Type 2 diabetes increases oxidative stress, and this may be central to the development of endotheliopathy. Relative CoQ deficiency may occur in diabetes as a consequence of changes in mitochondrial substrate utilization and an increase in cellular redox potential. CoQ, as a critical intermediate of the mitochondrial electron transport chain and also a potent antioxidant, has the ability to regulate oxidative stress and endothelial function by coupling both mitochondrial oxidative phosphorylation and eNOS activity.

Recent reports in type 2 diabetic patients suggest that CoQ supplementation may improve abnormal endothelial function in conduit arteries and augment the benefits of a PPAR-α agonist on microcirculatory dysfunction, possibly by co-activation of this nuclear receptor.

CoQ supplementation has also been reported to improve blood pressure and hyperglycaemia in type 2 diabetes, and hence may exert beneficial anti-atherogenic effects through a number of different mechanisms.

Beyond NO, diabetic vasculopathy also involves the pathological effects of endothelin-I and angiotensin II on vascular oxidative stress, vasotonicity and cellular proliferation 1, 6 and whether CoQ also plays a role in regulating the effects of these molecules requires examination.

In addition to improving endothelial function, the benefits of CoQ supplementation in diabetes may extend to cardiac function, 30—32, 49 with multiple myocardial and extramyocardial mechanisms of ventricular systolic and diastolic dysfunction that could potentially be correctable with CoQ.

This is especially relevant to the recent demonstration that subjects with well-controlled type 2 diabetes have altered myocardial energy metabolism. However, the benefits of CoQ supplementation may best be seen in clinical trials involving diabetic subjects who have not yet developed established vascular complications, a notion similar to that proposed by Steinberg to test the effects of conventional antioxidants on atherosclerosis.

However, the effects of CoQ supplementation merit particular examination in diabetic patients on treatment with statins, since these agents may specifically decrease the biosynthesis of CoQ.

CoQ may also potentially enhance the therapeutic effects of ACE inhibitors, angiotensin II receptor agonists, insulin sensitizers, and newer agents such as PKC inhibitors.

The preliminary experimental and clinical studies on the effects of CoQ supplementation in diabetes reviewed here require testing in clinical endpoint trials, including patients within the wider spectrum of the metabolic syndrome. Our research in this area is supported by research grants from the National Health and Medical Research Council of Australia, and from Fournier-Pharma.

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Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Oxidative stress in the arterial wall. Oxidative stress in diabetes: uncoupling of eNOS and mitochondrial oxidative phosphorylation.

Regulation of oxidative stress and endotheliopathy in diabetes: antioxidants and the therapeutic potential of CoQ. Coenzyme Q 10 : structure, function, significance in diabetes. CoQ supplementation and endothelial function.

Synergistic effects of CoQ: peroxisome proliferator-activated receptor alpha PPAR-α activation. CoQ supplementation and statin therapy: enhancing the effects on diabetic endotheliopathy? Journal Article. We performed an electrophilic addition reaction at the end of the side chain of CoQ10 to introduce a bromine atom and a hydroxyl group thereby exploiting the pharmacological potential of CoQ10 derivatives.

Then, the in vitro toxic activity of L was investigated by cellular experiments, and the anti-diabetic mechanism of L was analyzed by the ROS and protein signaling pathways. Chemical shifts δ were given in ppm with reference to solvent signals [ 1 H NMR: CDCl 3 δ 7.

To a stirred solution of coenzyme Q10 CoQ10 80 mg, 0. And THF was then added to the resulting mixture until the reaction just cleared. Then N-bromosuccinimide NBS 13 mg, 0. Finally, the reaction was quenched with water 10 mL. The resulting mixture was extracted with EA 3 × 10 mL.

The combined organic layers were washed with water 10 mL , brine 10 mL , dried over Na 2 SO 4 , filtered and concentrated in vacuo. Human HepG2 cells were obtained from China-US Institute of Oncology, Guangdong Medical University, China. In each experiment, the cells in each group were repeated three times in parallel experiments.

