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JNFS 2022, 7(2): 150-159 |
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Gerami H, Jamalzehi A, Javadi M, Hosseini S K, Lesani A. The Relationship between Antioxidants Consumption and Insulin Resistance/Insulin Sensitivity in Type 2 Diabetes without and with Coronary Stenosis: A Case-Control Study. JNFS 2022; 7 (2) :150-159
URL: http://jnfs.ssu.ac.ir/article-1-394-en.html
URL: http://jnfs.ssu.ac.ir/article-1-394-en.html
Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
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The Relationship between Antioxidants Consumption and Insulin Resistance/Insulin Sensitivity in Type 2 Diabetes without and with Coronary Stenosis: A Case-Control Study
Hadis Gerami; MSc 1,2, Atena Jamalzehi; MSc 3, Maryam Javadi; PhD 4,5,
Seyed Kianoosh Hosseini; MD 6 & Azadeh Lesani; MSc 7
Hadis Gerami; MSc 1,2, Atena Jamalzehi; MSc 3, Maryam Javadi; PhD 4,5,
Seyed Kianoosh Hosseini; MD 6 & Azadeh Lesani; MSc 7
1 Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
2 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
3 Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
4 Children Growth Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
5 Department of Nutrition, School of Health, Qazvin University of Medical Sciences, Qazvin, Iran.
6 Department of Cardiology, Tehran University of Medical Sciences, Tehran, Iran.
7 Department of Nutrition and Biochemistry, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
2 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
3 Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
4 Children Growth Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
5 Department of Nutrition, School of Health, Qazvin University of Medical Sciences, Qazvin, Iran.
6 Department of Cardiology, Tehran University of Medical Sciences, Tehran, Iran.
7 Department of Nutrition and Biochemistry, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
| ARTICLE INFO | ABSTRACT | |
| ORIGINAL ARTICLE | Background: Type 2 diabetes (T2D) is known as a common chronic metabolic disease worldwide. Coronary artery diseases are one of the hazardous disorders in diabetic patients. The current study aimed to investigate the relationship between dietary antioxidants intake with insulin resistance and insulin sensitivity among T2D without and with coronary stenosis (CS). Methods: This case-control study was conducted on 247 participants (65 diabetic patients suffered from CS and 172 diabetic patients without CS). Dietary antioxidants intake (vitamin E, Vitamin C, selenium, beta-carotene, and zinc) were assessed with a valid and reliable 168-item semi-quantitative food frequency questionnaire (FFQ). Blood pressure, weight, and height were measured. Blood sample was collected for glycaemic control assessment. Results: Diabetic patients with CS had significantly higher HbA1c levels (P = 0.004). There was a negative significant association between vitamin E (r = -0.91; P < 0.001) and Beta-carotene (r =-0.88; P < 0.001) with HbA1c among all participants. There was also a positive significant association between vitamin E, vitamin C, and selenium with insulin sensitivity among all the participants; (r = 0.59; P = 0.004) for vitamin E, (r = 0.91; P < 0.001) for vitamin C, and (r = 0.27; P = 0.04) for Beta-carotene. Conclusion: Antioxidants intake especially vitamin C and beta-carotene may have an anti-insulin resistance effect in metabolic disorders. Keywords: Diabetes mellitus; Coronary stenosis; Dietary intake; Antioxidants; Insulin resistanc.e |
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| Article history: Received: 8 Apr 2021 Revised: 25 Jul 2021 Accepted: 25 Aug 2021 |
||
| *Corresponding author atena.jamal@yahoo.com Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. Postal code: 98167-43181 Tel: +98 54-33295715 |
Introduction
Type 2 diabetes (T2D) is known as a serious metabolic disorder characterized by chronic hyperglycemia, which continues to disrupt the metabolism of carbohydrates, fats, and proteins (Tripathi and Srivastava, 2006). In a diabetic patient, the tissue's response to insulin or its production is impaired. As time progresses and the disorder becomes chronic, short-term and long-term complications occur in diabetes (Kaul K. et al., 2013). Studies have shown increased prevalence of diabetes in the world. It is estimated that more than 5-8% of adults have T2D. In addition, the International Diabetes Federation reported that the number of people suffer from diabetes in 2010 was 285 million and is expected to reach more than 438 million in 2030. In addition, indirect and direct costs of diabetes in the United States (US) have been reported to be more than 174 billion dollars per year (Lau, 2009, Whiting et al., 2011). Several studies have shown that the risk of premature death, cardiovascular disease (CVD), retinopathy, neuropathy, blindness in diabetic patients is two time more than people without diabetes (Deshpande et al., 2008). Oxidative stress plays an important role in the development of diabetes. overproduction of free radicals and defect of antioxidants protection worsen metabolic and vascular function (Wiernsperger, 2003). Hyperglycaemia could induce reactive oxygen species (ROS) production by the mitochondrial electron-transport system. Oxidative stress due to high blood levels of glucose and the overproduction of ROS can damage the islet cells and impair its function
(Savu et al., 2012).
CVD is known as a major cause of morbidity and mortality all over the world, so that it can be one of the causes of increase in sudden death. Also, these diseases could cost a lot for the patients. The most common cause of heart disease vascular was recognized atherosclerosis. In spite of designing methods as well as new therapy for the prevention and treatment of heart disease, the number of deaths associated with CVD in most countries remains stagnant (Roth et al., 2017). One of the most important causes of mortality among American men and women was known coronary artery disease (Khawaja et al., 2009). The American Heart Association has reported that 20% of men and women suffer from coronary artery disease and its cost was about 368 billion dollars in the USA in 2004 (Berra, 2011). Increased incidence of coronary artery disease in last decades has been due to improving the economy, well-being, and comfort. Nutritional factor is a key factor in epidemiologic research and previous study demonstrated positive correlation between well-being and comfort among atherosclerosis (Barquera et al., 2015).
Some of the most important risk factors affecting coronary artery disease and T2D are lifestyle, diet, and physical activity. Similarly, proper diet consumption can prevent coronary artery disease in patients with diabetes, and one of causes of coronary artery disease are excessive intakes of energy and fat in the diet (de Souza et al., 2015, Maki, 2004). Several studies have indicated that increasing intakes of fresh vegetables, fruits, and grains can prevent coronary artery disease and diabetes (Alissa and Ferns, 2017, Di Angelantonio et al., 2016). Also, high dietary intakes of fruits and vegetables can improve insulin levels and insulin sensitivity (Mathews et al., 2017, Wang et al., 2016). High antioxidants diet could inhibit oxidant formation and intercepting oxidants which have been formed, and repair oxidant-induced injury (Diaz et al., 1997). Vitamin E and C can reduce the damaging effects of free radicals on the structure and function of cells and vessel walls (Ashor et al., 2015). Some of trace elements (selenium, copper, zinc, and manganese) act as cofactors for enzymes with antioxidant activity like superoxide dismutase and glutathione peroxidase (Diplock, 1991). Previous studies have indicated the association between some vitamins and hemoglobin A1c (HbA1c) levels; for example high intakes of carotenoids are associated with low levels of HbA1c and vitamin D deficiency can be along with high levels of HbA1c (Abd Elgadir et al., 2018, Randhawa et al., 2017). However, a study showed that supplementation of vitamins E and C in pharmacological does have no impact on HbA1c levels (Regensteiner et al., 2003).
