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Kamali Z, Ziaei S, Kazemnejad A, Movahedinejad M. The Relationship between Insulin Resistance and Micronutrient Intake in Polycystic Ovary Syndrome Subgroups. JNFS 2023; 8 (1) :83-93
URL: http://jnfs.ssu.ac.ir/article-1-468-en.html
URL: http://jnfs.ssu.ac.ir/article-1-468-en.html
Department of Midwifery and Reproductive Health, Tarbiat Modares University, Tehran, Iran
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Zahra Kamali; MSc 1, Saeideh Ziaei; MD 2, Anoshirvan Kazemnejad; MD 3 & Maryam Movahedinejad; MSc* 4
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The Relationship between Insulin Resistance and Micronutrient Intake in Polycystic Ovary Syndrome Subgroups
Zahra Kamali; MSc 1, Saeideh Ziaei; MD 2, Anoshirvan Kazemnejad; MD 3 & Maryam Movahedinejad; MSc* 4
1 Department of Midwifery and Reproductive Health, School of Nursing and Midwifery, Neyshabur University of Medical Sciences, Neyshabur, Iran; 2 Department of Reproductive Health, Tarbiat Modares University, Tehran, Iran; 3 Department of Biostatistics, Tarbiat Modares University, Tehran, Iran; 4 Department of Midwifery and Reproductive Health, Tarbiat Modares University, Tehran, Iran.
| ARTICLE INFO | ABSTRACT | |
| ORIGINAL ARTICLE | Background: Polycystic ovary syndrome (PCOS) is with oxidative stress in women of reproductive age. Oxidative stress is an important factor in the development of insulin resistance. Some micronutrients are also linked to oxidative stress. The aim of this study was to determine the relationship between insulin resistance and micronutrient intake in PCOS subgroups. Methods: This case-control study was performed on 151 PCOS. They were divided into four groups according to the Rotterdam diagnostic criteria: D = 37, C = 40, B = 33, A = 41 and 31 women were also in the control group and did not have this syndrome. Micronutrient food intake was assessed with a 168-item FFQ feed frequency questionnaire. Insulin resistance was diagnosed with HOMA-IR index (Cut off> 2.5). The data were analyzed with SPSS 22 using Kruskal Wallis (KW), Spearman, and Chi-square tests. Results: The mean age of participants was 28.53 years. There was a significant relationship between the HOMA-IR and some dietary components (selenium depletion in group A, zinc depletion, vitamin D, and vitamin E in group D, and vitamin D and vitamin E depletion in control group) (P < 0.05). There was no relationship between subgroups B and C. Conclusion: Due to the significant relationship between insulin resistance indices, increasing the dietary intake of zinc, selenium, vitamin D, and vitamin E in women with PCOS, as well as increasing the dietary intake of these micronutrients in improving the physical health and fertility parameters of these people is recommended. Keywords: Micronutrient intake; Polycystic ovary syndrome; Insulin resistance |
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| Article history: Received: 31 Aug 2021 Revised: 22 Nov 2021 Accepted: 21 Dec 2021 |
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| *Corresponding author: Movahedinejadmaryam@gmail.com Al Ahmad Street، Jalal, Tarbiat Modares University, Tehran, Iran. Postal code: 14115-111 Tel: +98 915 9516438 |
Introduction
Polycystic ovary syndrome (PCOS) is a complicated endocrineopathy affecting women of reproductive age. According to the difference in the diagnostic criteria and ethnic background, the prevalence of this syndrome has been reported in the range of 11.9 +/- 2.4% (March et al., 2010).
In Iran, based on the National Institute of Health (NIH) criteria, the prevalence of PCOS according to Rotterdam criteria is 15.2% (Mehrabian et al., 2011).
PCOS is difficult to diagnose due to the heterogeneous nature and possible changes in patient’s status. At present, the most commonly used criterion for diagnosis is the Rotterdam criterion based on the 2003 agreement. In this method, two out of three disorders (hyperandrogenism, chronic ovulation, and ultrasound pattern of polycystic ovaries) are necessary (Kar, 2013).
It is not a disease-specific to fertility and adolescence but can have different effects on one's life. The main complications of adolescence are prevalence of amenorrhea, oligomenorrhea, hirsutism, obesity, and acne. At the fertility age, the patient's main complaint is infertility and irregular ovulation. Complications of adolescence are still present in this period. At premenopausal and postmenopausal ages, this syndrome can increase the risk of type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, and even endometrial cancer and possibly breast cancer (Norman et al., 2007) and insulin resistance (Javanmanesh et al., 2016, Moran and Teede, 2009).
Insulin resistance refers to conditions in which the biological effect of insulin is diminished at any given concentration. In addition, it reduces the sensitivity of target tissues to insulin hormone, leading to insulin resistance (Yildizhan et al., 2009).
Insulin resistance is also one of the pathophysiological factors in 50-80% of PCOS patients (Teede et al., 2010). Among patients, 80-70% of obese patients (BMI > 30) and 20-25% of lean women (BMI < 25) showed these features (Marshall and Dunaif, 2012).
One of the mechanisms involved in insulin resistance is the presence of genetic and environmental factors such as nutrition and physical activity (Teede et al., 2010). Proper diet and lifestyle modification reduce insulin resistance in PCOS patients (Salehpour, 2011).
In nutrition, micronutrients play an important role in human health, including the prevention and treatment of diseases, as well as the optimization of physical and mental performance (Woodside et al., 2005). The antioxidant effects of several micronutrients, such as zinc, selenium, chromium, and carotenoids (Zeng, 2009) were considered as contributing factors to the development of insulin resistance (González et al., 2006).
There is limited data investigating the diet composition of PCOS women (Douglas et al., 2006). There are inconsistent results from studies mostly conducted in western countries. Some studies have not reported any difference in nutrient intake in women with or without PCOS (Douglas et al., 2006, Wright et al., 2004) .
Previous studies have also shown an inverse association between carotenoid intake and fasting glucose and insulin concentrations due to their antioxidant effects (Sugiura et al., 2006). In some studies, the inverse relationship of insulin resistance to HOMA-IR with vitamins E and D due to inhibition of oxidative stress and inflammation has been reported (Chiu et al., 2004, Gabrielli and Aquino, 2012, Isharwal et al., 2009). There is also a negative association of insulin resistance with zinc, assuming that alpha-zinc glycoprotein may act as an adipokine that interferes with insulin resistance (Hashemipour et al., 2009). However, results regarding zinc levels in patients with PCOS are highly contradictory and some studies have not found zinc administration to be beneficial in these patients (Hashemipour et al., 2009, Kim et al., 2007). Evidence suggests that chromium plays a role in controlling blood sugar and improving insulin activity and enhancing insulin sensitivity, appetite regulation, and weight control (Vincent, 2018). Studies have shown that chromium has been shown to affect insulin function and increase insulin sensitivity in patients with PCOS (Lydic et al., 2006). It has also been suggested that high selenium intake reduces the risk of diseases due to oxidative stress and inflammation. The antioxidant and anti-inflammatory effects of selenium can have a protective effect on insulin resistance and diabetes (Rayman, 2012).
Accordingly, PCOS is a common, heterogeneous, and inherited disorder that affects women throughout their lives (Sirmans and Pate, 2014). The disease affects several systems. Early diagnosis and long-term management can help control this syndrome as well as prevent its long-term consequences, such as insulin resistance (Brady et al., 2009). There have been few studies investigating the association between insulin resistance and dietary intake, and there are many inconsistencies in their results. Eating habits are rooted in the culture of every region in the world (Shishehgar et al., 2016). Therefore, the researchers designed and conducted a study to determine the relationship between insulin resistance and micronutrient intake (chromium, selenium, zinc, carotenoids, vitamins D and E) in women with PCOS in four phenotypes based on Rotterdam criteria.
Materials and Methods
Study design and participants: The present study is a case-control study to investigating dietary intake of micronutrients in four subgroups of PCOS and control group with insulin resistance in Tehran, Iran during 2015-2016. The sample size based on the results of the pilot study and the correlation between insulin resistance index and dietary component showed that the minimum correlation between these indices was 0.50. Therefore, with 95% confidence and 80% test power, the number of samples required was 26.2 based on the following formula for each subgroup (approximately 27 samples). Considering 20% of sample loss, the final volume per phenotype was estimated at 31 samples.
n = z 1- ∝ 2 + z 1- β 2 c r 2 +3
C r = 1 2 e 1+ r 1- r = 1 2 e 1+0.5 1-0.5 =0.55
n = 1.96+0.84 2 0.55 2 +3=26.2≅27
27+0.2 27 =31
The participants were selected from referrals to gynecology and endocrinology ward of Arash hospital, and selected private clinic if they were eligible to enter the study after filling informed consent form. The inclusion criteria in the case group consisted of Iranian nationality, age of 18-40 years, lack of chronic metabolic and non-metabolic diseases affecting diet (such as diabetes mellitus, hyperthyroidism, hypothyroidism, and hyperlipidemia), not taking medicines that affect appetite and diet, no specific diet, no pregnancy, no hormone use for three months before starting the study. In the event of any problems, including pregnancy and illness requiring specific drug use, they were excluded. The inclusion criteria in the control group were age of 18-40 years and without any diagnostic criteria for PCOS (non-hirsute: without excessive hair growth, with regular ovulation cycles), referring to women's clinic for other reasons. Then the two groups were matched for education, body mass index (BMI), economic status, and physical activity and exercise status.