In the following experiments, we referred to the cells in the control group normal cells as HepG2 cells, and the cells in the model group which were insulin-induced to develop insulin resistance as IR-HepG2 cells. We considered rosiglitazone as a positive control drug, which belonged to the thiazolidinediones class of antidiabetic drugs for the treatment of type 2 diabetes mellitus by effectively controlling blood glucose by increasing the sensitivity of target tissues to insulin Derosa et al.

Cell viability was determined to avoid inaccuracies in experimental results due to the effects of drugs on the physical and metabolic state of the cells.

Also, this could be used as a cellular level drug toxicity assessment. The effect of different concentrations of L on the viability of HepG2 cells was examined by CCK8 China Tong Ren Chemical Co. HepG2 cells were inoculated into well plates at a density of 5.

After that, the medium was changed and the cells were treated with rosiglitazone Rosi , Coenzyme Q10 CoQ10 and L 1, 10, 20, 50, μM for 24 h. After treatment, 10 μL of CCK8 was added to each well, incubated at 37°C for 1 h, and OD was measured at nm with a microplate reader.

HepG2 cells in logarithmic growth phase were inoculated into well plates 5. The glucose consumption of HepG2 cells in the medium is measured using the Glucose Assay Kit China Nanjing Construction Co.

A well plate was prepared by adding the prepared working solution, taking cell supernatant or calibration solution and mixing it with the working solution. It was incubated in a cell incubator for 10 min and the absorbance was measured by an enzyme meter.

The method used in the kit was the glucose oxidase-peroxidase assay. The principle of the assay was as follows: glucose contained in the cell supernatant was generated by glucose oxidase to gluconic acid and hydrogen peroxide, the latter of which, in the presence of peroxidase, condenses reduced 4-aminoantipyrine coupled with phenol to quinone compounds that can be measured.

The supernatant glucose content could be obtained by formula calculation. The consumption of glucose by the cells was equal to the initial glucose content the results of the blank group minus the remaining glucose content the results of the other groups. HepG2 cells in logarithmic growth phase were inoculated into well plates 1.

Lactic acid content of cell supernatants was measured using Lactate Assay Kit-WST Tong Ren Chemical, Japan. The cell supernatant and calibration solution were added to the well plates, and then the prepared working solution was added and mixed well.

The plates were incubated in a cell culture incubator for 30 min, and then the absorbance was measured with an enzyme meter. Finally, the lactate concentration of the cell supernatant was calculated using a standard curve.

Reactive oxygen species ROS was measured to determine the relationship between insulin resistance and oxidative stress. It could also be used as one of the bases for drugs to improve insulin resistance. Intracellular ROS levels could be detected by laser confocal microscopy.

HepG2 cells were inoculated in 6-well plates at 3. After the modeling and drug administration treatments, 1. was added to each group of cells sepamiceely. In this case, we prepared DCFH-DA at a final concentration of 10 µM.

After incubation for 30 min at protection from light, the cells were replaced with serum-free medium and transferred to a laser confocal microscope under dark conditions for observation and photography. Groups of cells were lysed with RIPA buffer and collected. Primary antibodies include JNK AP, Proteintech, China , phosphorylated JNK p-JNK, T, CellSignalingTechnology, USA , AKT AP, Proteintech, China , phosphorylated AKT p-AKT, lg, Proteintech, China , GSK3β AP, Proteintech, China , β-actin Ig, Proteintech, China , and GAPDH AP, Proteintech, China were used in this study.

The dilutions of primary antibodies were as follows: for JNK; for p-JNK, GSK3β and GAPDH; and for AKT, p-AKT and β-actin. Protein expression was measured with luminescent solutions, incubated with the relevant secondary antibodies, both of which were at a dilution of Then, the color was developed by a multifunctional molecular imaging system, and the results of relevant protein band densities were analyzed with ImageJ software.

A total of 48 clean male KM mice 45 g ± 5 g Guangdong Animal Center were used. Mice were randomly divided into a normal group 8 mice, ad libitum feeding and drinking and a model group 40 animals, ad libitum feeding and drinking.

