8-Isoprostane and Coenzyme Q10 Levels in Patients with Metabolic Syndrome

Abstract

Background:

Objective:

We aimed to determine 8-isoprostane (8-IsoP) and coenzyme Q10 (CoQ10) levels in patients with metabolic syndrome and healthy individuals and demonstrate whether there was any relation between these parameters and metabolic syndrome criteria.

Materials and Methods:

A total of 30 patients (10 male, 20 female) with metabolic syndrome and 20 age-matched healthy individuals (9 male, 11 female) were involved in the study. Body mass index, waist and hip circumferences, systolic and diastolic blood pressures and serum glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, insulin, HbA1c, 8-IsoP and CoQ10 levels, and homeostasis model assessment of insulin resistance indexes of all participants were determined.

Results:

8-IsoP levels were significantly increased in metabolic syndrome compared to healthy individuals (P = 0.003), however, there was no significant difference between groups for CoQ10 levels. 8-IsoP levels were positively correlated with waist circumference (r = 0.303, P = 0.032), diastolic blood pressure (r = 0.337, P = 0.017), systolic blood pressure (r = 0.329, P = 0.020) values and total cholesterol levels (r = 0.354, P = 0.012).

Conclusion:

We can suggest that the levels of 8-IsoP, which is an indicator of the oxidative stress, increase in metabolic syndrome and this can be associated with high blood pressure and visceral adiposity, which are the components of metabolic syndrome.

Introduction

Metabolic syndrome has become an important health problem, which involves obesity, hyperlipidemia, insulin resistance, and high blood pressure values. The components of metabolic syndrome are all suggested as independent cardiovascular disease risk factors. Individuals with metabolic syndrome are at increased risk for development of type 2 diabetes mellitus and cardiovascular diseases. Insulin resistance and obesity are key factors in the pathogenesis of the metabolic syndrome and related. Also, obesity is thought to be associated with oxidative stress.^1
–3

Isoprostanes (isoPs) are produced by the nonenzymatic peroxidation of polyunsaturated fatty acids such as arachidonic acid induced by free radicals.⁴ Since their precursors are derived from arachidonic acid tissue phospholipids, in situ F2 isoPs get formed and accumulate in the target tissues.⁵

Coenzyme Q10 (CoQ10) belongs to a family of compounds known as ubiquinones. One of the critical features of CoQ10 scavenges free radicals and inhibits lipid and protein oxidation as an antioxidant.⁶

Although the systematic oxidative stress indicators have been shown to be higher in case of clinical type 2 diabetes, there are limited data showing the level of oxidative stress depending on insulin resistance in case of metabolic syndrome. We aimed to determine 8-isoprostane (8-IsoP) and CoQ10 levels in patients with metabolic syndrome and healthy individuals and demonstrate whether there was any relation between these parameters and metabolic syndrome criteria.

Materials and Methods

Establishment of the groups

A total of 30 patients (10 male, 20 female) who were newly diagnosed with metabolic syndrome in the family medicine outpatient clinics contributed to the study. The revised ATP III criteria were considered in diagnosis of metabolic syndrome.⁷ A total of 20 healthy individuals (9 male, 11 female), who have only one of the revised ATP III diagnostic criteria, were included in the study as the control group that are similar to the patient group in terms of age and gender and applied to the same clinic for a checkup without any acute or chronic diseases. The patients with a history of cardiovascular or cerebrovascular events, congestive heart failure, hepatic or renal disease, and those under medication such as ACE inhibitors, angiotensin receptor blockers, other type of antihypertensive drugs, lipid-lowering agents, supplementation of vitamins, CoQ10 and Omega-3, Omega-6, DHA, and others and also smokers and alcohol and drug abusers were excluded from the study.

Weight, stature, waist and hip circumference, and arterial systolic and diastolic blood pressure of all the participants were measured and recorded. Body mass index (BMI) values were calculated.

Biochemical analysis

Fasting venous blood samples were obtained from all the subjects. Plasma and serum samples were separated by centrifugation. Routine biochemical analysis was performed in serum and HbA1c in whole blood. Plasma samples were stored at −80°C for analysis of 8-IsoP and CoQ10 until the time of analysis.