Initially, the disease was diagnosed after excluding other abnormalities that mimic the PCOS phenotype )ovarian or adrenal neoplasm, Cushing's syndrome, hyperprolactinemia, thyroid disease, and congenital adrenal hyperplasia starting in adulthood (AOAH)) by assessing 17OHP, DHEAS, cortisol, thyroid hormones, and prolactin levels (Berek and Brerek, 2012). Then, based on the Rotterdam diagnostic criteria, two of the following three disorders are necessary:
In Iran, based on the National Institute of Health (NIH) criteria, the prevalence of PCOS according to Rotterdam criteria is 15.2% (Mehrabian et al., 2011).
PCOS is difficult to diagnose due to the heterogeneous nature and possible changes in patient’s status. At present, the most commonly used criterion for diagnosis is the Rotterdam criterion based on the 2003 agreement. In this method, two out of three disorders (hyperandrogenism, chronic ovulation, and ultrasound pattern of polycystic ovaries) are necessary (Kar, 2013).
It is not a disease-specific to fertility and adolescence but can have different effects on one's life. The main complications of adolescence are prevalence of amenorrhea, oligomenorrhea, hirsutism, obesity, and acne. At the fertility age, the patient's main complaint is infertility and irregular ovulation. Complications of adolescence are still present in this period. At premenopausal and postmenopausal ages, this syndrome can increase the risk of type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, and even endometrial cancer and possibly breast cancer (Norman et al., 2007) and insulin resistance (Javanmanesh et al., 2016, Moran and Teede, 2009).
Insulin resistance refers to conditions in which the biological effect of insulin is diminished at any given concentration. In addition, it reduces the sensitivity of target tissues to insulin hormone, leading to insulin resistance (Yildizhan et al., 2009).
Insulin resistance is also one of the pathophysiological factors in 50-80% of PCOS patients (Teede et al., 2010). Among patients, 80-70% of obese patients (BMI > 30) and 20-25% of lean women (BMI < 25) showed these features (Marshall and Dunaif, 2012).
One of the mechanisms involved in insulin resistance is the presence of genetic and environmental factors such as nutrition and physical activity (Teede et al., 2010). Proper diet and lifestyle modification reduce insulin resistance in PCOS patients (Salehpour, 2011).
In nutrition, micronutrients play an important role in human health, including the prevention and treatment of diseases, as well as the optimization of physical and mental performance (Woodside et al., 2005). The antioxidant effects of several micronutrients, such as zinc, selenium, chromium, and carotenoids (Zeng, 2009) were considered as contributing factors to the development of insulin resistance (González et al., 2006).
There is limited data investigating the diet composition of PCOS women (Douglas et al., 2006). There are inconsistent results from studies mostly conducted in western countries. Some studies have not reported any difference in nutrient intake in women with or without PCOS (Douglas et al., 2006, Wright et al., 2004) .
Previous studies have also shown an inverse association between carotenoid intake and fasting glucose and insulin concentrations due to their antioxidant effects (Sugiura et al., 2006). In some studies, the inverse relationship of insulin resistance to HOMA-IR with vitamins E and D due to inhibition of oxidative stress and inflammation has been reported (Chiu et al., 2004, Gabrielli and Aquino, 2012, Isharwal et al., 2009). There is also a negative association of insulin resistance with zinc, assuming that alpha-zinc glycoprotein may act as an adipokine that interferes with insulin resistance (Hashemipour et al., 2009). However, results regarding zinc levels in patients with PCOS are highly contradictory and some studies have not found zinc administration to be beneficial in these patients (Hashemipour et al., 2009, Kim et al., 2007). Evidence suggests that chromium plays a role in controlling blood sugar and improving insulin activity and enhancing insulin sensitivity, appetite regulation, and weight control (Vincent, 2018). Studies have shown that chromium has been shown to affect insulin function and increase insulin sensitivity in patients with PCOS (Lydic et al., 2006). It has also been suggested that high selenium intake reduces the risk of diseases due to oxidative stress and inflammation. The antioxidant and anti-inflammatory effects of selenium can have a protective effect on insulin resistance and diabetes (Rayman, 2012).
Accordingly, PCOS is a common, heterogeneous, and inherited disorder that affects women throughout their lives (Sirmans and Pate, 2014). The disease affects several systems. Early diagnosis and long-term management can help control this syndrome as well as prevent its long-term consequences, such as insulin resistance (Brady et al., 2009). There have been few studies investigating the association between insulin resistance and dietary intake, and there are many inconsistencies in their results. Eating habits are rooted in the culture of every region in the world (Shishehgar et al., 2016). Therefore, the researchers designed and conducted a study to determine the relationship between insulin resistance and micronutrient intake (chromium, selenium, zinc, carotenoids, vitamins D and E) in women with PCOS in four phenotypes based on Rotterdam criteria.
Materials and Methods
Study design and participants: The present study is a case-control study to investigating dietary intake of micronutrients in four subgroups of PCOS and control group with insulin resistance in Tehran, Iran during 2015-2016. The sample size based on the results of the pilot study and the correlation between insulin resistance index and dietary component showed that the minimum correlation between these indices was 0.50. Therefore, with 95% confidence and 80% test power, the number of samples required was 26.2 based on the following formula for each subgroup (approximately 27 samples). Considering 20% of sample loss, the final volume per phenotype was estimated at 31 samples.
The participants were selected from referrals to gynecology and endocrinology ward of Arash hospital, and selected private clinic if they were eligible to enter the study after filling informed consent form. The inclusion criteria in the case group consisted of Iranian nationality, age of 18-40 years, lack of chronic metabolic and non-metabolic diseases affecting diet (such as diabetes mellitus, hyperthyroidism, hypothyroidism, and hyperlipidemia), not taking medicines that affect appetite and diet, no specific diet, no pregnancy, no hormone use for three months before starting the study. In the event of any problems, including pregnancy and illness requiring specific drug use, they were excluded. The inclusion criteria in the control group were age of 18-40 years and without any diagnostic criteria for PCOS (non-hirsute: without excessive hair growth, with regular ovulation cycles), referring to women's clinic for other reasons. Then the two groups were matched for education, body mass index (BMI), economic status, and physical activity and exercise status.
Initially, the disease was diagnosed after excluding other abnormalities that mimic the PCOS phenotype )ovarian or adrenal neoplasm, Cushing's syndrome, hyperprolactinemia, thyroid disease, and congenital adrenal hyperplasia starting in adulthood (AOAH)) by assessing 17OHP, DHEAS, cortisol, thyroid hormones, and prolactin levels (Berek and Brerek, 2012). Then, based on the Rotterdam diagnostic criteria, two of the following three disorders are necessary:
- Clinical hyperandrogenism (Hirsutism or H). Clinical hyperandrogenism: The Ferriman-Gallwey score of 8 (Ramezani Tehrani et al., 2014), and above or biochemical hyperandrogenism: elevated serum total testosterone levels or free androgen index (FAI)): hyperandrogenic serum total testosterone (TT), greater than 0.68 ng/ml and free androgen index (FAI) more than 5.36% (Hashemi et al., 2014). TT and sex hormone-binding globulin (SHBG) assay methods were measured by electro quantitative luminescence using a Roche German kit by Cobas E411. FAI = TT (nmol/l)/SHBG (nmol / l) * 100 (Goodarzi et al., 2011).
- Ovulation disorder: (Oligo/anovulation or O). The menstrual cycle of more than 35 days (oligomenorrhea) or more than 3 months (amenorrhea) (Schorge et al., 2008).
- Polycystic ovary view in ultrasound (P)
An ovarian volume greater than 10 cubic centimeters in at least one ovary or observation of more than 5 to 8 multiple fine follicles (Schorge et al., 2008).
After entering the study, they were divided into the following four phenotypes:
1) Complete phenotype or A (H + P + O)
2) Ovulatory phenotype or B (H + P)
3) Normoandrogenic phenotype or C (P + O)
4) Phenotype or D (H + O) (Kar, 2013).
Finally, 182 participants were included in the study (31 people in control group, 41 people in group A, 33 people in group B, 40 people in group C, and 37 people in group D).
Measurements: The researcher assessed physical activity by asking research units about whether or not to exercise. The participants' physical activity was measured at three levels based on their responses. Level 1: Normal daily activities without exercise, Level 2: Moderate physical activity: (1 to 2 times a week, each time for at least 20 min). High physical activity: (3 or more 3 times a week, each time for at least 20 min) (Kim et al., 2007).
For all samples, a 168-item FFQ (Food Frequency Questionnaire) was completed. Validity and reliability have been evaluated by Asghari and Mirmiran (Asghari et al., 2012, Mirmiran et al., 2010). This questionnaire was used to obtain a person's usual diet during the past year. This questionnaire includes all food groups breads, rice, pasta, cereals, dairy (milk, yogurt, buttermilk, cheese, whey, and ice cream), meat group (minced and sliced lamb and beef, Fish, and poultry), group of vegetables (leafy and non-leafy vegetables), group of fruits (all kinds of fruits and juices), group of oils, all kinds of sweets, nuts, noodles, canned foods, beans, tea and coffee, soda, and eggs.
In order to analyze the nutritional information of the FFQ questionnaire, Excel software was used to analyze nutrient intakes (including formulas programmed in Excel in which the nutrients of the food frequency questionnaire are broken down into micronutrients). In the program above, for each micronutrient of each nutrient, a function is defined based on the amount of nutrients in one gram of each nutrient. Thus, by entering the consumption amount (gram) of each food item in its respective cell, Excel calculated the number of nutrients in the germ consumed in that nutrient. Finally, the total amount of nutrients consumed by each individual was obtained from the sum of all the nutrients in each food item consumed (Hosseini-Esfahani et al., 2015).