We established a diabetic mice model using high-fat diet HFD and streptozotocin STZ. The STZ solution was prepared as follows: 2. A:B was mixed in the ratio of Tail vein blood collection was performed on days 3, 5 and 7 after the completion of STZ modeling to measure their random blood glucose, and the T2DM model was considered successful when all three times were higher than The mice were weighed and recorded at the same time each week during the medication period.

Mice were fasted for 12 h after the end of dosing and fasting blood glucose FBG was measured in tail vein blood using a glucometer. Blood samples were collected from mice, and serum was obtained by centrifugation to measure fasting insulin levels FINS as well as triglyceride TG , total cholesterol T-CHO , low-density lipoprotein LDL-C , and high-density lipoprotein HDL-C levels in mice.

Finally, the mice were euthanized and their liver tissues were taken to determine the content of liver glycogen in the liver tissues. Glucometer provided direct readings of glucose concentration in mouse blood. The GPO-PAP method for determining TG in mouse serum was based on the reaction of TG with lipase, glycerol kinase, glycerolphosphate oxidase, and peroxidase to produce a red quinone compound.

T-CHO in mouse serum was measured by the reaction of T-CHO with cholesterol esterase, cholesterol oxidase and peroxidase to form red quinone compounds. The amount of TG and T-CHO could be calculated by measuring the absorbance of the quinone compound.

Determination of LDL-C and HDL-C in mouse serum was based on the principle that LDL-C and HDL-C were chemically modified by CHER and CHOD to produce benzoquinone pigments in the presence of peroxidase. The levels of LDL-C and HDL-C could be calculated by measuring benzoquinone pigments.

The principle of liver glycogen determination was as follows: Glycogen was dehydrated under the condition of strong acid to form 5-hydroxymethylfurfural, and then reacted with anthrone to form blue-green and blue-green furfural derivatives, and the product appeared a characteristic absorption peak at nm, and the change of absorbance was used to detect the content of glycogen quantitatively.

Data were expressed as mean ± SD. GraphPad Prism 9. The cell cytoxicity of L, CoQ10 and Rosi on HepG2 cells Figure 1A , and glucose consumption in insulin resistant HepG2 IR-HepG2 are investigated Figure 1B.

As shown in Figure 1A , the viability of HepG2 cells in the Ltreated group was decreased in a concentration-dependent manner. In addition, the viability of HepG2 cells under stimulation with L below 10 μM was higher than that of the Rosi group, suggesting a good safety profile of the cells with L FIGURE 1.

A L, CoQ10 and Rosi stimulated HepG2 cells for 24 h. B Treatment with L, CoQ10 and Rosi promoted glucose consumption in IR-HepG2 cells Model, pretreated with insulin for 24 h.

C Lactate concentration in the supernatant of each group of cells was assayed after treatment with L, CoQ10 and Rosi. In a high-insulin environment, HepG2 cells become less sensitive to insulin and develop insulin resistance IR. This results in diminished glucose uptake and utilization by HepG2 cells, manifested by a significant decrease in glucose consumption Xuguang et al.

As shown in Figure 1B , the glucose consumption of IR-HepG2 cells in the model group was significantly reduced compared with that of HepG2 cells in the control group.

This effect of inducing HepG2 cells to become IR-HepG2 cells in agreement with the study of Fan et al. After the intervention of drugs L and CoQ10 , glucose consumption was substantially increased compared with model group, showing that L and CoQ10 had effects on hypoglycemia in vitro. Increased glucose consumption implied an elevated cellular uptake and utilization of glucose, suggesting a positive effect of the drug on insulin resistance IR , which was accordance with the findings of Zheng et al.

Zheng et al. In addition, the glucose consumption in the L group was significantly higher than that in the CoQ10 group and close to the Rosi group. These results suggest that L could not only enhance the ability of cells to absorb and utilize glucose, but also alleviate IR better than CoQ Many studies had confirmed that cells utilize glucose mainly through glycolysis, aerobic oxidation and glycogen synthesis, and lactate was one of the metabolic products of glycolysis Sun et al.

