroxidase (P=0·03) activities were increased significantly after supplementation. Plasma coenzyme Q10 was correlated with the insulin level (P=0·05), homoeostatic model assessment-insulin resistance (P=0·07), quantitative insulin sensitivity check index (P=0·03) and the anti-hyperglycaemic agents' MES (P=0·03) after supplementation. Lipid profiles did not change after supplementation; however, the subjects in the placebo group had a significantly lower level of HDL-cholesterol after 12 weeks of intervention. In conclusion, oral intake of 100 mg/d liquid ubiquinol might benefit type 2 diabetes patients by increasing antioxidant enzyme activity levels, reducing HbA1c levels and maintaining HDL-cholesterol levels.

Topics: Administration, Oral; Adult; Aged; Anthropometry; Antioxidants; Blood Glucose; Blood Pressure; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diet; Dietary Supplements; Double-Blind Method; Female; Glucose; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Lipids; Male; Middle Aged; Oxidative Stress; Ubiquinone

Im Rahmen der vorliegenden Studie sollte der Einfluss des Weichteilschadens auf das klinische Ergebnis nach offener Ellenbogenluxation untersucht werden.. Von Oktober 2008 bis August 2015 wurden insgesamt 230 Patienten mit Ellenbogenluxation behandelt. Diese retrospektive Studie umfasst 21 Fälle von offenen Ellenbogenluxationen. Das Durchschnittsalter der Patienten betrug 49 Jahre alt (20–83 Jahre), 6 Patienten waren weiblich (29%), 15 männlich (71%). Das Bewegungsausmaß des verletzten und unverletzten Ellenbogens wurde erhoben und das funktionelle Ergebnis u. a. mittels Mayo Elbow Performance Score (MEPS), Mayo Wrist Score (MWS) und dem Disability of Arm, Shoulder and Hand (DASH) Score erfasst. Zusätzlich wurden Komplikationen und Revisionsoperationen aufgezeichnet. Der Einfluss des Weichteilschadens (I°/II° offen vs. III° offen) und des Luxationstyps (einfach vs. komplex) auf das klinische Ergebnis wurde analysiert.. Offene Ellenbogenluxationen können mit einem zufriedenstellenden klinischen Ergebnis einhergehen. Insbesondere komplexe offene Ellenbogenluxationen sind jedoch sehr komplikationsbehaftet, wobei neurovaskuläre Komplikationen am häufigsten auftreten.. The current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance.. The results indicated differential patterns of Inhibition of Return between the High and Low shape/weight based self-worth groups. The High group displayed increased inhibition of return for the shape/weight stimuli relative to control stimuli, while the Low group displayed reduced inhibition of return for the shape/weight stimuli compared to control stimuli. The ED group displayed a similar pattern of results to the High group, but this did not reach significance.. The current findings indicate that young women without an eating disorder who base their self-worth on shape/weight display a pattern of avoidance of shape/weight stimuli that is in direct contrast to those at low risk of developing eating disorders. The possible implications of these specific patterns of inhibition of return across those at varying levels of risk for an eating disorder are discussed along with their implications for intervention approaches.. These results indicated that Sr. An unusually high HbA

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Limited data are available indicating the effects of coenzyme Q10 (CoQ10) supplementation on metabolic status of patients with metabolic syndrome (MetS).. The present study was conducted to determine the effects of CoQ10 administration on glucose homeostasis parameters, lipid profiles, biomarkers of inflammation and oxidative stress among patients with MetS.. This randomized, double-blind, placebo-controlled trial was performed among 60 overweight or obese and type 2 diabetes mellitus patients with coronary heart disease aged 40-85 years old. Participants were randomly allocated into two groups. Group A (n = 30) received 100 mg CoQ10 supplements and group B (n = 30) received placebo for 8 weeks. Fasting blood samples were taken at the beginning of the study and after 8-week intervention to quantify glucose homeostasis parameters, lipid profiles and biomarkers of inflammation and oxidative stress.. Compared with the placebo, CoQ10 supplementation resulted in a significant reduction in serum insulin levels (-2.1 ± 7.1 vs. +4.1 ± 7.8 µIU/mL, P = 0.002) and homeostasis model of assessment-insulin resistance (-0.7 ± 2.1 vs. +1.0 ± 2.0, P = 0.002) and homeostatic model assessment-beta cell function (-5.9 ± 22.2 vs. +15.9 ± 34.0, P = 0.005). In addition, patients who received CoQ10 supplements had a significant increase in plasma total antioxidant capacity (TAC) concentrations (+26.0 ± 105.0 vs. -162.2 ± 361.8 mmol/L, P = 0.008) compared with the placebo group. However, after adjustment for the baseline levels, age and baseline BMI, the effect on TAC levels (P = 0.08) disappeared. Additionally, compared with the placebo group, a significant positive trends in plasma glutathione (P = 0.06) and a significant reduction in malondialdehyde (P = 0.08) were seen among patients who received CoQ10 supplement. We did not observe any significant changes in fasting plasma glucose, lipid concentrations and inflammatory markers.. Overall, daily intake of 100 mg CoQ10 supplements among patients with MetS for 8 weeks had beneficial effects on serum insulin levels, HOMA-IR, HOMA-B and plasma TAC concentrations.. www.irct.ir : IRCT201502245623N35.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Energy Intake; Glutathione; Homeostasis; Humans; Insulin; Insulin Resistance; Lipids; Malondialdehyde; Metabolic Syndrome; Middle Aged; Nitric Oxide; Obesity; Oxidative Stress; Ubiquinone

To assess the effects of Coenzyme Q10 supplementation on glycaemic control, oxidative stress and adiponectin levels in people with type 2 diabetes.. The randomised, single-blind, placebo-controlled study was conducted in the city of Shiraz, Iran, in 2012 and comprised type 2 diabetes subjects recruited from various health facilities. Subjects and controls received 100mg Coenzyme Q10 or placebo twice a day for eight weeks respectively. A variety of measurements were made at baseline and at the end of the intervention. These included measuring markers of glycaemic control (fasting blood glucose and glycated haemoglobin); a marker of oxidative stress (malondialdehyde); and an anti-inflammatory marker (adiponectin). SPSS 15 was used for statistical analysis.. Of the 52 patients, 28(54%) were male and 24(46%) were female, with an overall mean age of 51.73±7.34 years. There were 16(62% male and 10(39%) females in the intervention group, and 12(46%) male and 14(54%) female subjects in the control group. Among the cases, Coenzyme Q10 resulted in a significant reduction in malondialdehyde levels (p=0.04). However, the difference within the controls for this factor was not significant (p>-0.05). Moreover, fasting blood glucose, glycated haemoglobin and adiponectin levels showed no significant differences within or between the groups (p>0.05 each).. Coenzyme supplementation may reduce oxidative stress in type 2 diabetics. However, it may not have any effects on glycaemic control and adiponectin levels.