Given the different daily calorie intake of each individual, it is obvious that the ratio of each nutrient to the total daily calorie intake and consequently the contribution of one nutrient to the total calorie intake may also be different. Therefore, in order to make an accurate comparison between the information obtained from each individual with the other participants, after daily calorie intake of each of these macronutrients, they were calibrated for energy adjusting. Finally, the whole analysis was performed on the energy-regulated data.
Anthropometric evaluations (height, weight, and BMI), ovarian sonography, hirsutism as a clinical symptom of hyperandrogenism, hormonal tests were performed to determine serum androgens. Questions were raised about menstruation. Menstrual disorder was evaluated.
The studied micronutrients included zinc, selenium, carotenoids, chromium, vitamin D, and vitamin E.
In this study, insulin resistance was assessed using HOMA-IR index. The original HOMA-IR model was described in 1985 with a formula for approximate estimation by Mathews (Matthews et al., 1985). The formula of the HOMA-IR index was calculated by multiplying the fasting blood glucose concentration (mmol/l) and the fasting insulin concentration (mmol/ml) divided by a fixed number of 22.5. The cut-off point for defining insulin resistance was considered based on the HOMA-IR criterion (cut off > 2.5) (Wallace et al., 2004).
Five milliliters of venous blood (to check fasting blood glucose and insulin levels) were obtained from all research units in the laboratory and in the fasting state. Glucose was measured by glucose oxidase assay and insulin was measured by immunoradiometric method. Beck Man's immunotech kit was used to check the cases with an extra-test accuracy of 3.4% and an intra-test accuracy of 4.3%.
After entering the study, they were divided into the following four phenotypes:
1) Complete phenotype or A (H + P + O)
2) Ovulatory phenotype or B (H + P)
3) Normoandrogenic phenotype or C (P + O)
4) Phenotype or D (H + O) (Kar, 2013).
Finally, 182 participants were included in the study (31 people in control group, 41 people in group A, 33 people in group B, 40 people in group C, and 37 people in group D).
Measurements: The researcher assessed physical activity by asking research units about whether or not to exercise. The participants' physical activity was measured at three levels based on their responses. Level 1: Normal daily activities without exercise, Level 2: Moderate physical activity: (1 to 2 times a week, each time for at least 20 min). High physical activity: (3 or more 3 times a week, each time for at least 20 min) (Kim et al., 2007).
For all samples, a 168-item FFQ (Food Frequency Questionnaire) was completed. Validity and reliability have been evaluated by Asghari and Mirmiran (Asghari et al., 2012, Mirmiran et al., 2010). This questionnaire was used to obtain a person's usual diet during the past year. This questionnaire includes all food groups breads, rice, pasta, cereals, dairy (milk, yogurt, buttermilk, cheese, whey, and ice cream), meat group (minced and sliced lamb and beef, Fish, and poultry), group of vegetables (leafy and non-leafy vegetables), group of fruits (all kinds of fruits and juices), group of oils, all kinds of sweets, nuts, noodles, canned foods, beans, tea and coffee, soda, and eggs.
In order to analyze the nutritional information of the FFQ questionnaire, Excel software was used to analyze nutrient intakes (including formulas programmed in Excel in which the nutrients of the food frequency questionnaire are broken down into micronutrients). In the program above, for each micronutrient of each nutrient, a function is defined based on the amount of nutrients in one gram of each nutrient. Thus, by entering the consumption amount (gram) of each food item in its respective cell, Excel calculated the number of nutrients in the germ consumed in that nutrient. Finally, the total amount of nutrients consumed by each individual was obtained from the sum of all the nutrients in each food item consumed (Hosseini-Esfahani et al., 2015).
Given the different daily calorie intake of each individual, it is obvious that the ratio of each nutrient to the total daily calorie intake and consequently the contribution of one nutrient to the total calorie intake may also be different. Therefore, in order to make an accurate comparison between the information obtained from each individual with the other participants, after daily calorie intake of each of these macronutrients, they were calibrated for energy adjusting. Finally, the whole analysis was performed on the energy-regulated data.
Anthropometric evaluations (height, weight, and BMI), ovarian sonography, hirsutism as a clinical symptom of hyperandrogenism, hormonal tests were performed to determine serum androgens. Questions were raised about menstruation. Menstrual disorder was evaluated.
The studied micronutrients included zinc, selenium, carotenoids, chromium, vitamin D, and vitamin E.
In this study, insulin resistance was assessed using HOMA-IR index. The original HOMA-IR model was described in 1985 with a formula for approximate estimation by Mathews (Matthews et al., 1985). The formula of the HOMA-IR index was calculated by multiplying the fasting blood glucose concentration (mmol/l) and the fasting insulin concentration (mmol/ml) divided by a fixed number of 22.5. The cut-off point for defining insulin resistance was considered based on the HOMA-IR criterion (cut off > 2.5) (Wallace et al., 2004).
Five milliliters of venous blood (to check fasting blood glucose and insulin levels) were obtained from all research units in the laboratory and in the fasting state. Glucose was measured by glucose oxidase assay and insulin was measured by immunoradiometric method. Beck Man's immunotech kit was used to check the cases with an extra-test accuracy of 3.4% and an intra-test accuracy of 4.3%.
Ethical considerations: In this study, it has been tried to include all ethical considerations. The ethics code by the Ethics Committee is D52/5503.
Data analysis: SPSS software was used for data analysis and statistical tests. First, Kolmogorov-Smirnov test was used for data normality. Spearman correlation test (in case of non-normal data) was used to investigate the relationship between quantitative variables. Chi-square test was also used to investigate some underlying variables. Significance level was considered P-value ≤ 0.05.
Results
The results of Kruskal Wallis and Chi-square tests showed that there were no significant differences between the four subgroups of PCOS women and the control group in terms of age (P = 0.09), BMI (P = 0.99), education level (P = 0.30), economic status (P = 0.27), and physical activity status (P = 0.87). The two groups were homogeneous (Table 1).
Insulin resistance status was compared with the HOMA-IR index (Cut off > 2.5) in PCOS and control groups with the Chi-square test. There was a significant difference in the insulin resistance. The number of women with PCOS who also had insulin resistance was higher in phenotype A compared to other groups (61%).
In phenotype B, (51.5%), in phenotype D, (48.6%) and in phenotype C, (37.5%) had PCOS and HOMA-IR at the same time. In the control group, although they had no symptoms of PCOS, two participants (6.5%) had the syndrome (Table 2).
Spearman test results showed that insulin resistance in different PCOS subgroups and control group correlated with the frequency of oral consumption of micronutrients. In subgroup A, there was a significant negative relationship between the insulin resistance and selenium micronutrient intake (P = 0.01). In groups B and C, no significant relationship was found between the insulin resistance and any of the micronutrients. In subgroup D, a significant negative correlation was found between insulin resistance and micronutrient zinc (P = 0.02), vitamin D (P = 0.05), and vitamin E (P = 0.001). In the control group, there was a significant negative relationship between insulin resistance and vitamin D (P = 0.02) and vitamin E (P = 0.001, Table 3)
Results
The results of Kruskal Wallis and Chi-square tests showed that there were no significant differences between the four subgroups of PCOS women and the control group in terms of age (P = 0.09), BMI (P = 0.99), education level (P = 0.30), economic status (P = 0.27), and physical activity status (P = 0.87). The two groups were homogeneous (Table 1).
Insulin resistance status was compared with the HOMA-IR index (Cut off > 2.5) in PCOS and control groups with the Chi-square test. There was a significant difference in the insulin resistance. The number of women with PCOS who also had insulin resistance was higher in phenotype A compared to other groups (61%).
In phenotype B, (51.5%), in phenotype D, (48.6%) and in phenotype C, (37.5%) had PCOS and HOMA-IR at the same time. In the control group, although they had no symptoms of PCOS, two participants (6.5%) had the syndrome (Table 2).