Antioxidants in dietary intake, such as vitamin C, vitamin E, selenium, beta-carotene, and zinc associated to HbA1c level in T2D patients with and without coronary stenosis (CS) have not been examined. Therefore, the present study aimed to compare dietary intakes of antioxidants and insulin resistance levels in T2D patients with CS and T2D patients without CS. This study also examined the association between antioxidant components of dietary intakes with HbA1c and QUICKI index in T2D patients with and without CS.
Materials and Methods
Study design and participants: This case-control prospective study was conducted on T2D patients referred to the hospital. The study was carried out on 283 adult patients with newly diagnosed T2D without CS that were diagnosed with glucose tolerance test (GTT) and fasting blood glucose of 65 adult diabetic patients with CS that were diagnosed with angiography, GTT and fasting blood glucose that diagnosed by cardiologist. Subjects included if they diagnosed as having T2D and CS without any medical comorbidities or any other major chronic diseases. The subjects were excluded if they followed any especial diet, consumed any dietary supplements, multi-vitamin or mineral supplementation and fortified foods during the last four months. Finally, 111 T2D were excluded from the study, since they were on a diet or consumed dietary supplements.
Measurements: A valid and reliable 168- item semi-quantitative food frequency questionnaire (FFQ) modified for Iranian foods was completed in the present study (Esfahani et al., 2010). Frequencies of food intakes during the last four months were reported in day, week, or month. Vitamin C, vitamin E, selenium, beta-carotene, and zinc of foods were derived from Nutritionist 4 software. Written informed consent was signed by all the participants. This study was ethically approved by the university.
The demographic and clinical characteristics, including gender, age, body mass index (BMI), weight, systolic and diastolic blood pressure, and history of other disease were completed by using a structured questionnaire. All the patients had been taking 1500 mg/day oral doses of metformin. They had not taken any insulin therapy. HbA1c levels were measured by Diazyme direct enzymatic assay of HbA1c using auto-analyzer and whole blood samples (Penttilä et al., 2011).
Ethical considerations: Written informed consent was obtained from all the participants. This study was approved by the School of Nutrition and Food Sciences, Isfahan University of Medical Sciences (project code: 293113) and Qazvin University of Medical Sciences (project code: IR.QUMS.REC.2015).
Data analysis: Normal distribution of variables among the two groups of participants was determined by Shapiro-Wilk test. All variables, including vitamin C, vitamin E, selenium, beta-carotene, zinc, HbA1c, and QUICKI index (Quantitative insulin sensitivity check index) were normally distributed. Independent samples t-test was applied to compare the mean score of variables among T2D patients with and without CS. Gender and age was considered in Chi-square test and one-way ANOVA and independent samples t-test were used for quantitative variables. However, they did not change the results and therefore excluded from analysis. Pearson correlation test was used to assess the Chi-square test and one-way ANOVA and independent samples t-test were used for quantitative variables. However, they did not change the results and therefore excluded from analysis. Pearson correlation test was used to assess the relationship between vitamin C, vitamin E, selenium, beta-carotene, and zinc with HbA1c and QUICKI index among all the participants and in sub groups of T2D patients with CS and patients with T2D. All statistical analyses were performed by using SPSS version 20.0. P-values less than 0.05 were considered significant.
Results
Participants’ general characteristics are demonstrated in Table 1. There were no significant differences regarding age, gender, BMI, weight, systolic and diastolic blood pressure, and energy intake between the two groups.
Mean ± SD values of HbA1c, QUICKI index, vitamin E, vitamin C, selenium, beta-carotene, and zinc are shown in Table 2. Diabetic patients with CS had significantly higher HbA1c levels compared to the other group (P = 0.004). In addition, the index of insulin sensitivity in diabetic patients without CS higher than diabetic patients with CS (P = 0.03). The diabetic patients without CS consumed higher doses of dietary antioxidant components compared to diabetic patients with CS group. However, diabetic patients with CS had higher intakes of vitamin C and zinc compared to the other group.
Table 3 reveals the results of Pearson correlation test between variables and HbA1c levels in the two groups. There was negative correlation between all antioxidant components and HbA1c. In addition, there was a negative significant association between vitamin E and Beta-carotene with HbA1c among all the participants; (r = -0.88; P < 0.001) for vitamin E and (r = -0.80; P < 0.001) for Beta-carotene as well as T2D patients with CS, (r = -0.92; P < 0.001) for vitamin E, and (r = -0.92; P < 0.001) for Beta-carotene in T2D patients without CS. In addition, there was a marginally negative association between selenium with HbA1c in T2D group with CS (r =-0.20; P = 0.05), although this negative correlation in T2D group without CS was significant (r = -0.49; P < 0.001).
The results of Pearson correlation between antioxidants intake and QUICKI index in the two groups are presented in Table 4. There was a positive association between dietary intake of antioxidants and insulin sensitivity in QUICKI index. In addition, there was a positive significant association between vitamin C, vitamin E and selenium with insulin sensitivity among all the participants; (r = 0.59; P = 0.004) for vitamin E, (r = 0.91; P < 0.001) for vitamin C, and (r = 0.27; P = 0.04) for Beta-carotene.
(Savu et al., 2012).
CVD is known as a major cause of morbidity and mortality all over the world, so that it can be one of the causes of increase in sudden death. Also, these diseases could cost a lot for the patients. The most common cause of heart disease vascular was recognized atherosclerosis. In spite of designing methods as well as new therapy for the prevention and treatment of heart disease, the number of deaths associated with CVD in most countries remains stagnant (Roth et al., 2017). One of the most important causes of mortality among American men and women was known coronary artery disease (Khawaja et al., 2009). The American Heart Association has reported that 20% of men and women suffer from coronary artery disease and its cost was about 368 billion dollars in the USA in 2004 (Berra, 2011). Increased incidence of coronary artery disease in last decades has been due to improving the economy, well-being, and comfort. Nutritional factor is a key factor in epidemiologic research and previous study demonstrated positive correlation between well-being and comfort among atherosclerosis (Barquera et al., 2015).
Some of the most important risk factors affecting coronary artery disease and T2D are lifestyle, diet, and physical activity. Similarly, proper diet consumption can prevent coronary artery disease in patients with diabetes, and one of causes of coronary artery disease are excessive intakes of energy and fat in the diet (de Souza et al., 2015, Maki, 2004). Several studies have indicated that increasing intakes of fresh vegetables, fruits, and grains can prevent coronary artery disease and diabetes (Alissa and Ferns, 2017, Di Angelantonio et al., 2016). Also, high dietary intakes of fruits and vegetables can improve insulin levels and insulin sensitivity (Mathews et al., 2017, Wang et al., 2016). High antioxidants diet could inhibit oxidant formation and intercepting oxidants which have been formed, and repair oxidant-induced injury (Diaz et al., 1997). Vitamin E and C can reduce the damaging effects of free radicals on the structure and function of cells and vessel walls (Ashor et al., 2015). Some of trace elements (selenium, copper, zinc, and manganese) act as cofactors for enzymes with antioxidant activity like superoxide dismutase and glutathione peroxidase (Diplock, 1991). Previous studies have indicated the association between some vitamins and hemoglobin A1c (HbA1c) levels; for example high intakes of carotenoids are associated with low levels of HbA1c and vitamin D deficiency can be along with high levels of HbA1c (Abd Elgadir et al., 2018, Randhawa et al., 2017). However, a study showed that supplementation of vitamins E and C in pharmacological does have no impact on HbA1c levels (Regensteiner et al., 2003).
Antioxidants in dietary intake, such as vitamin C, vitamin E, selenium, beta-carotene, and zinc associated to HbA1c level in T2D patients with and without coronary stenosis (CS) have not been examined. Therefore, the present study aimed to compare dietary intakes of antioxidants and insulin resistance levels in T2D patients with CS and T2D patients without CS. This study also examined the association between antioxidant components of dietary intakes with HbA1c and QUICKI index in T2D patients with and without CS.