In our lactate content determination experiments, the cells were cultured under anaerobic conditions. Therefore, we considered that cells consumed glucose mainly through glycolysis after glucose intake. As shown in Figure 1C , the lactate concentration was significantly lower in the model group compared to the control group, indicating the inhibition of cellular glycolysis.

Compared with the model group, the lactate concentration in the L group was significantly higher, showing that L could promote the glycolysis process of the cells. These results validated our thoughts and verified each other with the results of Figure 1C.

Figure 2 showed the effect of L and Rosi on ROS in IR-HepG2 cells. As compared to the control group, the cells in the model group were in a state of high-glucose due to its difficulty in consuming glucose. Many studies had confirmed that high-glucose could induce cells to produce excessive ROS Luo et al.

Excessive ROS could cause oxidative stress and thus induce insulin resistance in HepG2 cells Newsholme et al. As seen in Figure 2 , the ROS fluorescence was apparently brighter in the model group compared to the control group, confirming that excess ROS is a contributing factor to IR.

This is consistent with the mechanism discussed above. The ROS fluorescence brightness of IR-HepG2 cells was significantly reduced after treatment with L, suggesting that intracellular ROS deposition can be reduced after drug administration.

FIGURE 2. A Representative photographs of IR-HepG2 cells Model, pretreated with insulin for 24 h treated with Rosi and L for 24 h and stained with H2DCFDA followed by laser confocal detection of ROS are shown. B Histogram of the effect of Rosi and L on intracellular ROS content in IR-HepG2 cells.

In addition, the fluorescence intensity of intracellular ROS was the weakest after 10 μM L treatment, indicating that L was the most effective in reducing the accumulation of intracellular ROS, which is concordance with the results of previous studies on cellular activity. Thus, these results suggested that L could alleviate IR by reducing the accumulation of ROS.

As shown in Figures 3A, D , the expression of p-JNK and JNK proteins was increased in IR-HepG2 cells compared with the control group, while both expressions were decreased after L treatment. These changes affected the activation and phosphorylation of the downstream molecule AKT.

As seen in Figures 3B, E , in IR-HepG2 cells, AKT expression was decreased and p-AKT expression was increased, while we found that AKT expression was upregulated and p-AKT expression was downregulated after L treatment.

These results revealed that L could inhibit the expression of JNK and p-JNK, improve insulin sensitivity, and enable correct insulin signaling to the downstream molecule AKT, which was in keeping with the results of changes in ROS content detected by laser confocal assay.

FIGURE 3. A—C Western blot showed JNK, p-JNK, AKT, p-AKT, GSK-3β protein bands after treatment of IR-HepG2 cells Model, pretreated with insulin for 24 h with L D—F Image J analysis of the relative expression levels of the proteins. Furthermore, it was demonstrated that GSK3β was a downstream substrate of insulin and Akt signaling, which played an important function in maintaining glucose homeostasis by negatively regulating glycogen synthesis in the insulin signaling pathway Yang et al.

As shown in Figures 3C, F , GSK3β expression was increased in IR-HepG2 cells compared with the control group, and GSK3β expression was downregulated after L treatment, suggesting that L could decrease intracellular glucose concentration and increase glucose uptake by regulating intracellular glycogen synthesis, which was validated with the previous cellular activity results.

Generally speaking, T2DM patients suffered from insulin deficiency and the body was unable to utilize glucose fully, which was reflected in weight loss Ramos et al.

Therefore, weight control is one of the indicators to determine the efficacy of diabetes mellitus. Notably, the recovered weights of the mice in the high-concentration HC L group were close to the normal group. In contrast, mice in the Rosi and CoQ10 groups were unable to reverse the trend of weight loss, which were consistent with the reported findings Derosa et al.