Spearman test results showed that insulin resistance in different PCOS subgroups and control group correlated with the frequency of oral consumption of micronutrients. In subgroup A, there was a significant negative relationship between the insulin resistance and selenium micronutrient intake (P = 0.01). In groups B and C, no significant relationship was found between the insulin resistance and any of the micronutrients. In subgroup D, a significant negative correlation was found between insulin resistance and micronutrient zinc (P = 0.02), vitamin D (P = 0.05), and vitamin E (P = 0.001). In the control group, there was a significant negative relationship between insulin resistance and vitamin D (P = 0.02) and vitamin E (P = 0.001, Table 3)
| Table 1. Comparison of demographic variable between groups. | ||||||||||||
| Variables | Phenotype A N=41 |
Phenotype B N=33 |
Phenotype C N=40 |
Phenotype D N=37 |
Control group N=31 |
P-value | ||||||
| Quantitative variables | ||||||||||||
| Age (y) | 28.07 ± 4.70a | 27.00 ± 5.44 | 29.70 ± 6.44 | 29.83 ± 5.93 | 28.07 ± 4.70 | 0.09b | ||||||
| BMI (kg/m2) | 25.48 ± 5.23 | 25.06 ± 4.28 | 25.08 ± 3.93 | 24.98 ± 4.80 | 25.48 ± 5.23 | 0.99b | ||||||
| Qualitative variables | ||||||||||||
| Educational status | N (%) | N (%) | N (%) | N (%) | N (%) | |||||||
| Under Diploma | 4 (9.8) | 3 (9.1) | 4 (10.0) | 2 (5.4) | 2 (6.5) | 0.30c |
||||||
| Diploma | 9 (22.0) | 5 (15.2) | 10 (25.0) | 15 (43.2) | 14 (45.2) | |||||||
| Bachelor | 19 (46.3) | 16 (48.5) | 20 (50.0) | 16 (40.5) | 10 (32.3) | |||||||
| Master’s degree and higher | 9 (22.0) | 9 (27.3) | 6 (15.0) | 4 (10.8) | 5 (16.1) | |||||||
| Economic situation | ||||||||||||
| Poor | 16 (39.0) | 23 (69.7) | 23 (57.5) | 21 (56.8) | 17 (54.8) | 0.27c |
||||||
| Medium | 16 (39.0) | 5 (15.2) | 11 (27.5) | 7 (18.9) | 7 (22.6) | |||||||
| Good | 9 (22.0) | 5 (15.2) | 6 (15.0) | 9 (24.3) | 7 (22.6) | |||||||
| Physical activity status | ||||||||||||
| Level 1 | 23 (56.1) | 20 (60.6) | 25 (62.5) | 25 (67.6) | 20 (67.6) | 0.87c |
||||||
| Level 2 | 6 (14.6) | 6 (18.2) | 7 (17.5) | 5 (13.5) | 5 (13.5) | |||||||
| Level 3 | 12 (29.3) | 7 (21.2) | 8 (20.0) | 7 (18.9) | 6 (18.9) | |||||||
| a: Mean ± SD, b: Kruskal Wallis test, c: Chi-square test, BMI: Body mass index, Level 1: Normal daily activities without exercise, Level 2: Moderate physical activity (1 to 2 times a week, each time for at least 20 minutes), Level 3: High physical activity (3 or more 3 times a week, Each time for at least 20 minutes). | ||||||||||||
| Table 2. Comparison of insulin resistance status in PCOS subgroups and control group. | ||||||||||||
| Insulin resistance | Phenotype A | Phenotype B | Phenotype C | Phenotype D | Control Group | |||||||
| No | 16 (39.5)a | 16 (48.5) | 25 (62.5) | 19 (51.4) | 29 (93.5) | |||||||
| Yes | 25 (61.0) | 17 (51.5) | 15 (37.5) | 18 (48.6) | 2 (6.5) | |||||||
| Total | 41 (100) | 33 (100) | 40 (100) | 37 (100) | 31 (100) | |||||||
| a: N (%), Chi-square; P <0.001 | ||||||||||||
| Table 3. Correlation between dietary components and HOMA-IR index in four subgroups of PCOS and control group. | |||||||
| Variables | Selenium | Zinc | Carotenoids | Chromium | Vitamin D | Vitamin E | |
| Phenotype A | R | -0.37 | -0.02 | -0.13 | -0.07 | 0.25 | -0.01 |
| P-value | 0.01 | 0.86 | 0.38 | 0.63 | 0.10 | 0.90 | |
| Phenotype B | R | 0.06 | -0.06 | -0.13 | 0.15 | -0.01 | 0.03 |
| P-value | 0.70 | 0.70 | 0.38 | 0.40 | 0.95 | 0.86 | |
| Phenotype C | R | -0.11 | -0.12 | -0.13 | 0.09 | -0.12 | 0.08 |
| P-value | 0.49 | 0.46 | 0.38 | 0.56 | 0.45 | 0.61 | |
| Phenotype D | R | -0.31 | -0.37 | -0.32 | 0.13 | -0.32 | -0.51 |
| P-value | 0.06 | 0.02 | 0.05 | 0.41 | 0.04 | 0.001 | |
| Control group | R | 0.12 | 0.27 | -0.13 | 0.12 | -0.40 | -0.57 |
| P-value | 0.48 | 0.14 | 0.38 | 0.45 | 0.02 | 0.001 | |
Discussion
Many studies have investigated and compared insulin resistance with nutritional factors, but so far no study has investigated the association between insulin resistance and micronutrient intake in four phenotypes of women with PCOS. Also, due to different dietary patterns in different countries, this study investigates the relationship between insulin resistance and micronutrient intake in Iran. In the present study, micronutrients were evaluated in two broad categories, including minerals and vitamins with the insulin resistance. The results showed that insulin resistance in different PCOS subgroups and the control groups was correlated with the frequency of oral micronutrient intake.
In subgroup A, there was a significant negative relationship between the insulin resistance and selenium intake. There was no significant relationship between insulin resistance and any of the micronutrients in groups B and C. In subgroup D, there was a significant negative relationship between insulin resistance and zinc, vitamin D, and vitamin E. In the control group there was a significant negative correlation between insulin resistance with vitamin D and vitamin E intake.
Zinc is an essential micronutrient that enhances the ability of insulin to bind to its receptors (Marreiro et al., 2004). Zinc deficiency reduces the response of tissues to insulin, possibly due to its similarity to insulin function (Miranda and Dey, 2004). Possible mechanisms of the effect of zinc deficiency on insulin resistance include impaired insulin secretion from the pancreas, impaired insulin binding to its receptors, impaired insulin receptor synthesis, impaired glucose carrier structure, and impaired glucose entry into the cell (Taghdir et al., 2009). There have been several studies on the relationship between insulin resistance and zinc. The study by Guler et al. is in line with the present study, this prospective study was performed on 53 women with PCOS and 33 healthy women without PCOS. Serum zinc levels in patients with PCOS were compared with insulin resistance. The results showed that serum zinc levels in women with PCOS with insulin resistance were significantly lower than women with PCOS and without insulin resistance (Guler et al., 2014). Also, a clinical trial study by Foroozanfard et al. on 52 patients with PCOS reported that administration of 220 mg/day of zinc sulfate supplementation after 12 weeks reduced insulin resistance (Foroozanfard et al., 2015).
The clinical trial study of Jamilian et al. contradicts the results of the present study. The results of this study showed that the administration of 8 weeks of zinc supplementation at 220 mg/day had no effect on insulin resistance. The reason for contradiction with the present study may be due to the small sample size and differences in method (Jamilian et al., 2016).
It has been suggested that high selenium intake reduces the risk of oxidative stress and inflammatory diseases. The antioxidant and anti-inflammatory effects of selenium can have a protective effect on insulin resistance and diabetes (Rayman, 2012). But there have been controversial studies on the association between insulin resistance and selenium intake. Consistent with the present study is the study of Wang et al (Wang et al., 2017). In a study by Wang, the results showed that insulin resistance increased when dietary intake of selenium was lower than 1.6 μg/day. In the present study, selenium intake was lower in
all PCOS phenotypes, and this micronutrient deficiency was associated with insulin resistance.
The results of the clinical trial study of Hosseinzadeh (Hosseinzadeh et al., 2016) were inconsistent with the results of the present study. Hosseinzadeh conducted a study on 53 patients with PCOS. After 12 weeks of intervention, in 26 patients (200 μg/day of selenium supplement) and 27 patients placebo group, despite the theoretical effects of selenium, the results showed that selenium supplementation in PCOS patients worsened insulin resistance status. Jamilian et al. aimed to determine the effect of selenium supplementation on the status of 70 patients with PCOS. Results showed that administration of 200 μg of selenium daily for 8 weeks did not have beneficial effects on insulin resistance. Perhaps the reason for the differences in the results of this study with the present study is the small sample size (Jamilian et al., 2015).
Chromium is one of the essential micronutrients in the body. Evidence suggests that it plays an important role in the natural metabolism of carbohydrates. In the 1950s, scientists found that chromium is essential for maintaining normal glucose tolerance and blood sugar control in rats. Chromium plays a role in controlling blood sugar and improving insulin activity and increasing insulin sensitivity, appetite regulation, and weight control (Vincent, 2018). Most studies have shown that chromium affects insulin function and increased insulin sensitivity in patients with PCOS (Lydic et al., 2006). In a study by Lydic et al., the administration of 1000 μg of chromium picolinate in women with PCOS for 2 months improved glucose levels and insulin sensitivity (Lydic et al., 2006). In a clinical trial of Amooee, which included 92 women with PCOS, receiving 200 micrograms of chromium picolinate reduced insulin sensitivity to the control group. These two studies are inconsistent with the present study. This may be due to differences in the type and method of study (Amooee et al., 2013).
Other micronutrients studied are carotenoids. Carotenoids are a group of pigments that play an important role in the absorption of light in plants. Carotenoids are not made in the vertebrate body and must be made available through the diet of these animals. Carotenoids perform various physiological functions in the body, including light absorption, antioxidant properties, and the strengthening of the immune system against various diseases (Dorfman, 2012). Consistent with the present study is a descriptive-analytical study by Gol Afroozi et al.. In this study, carotenoids were measured in the subjects with intake and there was no statistically significant difference between carotenoid intake and insulin resistance (Gol Afroozi and Koushak, 2006). The study by Ylonen was not in line with the results of the present study. The study by Ylonen on 81 individuals at risk for type II diabetes, reported that dietary carotenoids were inversely correlated with fasting blood glucose and insulin resistance. Thus, free radicals appear to impair insulin action by altering the physical status of the target cell membrane. Carotenoids, by neutralizing free radicals, improve the secretion and function of insulin in regulating blood sugar (Ylönen et al., 2003). Perhaps the reason for the difference between the results of this study and the present study is the difference in the type of research units.