Topics: Adiponectin; Blood Glucose; Diabetes Mellitus, Type 2; Drug Monitoring; Electron Transport Chain Complex Proteins; Female; Glycated Hemoglobin; Humans; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Treatment Outcome; Ubiquinone; Vitamins

According to many studies, supplementation with Coenzyme Q10 (CoQ10) yields beneficial results in terms of endothelial function in type 2 diabetes mellitus. Despite these promising results, data elucidating the effect of CoQ10 on plasma levels of asymmetric dimethylarginine (ADMA), as a recently discussed cardiovascular risk factor, is lacking. This study was designed to investigate the effect of CoQ10 supplementation on endothelial function, specifically by evaluating plasma ADMA levels.. Sixty-four type 2 diabetic patients were randomly assigned to two groups; either receiving 200mg/d oral dose of CoQ10 (N.=31) or receiving placebo (N.=33) for 12 weeks. Clinical and biochemical assessments were performed before and after the trial for evaluating ADMA, serum nitrite and nitrate (NOx), hemoglobin A1c and lipid profile.. The intervention resulted in a significant improvement in ADMA, NOx , low-density lipoprotein and hemoglobin A1c levels in CoQ10 compared to placebo group. Interestingly, difference in changes of these parameters were also significant (P=0.01, 0.03, 0.04 and 0.03, respectively).. Supplementation with CoQ10 yields beneficial effects on ADMA levels, leading to decreased diabetic cardiovascular events.

Topics: Adult; Aged; Antioxidants; Arginine; Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Ubiquinone

Increased oxidative stress and impaired antioxidant defense contribute to pathogenesis and progression of type 2 diabetes. Consistent with this fact, it has been shown that diabetic patients have reduced coenzyme Q10 level. In this study we sought to compare the effect of coenzyme Q10 versus placebo on glycemic control and lipid profile in type 2 diabetic patients.. In a randomized double-blind placebo-controlled trial, 64 type 2 diabetic patients were randomly assigned to receive either 200 mg Q10 or placebo daily for 12 weeks. Fasting blood samples were obtained and fasting plasma glucose (FPG), HbA1c, total cholesterol (TC), triglycerides (TG), LDL-C and HDL-C were measured.. In this study no significant differences considering age, body mass index (BMI), diabetes duration, FPG, HbA1c, TC, TG, LDL-C and HDL-C were shown between two groups. Serum HbA1C concentration decreased in the Q10 treated group (8 ± 2.28 vs. 8.61 ± 2.47%) with no significant effect in the placebo group. Following intervention no differences have been shown regarding FPG, TG and HDL-C in Q10 treated group. Furthermore, mean differences of TC and LDL-C level were statistically altered between two groups (P value=0.027 and 0.039 respectively).. In this study, Q10 treatment improved glycemic control, total and LDL cholesterol but these differences were associated with no favourable effects on TG and HDL-C.

Topics: Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Male; Middle Aged; Ubiquinone

Our aim was to examine the effects of adjunctive coenzyme Q(10) therapy on 24-h ambulatory blood pressure (BP) in subjects with the metabolic syndrome and inadequate BP control.. In a randomized, double-blind, placebo-controlled 12-week crossover trial, coenzyme Q(10) (100 mg twice daily) or placebo was administrated to 30 subjects with the metabolic syndrome, and inadequate BP control (an average clinic BP of ≥140 systolic mm Hg or ≥130 mm Hg for patients with type 2 diabetes) while taking an unchanged, conventional antihypertensive regimen. Clinic and 24-h ambulatory BP were assessed pre- and post-treatment phases. The primary outcomes were the changes in 24-h systolic and diastolic BP during adjunctive therapy with coenzyme Q(10) vs. placebo and prespecified secondary outcomes included changes in BP loads.. Compared with placebo, treatment with coenzyme Q(10) was not associated with statistically significant reductions in systolic (P = 0.60) or diastolic 24-h ambulatory BP (P = 0.12) or heart rate (P = 0.10), although daytime diastolic BP loads, were significantly lower during coenzyme Q(10) administration with thresholds set at >90 mm Hg (P = 0.007) and ≥85 mm Hg (P = 0.03). Coenzyme Q(10) was well tolerated and was not associated with any clinically relevant changes in safety parameters.. Although it is possible that coenzyme Q(10) may improve BP control under some circumstances, any effects are likely to be smaller than reported in previous meta-analyses. Furthermore, our data suggest that coenzyme Q(10) is not currently indicated as adjunctive antihypertensive treatment for patients with the metabolic syndrome whose BP control is inadequate, despite regular antihypertensive therapy.