FIGURE 4. Correspondingly, homeostatic model assessment of insulin resistance HOMA-IR calculated by FBG and FINS was also improved see Figure 4F. After treatment with L, triglyceride TG , total cholesterol T-CHO , and high-density lipoprotein HDL-C levels were decreased, while low-density lipoprotein LDL-C levels was increased see Figure 4B.

It was supported by the clinical trial reported by Fallah et al. Gholnari et al. In summary, a novel CoQ10 derivative was successfully obtained after the modification of CoQ10 terminus. Cellular assays showed that L had low toxicity and increased glucose consumption by IR-HepG2 to improve cyto-insulin resistance.

Therefore, L, a novel CoQ10 derivative, has a very promising future as an anti-hyperglycemic agent to help insulin-resistant T2DM patients.

The animal study was approved by Guangdong Medical University Laboratory Animal Ethics Committee Discipline construction project of Guangdong Medical University LAEC. The study was conducted in accordance with the local legislation and institutional requirements.

XT: Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Project administration, Software, Validation, Visualization, Writing—original draft, Writing—review and editing.

XY: Conceptualization, Formal Analysis, Investigation, Methodology, Writing—review and editing. XX: Formal Analysis, Investigation, Methodology. YP: Investigation, Writing—review and editing. XL: Methodology, Software, Validation, Writing—review and editing. YD: Methodology, Validation, Writing—review and editing.

XZ: Writing—review and editing. WQ: Supervision, Writing—review and editing. DW: Funding acquisition, Resources, Writing—review and editing. YR: Funding acquisition, Resources, Writing—review and editing.

CZ: Funding acquisition, Resources, Writing—review and editing. National Natural Science Foundation of Guangdong Province No. GDMUZ , Dongguan social development science and technology project No.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

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Department of Pharmaceutics, Glocal School of Pharmacy, Glocal University, Mirzapur Pole, Saharanpur, Uttar Pradesh, India. You can also search for this author in PubMed Google Scholar. Al-Taie A conceived of the study.

Al-Taie A, Victoria AQ and Hafeez A reviewed the literature, conducted the quality assessment and extracted the data. Al-Taie A and Victoria AQ developed the methods and drafted the manuscript. Hafeez A reviewed the data, participated in the data interpretation and supported the data interpretation.

Al-Taie A was the project manager and advisor on the project. All authors read and approved the final manuscript. Correspondence to Anmar Al-Taie. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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CAS PubMed Google Scholar Kern TS, Barber AJ. Scientists believe free radicals contribute to the aging process, as well as a number of health problems, including heart disease and cancer. Antioxidants, such as CoQ10, can neutralize free radicals and may reduce or even help prevent some of the damage they cause.

Some researchers believe that CoQ10 may help with heart-related conditions, because it can improve energy production in cells, prevent blood clot formation, and act as an antioxidant.

Some studies suggest that coenzyme Q10 supplements, either by themselves or in with other drug therapies, may help prevent or treat the following conditions:. One clinical study found that people who took daily CoQ10 supplements within 3 days of a heart attack were less likely to have subsequent heart attacks and chest pain.

They were also less likely to die of heart disease than those who did not take the supplements. Anyone who has had a heart attack should talk with their health care provider before taking any herbs or supplements, including CoQ There is evidence that CoQ10 may help treat heart failure when combined with conventional medications.

People who have congestive heart failure, where the heart is not able to pump blood as well as it should may also have low levels of CoQ Heart failure can cause blood to pool in parts of the body, such as the lungs and legs.

It can also cause shortness of breath. Several clinical studies suggests that CoQ10 supplements help reduce swelling in the legs; reduce fluid in the lungs, making breathing easier; and increase exercise capacity in people with heart failure.

But not all studies are positive, and some found no effect, so using CoQ10 for heart failure remains controversial. You should never use CoQ10 itself to treat heart failure, and you should ask your provider before taking it for this condition.

Several clinical studies involving small numbers of people suggest that CoQ10 may lower blood pressure. However, it may take 4 to 12 weeks to see any change.