Vitamin D, called calciferol, is one of the essential vitamins and fat-soluble vitamins that help bone growth and health by controlling calcium and phosphorus balance. It helps in bone metabolism by increasing phosphorus and calcium uptake by the intestines and by reducing the excretion of the kidneys, as well as by helping to translate nucleus genes into cell growth (Chung et al., 2009). A review by Thomson et al. suggests that there is a relationship between vitamin D status and hormonal and metabolic disorders in PCOS (Thomson et al., 2012). The mechanism of this effect is unknown, but a possible reason is the disruption of the mechanisms regulating ovarian apoptosis. Also due to its immune-modulating role, vitamin D deficiency may induce inflammatory responses and consequently insulin resistance (Bikle, 2009). Studies by Yildizhan, Hahn, and Krul-Poel reported lower levels of vitamin D in women with PCOS (Hahn et al., 2006, Krul-Poel et al., 2018, Yildizhan et al., 2009).
The results of the study by Ardabili were not consistent with the results of the present study. This clinical trial study was performed on 50 patients with PCOS. The results showed that vitamin D supplementation containing 50,000 units every 20 days for two months did not affect HOMA-IR. Perhaps the reason for this difference in the results with the present study is the small sample size and short interval of intervention (Ardabili et al., 2012)
Vitamin E is one of the fat-soluble vitamins. Vitamin E was discovered in 1920 and was isolated from the wheat germ in 1936 and is called
alpha-tocopherol. It is contained in the fat layer of the cell wall and inside the cell and prevents cell wall damage (Dorfman, 2012). Limited studies have been conducted on the effect of vitamin E on PCOS. The favorable effects of vitamin E on insulin resistance have been observed due to the inhibition of oxidative stress and inflammation. The effects
of plasma alpha-tocopherol-induced partial improvement on insulin resistance have been observed in studies of Manning and Caballero (Caballero, 1993, Manning et al., 2004). In Manning's study, 800 IU of vitamin E was used and there was a significant decrease in serum insulin and insulin resistance compared to the control group. Vitamin E appears to decrease insulin action, decrease insulin and fasting serum glucose by decreasing cellular oxidative stress, altering membrane properties, and decreasing inflammatory activity. Vitamin E administration can improve insulin action by improving the Physico-chemical status of the plasma membrane due to reduced oxidative stress (Manning et al., 2004).
Given the association of insulin resistance with micronutrient deficiencies of zinc, selenium, vitamin D, and vitamin E levels in the diet of people with PCOS, it is recommended that clinical trials with a larger sample size be designed and performed to evaluate the administration of micronutrient supplements to these patients.
The limitations of this study include the lack of cooperation of many physicians in requesting appropriate tests and also some research units did not perform the requested tests.
Acknowledgement
In this regard, thanks are owed to the Vice-Chancellor for Research in Tarbiat Modarres University of Medical Science, Tehran, Iran, as well as the personnel of the women's ward of Arash Hospital of Tehran for their cooperation in the study.
Authors' contributions
Kamali Z: Article writing and idea generation. Ziaei S: performed research plan, and supervised the study. Kazemnezhad A: analyzed the data. Movahedinejad M: designed the research and had primary responsibility for final content.
Conflict of interest
The authors declare that there is no conflict of interest in this study.
References
Amooee S, Parsanezhad ME, Shirazi MR, Alborzi S & Samsami A 2013. Metformin versus chromium picolinate in clomiphene citrate-resistant patients with PCOs: A double-blind randomized clinical trial. Iranian journal of reproductive medicine. 11 (8): 611.
Ardabili HR, Gargari BP & Farzadi L 2012. Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency. Nutrition research. 32 (3): 195-201.
Asghari G, et al. 2012. Reliability, comparative validity and stability of dietary patterns derived from an FFQ in the Tehran Lipid and Glucose Study. British journal of nutrition. 108 (6): 1109-1117.
Berek J & Brerek N 2012. Novak's gynecology, Chapter 35, endocrine disorders.
Bikle D 2009. Nonclassic actions of vitamin D. Journal of clinical endocrinology & metabolism. 94 (1): 26-34.
Brady C, Mousa S & Mousa S 2009. Polycystic ovary syndrome and its impact on women’s quality of life: More than just an endocrine disorder. Drug, healthcare and patient safety. 1: 9-15.
Caballero B 1993. Vitamin E improves the action of insulin. Nutrition reviews. 51 (11): 339-340.
Chiu K, Chu A, Go V & Saad M 2004. Hypovitaminosis D is associated with insulin resistance and β cell dysfunction. American journal of clinical nutrition. 79 (5): 820-825.
Chung M, et al. 2009. Vitamin D and calcium: a systematic review of health outcomes. Evidence report/technology assessment. 1 (183): 1-42.
Dorfman L 2012. Nutrition for Exercise and Sports Performance. In Krause's Food & The Nutrition Care Process (ed. L. Kathleen Mahan).
Douglas CC, et al. 2006. Difference in dietary intake between women with polycystic ovary syndrome and healthy controls. Fertility and sterility. 86 (2): 411-417.
Foroozanfard F, et al. 2015. Effects of zinc supplementation on markers of insulin resistance and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Experimental and clinical endocrinology & diabetes. 123 (4): 215-220.
Gabrielli L & Aquino E 2012. Polycystic ovary syndrome in Salvador, Brazil: a prevalence study in primary healthcare. Reproductive biology and endocrinology. 10 (1): 1-10.
Gol Afroozi M & Koushak A 2006. The Relationship between Carotenoids Received with Blood Glucose and Lipid Indicators in Type II Diabetes Mellitus. Journal of Ardabil University of medical sciences. 3 (6): 287-290.
González F, Rote NS, Minium J & Kirwan JP 2006. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. Journal of clinical endocrinology & metabolism. 91 (1): 336-340.
Goodarzi M, Dumesic D, Chazenbalk G & Aziz R 2011. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nature reviews endocrinology. 7 (4): 219-231.
Guler I, et al. 2014. Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance. Biological trace element research. 158 (3): 297-304.
Hahn S, et al. 2006. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Experimental and clinical endocrinology & diabetes. 114 (10): 577-583.
Hashemi S, Tehrani F, Noroozzadeh M & Azizi F 2014. Normal cut-off values for hyperandrogenaemia in Iranian women of reproductive age. European journal of obstetrics & gynecology and reproductive biology. 172: 51-55.
Hashemipour M, et al. 2009. Effect of zinc supplementation on insulin resistance and components of the metabolic syndrome in prepubertal obese children. Hormones (Athens). 8 (4): 279-285.
Hosseini-Esfahani F, et al. 2015. Interaction of APOC3 polymorphism and dietary fats on the risk of metabolic syndrome. Iranian journal of endocrinology and metabolism. 16 (5): 345-355.
Hosseinzadeh FM, Hosseinzadeh-Attar MJ, Yekaninejad MS & Rashidi B 2016. Effects of selenium supplementation on glucose homeostasis and free androgen index in women with polycystic ovary syndrome: a randomized, double blinded, placebo controlled clinical trial. Journal of trace elements in medicine and biology. 34: 56-61.
Isharwal S, Misra A, Wasir J & Nigam P 2009. Diet & insulin resistance: a review & Asian Indian perspective. Indian journal of medical research. 129 (5): 485-499.
Jamilian M, et al. 2016. Effects of zinc supplementation on endocrine outcomes in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biological trace element research. 170 (2): 271-278.
Jamilian M, et al. 2015. Metabolic response to selenium supplementation in women with polycystic ovary syndrome: a randomized, double‐blind, placebo‐controlled trial. Clinical endocrinology. 82 (6): 885-891.
Javanmanesh F, Kashanian M, Rahimi M & Sheikhansari N 2016. Comparison between the effects of metformin and N-acetyl cysteine (NAC) on some metabolic and endocrine characteristics of women with polycystic ovary syndrome. Gynecological endocrinology. 32 (4): 285-289.
Kar S 2013. Anthropometric, clinical, and metabolic comparisons of the four Rotterdam PCOS phenotypes: A prospective study of PCOS women. Journal of human reproductive sciences. 6 (3): 194-200.
Kim HM, Park J, Ryu SY & Kim J 2007. The effect of menopause on the metabolic syndrome among Korean women: the Korean National Health and Nutrition Examination Survey, 2001. Diabetes care. 30 (3): 701-706.
Krul-Poel Y, et al. 2018. Vitamin D and metabolic disturbances in polycystic ovary syndrome (PCOS): A cross-sectional study. PloS one. 13 (12): e0204748.
Lydic ML, et al. 2006. Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertility and sterility. 86 (1): 243-246.
Manning P, Sutherland W, Walker R & Williams S 2004. Effect of high- dose vitamin E on insulin resistance and associated parameters in overweight subjects. Diabetes care. 27 (9): 2166-2171.
March W, et al. 2010. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Human reproduction. 25 (2): 544-551.
Marreiro DN, et al. 2004. Participation of zinc in insulin resistance. Arquivos Brasileiros de endocrinologia & metabologia. 48 (2): 234-239.
Marshall JC & Dunaif A 2012. Should all women with PCOS be treated for insulin resistance? Fertility and sterility. 97 (1):
18-22.
Matthews D, et al. 1985. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28 (7): 412-419.
Mehrabian F, Khani B, Kelishadi R & Kermani N 2011. The prevalence of metabolic syndrome and insulin resistance according to the phenotypic subgroups of polycystic ovary syndrome in a representative sample of Iranian females. Jjournal of Isfahan University of medical sciences. 16 (6): 763-769.