8-IsoP measurements were carried out with ELISA technique using 8-isoprostan kit (Cayman). In determination of CoQ10 levels, HPLC analysis kit (Immuchrom) and HPLC column (Bischoff Prontosil AQ, 5 μm, 125 × 4 mm) manufactured by the same company have been used.

Routine biochemical tests were measured with enzymatic colorimetric methods on Synchron LX20 analyzer (Beckman Coulter) with the original Beckman kits. Low-density lipoprotein cholesterol (LDL-C) levels were calculated with the Friedewald formula. Insulin levels were determined with electrochemiluminescence method using Cobas Insulin kit (Roche) on Roche E170 (Roche) modular analyzer. The analysis of HbA1c was performed with HPLC technique using Variant II hemoglobin analyzer (BioRad Hemoglobin Analyzing System; BioRad Laboratories). The homeostasis model assessment of insulin resistance (HOMA-IR) was used to determine the insulin resistance.

Statistical analysis

SPSS 15.0 for Windows (SPSS, Inc.) was used for statistical analysis. Distribution pattern of the numeric data was tested with Shapiro–Wilk test. Independent sample t-test was performed for the parameters showing normal distribution and Mann–Whitney U test for those with nonparametric distribution. Chi-squared test was used for evaluation of the categorical variables. The correlations between the tested parameters were evaluated by the Spearman nonparametric correlation analysis as pairs. The data were given as mean ± standard deviation. P < 0.05 was considered as statistically significant.

Results

Demographic characteristics of metabolic syndrome and control groups are presented in Table 1. BMI, waist and hip circumference, systolic and diastolic blood pressure values were significantly higher in metabolic syndrome group than the control. Serum levels of glucose, total cholesterol, triglyceride, LDL-C, HbA1c, and 8-IsoP were significantly higher in metabolic syndrome group than the control. In addition, HOMA-IR and insulin values of the subjects with metabolic syndrome were significantly higher than the control group. High-density lipoprotein cholesterol (HDL-C) and CoQ10 levels were similar in both of the groups. There was no significant difference between genders in terms of 8-IsoP and CoQ10 levels (P > 0.05) (Table 1).

Table 1.

Demographic, Anthropometric and Metabolic Characteristics of Metabolic Syndrome and Control Groups

Parameters	Metabolic syndrome	Control	P
N (F/M)	30 (10/20)	20 (9/11)	0.763
Age (year)	50.60 ± 10.51	51.10 ± 11.13	0.873
BMI (kg/m²)	33.78 ± 5.08	25.97 ± 3.63	0.0001
Waist circumference (cm)	107.30 ± 8.108	78.10 ± 12.056	0.0001
Hip circumference (cm)	119.37 ± 15.24	89.95 ± 15.62	0.0001
Systolic blood pressure (mmHg)	139.17 ± 24.638	119.25 ± 10.29	0.0001
Glucose (mg/dL)	114.93 ± 37.68	89.90 ± 9.18	0.0001
Triglyceride (mg/dL)	167.57 ± 96.78	86.95 ± 34.94	0.0001
Total cholesterol (mg/dL)	200.80 ± 47.44	163.65 ± 31.88	0.004
HDL-cholesterol (mg/dL)	36.91 ± 8.04	39.43 ± 13.05	0.851
LDL-cholesterol (mg/dL)	129.97 ± 43.9	108.44 ± 23.19	0.05
HbA1c (mg/dL)	5.54 ± 0.98	4.90 ± 0.75	0.023
Insulin (U/L)	11.21 ± 6.6	6.58 ± 3.51	0.004
HOMA-IR	3.06 ± 1.67	1.45 ± 0.83	0.0001
8-isoprostane (pg/mL)	32.67 ± 19.90	18.03 ± 7.38	0.003
Coenzyme Q10 (μg/mL)	1.32 ± 0.77	2.19 ± 1.78	0.212

Data are presented as mean ± SD.

BMI, body mass index; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance; LDL-C, low-density lipoprotein cholesterol.