In one analysis, after reviewing 12 clinical studies, researchers concluded that CoQ10 has the potential to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by 10 mm Hg, without significant side effects.

More research with greater numbers of people is needed. DO NOT try to treat high blood pressure by yourself. See your provider for treatment. People with high cholesterol tend to have lower levels of CoQ10, so CoQ10 has been proposed as a treatment for high cholesterol, but scientific studies are lacking.

There is some evidence it may reduce side effects from conventional treatment with cholesterol-lowering drugs called statins, which reduce natural levels of CoQ10 in the body. Taking CoQ10 supplements can bring levels back to normal. Plus, studies show that CoQ10 may reduce the muscle pain associated with statin treatment.

Ask your provider if you are interested in taking CoQ10 with statins. CoQ10 supplements may improve heart health and blood sugar and help manage high blood pressure in people with diabetes.

Preliminary studies found that CoQ10 improves blood sugar control. But other studies show no effect. If you have diabetes, talk to your doctor or registered dietitian before taking CoQ Several clinical studies suggest that CoQ10 may help prevent heart damage caused by certain chemotherapy drugs, adriamycin, or other athracycline medications.

More studies are needed. Talk to your provider before taking any herbs or supplements if you are undergoing chemotherapy. Clinical research indicates that introducing CoQ10 prior to heart surgery, including bypass surgery and heart transplantation, can reduce damage caused by free radicals, strengthen heart function, and lower the incidence of irregular heart beat arrhythmias during the recovery phase.

You should not take any supplements before surgery unless your provider approves. Gum disease is a common problem that causes swelling, bleeding, pain, and redness of the gums. Clinical studies show that people with gum disease tend to have low levels of CoQ10 in their gums.

A few studies with small numbers of people found that CoQ10 supplements led to faster healing and tissue repair, but more research is needed. Scientific studies are needed to see whether CoQ10 can be safely and effectively used for these health problems and needs.

Primary dietary sources of CoQ10 include oily fish such as salmon and tuna , organ meats such as liver , and whole grains.

Most people get enough CoQ10 through a balanced diet, but supplements may help people with particular health conditions see Uses section , or those taking certain medications see Interactions section.

CoQ10 is available as a supplement in several forms, including soft gel capsules, oral spray, hard shell capsules, and tablets.

CoQ10 is also added to various cosmetics. Pediatric DO NOT give CoQ10 to a child under 18 except under the supervision of a health care provider. For adults 19 years and older: The recommended dose for CoQ10 supplementation is 30 to mg daily.

Soft gels tend to be better absorbed than capsules or other preparations. Higher doses may be recommended for specific conditions.

CoQ10 is fat soluble, so it should be taken with a meal containing fat so your body can absorb it. Also, taking CoQ10 at night may help with the body's ability to use it.

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

CoQ10 appears to be safe with no major side effects, except occasional stomach upset. However, researchers have not done studies and do not know if CoQ10 supplements are safe during pregnancy and breastfeeding.

CoQ10 may lower blood sugar, so people with diabetes should talk with their provider before taking it to avoid the risk of low blood sugar. Some suggest that it may also lower blood pressure. If you are being treated with any of the following medications, you should not use CoQ10 without first talking to your health care provider.

Chemotherapy medications: Researchers are not sure whether CoQ10's antioxidant effect might make some chemotherapy drugs less effective. Ask your oncologist before taking antioxidants or any supplement along with chemotherapy.

Daunorubicin and doxorubicin: CoQ10 may help reduce the toxic effects on the heart caused by daunorubicin Cerubidin and doxorubicin Adriamycin , two chemotherapy medications that are used to treat several kinds of cancer.

Blood pressure medications: CoQ10 may work with blood pressure medications to lower blood pressure. In a clinical study of people taking blood pressure medications, adding CoQ10 supplements allowed them to reduce the doses of these medications.

More research is needed, however. If you take medication for high blood pressure, talk to your provider before taking CoQ10, and DO NOT stop taking your regular medication. Blood-thinning medications: There have been reports that CoQ10 may make medications such as warfarin Coumadin or clopidigrel Plavix less effective at thinning the blood.