Miranda E & Dey C 2004. Effect of chromium and zinc on insulin signaling in skeletal muscle cells. Biological trace element research. 101 (1): 19-36.
Mirmiran P, Esfahani FH, Mehrabi Y, Hedayati M & Azizi F 2010. Reliability and relative validity of an FFQ for nutrients in the Tehran lipid and glucose study. Public health nutrition. 13 (5): 654-662.
Moran L & Teede H 2009. Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Human reproduction update. 15 (4): 477-488.
Norman R, Dewailly D, Legro R, Hickey T & 370:685–697. L 2007. Polycystic ovary syndrome. Lancet. 9588 (9588): 685-697.
Ramezani Tehrani F, Rashidi H, Bahri Khomami M, Tohidi M & Azizi F 2014. The prevalence of metabolic disorders in various phenotypes of polycystic ovary syndrome: a community based study in Southwest of Iran. Reproductive biology and endocrinology. 12 (89): 1-6.
Rayman M 2012. Selenium and human health. Lancet. 379 (9822): 1256-1268.
Salehpour S 2011. Evaluation of homocysteine levels in patients with polycystic ovarian syndrome. International journal of fertility & sterility. 4 (4): 168.
Schorge J, et al. 2008. Williams gynecology. McGraw-Hill Medical: New York.
Shishehgar F, et al. 2016. Comparison of dietary intake between polycystic ovary syndrome women and controls. Global journal of health science. 8 (9): 302.
Sirmans SM & Pate KA 2014. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical epidemiology. 6: 1-13.
Sugiura M, et al. 2006. The homeostasis model assessment-insulin resistance index is inversely associated with serum carotenoids in non-diabetic subjects. Journal of epidemiology. 16 (2): 71-78.
Taghdir M, et al. 2009. XML Relationship Between Serum Zinc and Insulin Concentration, Insulin Resistance and Oxidative Stress in Postmenopausal Diabetic Women. Iranian journal of endocrinology and metabolism. 11 (5): 485-596.
Teede H, Deeks A & Moran L 2010. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC medicine. 8 (1): 1-10.
Thomson RL, Spedding S & Buckley JD 2012. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clinical endocrinology. 77 (3): 343-350.
Vincent J 2018. The nutritional biochemistry of chromium (III). Elsevier.
Wallace T, Levy J & Matthews D 2004. Use and abuse of HOMA modeling. Diabetes care. 27 (6): 1487-1495.
Wang Y, et al. 2017. High dietary selenium intake is associated with less insulin resistance in the Newfoundland population. PloS one. 12 (4): e0174149.
Woodside J, McCall D, McGartland C & Young I 2005. Micronutrients: dietary intake v. supplement use. Proceedings of the nutrition society. 64 (4): 543-553.
Wright C, Zborowski J, Talbott E, McHugh-Pemu K & Youk A 2004. Dietary intake, physical activity, and obesity in women with polycystic ovary syndrome. International journal of obesity. 28 (8): 1026-1032.
Yildizhan R, et al. 2009. Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Archives of gynecology and obstetrics. 280 (4): 559-563.
Ylönen K, et al. 2003. Dietary intakes and plasma concentrations of carotenoids and tocopherols in relation to glucose metabolism in subjects at high risk of type 2 diabetes: the Botnia Dietary Study. American journal of clinical nutrition. 77 (6): 1434-1441.
Zeng H 2009. Selenium as an essential micronutrient: roles in cell cycle and apoptosis. Molecules. 14 (3): 1263-1278.
Many studies have investigated and compared insulin resistance with nutritional factors, but so far no study has investigated the association between insulin resistance and micronutrient intake in four phenotypes of women with PCOS. Also, due to different dietary patterns in different countries, this study investigates the relationship between insulin resistance and micronutrient intake in Iran. In the present study, micronutrients were evaluated in two broad categories, including minerals and vitamins with the insulin resistance. The results showed that insulin resistance in different PCOS subgroups and the control groups was correlated with the frequency of oral micronutrient intake.
In subgroup A, there was a significant negative relationship between the insulin resistance and selenium intake. There was no significant relationship between insulin resistance and any of the micronutrients in groups B and C. In subgroup D, there was a significant negative relationship between insulin resistance and zinc, vitamin D, and vitamin E. In the control group there was a significant negative correlation between insulin resistance with vitamin D and vitamin E intake.
Zinc is an essential micronutrient that enhances the ability of insulin to bind to its receptors (Marreiro et al., 2004). Zinc deficiency reduces the response of tissues to insulin, possibly due to its similarity to insulin function (Miranda and Dey, 2004). Possible mechanisms of the effect of zinc deficiency on insulin resistance include impaired insulin secretion from the pancreas, impaired insulin binding to its receptors, impaired insulin receptor synthesis, impaired glucose carrier structure, and impaired glucose entry into the cell (Taghdir et al., 2009). There have been several studies on the relationship between insulin resistance and zinc. The study by Guler et al. is in line with the present study, this prospective study was performed on 53 women with PCOS and 33 healthy women without PCOS. Serum zinc levels in patients with PCOS were compared with insulin resistance. The results showed that serum zinc levels in women with PCOS with insulin resistance were significantly lower than women with PCOS and without insulin resistance (Guler et al., 2014). Also, a clinical trial study by Foroozanfard et al. on 52 patients with PCOS reported that administration of 220 mg/day of zinc sulfate supplementation after 12 weeks reduced insulin resistance (Foroozanfard et al., 2015).
The clinical trial study of Jamilian et al. contradicts the results of the present study. The results of this study showed that the administration of 8 weeks of zinc supplementation at 220 mg/day had no effect on insulin resistance. The reason for contradiction with the present study may be due to the small sample size and differences in method (Jamilian et al., 2016).
It has been suggested that high selenium intake reduces the risk of oxidative stress and inflammatory diseases. The antioxidant and anti-inflammatory effects of selenium can have a protective effect on insulin resistance and diabetes (Rayman, 2012). But there have been controversial studies on the association between insulin resistance and selenium intake. Consistent with the present study is the study of Wang et al (Wang et al., 2017). In a study by Wang, the results showed that insulin resistance increased when dietary intake of selenium was lower than 1.6 μg/day. In the present study, selenium intake was lower in
all PCOS phenotypes, and this micronutrient deficiency was associated with insulin resistance.
The results of the clinical trial study of Hosseinzadeh (Hosseinzadeh et al., 2016) were inconsistent with the results of the present study. Hosseinzadeh conducted a study on 53 patients with PCOS. After 12 weeks of intervention, in 26 patients (200 μg/day of selenium supplement) and 27 patients placebo group, despite the theoretical effects of selenium, the results showed that selenium supplementation in PCOS patients worsened insulin resistance status. Jamilian et al. aimed to determine the effect of selenium supplementation on the status of 70 patients with PCOS. Results showed that administration of 200 μg of selenium daily for 8 weeks did not have beneficial effects on insulin resistance. Perhaps the reason for the differences in the results of this study with the present study is the small sample size (Jamilian et al., 2015).
Chromium is one of the essential micronutrients in the body. Evidence suggests that it plays an important role in the natural metabolism of carbohydrates. In the 1950s, scientists found that chromium is essential for maintaining normal glucose tolerance and blood sugar control in rats. Chromium plays a role in controlling blood sugar and improving insulin activity and increasing insulin sensitivity, appetite regulation, and weight control (Vincent, 2018). Most studies have shown that chromium affects insulin function and increased insulin sensitivity in patients with PCOS (Lydic et al., 2006). In a study by Lydic et al., the administration of 1000 μg of chromium picolinate in women with PCOS for 2 months improved glucose levels and insulin sensitivity (Lydic et al., 2006). In a clinical trial of Amooee, which included 92 women with PCOS, receiving 200 micrograms of chromium picolinate reduced insulin sensitivity to the control group. These two studies are inconsistent with the present study. This may be due to differences in the type and method of study (Amooee et al., 2013).
Other micronutrients studied are carotenoids. Carotenoids are a group of pigments that play an important role in the absorption of light in plants. Carotenoids are not made in the vertebrate body and must be made available through the diet of these animals. Carotenoids perform various physiological functions in the body, including light absorption, antioxidant properties, and the strengthening of the immune system against various diseases (Dorfman, 2012). Consistent with the present study is a descriptive-analytical study by Gol Afroozi et al.. In this study, carotenoids were measured in the subjects with intake and there was no statistically significant difference between carotenoid intake and insulin resistance (Gol Afroozi and Koushak, 2006). The study by Ylonen was not in line with the results of the present study. The study by Ylonen on 81 individuals at risk for type II diabetes, reported that dietary carotenoids were inversely correlated with fasting blood glucose and insulin resistance. Thus, free radicals appear to impair insulin action by altering the physical status of the target cell membrane. Carotenoids, by neutralizing free radicals, improve the secretion and function of insulin in regulating blood sugar (Ylönen et al., 2003). Perhaps the reason for the difference between the results of this study and the present study is the difference in the type of research units.
Vitamin D, called calciferol, is one of the essential vitamins and fat-soluble vitamins that help bone growth and health by controlling calcium and phosphorus balance. It helps in bone metabolism by increasing phosphorus and calcium uptake by the intestines and by reducing the excretion of the kidneys, as well as by helping to translate nucleus genes into cell growth (Chung et al., 2009). A review by Thomson et al. suggests that there is a relationship between vitamin D status and hormonal and metabolic disorders in PCOS (Thomson et al., 2012). The mechanism of this effect is unknown, but a possible reason is the disruption of the mechanisms regulating ovarian apoptosis. Also due to its immune-modulating role, vitamin D deficiency may induce inflammatory responses and consequently insulin resistance (Bikle, 2009). Studies by Yildizhan, Hahn, and Krul-Poel reported lower levels of vitamin D in women with PCOS (Hahn et al., 2006, Krul-Poel et al., 2018, Yildizhan et al., 2009).