Materials and Methods
Study design and participants: This case-control prospective study was conducted on T2D patients referred to the hospital. The study was carried out on 283 adult patients with newly diagnosed T2D without CS that were diagnosed with glucose tolerance test (GTT) and fasting blood glucose of 65 adult diabetic patients with CS that were diagnosed with angiography, GTT and fasting blood glucose that diagnosed by cardiologist. Subjects included if they diagnosed as having T2D and CS without any medical comorbidities or any other major chronic diseases. The subjects were excluded if they followed any especial diet, consumed any dietary supplements, multi-vitamin or mineral supplementation and fortified foods during the last four months. Finally, 111 T2D were excluded from the study, since they were on a diet or consumed dietary supplements.
Measurements: A valid and reliable 168- item semi-quantitative food frequency questionnaire (FFQ) modified for Iranian foods was completed in the present study (Esfahani et al., 2010). Frequencies of food intakes during the last four months were reported in day, week, or month. Vitamin C, vitamin E, selenium, beta-carotene, and zinc of foods were derived from Nutritionist 4 software. Written informed consent was signed by all the participants. This study was ethically approved by the university.
The demographic and clinical characteristics, including gender, age, body mass index (BMI), weight, systolic and diastolic blood pressure, and history of other disease were completed by using a structured questionnaire. All the patients had been taking 1500 mg/day oral doses of metformin. They had not taken any insulin therapy. HbA1c levels were measured by Diazyme direct enzymatic assay of HbA1c using auto-analyzer and whole blood samples (Penttilä et al., 2011).
Ethical considerations: Written informed consent was obtained from all the participants. This study was approved by the School of Nutrition and Food Sciences, Isfahan University of Medical Sciences (project code: 293113) and Qazvin University of Medical Sciences (project code: IR.QUMS.REC.2015).
Data analysis: Normal distribution of variables among the two groups of participants was determined by Shapiro-Wilk test. All variables, including vitamin C, vitamin E, selenium, beta-carotene, zinc, HbA1c, and QUICKI index (Quantitative insulin sensitivity check index) were normally distributed. Independent samples t-test was applied to compare the mean score of variables among T2D patients with and without CS. Gender and age was considered in Chi-square test and one-way ANOVA and independent samples t-test were used for quantitative variables. However, they did not change the results and therefore excluded from analysis. Pearson correlation test was used to assess the Chi-square test and one-way ANOVA and independent samples t-test were used for quantitative variables. However, they did not change the results and therefore excluded from analysis. Pearson correlation test was used to assess the relationship between vitamin C, vitamin E, selenium, beta-carotene, and zinc with HbA1c and QUICKI index among all the participants and in sub groups of T2D patients with CS and patients with T2D. All statistical analyses were performed by using SPSS version 20.0. P-values less than 0.05 were considered significant.
Results
Participants’ general characteristics are demonstrated in Table 1. There were no significant differences regarding age, gender, BMI, weight, systolic and diastolic blood pressure, and energy intake between the two groups.
Mean ± SD values of HbA1c, QUICKI index, vitamin E, vitamin C, selenium, beta-carotene, and zinc are shown in Table 2. Diabetic patients with CS had significantly higher HbA1c levels compared to the other group (P = 0.004). In addition, the index of insulin sensitivity in diabetic patients without CS higher than diabetic patients with CS (P = 0.03). The diabetic patients without CS consumed higher doses of dietary antioxidant components compared to diabetic patients with CS group. However, diabetic patients with CS had higher intakes of vitamin C and zinc compared to the other group.
Table 3 reveals the results of Pearson correlation test between variables and HbA1c levels in the two groups. There was negative correlation between all antioxidant components and HbA1c. In addition, there was a negative significant association between vitamin E and Beta-carotene with HbA1c among all the participants; (r = -0.88; P < 0.001) for vitamin E and (r = -0.80; P < 0.001) for Beta-carotene as well as T2D patients with CS, (r = -0.92; P < 0.001) for vitamin E, and (r = -0.92; P < 0.001) for Beta-carotene in T2D patients without CS. In addition, there was a marginally negative association between selenium with HbA1c in T2D group with CS (r =-0.20; P = 0.05), although this negative correlation in T2D group without CS was significant (r = -0.49; P < 0.001).
The results of Pearson correlation between antioxidants intake and QUICKI index in the two groups are presented in Table 4. There was a positive association between dietary intake of antioxidants and insulin sensitivity in QUICKI index. In addition, there was a positive significant association between vitamin C, vitamin E and selenium with insulin sensitivity among all the participants; (r = 0.59; P = 0.004) for vitamin E, (r = 0.91; P < 0.001) for vitamin C, and (r = 0.27; P = 0.04) for Beta-carotene.
| Table 1. General characteristics of the study population. | |||
| Variables | T2D patients with CS (N= 65) | T2D patients without CS (N=172) | P-valuea |
| Gender Male Female |
26 (40.0)b 39 (60.0) |
70 (37.2) 102 (62.8) |
0.75 |
| Age (year) | 50.14 ± 9.57c | 48.44 ± 9.21 | 0.12 |
| Body mass index (kg/m2) | 29.14 ± 3.26 | 27.58 ± 3.02 | 0.11 |
| Weight (kg) | 77.57 ± 7.82 | 74.88 ± 7.79 | 0.11 |
| SBP (mm Hg) | 13.98 ± 0.87 | 12.13 ± 0.65 | 0.07 |
| DBP (mm Hg) | 9.41 ± 0.54 | 8.13 ± 0.46 | 0.28 |
| Energy intake (kcal/day) | 2587.28 ± 248.12 | 2386.25 ± 233.50 | 0.06 |
| a: P-values are obtained from independent samples t-test and Chi-square test; b: N (%); c: Mean ± SD; T2D: Type 2 diabetes; CS: coronary stenosis; SBP: Systolic blood pressure; DBP: Diastolic blood pressure. | |||
| Table 2. Mean (±SD) values of variables between T2D patients with and without CS. | |||
| Variables | T2D patients with CS (N = 65) | T2D patients without CS (N = 172) | P-valuea |
| Vitamin E (IU/day) | 29.19 ± 5.12 | 33.24 ± 7.33 | 0.01 |
| Vitamin C (mg/day) | 298.32 ± 81.15 | 300.30 ± 85.77 | 0.17 |
| Selenium (mg/day) | 0.09 ± 0.04 | 0.10 ± 0.05 | 0.04 |
| Beta-carotene (mg/day) | 1081.74 ± 413.24 | 1393.49 ± 509.96 | <0.001 |
| Zinc (mg/day) | 8.98 ± 1.49 | 9.67 ± 1.59 | 0.19 |
| HbA1c (%) | 7.62 ± 0.97 | 7.11 ± 0.63 | 0.004 |
| QUICKI index (%) | 0.28 ± 0.02 | 0.30 ± 0.03 | 0.03 |
| a: P-values are obtained from independent samples t-test; T2D: Type 2 diabetes; CS: coronary stenosis; HbA1c: Hemoglobin A1c; QUICKI: Quantitative insulin sensitivity check index. | |||
| Table 3: Pearson correlation of HbA1c in the groups with antioxidant components. | ||||
| Variables | T2D patients with CS (N = 65) | T2D patients without CS (N = 172) | ||
| R | P-valuea | R | P-value | |
| Vitamin E | -0.88 | <0.001 | -0.92 | <0.001 |
| Vitamin C | -0.19 | 0.06 | -0.20 | 0.05 |
| Selenium | -0.20 | 0.05 | -0.49 | <0.001 |
| Beta-carotene | -0.80 | <0.001 | -0.92 | <0.001 |
| Zinc | -0.05 | 0.60 | -0.02 | 0.34 |
| a: P-values are obtained from Pearson correlation.; T2D: Type 2 diabetes; CS: coronary stenosis; HbA1c: Hemoglobin A1c. | ||||
| Table 4: Pearson correlation of QUICKI index in the groups with the study components. | ||||
| Variables | T2D patients with CS (N = 65) | T2D patients without CS (N = 172) | ||
| R | P-value1 | R | P-value | |
| Vitamin E | 0.568 | <0.008 | 0.612 | <0.003 |
| Vitamin C | 0.847 | 0.001 | 0.941 | 0.001 |
| Selenium | 0.812 | <0.001 | 0.918 | <0.001 |
| Beta-carotene | 0.218 | <0.061 | 0.294 | 0.042 |
| Zinc | 0.053 | 0.612 | 0.058 | 0.608 |
| a: P-values are obtained from Pearson correlation.; T2D: Type 2 diabetes; CS: coronary stenosis; QUICKI: Quantitative insulin sensitivity check index. | ||||
Discussion
The present study was conducted as the first attempt to investigate the association between dietary intake of antioxidants with insulin sensitivity and insulin resistance in T2D with and without CS. HbA1c levels among T2D with CS compared to the other group were significantly higher. In addition, the insulin sensitivity index compared to the two groups was significantly lower. There was a positive significant correlation between vitamin C, vitamin E, and selenium intake with insulin sensitivity among all the participants.