Topics: Aged; Antihypertensive Agents; Antioxidants; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Treatment Outcome; Ubiquinone; Vitamins

The vascular benefits of statins might be attenuated by inhibition of coenzyme Q(10) (CoQ(10)) synthesis. We investigated whether oral CoQ(10) supplementation improves endothelial dysfunction in statin-treated type 2 diabetic patients.. In a double-blind crossover study, 23 statin-treated type 2 diabetic patients with LDL cholesterol <2.5 mmol/l and endothelial dysfunction (brachial artery flow-mediated dilatation [FMD] <5.5%) were randomized to oral CoQ(10) (200 mg/day) or placebo for 12 weeks. We measured brachial artery FMD and nitrate-mediated dilatation (NMD) by ultrasonography. Plasma F(2)-isoprostane and 24-h urinary 20-hydroxyeicosatetraenoic acid (HETE) levels were measured as systemic oxidative stress markers.. Compared with placebo, CoQ(10) supplementation increased brachial artery FMD by 1.0 +/- 0.5% (P = 0.04), but did not alter NMD (P = 0.66). CoQ(10) supplementation also did not alter plasma F(2)-isoprostane (P = 0.58) or urinary 20-HETE levels (P = 0.28).. CoQ(10) supplementation improved endothelial dysfunction in statin-treated type 2 diabetic patients, possibly by altering local vascular oxidative stress.

Topics: Adult; Aged; Blood Flow Velocity; Blood Pressure; Brachial Artery; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Endothelium, Vascular; Humans; Hydroxyeicosatetraenoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Middle Aged; Oxidative Stress; Placebos; Ubiquinone; Vasodilation

Topics: Adult; Cell Adhesion Molecules; Coenzymes; Diabetes Mellitus, Type 2; Endothelium, Vascular; Female; Humans; Male; Microcirculation; Middle Aged; 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

To assess the effects of fenofibrate therapy on concentrations of plasma ubiquinol-10 and ubiquinone-10-the reduced and oxidized forms, respectively, of coenzyme Q(10).. Prospective, open-label, non-controlled study.. University clinic and laboratory.. Eighteen patients with hyperlipidemia and type 2 diabetes mellitus.. Patients received fenofibrate 150 mg/day for 12 weeks.. Metabolic parameters were assessed 4, 8, and 12 weeks after the start of fenofibrate treatment. Plasma ubiquinol-10 and ubiquinone-10 levels were measured by reverse-phase high-performance liquid chromatography. At 4, 8, and 12 weeks, significant reductions in fasting triglyceride levels and significant increases in high-density lipoprotein cholesterol levels were noted. Total cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and adiponectin levels, however, did not change significantly. Plasma ubiquinol-10 concentrations significantly increased after 8 and 12 weeks (p<0.05 for both), whereas ubiquinone-10 concentrations tended to decrease, especially at 12 weeks.. Our findings suggest that fenofibrate may help produce energy or prevent oxidation by increasing plasma ubiquinol-10 concentration; this effect may protect against the development and progression of atherosclerosis. In addition, treatment with fenofibrate demonstrated a favorable effect on serum lipid parameters.

Topics: Coenzymes; Diabetes Mellitus, Type 2; Disease Progression; Female; Fenofibrate; Humans; Hyperlipidemias; Male; Middle Aged; Prospective Studies; Ubiquinone

Arteriopathy is the principal complication of type 2 diabetes mellitus. It develops from endothelial dysfunction, which we have hypothesised occurs in diabetes primarily as a consequence of dyslipidaemia and oxidative stress. Fenofibrate and CoQ may improve endothelial function by regulating dyslipidaemia and oxidative stress, respectively. We therefore aimed to assess the independent and combined effects of fenofibrate and coenzyme Q(10) (CoQ) on endothelium-dependent and endothelium-independent vasodilator function of the forearm microcirculation in type 2 diabetes. Eighty dyslipidaemic type 2 diabetics were randomized to receive fenofibrate (200 mg/daily), CoQ (200 mg/daily), fenofibrate plus CoQ (200+200 mg daily), or placebo for 12 weeks. Forearm microcirculatory function was assessed with venous occlusion plethysmography during the infusion of acetylcholine (ACh), bradykinin (BK), sodium nitroprusside (SNP) and N(G)-monomethyl-L-arginine (L-NMMA) into the brachial artery. Blood flow responses were calculated as area under the curve (AUC). Fenofibrate significantly lowered plasma cholesterol, triglyceride and fibrinogen (P<0.001), and elevated HDL-cholesterol and homocysteine (P<0.001). CoQ did not change plasma isoprostanes, but significantly lowered systolic blood pressure and HbA(1c) (P<0.05). Fenofibrate plus CoQ significantly improved (P<0.05) the AUC for ACh, BK and SNP without significantly altering basal responses to L-NMMA. Fenofibrate or CoQ alone did not significantly alter blood flow responses. Improvements in blood flow were independent of changes in plasma lipids, blood pressure, homocysteine and isoprostanes, but were correlated (P=0.013) with HbA(1c). In conclusion, in this factorial trial we found that only the combination of fenofibrate and CoQ markedly improved endothelial and non-endothelial forearm vasodilator function in dyslipidemic type 2 diabetic patients. The favourable vascular effect of this therapeutic combination could be due to increase in the bioactivity of and/or responses to endothelium-derived relaxing factors, including nitric oxide, and this may entail synergistic stimulation of peroxisome proliferator-activated receptors.

Topics: Acetylcholine; Antioxidants; Apolipoprotein A-I; Area Under Curve; Blood Circulation; Blood Pressure; Bradykinin; Cholesterol, HDL; Cholesterol, LDL; Coenzymes; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Enzyme Inhibitors; F2-Isoprostanes; Female; Fenofibrate; Forearm; Glycated Hemoglobin; Homocysteine; Humans; Hypolipidemic Agents; Male; Middle Aged; Nitroprusside; omega-N-Methylarginine; Regional Blood Flow; Statistics as Topic; Systole; Treatment Outcome; Triglycerides; Ubiquinone; Vasodilator Agents