The results of the study by Ardabili were not consistent with the results of the present study. This clinical trial study was performed on 50 patients with PCOS. The results showed that vitamin D supplementation containing 50,000 units every 20 days for two months did not affect HOMA-IR. Perhaps the reason for this difference in the results with the present study is the small sample size and short interval of intervention (Ardabili et al., 2012)
Vitamin E is one of the fat-soluble vitamins. Vitamin E was discovered in 1920 and was isolated from the wheat germ in 1936 and is called
alpha-tocopherol. It is contained in the fat layer of the cell wall and inside the cell and prevents cell wall damage (Dorfman, 2012). Limited studies have been conducted on the effect of vitamin E on PCOS. The favorable effects of vitamin E on insulin resistance have been observed due to the inhibition of oxidative stress and inflammation. The effects
of plasma alpha-tocopherol-induced partial improvement on insulin resistance have been observed in studies of Manning and Caballero (Caballero, 1993, Manning et al., 2004). In Manning's study, 800 IU of vitamin E was used and there was a significant decrease in serum insulin and insulin resistance compared to the control group. Vitamin E appears to decrease insulin action, decrease insulin and fasting serum glucose by decreasing cellular oxidative stress, altering membrane properties, and decreasing inflammatory activity. Vitamin E administration can improve insulin action by improving the Physico-chemical status of the plasma membrane due to reduced oxidative stress (Manning et al., 2004).
Given the association of insulin resistance with micronutrient deficiencies of zinc, selenium, vitamin D, and vitamin E levels in the diet of people with PCOS, it is recommended that clinical trials with a larger sample size be designed and performed to evaluate the administration of micronutrient supplements to these patients.
The limitations of this study include the lack of cooperation of many physicians in requesting appropriate tests and also some research units did not perform the requested tests.
Acknowledgement
In this regard, thanks are owed to the Vice-Chancellor for Research in Tarbiat Modarres University of Medical Science, Tehran, Iran, as well as the personnel of the women's ward of Arash Hospital of Tehran for their cooperation in the study.
Authors' contributions
Kamali Z: Article writing and idea generation. Ziaei S: performed research plan, and supervised the study. Kazemnezhad A: analyzed the data. Movahedinejad M: designed the research and had primary responsibility for final content.
Conflict of interest
The authors declare that there is no conflict of interest in this study.
References
Amooee S, Parsanezhad ME, Shirazi MR, Alborzi S & Samsami A 2013. Metformin versus chromium picolinate in clomiphene citrate-resistant patients with PCOs: A double-blind randomized clinical trial. Iranian journal of reproductive medicine. 11 (8): 611.
Ardabili HR, Gargari BP & Farzadi L 2012. Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency. Nutrition research. 32 (3): 195-201.
Asghari G, et al. 2012. Reliability, comparative validity and stability of dietary patterns derived from an FFQ in the Tehran Lipid and Glucose Study. British journal of nutrition. 108 (6): 1109-1117.
Berek J & Brerek N 2012. Novak's gynecology, Chapter 35, endocrine disorders.
Bikle D 2009. Nonclassic actions of vitamin D. Journal of clinical endocrinology & metabolism. 94 (1): 26-34.
Brady C, Mousa S & Mousa S 2009. Polycystic ovary syndrome and its impact on women’s quality of life: More than just an endocrine disorder. Drug, healthcare and patient safety. 1: 9-15.
Caballero B 1993. Vitamin E improves the action of insulin. Nutrition reviews. 51 (11): 339-340.
Chiu K, Chu A, Go V & Saad M 2004. Hypovitaminosis D is associated with insulin resistance and β cell dysfunction. American journal of clinical nutrition. 79 (5): 820-825.
Chung M, et al. 2009. Vitamin D and calcium: a systematic review of health outcomes. Evidence report/technology assessment. 1 (183): 1-42.
Dorfman L 2012. Nutrition for Exercise and Sports Performance. In Krause's Food & The Nutrition Care Process (ed. L. Kathleen Mahan).
Douglas CC, et al. 2006. Difference in dietary intake between women with polycystic ovary syndrome and healthy controls. Fertility and sterility. 86 (2): 411-417.
Foroozanfard F, et al. 2015. Effects of zinc supplementation on markers of insulin resistance and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Experimental and clinical endocrinology & diabetes. 123 (4): 215-220.
Gabrielli L & Aquino E 2012. Polycystic ovary syndrome in Salvador, Brazil: a prevalence study in primary healthcare. Reproductive biology and endocrinology. 10 (1): 1-10.
Gol Afroozi M & Koushak A 2006. The Relationship between Carotenoids Received with Blood Glucose and Lipid Indicators in Type II Diabetes Mellitus. Journal of Ardabil University of medical sciences. 3 (6): 287-290.
González F, Rote NS, Minium J & Kirwan JP 2006. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. Journal of clinical endocrinology & metabolism. 91 (1): 336-340.
Goodarzi M, Dumesic D, Chazenbalk G & Aziz R 2011. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nature reviews endocrinology. 7 (4): 219-231.
Guler I, et al. 2014. Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance. Biological trace element research. 158 (3): 297-304.
Hahn S, et al. 2006. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Experimental and clinical endocrinology & diabetes. 114 (10): 577-583.
Hashemi S, Tehrani F, Noroozzadeh M & Azizi F 2014. Normal cut-off values for hyperandrogenaemia in Iranian women of reproductive age. European journal of obstetrics & gynecology and reproductive biology. 172: 51-55.
Hashemipour M, et al. 2009. Effect of zinc supplementation on insulin resistance and components of the metabolic syndrome in prepubertal obese children. Hormones (Athens). 8 (4): 279-285.
Hosseini-Esfahani F, et al. 2015. Interaction of APOC3 polymorphism and dietary fats on the risk of metabolic syndrome. Iranian journal of endocrinology and metabolism. 16 (5): 345-355.
Hosseinzadeh FM, Hosseinzadeh-Attar MJ, Yekaninejad MS & Rashidi B 2016. Effects of selenium supplementation on glucose homeostasis and free androgen index in women with polycystic ovary syndrome: a randomized, double blinded, placebo controlled clinical trial. Journal of trace elements in medicine and biology. 34: 56-61.
Isharwal S, Misra A, Wasir J & Nigam P 2009. Diet & insulin resistance: a review & Asian Indian perspective. Indian journal of medical research. 129 (5): 485-499.
Jamilian M, et al. 2016. Effects of zinc supplementation on endocrine outcomes in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biological trace element research. 170 (2): 271-278.
Jamilian M, et al. 2015. Metabolic response to selenium supplementation in women with polycystic ovary syndrome: a randomized, double‐blind, placebo‐controlled trial. Clinical endocrinology. 82 (6): 885-891.
Javanmanesh F, Kashanian M, Rahimi M & Sheikhansari N 2016. Comparison between the effects of metformin and N-acetyl cysteine (NAC) on some metabolic and endocrine characteristics of women with polycystic ovary syndrome. Gynecological endocrinology. 32 (4): 285-289.
Kar S 2013. Anthropometric, clinical, and metabolic comparisons of the four Rotterdam PCOS phenotypes: A prospective study of PCOS women. Journal of human reproductive sciences. 6 (3): 194-200.
Kim HM, Park J, Ryu SY & Kim J 2007. The effect of menopause on the metabolic syndrome among Korean women: the Korean National Health and Nutrition Examination Survey, 2001. Diabetes care. 30 (3): 701-706.
Krul-Poel Y, et al. 2018. Vitamin D and metabolic disturbances in polycystic ovary syndrome (PCOS): A cross-sectional study. PloS one. 13 (12): e0204748.
Lydic ML, et al. 2006. Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertility and sterility. 86 (1): 243-246.
Manning P, Sutherland W, Walker R & Williams S 2004. Effect of high- dose vitamin E on insulin resistance and associated parameters in overweight subjects. Diabetes care. 27 (9): 2166-2171.
March W, et al. 2010. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Human reproduction. 25 (2): 544-551.
Marreiro DN, et al. 2004. Participation of zinc in insulin resistance. Arquivos Brasileiros de endocrinologia & metabologia. 48 (2): 234-239.
Marshall JC & Dunaif A 2012. Should all women with PCOS be treated for insulin resistance? Fertility and sterility. 97 (1):
18-22.
Matthews D, et al. 1985. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28 (7): 412-419.
Mehrabian F, Khani B, Kelishadi R & Kermani N 2011. The prevalence of metabolic syndrome and insulin resistance according to the phenotypic subgroups of polycystic ovary syndrome in a representative sample of Iranian females. Jjournal of Isfahan University of medical sciences. 16 (6): 763-769.
Miranda E & Dey C 2004. Effect of chromium and zinc on insulin signaling in skeletal muscle cells. Biological trace element research. 101 (1): 19-36.
Mirmiran P, Esfahani FH, Mehrabi Y, Hedayati M & Azizi F 2010. Reliability and relative validity of an FFQ for nutrients in the Tehran lipid and glucose study. Public health nutrition. 13 (5): 654-662.