Cardiovascular risk factors and their pathologic factors begin predominantly from the childhood (Hong, 2010). Several studies have acknowledged that obesity with abnormal lipid profile among youth was strongly associated with insulin resistance (Polgreen et al., 2012, Steinberger et al., 2001). Studies have shown that lots of factors, such as overweight or obesity, abnormal lipid profiles, and insulin resistance play a significant role in the incidence of heart disease (DeBoer, 2013).
Under physiological conditions, insulin stimulates the utility of metabolic subclass in several tissues, such as heart, liver, skeletal muscle, and adipose tissue. In heart cells (cardiomyocytes), insulin increases glucose and fatty acid absorption, but inhibits the use of fatty acids as an energy source. As a result of this insulin resistance, the pancreas tries to compensate for insulin activity by secreting greater insulin (Abel et al., 2012). During insulin resistance, the natural tolerance of sugar is maintained due to physiological changes activated by this phenomenon (Ferrannini et al., 2003). It is very interesting to note that there is a direct and strong relationship between insulin resistance and the risk of heart disease (Nesto, 2003). Molecular and cellular mechanisms contribute to this direct relationship between insulin resistance and CVD (Saltiel, 2000, Wang et al., 2004, Zeadin et al., 2013). Insulin resistance helps increase oxidative stress, then results in mitochondrial function alteration which should aggravate insulin resistance. Atherosclerosis increased because of insulin resistance, vascular dysfunction, hypertension and accumulation of macrophages (Razani et al., 2008). Also, according to recent studies smoking, high levels of low density lipoprotein (LDL), high blood pressure, and diabetes are known some risk factors for CVD. In addition, hyperglycemia, insulin resistance and inflammation can also lead to a prognosis of cardiovascular events. Also, insulin resistance is associated with disorders, such as hypertriglyceridemia and low high density lipoprotein (HDL) (Howard et al., 2008).
In 1996, investigation of insulin resistant in atherosclerosis studies (Garcia-Bailo et al., 2011) showed a direct and consistent relationship between insulin resistance and atherosclerosis. A prospective study in a group of 2,938 patients showed insulin resistance as an important risk factor for the disease Cardiopulmonary bypass (De Hert et al., 2018, Wagenknecht et al., 1995). A meta-analysis in 2012 from 65 studies indicated that insulin resistance and HOMA-IR index were good predictors for CVD (Gast et al., 2012). Researchers also found that preventing insulin resistance could reduce about 42% of heart attacks in participants who had over 60-year follow-up period (Kozakova and Palombo, 2016, Laakso and Kuusisto, 2014). In addition to insulin resistance, compensatory hyperinsulinemia associated with insulin resistance which can play a key role in the formation of atherosclerotic plaques. It can be linked to a change in the gene expression pattern related to estrogen receptor (Min et al., 2016). Moreover, hyperglycemia causes changes in various metabolic and cellular levels (Wang et al., 2004), including schizophrenia, high blood pressure, oxidative stress, endothelial dysfunction, and changes in heart metabolism.
Studies have suggested that approximately
70-50% of the ATP needed as fuel for heart cells is produced by oxidation of long chain fatty acids. Glycolysis accounts for less than (10%) of total ATP production in the heart tissue. Although fatty acids are used for the production of preferential energy for the heart, the heart has the ability to alter the substrate to produce it for ATP. Substrate transducers, GLUT4 for glucose, and CD36 for fatty acids play a key role in this dynamic balance using substrate (Grynberg and Demaison, 1996).
However, under the effect of insulin resistance, fatty acid is known the only source of fuel that entered. Alterations in substrate increase the absorption and accumulation of fat in the heart, then cause fatty toxicity (Goldberg et al., 2012). In this way, the balance between fat degradation and glucose oxidation can reduce the activity of cardiac cells in patients with insulin resistance (Nagoshi et al., 2011).
Researchers have shown that oxidative stress is associated not only with diabetes complications, but also with insulin resistance (Asmat et al., 2016, Chueakula et al., 2018, Henriksen et al., 2011, Tangvarasittichai, 2015). Insulin resistance and declined insulin secretion are the main characteristics of T2D (Asmat et al., 2016, Tangvarasittichai, 2015). Insulin resistance often precedes the onset of T2D, in most cases, among lots of the general population, and several factorials (Rosenberg et al., 2005). Insulin resistance can be caused by effective factors, such as overweight or obesity, lifestyle, pregnancy, and excess in hormone secretin (Czech, 2017, McIntyre et al., 2010). Initially, insulin resistance is compensated by hyperinsulinemia, so blood glucose levels remain normal. Facchini reported that at least 25% of non-diabetic people with insulin resistance were found in a range of patients with T2D, and these people were exposed to age-related illnesses. Declined glucose tolerance occurs when insulin resistance increases, or insulin secretion declines, or both of them (Facchini et al., 2001).
Studies in diabetic animal models have indicated that antioxidants improve insulin sensitivity (Styskal et al., 2012). Several antioxidants have been promising as new approaches to treating insulin resistance, such as N-acetyl-cysteine, a-lipoic acid (LA), and flavonoids. Some studies have shown that antioxidants LA, glutathione, vitamin E, and vitamin C increase insulin resistance in patients with insulin resistance, T2D and/or CVD (Garcia-Bailo et al., 2011, Khodaeian et al., 2015). Antioxidant defence system includes endogenous and exogenous diet derived compounds. Dietary antioxidants, including vitamin C or ascorbic acid, vitamin E or α-tocopherol, and β-carotene or pro-vitamin A have attracted the most attention to prevent coronary heart disease (Diplock, 1991).