Our objective was to assess effects of dietary supplementation with coenzyme Q10 (CoQ) on blood pressure and glycaemic control in subjects with type 2 diabetes, and to consider oxidative stress as a potential mechanism for any effects.. Seventy-four subjects with uncomplicated type 2 diabetes and dyslipidaemia were involved in a randomised double blind placebo-controlled 2x2 factorial intervention.. The study was performed at the University of Western Australia, Department of Medicine at Royal Perth Hospital, Australia.. Subjects were randomly assigned to receive an oral dose of 100 mg CoQ twice daily (200 mg/day), 200 mg fenofibrate each morning, both or neither for 12 weeks.. We report an analysis and discussion of the effects of CoQ on blood pressure, on long-term glycaemic control measured by glycated haemoglobin (HbA(1c)), and on oxidative stress assessed by measurement of plasma F2-isoprostanes.. Fenofibrate did not alter blood pressure, HbA(1c), or plasma F2-isoprostanes. There was a 3-fold increase in plasma CoQ concentration (3.4+/-0.3 micro mol/l, P<0.001) as a result of CoQ supplementation. The main effect of CoQ was to significantly decrease systolic (-6.1+/-2.6 mmHg, P=0.021) and diastolic (-2.9+/-1.4 mmHg, P=0.048) blood pressure and HbA(1c) (-0.37+/-0.17%, P=0.032). Plasma F2-isoprostane concentrations were not altered by CoQ (0.14+/-0.15 nmol/l, P=0.345).. These results show that CoQ supplementation may improve blood pressure and long-term glycaemic control in subjects with type 2 diabetes, but these improvements were not associated with reduced oxidative stress, as assessed by F2-isoprostanes.. This study was supported by a grant from the NH&MRC, Australia.

Topics: Antioxidants; Blood Glucose; Blood Pressure; Coenzymes; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; F2-Isoprostanes; Female; Fenofibrate; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Oxidative Stress; Ubiquinone

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

Serum coenzyme Q10 (CoQ10: 2-(3,7,11,15,19,23,27,31,35,39-decamethyl-2,6,10,14,18,22,26,30,34 ,38 -tetracontadecaenyl)-5,6-dimethoxy-3-methyl-1,4-benzoquinone, CAS 303-98-0) and cholesterol levels were measured to assess the effect of cholesterol-lowering therapy in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty healthy volunteers, 97 NIDDM patients and 2 patients with familial hypercholesterolemia were studied. None had overt heart failure or any other heart disease. Mean serum CoQ10 concentrations were significantly (p < 0.01) lower in diabetic patients with normal serum cholesterol concentrations, either with or without administration of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA RIs) including simvastatin (normal: 0.91 +/- 0.26 (mean +/- SD) mumol 1(-1); diabetic with HMG-CoA RI: 0.63 +/- 0.19; diabetic without HMG-CoA RI: 0.66 +/- 0.21). CoQ10 concentrations were higher (1.37 +/- 0.48, p < 0.001) in diabetic patients with hypercholesterolemia. Simvastatin or low density lipoprotein apheresis decreased serum CoQ10 concentrations along with decreasing serum cholesterol. Oral CoQ10 supplementation in diabetic patients receiving HMG-CoA RI significantly (p < 0.001) increased serum CoQ10 from 0.81 +/- 0.24 to 1.47 +/- 0.44 mumol 1(-1), without affecting cholesterol levels. It significantly (p < 0.03) decreased cardiothoracic ratios from 51.4 +/- 5.1 to 49.2 +/- 4.7%. In conclusion, serum CoQ10 levels in NIDDM patients are decreased and may be associated with subclinical diabetic cardiomyopathy reversible by CoQ10 supplementation.

Topics: Adult; Anticholesteremic Agents; Antioxidants; Cholesterol; Chromatography, High Pressure Liquid; Coenzymes; Diabetes Mellitus, Type 2; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Pravastatin; Simvastatin; Ubiquinone

A possible relationship between the pathogenesis of type 2 diabetes and coenzyme Q10 (CoQ10) deficiency has been proposed. The aim of this study was to assess the effect of CoQ10 on metabolic control in 23 type 2 diabetic patients in a randomized, placebo-controlled trial. Treatment with CoQ10 100 mg bid caused a more than 3-fold rise in serum CoQ10 concentration (p < 0.001). No correlation was observed between serum CoQ10 concentration and metabolic control. No significant changes in metabolic parameters were observed during CoQ10 supplementation. The treatment was well tolerated and did not interfere with glycemic control, therefore CoQ10 may be used as adjunctive therapy in patients with associated cardiovascular diseases.

Topics: Aged; Antioxidants; Blood Glucose; Blood Pressure; Cholesterol; Cholesterol, HDL; Coenzymes; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Middle Aged; Placebos; Triglycerides; Ubiquinone; Vitamin E

Diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) have become some of the most urgent and prevalent health problems in recent decades, side by side with the growing obesity crisis. The close relationship between T2DM and CVD has become clear: endothelial dysfunction caused by oxidative stress and inflammation resulting from hyperglycaemia are the key factors in the development of vascular complications of T2DM, leading to CVD. Coenzyme Q10 (CoQ10) is a great candidate for the treatment of these diseases, acting precisely at the intersection between T2DM and CVD that is oxidative stress, due to its strong antioxidant activity and fundamental physiological role in mitochondrial bioenergetics. CoQ10 is a biologically active liposoluble compound comprising a quinone group and a side chain of 10 isoprenoid units, which is synthesized endogenously in the body from tyrosine and mevalonic acid. The main biochemical action of CoQ10 is as a cofactor in the electron transport chain that synthesizes adenosine triphosphate (ATP). As most cellular functions depend on an adequate supply of ATP, CoQ10 is essential for the health of virtually all human tissues and organs. CoQ10 supplementation has been used as an intensifier of mitochondrial function and an antioxidant with the aim of palliating or reducing oxidative damage that can worsen the physiological outcome of a wide range of diseases including T2DM and CVDs.. Although there is not enough evidence to conclude it is effective for different therapeutic indications, CoQ10 supplementation is probably safe and well-tolerated, with few drug interactions and minor side effects. Many valuable advances have been made in the use of CoQ10 in clinical practice for patients with T2DM and a high risk of CVD. However, further research is needed to assess the real safety and benefit to indicate CoQ10 supplementation in patients with T2DM.