If you take blood thinners, ask your provider before taking CoQ After a 4-week washout, participants crossed over to the alternate treatment. Brachial artery ultrasonography was performed, and fasting blood and h urine samples were collected at the start and end of each treatment period.

The Royal Perth Hospital Ethics Committee approved the study. The brachial artery was imaged using a MHz transducer connected to an Acuson Aspen ultrasound system Siemens Medical Solutions, Malvern, PA , and FMD was measured as previously described 4.

Endothelium-independent nitrate-mediated dilatation was measured following sublingual administration of glyceryl trinitrate μg.

Ultrasound images were analyzed using semiautomated edge-detection software 5. Total cholesterol, triglycerides, and HDL cholesterol were determined by enzymatic methods, and LDL cholesterol was calculated using the Friedewald equation. GHb was measured using high-performance liquid chromatography.

Plasma F 2 -isoprostane and h urinary hydroxyeicosatetraenoic acid levels markers of systemic oxidative stress were measured by gas chromatography-mass spectrometry interassay coefficients of variation 5. Data were analyzed using SPSS Plasma CoQ 10 data skewed distribution were logarithmically transformed for parametric analysis.

Treatment effects were compared using mixed-effects models. Carryover effects were examined for and excluded. Median duration of diabetes was 8 years. Baseline brachial artery diameter was similar at all assessments and unaltered by CoQ 10 supplementation Table 1. CoQ 10 increased brachial artery FMD by mean ± SEM 1.

Despite increasing plasma CoQ 10 levels 2. Effect of placebo and oral CoQ 10 on arterial function, biochemical variables, and blood pressure. Data are means ± SEM or medians interquartile range.

Treatment effects compared using mixed-effects models, with adjustment for baseline, treatment sequence, and period. The new finding was that CoQ 10 supplementation improved endothelial dysfunction in statin-treated type 2 diabetic patients, with no alteration in two markers of systemic oxidative stress.

This is consistent with our previous study in statin-naive dyslipidemic type 2 diabetic patients in whom oral CoQ 10 also improved brachial artery FMD but did not alter plasma F 2 -isoprostane levels 4.

The fact that plasma F 2 -isoprostane levels in our diabetic subjects were not significantly different from those in our previously studied nondiabetic control subjects 1, ± 74 vs.

Whether CoQ 10 supplementation might improve endothelial function by modulating other vasoactive mediators, such as endothelin 1 10 or asymmetric dimethylarginine, 11 merits further investigation.

Our statin-treated subjects had lower plasma CoQ 10 concentrations compared with those in the statin-naive dyslipidemic type 2 diabetic patients in our previous study 0. placebo and inhibition of endogenous CoQ 10 production may be greater with higher doses of more potent statins 3.

The patients in our study had endothelial dysfunction despite satisfactory control of blood pressure, glycemia, and lipids and may be representative of the proportion of statin-treated patients at increased residual risk of cardiovascular disease.

Impaired FMD is a consistent predictor of adverse cardiovascular events. Several interventions that improve FMD also improve cardiovascular outcomes 13 , — The significance of the findings in our report, however, requires further investigation in a clinical end point trial.

The costs of publication of this article were defrayed in part by the payment of page charges. Section solely to indicate this fact. and G. were supported by National Health and Medical Research Council Postgraduate Research Scholarships.

This study was funded by a Cardiovascular Lipid Research Grant from Pfizer West Ryde, Australia. Blackmores Balgowlah, Australia kindly supplied the CoQ 10 and matching placebo capsules.

No other potential conflicts of interest relevant to this article were reported. Parts of this study were presented in poster form at the annual scientific meeting of the Australian Atherosclerosis Society, Sydney, Australia, 28—31 October We thank Lisa Rich for assistance with ultrasonography, Professor Kevin Croft and Adeline Indrawan for assistance with laboratory analyses, and the study participants involved.