Additionally, the short-term oral administration (6-wk) of LA reduced fructosamine levels in patients with T2D (Evans and Goldfine, 2000). Vitamin C, in addition to the main role of endothelial dysfunction improvement, can reduce insulin resistance (Khodaeian et al., 2015). Oxidation may indirectly affect insulin sensitivity, declined peripheral blood flow, increased nitric-oxide, and declined glucose transport of insulin mobility in skeletal muscle (Krebs and Roden, 2005). Early reports aimed at investigating the effects of vitamin E on insulin activity in T2D with have been published more than 10 years ago and have shown positive effects in these patients (D. Pavithra et al., 2018, Wagenknecht et al., 1995). Twenty-five patients with T2D were treated with Vitamin E (tocopherol 900 mg/day) versus placebo for three months in a randomised controlled trial (RCT), cross-linked. The process of declining plasma glucose was associated with a significant reduction in HbA1c (7.8 vs. 7.1), triglycerides, free fatty acids, total cholesterol, low lipoprotein cholesterol, and apoprotein B. Cellular response to glucose was not observed. These interesting results increased the evaluation of Paolisso by using a more sensitive technique for estimating the insulin sensitivity index (Paolisso et al., 1991, Park et al., 2015).
Conclusion
This study showed that diabetic patients with CS have higher levels of HbA1c. In addition, there was a significant correlation between vitamin C and beta-carotene with HbA1c in patients with coronary artery disease and in patients without coronary artery disease. In addition, there was a significant correlation between selenium and HbA1c in T2D mellitus without coronary artery disease. There was a positive correlation between the amount of antioxidants and insulin sensitivity in the QUICKI index. In addition, there was a positive and significant correlation between insulin sensitivity of vitamin E, C, and beta-carotene among all the participants. It seems that antioxidants, especially vitamin C and beta-carotene, may have insulin resistance effects on metabolic disturbances.
Acknowledgment
Thanks are owed to all those who participated in this study.
Conflict of interest
The authors declare that there is no conflict of interest.
Authors’ contributions
Idea of study: Gerami H; Study design: Gerami H, Hosseini SK; Data collection: Gerami H, Hosseini SK, Jamalzehi A; Data analysis: Javadi M, Jamalzehi A, Lesani A; Manuscript draft: Javadi M, Gerami H, Hosseini SK, Jamalzehi A, Lesani A; Manuscript final edition: Gerami H, Lesani A, Jamalzehi A.
References
Abd Elgadir AA, Ahmed LO & Asaad Ma B 2018. Correlation of oxidative stress markers malondiadehyde (MDA), antioxidant vitamins A, E and C with glycated hemoglobin (HbA1c)level s in type 2 diabetes mellitus. Asian journal of pharmaceutical and clinical research. 11 (5): 281-283.
Abel ED, O'Shea KM & Ramasamy R 2012. Insulin resistance: metabolic mechanisms and consequences in the heart. Arterioscler Thromb Vasc Biol. 32 (9): 2068-2076.
Alissa EM & Ferns GA 2017. Dietary fruits and vegetables and cardiovascular diseases risk. Critical reviews in food science and nutrition. 57 (9): 1950-1962.
Ashor AW, et al. 2015. Effect of vitamin C and vitamin E supplementation on endothelial function: a systematic review and meta-analysis of randomised controlled trials. British journal of nutrition. 113 (8): 1182-1194.
Asmat U, Abad K & Ismail K 2016. Diabetes mellitus and oxidative stress-A concise review. Saudi pharmaceutical journal. 24 (5): 547-553.
Barquera S, et al. 2015. Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease. Archives of medical research. 46 (5): 328-338.
Berra K 2011. Does nurse case management improve implementation of guidelines for cardiovascular disease risk reduction? Journal of cardiovascular nursing. 26 (2): 145-167.
Chueakula N, et al. 2018. Diacerein alleviates kidney injury through attenuating inflammation and oxidative stress in obese insulin-resistant rats. Free radical biology and medicin. 115: 146-155.
Czech MP 2017. Insulin action and resistance in obesity and type 2 diabetes. Nat Med. 23 (7): 804-814.
D. Pavithra , D. Praveen , Chowdary PR & Aanandhi MV 2018. A review on role of Vitamin E supplementation in type 2 diabetes mellitus. Drug invention today. 234-260.
De Hert S, et al. 2018. Pre-operative evaluation of adults undergoing elective noncardiac surgery: Updated guideline from the European Society of Anaesthesiology. European journal of anaesthesiology. 35 (6): 407-465.
de Souza RJ, et al. 2015. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. British medical journal. 351: h3978.
DeBoer MD 2013. Obesity, systemic inflammation, and increased risk for cardiovascular disease and diabetes among adolescents: a need for screening tools to target interventions. Nutrition (Burbank, Los Angeles County, Calif.). 29 (2): 379-386.
Deshpande AD, Harris-Hayes M & Schootman M 2008. Epidemiology of diabetes and diabetes-related complications. Physical therapy. 88 (11): 1254-1264.
Di Angelantonio E, et al. 2016. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 388 (10046): 776-786.
Diaz MN, Frei B, Vita JA & Keaney JF, Jr. 1997. Antioxidants and atherosclerotic heart disease. New England journal of medicine 337 (6): 408-416.
Diplock AT 1991. Antioxidant nutrients and disease prevention: an overview. American journal clinical nutrition. 53 (1 Suppl): 189s-193s.
Esfahani FH, Asghari G, Mirmiran P & Azizi F 2010. Reproducibility and relative validity of food group intake in a food frequency questionnaire developed for the Tehran Lipid and Glucose Study. Journal of epidemiology. 20 (2): 150-158.
Evans JL & Goldfine ID 2000. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes technology & therapeutics. 2 (3): 401-413.
Facchini FS, Hua N, Abbasi F & Reaven GM 2001. Insulin resistance as a predictor of age-related diseases. Journal of clinical endocrinology & metabolism. 86 (8): 3574-3578.
Ferrannini E, et al. 2003. Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance. Diabetologia. 46 (9): 1211-1219.
Garcia-Bailo B, et al. 2011. Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress. Biologics. 5: 7-19.
Gast KB, Tjeerdema N, Stijnen T, Smit JW & Dekkers OM 2012. Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis. PloS one. 7 (12): e52036.
Goldberg IJ, Trent CM & Schulze PC 2012. Lipid metabolism and toxicity in the heart. Cell Metab. 15 (6): 805-812.
Grynberg A & Demaison L 1996. Fatty Acid Oxidation in the Heart. Journal of cardiovascular pharmacology. 28: 11-17.
Henriksen EJ, Diamond-Stanic MK & Marchionne EM 2011. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free radical biology and medicine 51 (5): 993-999.
Hong YM 2010. Atherosclerotic cardiovascular disease beginning in childhood. Korean Circ J. 40 (1): 1-9.
Howard BV, et al. 2008. Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial. Journal of the American medical association (JAMA). 299 (14): 1678-1689.
Kaul K., Tarr J.M., Ahmad S.I., Kohner E.M. & R. C 2013. Introduction to Diabetes Mellitus In Diabetes. Advances in Experimental Medicine and Biology (ed. S. Ahmad). Springer: New York.
Khawaja IS, Westermeyer JJ, Gajwani P & Feinstein RE 2009. Depression and coronary artery disease: the association, mechanisms, and therapeutic implications. Psychiatry (Edgmont). 6 (1): 38-51.
Khodaeian M, et al. 2015. Effect of vitamins C and E on insulin resistance in diabetes: a meta-analysis study. European journal of clinical investigation. 45 (11): 1161-1174.
Kozakova M & Palombo C 2016. Diabetes Mellitus, Arterial Wall, and Cardiovascular Risk Assessment. Int J Environ Res Public Health. 13 (2): 201-201.