Topics: Adenosine Triphosphate; Antioxidants; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Ubiquinone

Aim of the present study was to investigate the effect of co-administration coenzyme Q10 and pioglitazone on the mRNA expression of adipocytokines in white adipose tissues of chemically induced type 2 diabetes mellitus in rats.. Diabetes was induced by administration of streptozotocin (65 mg/kg, i.p.), followed by nicotinamide (110 mg/kg, i.p.) 15 min later. The diabetic rats were treated coenzyme Q10 (Q10, 10 mg/kg, p.o.) or pioglitazone (PIO, 20 mg/kg, p.o.) alone and their combination for four weeks. Biochemical parameters like FBS level, insulin and HbA1c along with tissue levels of MDA, SOD, CAT and GSH were estimated. The mRNA levels of ADIPOQ, RBP4, RETN, IL-6 and TNF-α in White Adipose Tissue (WAT) were measured.. Treatment with Q10 + PIO showed a significant reduction in the levels of FBS, HbA1c and a significant increase in insulin levels as compared to normal control group. Additionally, there was a significant change in the levels of biomarkers of oxidative stress after treatment with Q10 + PIO as compared to streptozotocin-nicotinamide group. Treatment with Q10 + PIO also significantly altered the mRNA expression of ADIPOQ, RETN, IL-6 and TNF-α when compared to monotherapy. However, mRNA expression of RBP4 did not alter in Q10 + PIO treated animal as compared to Q10 or PIO alone.. It is concluded that co-administration of Q10 and PIO has been shown the better therapeutic effect on the mRNA expression of adipocytokines and oxidative stress parameters as compared to either Q10 or PIO.

Topics: Adipokines; Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Drug Synergism; Gene Expression; Hypoglycemic Agents; Male; Pioglitazone; Rats; Rats, Wistar; RNA, Messenger; Ubiquinone; Vitamins

Major long-term complications in patients with diabetes are related to oxidative stress, caused by the hyperglycaemia characteristic for diabetes mellitus. The anti-oxidant coenzyme Q10 (CoQ10) has therefore been proposed as a beneficial supplement to diabetes treatment. Apart from its anti-oxidative function, CoQ10 appears to modulate immune functions by largely unknown mechanisms. The aim of this study was therefore to investigate the effect of CoQ10 on antimicrobial peptides and natural killer (NK) cells, both innate immune components implicated in the pathogenesis of diabetes and diabetes-associated long-term complications such as cardiovascular disease. We determined serum levels of antimicrobial peptides and the phenotype of NK cells isolated from peripheral blood of patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM) and from healthy controls. In addition, the same parameters were determined in diabetic patients after a 12-week period of CoQ10 supplementation. Two antimicrobial peptides, the human cathelicidin antimicrobial peptide (CAMP) and the human beta defensin 1 (hBD1), were reduced in serum from patients with T1DM. This defect was not reversible by CoQ10 supplementation. In contrast, CoQ10 reduced the levels of circulating hBD2 in these patients and induced changes in subset distribution and activation markers in peripheral NK cells. The results of the present study open up novel approaches in the prevention of long-term complications associated to T1DM, although further investigations are needed.

Topics: Adult; Aged; Antimicrobial Cationic Peptides; Antioxidants; beta-Defensins; Biomarkers; Case-Control Studies; Cytokines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Immunity, Innate; Inflammation; Killer Cells, Natural; Middle Aged; Oxidative Stress; Ubiquinone

Topics: Adenosine Triphosphate; Animals; Diabetes Mellitus, Type 2; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Muscular Diseases; Ubiquinone

The early onset of type 2 diabetes mellitus (DM), driven by increasing obesity, is associated with peripheral neuropathy. Here, we characterize diabetic neuropathic pain in New Zealand obese diabetic mice (NZO/HILtJ) as a polygenic model of obesity with type 2 diabetes and investigate the role of coenzyme Q10 (CoQ10) in the prevention and treatment of diabetic neuropathic pain. Since the overexpression of mitogen-activated protein kinase (MAPK), nuclear factor-κB proteins (NF-Kb), toll-like receptor 4 (TLR4) and downstream cytokines (such as CCL2, CXCL10) are considered important factors contributing to the development of neuropathic pain, the expression of these factors and the inhibitory effects of CoQ10 were evaluated. NZO/HILtJ mice spontaneously developed type 2 DM and increased body mass with diabetic neuropathic pain. CoQ10 treatment decreased pain hypersensitivity and long-term supplementation prevented the development of diabetic neuropathic pain but did not attenuate diabetes. Spinal cord, blood serum, liver tissue, and dorsal root ganglia (DRG) from diabetic mice demonstrated increased lipid peroxidation, which was decreased by CoQ10 treatment. The percentage of positive neurons of p65 (the activated marker of NF-KB) and MAPK in DRG were significantly higher in DM mice compared to controls. However, CoQ10 treatment significantly decreased p65 and MAPK positive neurons in the DRG of DM mice. RT-PCR demonstrated that elevated levels of mRNA of CCL2, CXCL10 or TLR4 in the spinal cord of DM mice decreased significantly when DM mice were treated with CoQ10.. This model may be useful in understanding the mechanisms of neuropathic pain in type 2 DM induced neuropathic pain and may facilitate preclinical testing of therapies. CoQ10 may decrease oxidative stress in the central and peripheral nervous system by acting as an anti-oxidant and free-radical scavenger. These results suggest that CoQ10 might be a reasonable preventative strategy for long-term use and using CoQ10 treatment may be a safe and effective long-term approach in the treatment of diabetic neuropathy.