Positive correlations were observed between 8-IsoP levels and waist circumference (r = 0.303, P = 0.032), diastolic blood pressure (r = 0.337, P = 0.017), systolic blood pressure (r = 0.329, P = 0.020) values, and total cholesterol (r = 0.354, P = 0.012) levels. No other correlation existed between 8-IsoP levels and the other parameters tested.

No correlation was observed between CoQ10 levels and the other parameters tested.

Discussion

In this study, we have observed that BMI, waist and hip circumference, systolic and diastolic blood pressure, serum glucose, triglycerides, total cholesterol, LDL-C, HbA1c, insulin levels, HOMA-IR index, and plasma 8-IsoP levels were significantly higher in metabolic syndrome.

In our study, 8-IsoP levels were significantly higher in the metabolic syndrome group compared to the control group and our results are in concordance with most of the previous data. According to a study conducted by Fujita et al. urinary 8-epiprostoglandin F₂ concentration was significantly higher in the metabolic syndrome.⁸ Kim et al. compared postmenopausal women without metabolic syndrome and metabolic syndrome patients with normal weight and evaluated urinary 8-IsoP and ox-LDL levels. They suggested that 8-IsoP and ox-LDL levels were elevated in women with normal weight and metabolic syndrome than obese women without metabolic syndrome; however, there was no correlation between 8-IsoPs and ox-LDL.⁹ In another study carried out by Jialal et al. there was a relation between biomarkers of oxidative stress and features of metabolic syndrome.¹⁰

There are also conflicting reports in the literature. Sjogren et al. suggested that there was no relation between oxidized LDL and 8-IsoP-F2α, in healthy men with metabolic syndrome.¹¹

Our findings regarding 8-IsoP levels in the metabolic syndrome are consistent with most of the previous results in the literature, because increased 8-IsoP levels in hyperlipidemia, hypertension, obesity, and insulin resistance that are the components of the metabolic syndrome were also reported by several researchers.^12
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We observed that 8-IsoP was positively correlated with waist circumference, systolic and diastolic blood pressures, and total cholesterol levels in our study and these findings suggest that central obesity, hypertension, and hyperlipidemia, which are the major components of metabolic syndrome, were related with increased oxidative stress.

In our study, we have observed that the levels of CoQ10 were decreased in metabolic syndrome group compared to the control, but this difference was not statistically significant. Different forms of CoQ10 were evaluated in metabolic syndrome and various reports exist in the literature. One of these previous reports is from Miles et al. and after classifying the patients by their age, sex and race, they have determined the levels of total CoQ10, ubiquinol and CRP and demonstrated that all of these parameters were significantly higher in those with metabolic syndrome.¹⁵ However, there are different findings on this issue as well. In a study conducted by Menke et al. a total of 67 obese and 50 normal weight children were included and no significant difference was observed for plasma CoQ10 levels between these children.¹⁶ The findings of Kontush et al. are also similar. Plasma ubiquinol-10 levels of the patients exposed to the increased oxidative stress and healthy individuals were investigated, and the level of ubiquinol-10 was lower in hyperlipidemic patients who were presenting high blood pressure and also smokers compared to the ones without hypertension.¹⁷ Controversial to these two reports, CoQ10 levels were suggested to be significantly increased in the metabolic syndrome group compared to the control by Yen et al. after evaluating 75 metabolic syndrome patients and 105 controls.¹⁸

In our study, although the levels of CoQ10 were lower in metabolic syndrome group compared to the control, this difference was not statically significant. Probably, the small size of our population was the cause of this result, and we could also find significantly decreased CoQ10 levels similar with the report of Kontush et al. if our population was larger.

Conclusion

We can suggest that the levels of 8-IsoP increase in metabolic syndrome and the levels are associated with high blood pressure and visceral adiposity, which are the components of metabolic syndrome. Our findings demonstrating the correlations between 8-IsoP and the waist circumference and blood pressure support this conclusion.

Footnotes

Acknowledgment

This study was carried out with the grant from the Scientific Research Projects Unit of Selcuk University (BAP09202038).

Author Disclosure Statement

No competing financial interests exist.

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