Krebs M & Roden M 2005. Molecular mechanisms of lipid-induced insulin resistance in muscle, liver and vasculature. Diabetes, obesity and metabolism. 7 (6): 621-632.
Laakso M & Kuusisto J 2014. Insulin resistance and hyperglycaemia in cardiovascular disease development. Nature reviews endocrinology. 10 (5): 293-302.
Lau DCW 2009. Fighting Diabetes, The Tsunami of Noncommunicable Diseases. Canadian journal of diabetes. 33 (4): 348-349.
Maki KC 2004. Dietary factors in the prevention of diabetes mellitus and coronary artery disease associated with the metabolic syndrome. American journal of cardiology. 93 (11a):
12c-17c.
Mathews AT, et al. 2017. Efficacy of nutritional interventions to lower circulating ceramides in young adults: FRUVEDomic pilot study. Physiol Rep. 5 (13): e13329.
McIntyre HD, et al. 2010. Hormonal and metabolic factors associated with variations in insulin sensitivity in human pregnancy. Diabetes Care. 33 (2): 356-360.
Min J, et al. 2016. Correlation between insulin-induced estrogen receptor methylation and atherosclerosis. Cardiovascular diabetology. 15 (1): 156.
Nagoshi T, Yoshimura M, Rosano GMC, Lopaschuk GD & Mochizuki S 2011. Optimization of cardiac metabolism in heart failure. Curr Pharm Des. 17 (35): 3846-3853.
Nesto RW 2003. The relation of insulin resistance syndromes to risk of cardiovascular disease. Reviews in cardiovascular medicine. 4 Suppl 6: S11-18.
Paolisso G, et al. 1991. Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure. Metabolism: clinical and experimental. 40 (9): 972-977.
Park SE, Park CY & Sweeney G 2015. Biomarkers of insulin sensitivity and insulin resistance: Past, present and future. Critical reviews in clinical laboratory sciences. 52 (4): 180-190.
Penttilä I, et al. 2011. Adaptation of the Diazyme Direct Enzymatic HbA1c Assay for a microplate reader at room temperature. Clinical chemistry and laboratory medicine. 49 (7): 1221-1223.
Polgreen LE, et al. 2012. Association of osteocalcin with obesity, insulin resistance, and cardiovascular risk factors in young adults. Obesity. 20 (11): 2194-2201.
Randhawa FA, Mustafa S, Khan DM & Hamid S 2017. Effect of Vitamin D supplementation on reduction in levels of HbA1 in patients recently diagnosed with type 2 Diabetes Mellitus having asymptomatic Vitamin D deficiency. Pak J Med Sci. 33 (4): 881-885.
Razani B, Chakravarthy MV & Semenkovich CF 2008. Insulin resistance and atherosclerosis. Endocrinol Metab Clin North Am. 37 (3): 603-viii.
Regensteiner JG, et al. 2003. Oral L-arginine and vitamins E and C improve endothelial function in women with type 2 diabetes. Vascular medicine. 8 (3): 169-175.
Rosenberg DE, Jabbour SA & Goldstein BJ 2005. Insulin resistance, diabetes and cardiovascular risk: approaches to treatment. Diabetes, obesity and metabolism. 7 (6): 642-653.
Roth GA, et al. 2017. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. Journal of the American College of Cardiology. 70 (1): 1-25.
Saltiel AR 2000. Series introduction: the molecular and physiological basis of insulin resistance: emerging implications for metabolic and cardiovascular diseases. Journal of clinical investigation. 106 (2): 163-164.
Savu O, et al. 2012. Increase in total antioxidant capacity of plasma despite high levels of oxidative stress in uncomplicated type 2 diabetes mellitus. Journal of international medical research. 40 (2): 709-716.
Steinberger J, Moran A, Hong C-P, Jacobs DR, Jr. & Sinaiko AR 2001. Adiposity in childhood predicts obesity and insulin resistance in young adulthood. Journal of pediatrics. 138 (4): 469-473.
Styskal J, Van Remmen H, Richardson A & Salmon AB 2012. Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models? Free radical biology and medicine. 52 (1): 46-58.
Tangvarasittichai S 2015. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World journal of diabetes. 6 (3): 456-480.
Tripathi BK & Srivastava AK 2006. Diabetes mellitus: complications and therapeutics. Medical science monitor. 12 (7): Ra130-147.
Wagenknecht LE, et al. 1995. The insulin resistance atherosclerosis study (IRAS) objectives, design, and recruitment results. Annals of epidemiology. 5 (6): 464-472.
Wang CC, Goalstone ML & Draznin B 2004. Molecular mechanisms of insulin resistance that impact cardiovascular biology. Diabetes. 53 (11): 2735-2740.
Wang PY, Fang JC, Gao ZH, Zhang C & Xie SY 2016. Higher intake of fruits, vegetables or their fiber reduces the risk of type 2 diabetes: A meta-analysis. Journal of diabetes investigation. 7 (1): 56-69.
Whiting DR, Guariguata L, Weil C & Shaw J 2011. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes research and clinical practice. 94 (3): 311-321.
Wiernsperger NF 2003. Oxidative stress as a therapeutic target in diabetes: revisiting the controversy. Diabetes & metabolism journal. 29 (6): 579-585.
Zeadin MG, Petlura CI & Werstuck GH 2013. Molecular mechanisms linking diabetes to the accelerated development of atherosclerosis. Canadian journal of diabetes. 37 (5):345-350.
The present study was conducted as the first attempt to investigate the association between dietary intake of antioxidants with insulin sensitivity and insulin resistance in T2D with and without CS. HbA1c levels among T2D with CS compared to the other group were significantly higher. In addition, the insulin sensitivity index compared to the two groups was significantly lower. There was a positive significant correlation between vitamin C, vitamin E, and selenium intake with insulin sensitivity among all the participants.
Cardiovascular risk factors and their pathologic factors begin predominantly from the childhood (Hong, 2010). Several studies have acknowledged that obesity with abnormal lipid profile among youth was strongly associated with insulin resistance (Polgreen et al., 2012, Steinberger et al., 2001). Studies have shown that lots of factors, such as overweight or obesity, abnormal lipid profiles, and insulin resistance play a significant role in the incidence of heart disease (DeBoer, 2013).
Under physiological conditions, insulin stimulates the utility of metabolic subclass in several tissues, such as heart, liver, skeletal muscle, and adipose tissue. In heart cells (cardiomyocytes), insulin increases glucose and fatty acid absorption, but inhibits the use of fatty acids as an energy source. As a result of this insulin resistance, the pancreas tries to compensate for insulin activity by secreting greater insulin (Abel et al., 2012). During insulin resistance, the natural tolerance of sugar is maintained due to physiological changes activated by this phenomenon (Ferrannini et al., 2003). It is very interesting to note that there is a direct and strong relationship between insulin resistance and the risk of heart disease (Nesto, 2003). Molecular and cellular mechanisms contribute to this direct relationship between insulin resistance and CVD (Saltiel, 2000, Wang et al., 2004, Zeadin et al., 2013). Insulin resistance helps increase oxidative stress, then results in mitochondrial function alteration which should aggravate insulin resistance. Atherosclerosis increased because of insulin resistance, vascular dysfunction, hypertension and accumulation of macrophages (Razani et al., 2008). Also, according to recent studies smoking, high levels of low density lipoprotein (LDL), high blood pressure, and diabetes are known some risk factors for CVD. In addition, hyperglycemia, insulin resistance and inflammation can also lead to a prognosis of cardiovascular events. Also, insulin resistance is associated with disorders, such as hypertriglyceridemia and low high density lipoprotein (HDL) (Howard et al., 2008).