Topics: Age Factors; Animals; Blood Glucose; Body Weight; Chemokine CCL2; Chemokine CXCL10; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Models, Animal; Female; Gene Expression Regulation; Hyperalgesia; Lipid Peroxidation; Male; Mice; Pain Measurement; Pain Threshold; Recombinant Fusion Proteins; Toll-Like Receptor 4; Ubiquinone; Vitamins

Diabetic peripheral neuropathy (DPN) is the most common complication in both type 1 and type 2 diabetes. Here we studied some phenotypic features of a well-established animal model of type 2 diabetes, the leptin receptor-deficient db(-)/db(-) mouse, and also the effect of long-term (6 mo) treatment with coenzyme Q10 (CoQ10), an endogenous antioxidant. Diabetic mice at 8 mo of age exhibited loss of sensation, hypoalgesia (an increase in mechanical threshold), and decreases in mechanical hyperalgesia, cold allodynia, and sciatic nerve conduction velocity. All these changes were virtually completely absent after the 6-mo, daily CoQ10 treatment in db(-)/db(-) mice when started at 7 wk of age. There was a 33% neuronal loss in the lumbar 5 dorsal root ganglia (DRGs) of the db(-)/db(-) mouse versus controls at 8 mo of age, which was significantly attenuated by CoQ10. There was no difference in neuron number in 5/6-wk-old mice between diabetic and control mice. We observed a strong down-regulation of phospholipase C (PLC) β3 in the DRGs of diabetic mice at 8 mo of age, a key molecule in pain signaling, and this effect was also blocked by the 6-mo CoQ10 treatment. Many of the phenotypic, neurochemical regulations encountered in lumbar DRGs in standard models of peripheral nerve injury were not observed in diabetic mice at 8 mo of age. These results suggest that reactive oxygen species and reduced PLCβ3 expression may contribute to the sensory deficits in the late-stage diabetic db(-)/db(-) mouse, and that early long-term administration of the antioxidant CoQ10 may represent a promising therapeutic strategy for type 2 diabetes neuropathy.

Topics: Age Factors; Animals; Blotting, Western; Diabetes Mellitus, Type 2; Electric Stimulation; Ganglia, Spinal; Hyperalgesia; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neural Conduction; Neurons; Peripheral Nervous System Diseases; Phospholipase C beta; Receptors, Leptin; Sciatic Nerve; Statistics, Nonparametric; Ubiquinone

Cardiovascular benefits of ubiquinone have been previously demonstrated, and we administered it as a novel therapy in an experimental model of type 2 diabetic nephropathy. db/db and dbH mice were followed for 10 weeks, after randomization to receive either vehicle or ubiquinone (CoQ10; 10mg/kg/day) orally. db/db mice had elevated urinary albumin excretion rates and albumin:creatinine ratio, not seen in db/db CoQ10-treated mice. Renal cortices from db/db mice had lower total and oxidized CoQ10 content, compared with dbH mice. Mitochondria from db/db mice also contained less oxidized CoQ10(ubiquinone) compared with dbH mice. Diabetes-induced increases in total renal collagen but not glomerulosclerosis were significantly decreased with CoQ10 therapy. Mitochondrial superoxide and ATP production via complex II in the renal cortex were increased in db/db mice, with ATP normalized by CoQ10. However, excess renal mitochondrial hydrogen peroxide production and increased mitochondrial membrane potential seen in db/db mice were attenuated with CoQ10. Renal superoxide dismutase activity was also lower in db/db mice compared with dbH mice. Our results suggest that a deficiency in mitochondrial oxidized CoQ10 (ubiquinone) may be a likely precipitating factor for diabetic nephropathy. Therefore CoQ10 supplementation may be renoprotective in type 2 diabetes, via preservation of mitochondrial function.

Topics: Adenosine Triphosphate; Albuminuria; Animals; Citrate (si)-Synthase; Creatinine; Cystatin C; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Hepatitis A Virus Cellular Receptor 1; Kidney; Kidney Function Tests; Membrane Potential, Mitochondrial; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Oxidation-Reduction; Random Allocation; Reactive Oxygen Species; Ubiquinone

Increased oxygen consumption results in kidney tissue hypoxia, which is proposed to contribute to the development of diabetic nephropathy. Oxidative stress causes increased oxygen consumption in type 1 diabetic kidneys, partly mediated by uncoupling protein-2 (UCP-2)-induced mitochondrial uncoupling. The present study investigates the role of UCP-2 and oxidative stress in mitochondrial oxygen consumption and kidney function in db/db mice as a model of type 2 diabetes.. Mitochondrial oxygen consumption, glomerular filtration rate and proteinuria were investigated in db/db mice and corresponding controls with and without coenzyme Q10 (CoQ10) treatment.. Untreated db/db mice displayed mitochondrial uncoupling, manifested as glutamate-stimulated oxygen consumption (2.7 ± 0.1 vs 0.2 ± 0.1 pmol O(2) s(-1) [mg protein](-1)), glomerular hyperfiltration (502 ± 26 vs 385 ± 3 μl/min), increased proteinuria (21 ± 2 vs 14 ± 1, μg/24 h), mitochondrial fragmentation (fragmentation score 2.4 ± 0.3 vs 0.7 ± 0.1) and size (1.6 ± 0.1 vs 1 ± 0.0 μm) compared with untreated controls. All alterations were prevented or reduced by CoQ10 treatment. Mitochondrial uncoupling was partly inhibited by the UCP inhibitor GDP (-1.1 ± 0.1 pmol O(2) s(-1) [mg protein](-1)). UCP-2 protein levels were similar in untreated control and db/db mice (67 ± 9 vs 67 ± 4 optical density; OD) but were reduced in CoQ10 treated groups (43 ± 2 and 38 ± 7 OD).. db/db mice displayed oxidative stress-mediated activation of UCP-2, which resulted in mitochondrial uncoupling and increased oxygen consumption. CoQ10 prevented altered mitochondrial function and morphology, glomerular hyperfiltration and proteinuria in db/db mice, highlighting the role of mitochondria in the pathogenesis of diabetic nephropathy and the benefits of preventing increased oxidative stress.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Glomerular Filtration Rate; Guanosine Diphosphate; Ion Channels; Kidney Glomerulus; Mice; Mitochondria; Mitochondrial Proteins; Oxidative Stress; Oxygen Consumption; Proteinuria; Ubiquinone; Uncoupling Protein 2; Vitamins

An increase in the production of reactive oxygen species is commonly thought to contribute to the development of diabetic cardiomyopathy. This study aimed to assess whether administration of the antioxidant coenzyme Q(10) would protect the diabetic heart against dysfunction and remodelling, using the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the efficacy of coenzyme Q(10) to that of the ACE inhibitor ramipril.. Six-week-old non-diabetic db/+ mice and diabetic db/db mice received either normal drinking water or water supplemented with coenzyme Q(10) for 10 weeks. Endpoint cardiac function was assessed by echocardiography and catheterisation. Ventricular tissue was collected for histology, gene expression and protein analysis.. Untreated db/db diabetic mice exhibited hyperglycaemia, accompanied by diastolic dysfunction and adverse structural remodelling, including cardiomyocyte hypertrophy, myocardial fibrosis and increased apoptosis. Systemic lipid peroxidation and myocardial superoxide generation were also elevated in db/db mice. Coenzyme Q(10) and ramipril treatment reduced superoxide generation, ameliorated diastolic dysfunction and reduced cardiomyocyte hypertrophy and fibrosis in db/db mice. Phosphorylation of Akt, although depressed in untreated db/db mice, was restored with coenzyme Q(10) administration. We postulate that preservation of cardioprotective Akt signalling may be a mechanism by which coenzyme Q(10)-treated db/db mice are protected from pathological cardiac hypertrophy.. These data demonstrate that coenzyme Q(10) attenuates oxidative stress and left ventricular diastolic dysfunction and remodelling in the diabetic heart. Addition of coenzyme Q(10) to the current therapy used in diabetic patients with diastolic dysfunction warrants further investigation.

Topics: Animals; Antihypertensive Agents; Apoptosis; Cardiomegaly; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Disease Models, Animal; Endomyocardial Fibrosis; Female; Hyperglycemia; Lipid Peroxidation; Mice; Mice, Inbred C57BL; Oxidative Stress; Proto-Oncogene Proteins c-akt; Ramipril; Superoxides; Ubiquinone; Ultrasonography; Ventricular Remodeling; Vitamins

This study investigated the level of platelet malondialdehyde (MDA) as a marker of oxidative stress and coenzyme Q10 (CoQ10) as an index of antioxidant capacity in patients with type 2 diabetes mellitus and their relation to glycemic control. The study group consisted of 28 patients with type 2 diabetes mellitus (10 men and 18 women) with mean age of 48 +/- 2 years. Ten healthy individuals, age and sex matched with the patients, were used as a control group. Laboratory investigations in the form of lipid profile, glycosylated hemoglobin, plasma MDA, platelet MDA and plasma CoQ10 were assessed for all patients and controls. The study revealed that plasma and platelet MDA, as a marker of oxidative stress, were significantly higher in diabetic patients than in controls. The level of CoQ10, as antioxidant capacity, was significantly lower in diabetic patients than in controls. There was a negative correlation between plasma CoQ10 concentrations and glycosylated hemoglobin. Type 2 diabetic patients are at increased risk of oxidative stress manifested by increased plasma MDA as well as platelet MDA and decreased CoQ10, and this oxidative stress increases with poor glycemic control.

Topics: Antioxidants; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Risk Factors; Ubiquinone

Mutations in mitochondrial DNA are rare etiologies of adult-onset diabetes mellitus (DM) that merit identification to 1) prevent iatrogenic lactic acidosis, 2) prompt appropriate screening of affected patients and their families, 3) provide genetic counseling, and 4) provide an opportunity to investigate strategies for preventing diabetes.. The objective of this study is to raise awareness of this rare form of adult-onset nonobese DM so that these patients are identified and provided with appropriate care.. We describe a kindred in which four of seven siblings have adult-onset DM and sensorineural hearing loss with a confirmed genetic mutation at position 3243 in the tRNA. Two other siblings in this kindred demonstrate different phenotypes of mitochondrial disease.. The proband was treated with coenzyme Q10 for 1 yr.. Outcome measures included stress thallium exercise testing and audiometry testing.. After 1 yr of treatment of with coenzyme Q10, repeat stress thallium testing demonstrated improvement in the exercise tolerance of the proband from 7-12 min. Audiometry testing did not demonstrate a change in the rate of hearing decline.. Maternally inherited diabetes and deafness is a rare cause of DM that is important to diagnose because of the unique management issues and associated comorbidities. This work highlights clues to the identification of this rare monogenic form of adult- onset diabetes.

Topics: Adult; Coenzymes; Diabetes Mellitus, Type 2; Exercise Test; Female; Genes, X-Linked; Hearing Loss, Sensorineural; Humans; Mitochondrial Diseases; Models, Biological; North America; Pedigree; RNA, Transfer, Leu; Ubiquinone

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

Using brain mitochondria isolated from 20-month-old diabetic Goto-Kakizaki rats, we evaluated the efficacy of CoQ10 treatment against mitochondrial dysfunction induced by Abeta1-40. For that purpose, several mitochondrial parameters were evaluated: respiratory indexes (RCR and ADP/O ratio), transmembrane potential (DeltaPsim), repolarization lag phase, repolarization and ATP levels and the capacity of mitochondria to produce hydrogen peroxide. We observed that 4 microM Abeta1-40 induced a significant decrease in the RCR and ATP content and a significant increase in hydrogen peroxide production. CoQ10 treatment attenuated the decrease in oxidative phosphorylation efficiency and avoided the increase in hydrogen peroxide production induced by the neurotoxic peptide. These results indicate that CoQ10 treatment counteracts brain mitochondrial alterations induced by Abeta1-40 suggesting that CoQ10 therapy can help to avoid a drastic energy deficiency that characterizes diabetes and Alzheimer's disease pathophysiology.