In 1996, investigation of insulin resistant in atherosclerosis studies (Garcia-Bailo et al., 2011) showed a direct and consistent relationship between insulin resistance and atherosclerosis. A prospective study in a group of 2,938 patients showed insulin resistance as an important risk factor for the disease Cardiopulmonary bypass (De Hert et al., 2018, Wagenknecht et al., 1995). A meta-analysis in 2012 from 65 studies indicated that insulin resistance and HOMA-IR index were good predictors for CVD (Gast et al., 2012). Researchers also found that preventing insulin resistance could reduce about 42% of heart attacks in participants who had over 60-year follow-up period (Kozakova and Palombo, 2016, Laakso and Kuusisto, 2014). In addition to insulin resistance, compensatory hyperinsulinemia associated with insulin resistance which can play a key role in the formation of atherosclerotic plaques. It can be linked to a change in the gene expression pattern related to estrogen receptor (Min et al., 2016). Moreover, hyperglycemia causes changes in various metabolic and cellular levels (Wang et al., 2004), including schizophrenia, high blood pressure, oxidative stress, endothelial dysfunction, and changes in heart metabolism.
Studies have suggested that approximately
70-50% of the ATP needed as fuel for heart cells is produced by oxidation of long chain fatty acids. Glycolysis accounts for less than (10%) of total ATP production in the heart tissue. Although fatty acids are used for the production of preferential energy for the heart, the heart has the ability to alter the substrate to produce it for ATP. Substrate transducers, GLUT4 for glucose, and CD36 for fatty acids play a key role in this dynamic balance using substrate (Grynberg and Demaison, 1996).
However, under the effect of insulin resistance, fatty acid is known the only source of fuel that entered. Alterations in substrate increase the absorption and accumulation of fat in the heart, then cause fatty toxicity (Goldberg et al., 2012). In this way, the balance between fat degradation and glucose oxidation can reduce the activity of cardiac cells in patients with insulin resistance (Nagoshi et al., 2011).
Researchers have shown that oxidative stress is associated not only with diabetes complications, but also with insulin resistance (Asmat et al., 2016, Chueakula et al., 2018, Henriksen et al., 2011, Tangvarasittichai, 2015). Insulin resistance and declined insulin secretion are the main characteristics of T2D (Asmat et al., 2016, Tangvarasittichai, 2015). Insulin resistance often precedes the onset of T2D, in most cases, among lots of the general population, and several factorials (Rosenberg et al., 2005). Insulin resistance can be caused by effective factors, such as overweight or obesity, lifestyle, pregnancy, and excess in hormone secretin (Czech, 2017, McIntyre et al., 2010). Initially, insulin resistance is compensated by hyperinsulinemia, so blood glucose levels remain normal. Facchini reported that at least 25% of non-diabetic people with insulin resistance were found in a range of patients with T2D, and these people were exposed to age-related illnesses. Declined glucose tolerance occurs when insulin resistance increases, or insulin secretion declines, or both of them (Facchini et al., 2001).
Studies in diabetic animal models have indicated that antioxidants improve insulin sensitivity (Styskal et al., 2012). Several antioxidants have been promising as new approaches to treating insulin resistance, such as N-acetyl-cysteine, a-lipoic acid (LA), and flavonoids. Some studies have shown that antioxidants LA, glutathione, vitamin E, and vitamin C increase insulin resistance in patients with insulin resistance, T2D and/or CVD (Garcia-Bailo et al., 2011, Khodaeian et al., 2015). Antioxidant defence system includes endogenous and exogenous diet derived compounds. Dietary antioxidants, including vitamin C or ascorbic acid, vitamin E or α-tocopherol, and β-carotene or pro-vitamin A have attracted the most attention to prevent coronary heart disease (Diplock, 1991).
Additionally, the short-term oral administration (6-wk) of LA reduced fructosamine levels in patients with T2D (Evans and Goldfine, 2000). Vitamin C, in addition to the main role of endothelial dysfunction improvement, can reduce insulin resistance (Khodaeian et al., 2015). Oxidation may indirectly affect insulin sensitivity, declined peripheral blood flow, increased nitric-oxide, and declined glucose transport of insulin mobility in skeletal muscle (Krebs and Roden, 2005). Early reports aimed at investigating the effects of vitamin E on insulin activity in T2D with have been published more than 10 years ago and have shown positive effects in these patients (D. Pavithra et al., 2018, Wagenknecht et al., 1995). Twenty-five patients with T2D were treated with Vitamin E (tocopherol 900 mg/day) versus placebo for three months in a randomised controlled trial (RCT), cross-linked. The process of declining plasma glucose was associated with a significant reduction in HbA1c (7.8 vs. 7.1), triglycerides, free fatty acids, total cholesterol, low lipoprotein cholesterol, and apoprotein B. Cellular response to glucose was not observed. These interesting results increased the evaluation of Paolisso by using a more sensitive technique for estimating the insulin sensitivity index (Paolisso et al., 1991, Park et al., 2015).
Conclusion
This study showed that diabetic patients with CS have higher levels of HbA1c. In addition, there was a significant correlation between vitamin C and beta-carotene with HbA1c in patients with coronary artery disease and in patients without coronary artery disease. In addition, there was a significant correlation between selenium and HbA1c in T2D mellitus without coronary artery disease. There was a positive correlation between the amount of antioxidants and insulin sensitivity in the QUICKI index. In addition, there was a positive and significant correlation between insulin sensitivity of vitamin E, C, and beta-carotene among all the participants. It seems that antioxidants, especially vitamin C and beta-carotene, may have insulin resistance effects on metabolic disturbances.
Acknowledgment
Thanks are owed to all those who participated in this study.
Conflict of interest
The authors declare that there is no conflict of interest.
Authors’ contributions
Idea of study: Gerami H; Study design: Gerami H, Hosseini SK; Data collection: Gerami H, Hosseini SK, Jamalzehi A; Data analysis: Javadi M, Jamalzehi A, Lesani A; Manuscript draft: Javadi M, Gerami H, Hosseini SK, Jamalzehi A, Lesani A; Manuscript final edition: Gerami H, Lesani A, Jamalzehi A.
References
Abd Elgadir AA, Ahmed LO & Asaad Ma B 2018. Correlation of oxidative stress markers malondiadehyde (MDA), antioxidant vitamins A, E and C with glycated hemoglobin (HbA1c)level s in type 2 diabetes mellitus. Asian journal of pharmaceutical and clinical research. 11 (5): 281-283.
Abel ED, O'Shea KM & Ramasamy R 2012. Insulin resistance: metabolic mechanisms and consequences in the heart. Arterioscler Thromb Vasc Biol. 32 (9): 2068-2076.
Alissa EM & Ferns GA 2017. Dietary fruits and vegetables and cardiovascular diseases risk. Critical reviews in food science and nutrition. 57 (9): 1950-1962.
Ashor AW, et al. 2015. Effect of vitamin C and vitamin E supplementation on endothelial function: a systematic review and meta-analysis of randomised controlled trials. British journal of nutrition. 113 (8): 1182-1194.
Asmat U, Abad K & Ismail K 2016. Diabetes mellitus and oxidative stress-A concise review. Saudi pharmaceutical journal. 24 (5): 547-553.
Barquera S, et al. 2015. Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease. Archives of medical research. 46 (5): 328-338.