Topics: Adenosine Triphosphate; Age Factors; Amyloid beta-Peptides; Animals; Antioxidants; Brain; Cell Respiration; Coenzymes; Diabetes Mellitus, Type 2; Hydrogen Peroxide; Male; Membrane Potentials; Mitochondria; Oxidative Phosphorylation; Peptide Fragments; Rats; Rats, Wistar; Ubiquinone

The purpose of this study was to investigate the effect of regular meals on the daily profile of blood oxidative stress markers in type 2 diabetic patients with postprandial hyperglycaemia. %CoQ10, calculated as the ratio of ubiquinone-10 (oxidised form of coenzyme Q10) to ubiquinol-10 (reduced form), was used as a sensitive marker of oxidative stress. Blood samples were collected from patients before and 2 h after breakfast, lunch and supper, and at 10 p.m. Patients were selected for the study if their blood glucose levels were <7 mmol/l before breakfast and > or =11.1 mmol/l on at least one occasion after breakfast. %CoQ10 levels after breakfast and throughout the day were significantly higher than those before breakfast (p=0.006-0.04). In contrast to the wave-like changes in plasma glucose levels, %CoQ10 levels increased after breakfast and remained at high levels throughout the day. These results indicated that diabetic patients with postprandial hyperglycaemia were exposed to meal-induced periods of oxidative stress during the day. Postprandial hyperglycaemia therefore has the potential to increase the risk of atherosclerotic cardiovascular disease through induction of oxidative stress.

Topics: Ascorbic Acid; Biomarkers; Blood Glucose; Coenzymes; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Oxidative Stress; Patient Selection; Postprandial Period; Ubiquinone; Vitamin E

Topics: Aged; Antioxidants; Coenzymes; Deafness; Diabetes Mellitus, Type 2; DNA Mutational Analysis; DNA, Mitochondrial; Female; Humans; Mitochondrial Diseases; Phenotype; Point Mutation; Ubiquinone

Because diabetes mellitus is associated with impairment of testicular function, ultimately leading to reduced fertility, this study was conducted to evaluate the existence of a cause-effect relationship between increased oxidative stress in diabetes and reduced mitochondrial antioxidant capacity. The susceptibility to oxidative stress and antioxidant capacity (in terms of glutathione, coenzyme Q, and vitamin E content) of testis mitochondrial preparations isolated from Goto-Kakizaki (GK) non-insulin-dependent diabetic rats and from Wistar control rats, 1 yr of age, was evaluated. It was found that GK mitochondrial preparations showed a lower susceptibility to lipid peroxidation induced by ADP/Fe(2+), as evaluated by oxygen consumption and reactive oxygen species generation. The decreased susceptibility to oxidative stress in diabetic rats was associated with an increase in mitochondrial glutathione and coenzyme Q9 contents, whereas vitamin E was not changed. These results demonstrate a higher antioxidant capacity in diabetic GK rats. We suggest this is an adaptive response of testis mitochondria to the increased oxidative damage in diabetes mellitus.

Topics: Animals; Antioxidants; Coenzymes; Diabetes Mellitus, Type 2; Disease Models, Animal; Glutathione; Glutathione Disulfide; Male; Mitochondria; Oxidative Stress; Oxygen Consumption; Rats; Rats, Inbred Strains; Rats, Wistar; Reactive Oxygen Species; Testis; Ubiquinone; Vitamin E

It may now be feasible to target specific supplemental nutrients to each of the key dysfunctions which conspire to maintain hyperglycemia in type 2 diabetes: bioactive chromium for skeletal muscle insulin resistance, conjugated linoleic acid for adipocyte insulin resistance, high-dose biotin for excessive hepatic glucose output, and coenzyme Q(10) for beta cell failure. Nutritional strategies which disinhibit hepatic fatty acid oxidation (involving hydroxycitrate, carnitine, pyruvate, and other adjuvants) may likewise prove beneficial - in the short term, by decreasing serum free fatty acids and, in the longer term, by promoting regression of visceral obesity. The nutrients and food factors recommended here appear to be safe and well tolerated, and thus may have particular utility for diabetes prevention.

Topics: Biotin; Chromium; Coenzymes; Diabetes Mellitus, Type 2; Dietary Supplements; Fatty Acids, Nonesterified; Humans; Linoleic Acid; Ubiquinone

Even in individuals who are unwilling to make prudent changes in their diets and sedentary habits, the administration of certain nutrients and/or drugs may help to prevent or postpone the onset of type 2 diabetes. The evident ability of fiber-rich cereal products to decrease diabetes risk, as documented in prospective epidemiological studies, may be mediated primarily by the superior magnesium content of such foods. High-magnesium diets have preventive (though not curative) activity in certain rodent models of diabetes; conversely, magnesium depletion provokes insulin resistance. Epidemiology also strongly suggests that regular moderate alcohol consumption has a major favorable impact on diabetes risk, particularly in women; this may reflect a direct insulin-sensitizing effect on muscle and, in women, a reduced risk for obesity. Chromium picolinate can also aid muscle insulin sensitivity, and initial reports suggest that it is an effective therapy for type 2 diabetes. High-dose biotin has shown therapeutic activity in diabetic rats and in limited clinical experience; increased expression of glucokinase in hepatocytes may mediate this benefit. Other nutrients that might prove to aid diabetic glycemic control, and thus have potential for prevention, include coenzyme Q and conjugated linoleic acids (CLA). Since the nutrients cited here - including ethanol in moderation - appear to be quite safe and (with the exception of CLA) quite affordable, supplementation with these nutrients may prove to be a practical strategy for diabetes prevention. Drugs such as metformin and troglitazone, which are expensive and require regular physician monitoring to avoid potentially dangerous side-effects, would appear to be less practical options from cost-effectiveness, convenience and safety standpoints, given the fact that the population at-risk for diabetes is huge.

Topics: alpha-Linolenic Acid; Animals; Biotin; Calcium; Chromans; Coenzymes; Diabetes Mellitus, Type 2; Ethanol; Female; Humans; Liver; Magnesium; Male; Metformin; Rats; Risk Factors; Thiazoles; Thiazolidinediones; Troglitazone; Ubiquinone

Topics: Blood Glucose; C-Peptide; Carnitine; Coenzymes; Deafness; Diabetes Mellitus, Type 2; DNA, Mitochondrial; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin; Magnetic Resonance Spectroscopy; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Point Mutation; Retinitis; RNA, Transfer, Leu; Ubiquinone