Berra K 2011. Does nurse case management improve implementation of guidelines for cardiovascular disease risk reduction? Journal of cardiovascular nursing. 26 (2): 145-167.
Chueakula N, et al. 2018. Diacerein alleviates kidney injury through attenuating inflammation and oxidative stress in obese insulin-resistant rats. Free radical biology and medicin. 115: 146-155.
Czech MP 2017. Insulin action and resistance in obesity and type 2 diabetes. Nat Med. 23 (7): 804-814.
D. Pavithra , D. Praveen , Chowdary PR & Aanandhi MV 2018. A review on role of Vitamin E supplementation in type 2 diabetes mellitus. Drug invention today. 234-260.
De Hert S, et al. 2018. Pre-operative evaluation of adults undergoing elective noncardiac surgery: Updated guideline from the European Society of Anaesthesiology. European journal of anaesthesiology. 35 (6): 407-465.
de Souza RJ, et al. 2015. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. British medical journal. 351: h3978.
DeBoer MD 2013. Obesity, systemic inflammation, and increased risk for cardiovascular disease and diabetes among adolescents: a need for screening tools to target interventions. Nutrition (Burbank, Los Angeles County, Calif.). 29 (2): 379-386.
Deshpande AD, Harris-Hayes M & Schootman M 2008. Epidemiology of diabetes and diabetes-related complications. Physical therapy. 88 (11): 1254-1264.
Di Angelantonio E, et al. 2016. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 388 (10046): 776-786.
Diaz MN, Frei B, Vita JA & Keaney JF, Jr. 1997. Antioxidants and atherosclerotic heart disease. New England journal of medicine 337 (6): 408-416.
Diplock AT 1991. Antioxidant nutrients and disease prevention: an overview. American journal clinical nutrition. 53 (1 Suppl): 189s-193s.
Esfahani FH, Asghari G, Mirmiran P & Azizi F 2010. Reproducibility and relative validity of food group intake in a food frequency questionnaire developed for the Tehran Lipid and Glucose Study. Journal of epidemiology. 20 (2): 150-158.
Evans JL & Goldfine ID 2000. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes technology & therapeutics. 2 (3): 401-413.
Facchini FS, Hua N, Abbasi F & Reaven GM 2001. Insulin resistance as a predictor of age-related diseases. Journal of clinical endocrinology & metabolism. 86 (8): 3574-3578.
Ferrannini E, et al. 2003. Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance. Diabetologia. 46 (9): 1211-1219.
Garcia-Bailo B, et al. 2011. Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress. Biologics. 5: 7-19.
Gast KB, Tjeerdema N, Stijnen T, Smit JW & Dekkers OM 2012. Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis. PloS one. 7 (12): e52036.
Goldberg IJ, Trent CM & Schulze PC 2012. Lipid metabolism and toxicity in the heart. Cell Metab. 15 (6): 805-812.
Grynberg A & Demaison L 1996. Fatty Acid Oxidation in the Heart. Journal of cardiovascular pharmacology. 28: 11-17.
Henriksen EJ, Diamond-Stanic MK & Marchionne EM 2011. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free radical biology and medicine 51 (5): 993-999.
Hong YM 2010. Atherosclerotic cardiovascular disease beginning in childhood. Korean Circ J. 40 (1): 1-9.
Howard BV, et al. 2008. Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial. Journal of the American medical association (JAMA). 299 (14): 1678-1689.
Kaul K., Tarr J.M., Ahmad S.I., Kohner E.M. & R. C 2013. Introduction to Diabetes Mellitus In Diabetes. Advances in Experimental Medicine and Biology (ed. S. Ahmad). Springer: New York.
Khawaja IS, Westermeyer JJ, Gajwani P & Feinstein RE 2009. Depression and coronary artery disease: the association, mechanisms, and therapeutic implications. Psychiatry (Edgmont). 6 (1): 38-51.
Khodaeian M, et al. 2015. Effect of vitamins C and E on insulin resistance in diabetes: a meta-analysis study. European journal of clinical investigation. 45 (11): 1161-1174.
Kozakova M & Palombo C 2016. Diabetes Mellitus, Arterial Wall, and Cardiovascular Risk Assessment. Int J Environ Res Public Health. 13 (2): 201-201.
Krebs M & Roden M 2005. Molecular mechanisms of lipid-induced insulin resistance in muscle, liver and vasculature. Diabetes, obesity and metabolism. 7 (6): 621-632.
Laakso M & Kuusisto J 2014. Insulin resistance and hyperglycaemia in cardiovascular disease development. Nature reviews endocrinology. 10 (5): 293-302.
Lau DCW 2009. Fighting Diabetes, The Tsunami of Noncommunicable Diseases. Canadian journal of diabetes. 33 (4): 348-349.
Maki KC 2004. Dietary factors in the prevention of diabetes mellitus and coronary artery disease associated with the metabolic syndrome. American journal of cardiology. 93 (11a):
12c-17c.
Mathews AT, et al. 2017. Efficacy of nutritional interventions to lower circulating ceramides in young adults: FRUVEDomic pilot study. Physiol Rep. 5 (13): e13329.
McIntyre HD, et al. 2010. Hormonal and metabolic factors associated with variations in insulin sensitivity in human pregnancy. Diabetes Care. 33 (2): 356-360.
Min J, et al. 2016. Correlation between insulin-induced estrogen receptor methylation and atherosclerosis. Cardiovascular diabetology. 15 (1): 156.
Nagoshi T, Yoshimura M, Rosano GMC, Lopaschuk GD & Mochizuki S 2011. Optimization of cardiac metabolism in heart failure. Curr Pharm Des. 17 (35): 3846-3853.
Nesto RW 2003. The relation of insulin resistance syndromes to risk of cardiovascular disease. Reviews in cardiovascular medicine. 4 Suppl 6: S11-18.
Paolisso G, et al. 1991. Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure. Metabolism: clinical and experimental. 40 (9): 972-977.
Park SE, Park CY & Sweeney G 2015. Biomarkers of insulin sensitivity and insulin resistance: Past, present and future. Critical reviews in clinical laboratory sciences. 52 (4): 180-190.
Penttilä I, et al. 2011. Adaptation of the Diazyme Direct Enzymatic HbA1c Assay for a microplate reader at room temperature. Clinical chemistry and laboratory medicine. 49 (7): 1221-1223.
Polgreen LE, et al. 2012. Association of osteocalcin with obesity, insulin resistance, and cardiovascular risk factors in young adults. Obesity. 20 (11): 2194-2201.
Randhawa FA, Mustafa S, Khan DM & Hamid S 2017. Effect of Vitamin D supplementation on reduction in levels of HbA1 in patients recently diagnosed with type 2 Diabetes Mellitus having asymptomatic Vitamin D deficiency. Pak J Med Sci. 33 (4): 881-885.
Razani B, Chakravarthy MV & Semenkovich CF 2008. Insulin resistance and atherosclerosis. Endocrinol Metab Clin North Am. 37 (3): 603-viii.
Regensteiner JG, et al. 2003. Oral L-arginine and vitamins E and C improve endothelial function in women with type 2 diabetes. Vascular medicine. 8 (3): 169-175.
Rosenberg DE, Jabbour SA & Goldstein BJ 2005. Insulin resistance, diabetes and cardiovascular risk: approaches to treatment. Diabetes, obesity and metabolism. 7 (6): 642-653.
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Received: 2021/04/8 | Published: 2022/05/30 | ePublished: 2022/05/30
Received: 2021/04/8 | Published: 2022/05/30 | ePublished: 2022/05/30
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