Moran L & Teede H 2009. Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Human reproduction update. 15 (4): 477-488.
Norman R, Dewailly D, Legro R, Hickey T & 370:685–697. L 2007. Polycystic ovary syndrome. Lancet. 9588 (9588): 685-697.
Ramezani Tehrani F, Rashidi H, Bahri Khomami M, Tohidi M & Azizi F 2014. The prevalence of metabolic disorders in various phenotypes of polycystic ovary syndrome: a community based study in Southwest of Iran. Reproductive biology and endocrinology. 12 (89): 1-6.
Rayman M 2012. Selenium and human health. Lancet. 379 (9822): 1256-1268.
Salehpour S 2011. Evaluation of homocysteine levels in patients with polycystic ovarian syndrome. International journal of fertility & sterility. 4 (4): 168.
Schorge J, et al. 2008. Williams gynecology. McGraw-Hill Medical: New York.
Shishehgar F, et al. 2016. Comparison of dietary intake between polycystic ovary syndrome women and controls. Global journal of health science. 8 (9): 302.
Sirmans SM & Pate KA 2014. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical epidemiology. 6: 1-13.
Sugiura M, et al. 2006. The homeostasis model assessment-insulin resistance index is inversely associated with serum carotenoids in non-diabetic subjects. Journal of epidemiology. 16 (2): 71-78.
Taghdir M, et al. 2009. XML Relationship Between Serum Zinc and Insulin Concentration, Insulin Resistance and Oxidative Stress in Postmenopausal Diabetic Women. Iranian journal of endocrinology and metabolism. 11 (5): 485-596.
Teede H, Deeks A & Moran L 2010. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC medicine. 8 (1): 1-10.
Thomson RL, Spedding S & Buckley JD 2012. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clinical endocrinology. 77 (3): 343-350.
Vincent J 2018. The nutritional biochemistry of chromium (III). Elsevier.
Wallace T, Levy J & Matthews D 2004. Use and abuse of HOMA modeling. Diabetes care. 27 (6): 1487-1495.
Wang Y, et al. 2017. High dietary selenium intake is associated with less insulin resistance in the Newfoundland population. PloS one. 12 (4): e0174149.
Woodside J, McCall D, McGartland C & Young I 2005. Micronutrients: dietary intake v. supplement use. Proceedings of the nutrition society. 64 (4): 543-553.
Wright C, Zborowski J, Talbott E, McHugh-Pemu K & Youk A 2004. Dietary intake, physical activity, and obesity in women with polycystic ovary syndrome. International journal of obesity. 28 (8): 1026-1032.
Yildizhan R, et al. 2009. Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Archives of gynecology and obstetrics. 280 (4): 559-563.
Ylönen K, et al. 2003. Dietary intakes and plasma concentrations of carotenoids and tocopherols in relation to glucose metabolism in subjects at high risk of type 2 diabetes: the Botnia Dietary Study. American journal of clinical nutrition. 77 (6): 1434-1441.
Zeng H 2009. Selenium as an essential micronutrient: roles in cell cycle and apoptosis. Molecules. 14 (3): 1263-1278.
Type of article: orginal article |
Subject:
public specific
Received: 2021/08/31 | Published: 2023/02/21 | ePublished: 2023/02/21
Received: 2021/08/31 | Published: 2023/02/21 | ePublished: 2023/02/21
References
1. Amooee S, Parsanezhad ME, Shirazi MR, Alborzi S & Samsami A 2013. Metformin versus chromium picolinate in clomiphene citrate-resistant patients with PCOs: A double-blind randomized clinical trial. Iranian journal of reproductive medicine. 11 (8): 611.
2. Ardabili HR, Gargari BP & Farzadi L 2012. Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency. Nutrition research. 32 (3): 195-201.
3. Asghari G, et al. 2012. Reliability, comparative validity and stability of dietary patterns derived from an FFQ in the Tehran Lipid and Glucose Study. British journal of nutrition. 108 (6): 1109-1117.
4. Berek J & Brerek N 2012. Novak's gynecology, Chapter 35, endocrine disorders.
5. Bikle D 2009. Nonclassic actions of vitamin D. Journal of clinical endocrinology & metabolism. 94 (1): 26-34.
6. Brady C, Mousa S & Mousa S 2009. Polycystic ovary syndrome and its impact on women’s quality of life: More than just an endocrine disorder. Drug, healthcare and patient safety. 1: 9-15.
7. Caballero B 1993. Vitamin E improves the action of insulin. Nutrition reviews. 51 (11): 339-340.
8. Chiu K, Chu A, Go V & Saad M 2004. Hypovitaminosis D is associated with insulin resistance and β cell dysfunction. American journal of clinical nutrition. 79 (5): 820-825.
9. Chung M, et al. 2009. Vitamin D and calcium: a systematic review of health outcomes. Evidence report/technology assessment. 1 (183): 1-42.
10. Dorfman L 2012. Nutrition for Exercise and Sports Performance. In Krause's Food & The Nutrition Care Process (ed. L. Kathleen Mahan).
11. Douglas CC, et al. 2006. Difference in dietary intake between women with polycystic ovary syndrome and healthy controls. Fertility and sterility. 86 (2): 411-417.
12. Foroozanfard F, et al. 2015. Effects of zinc supplementation on markers of insulin resistance and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Experimental and clinical endocrinology & diabetes. 123 (4): 215-220.
13. Gabrielli L & Aquino E 2012. Polycystic ovary syndrome in Salvador, Brazil: a prevalence study in primary healthcare. Reproductive biology and endocrinology. 10 (1): 1-10.
14. Gol Afroozi M & Koushak A 2006. The Relationship between Carotenoids Received with Blood Glucose and Lipid Indicators in Type II Diabetes Mellitus. Journal of Ardabil University of medical sciences. 3 (6): 287-290.
15. González F, Rote NS, Minium J & Kirwan JP 2006. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. Journal of clinical endocrinology & metabolism. 91 (1): 336-340.
16. Goodarzi M, Dumesic D, Chazenbalk G & Aziz R 2011. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nature reviews endocrinology. 7 (4): 219-231.
17. Guler I, et al. 2014. Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance. Biological trace element research. 158 (3): 297-304.
18. Hahn S, et al. 2006. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Experimental and clinical endocrinology & diabetes. 114 (10): 577-583.
19. Hashemi S, Tehrani F, Noroozzadeh M & Azizi F 2014. Normal cut-off values for hyperandrogenaemia in Iranian women of reproductive age. European journal of obstetrics & gynecology and reproductive biology. 172: 51-55.
20. Hashemipour M, et al. 2009. Effect of zinc supplementation on insulin resistance and components of the metabolic syndrome in prepubertal obese children. Hormones (Athens). 8 (4): 279-285.
21. Hosseini-Esfahani F, et al. 2015. Interaction of APOC3 polymorphism and dietary fats on the risk of metabolic syndrome. Iranian journal of endocrinology and metabolism. 16 (5): 345-355.
22. Hosseinzadeh FM, Hosseinzadeh-Attar MJ, Yekaninejad MS & Rashidi B 2016. Effects of selenium supplementation on glucose homeostasis and free androgen index in women with polycystic ovary syndrome: a randomized, double blinded, placebo controlled clinical trial. Journal of trace elements in medicine and biology. 34: 56-61.
23. Isharwal S, Misra A, Wasir J & Nigam P 2009. Diet & insulin resistance: a review & Asian Indian perspective. Indian journal of medical research. 129 (5): 485-499.
24. Jamilian M, et al. 2016. Effects of zinc supplementation on endocrine outcomes in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biological trace element research. 170 (2): 271-278.
25. Jamilian M, et al. 2015. Metabolic response to selenium supplementation in women with polycystic ovary syndrome: a randomized, double‐blind, placebo‐controlled trial. Clinical endocrinology. 82 (6): 885-891.
26. Javanmanesh F, Kashanian M, Rahimi M & Sheikhansari N 2016. Comparison between the effects of metformin and N-acetyl cysteine (NAC) on some metabolic and endocrine characteristics of women with polycystic ovary syndrome. Gynecological endocrinology. 32 (4): 285-289.
27. Kar S 2013. Anthropometric, clinical, and metabolic comparisons of the four Rotterdam PCOS phenotypes: A prospective study of PCOS women. Journal of human reproductive sciences. 6 (3): 194-200.
28. Kim HM, Park J, Ryu SY & Kim J 2007. The effect of menopause on the metabolic syndrome among Korean women: the Korean National Health and Nutrition Examination Survey, 2001. Diabetes care. 30 (3): 701-706.
29. Krul-Poel Y, et al. 2018. Vitamin D and metabolic disturbances in polycystic ovary syndrome (PCOS): A cross-sectional study. PloS one. 13 (12): e0204748.
30. Lydic ML, et al. 2006. Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertility and sterility. 86 (1): 243-246.
31. Manning P, Sutherland W, Walker R & Williams S 2004. Effect of high- dose vitamin E on insulin resistance and associated parameters in overweight subjects. Diabetes care. 27 (9): 2166-2171.
32. March W, et al. 2010. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Human reproduction. 25 (2): 544-551.
33. Marreiro DN, et al. 2004. Participation of zinc in insulin resistance. Arquivos Brasileiros de endocrinologia & metabologia. 48 (2): 234-239.
34. Marshall JC & Dunaif A 2012. Should all women with PCOS be treated for insulin resistance? Fertility and sterility. 97 (1): 18-22.
36. Matthews D, et al. 1985. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28 (7): 412-419.
37. Mehrabian F, Khani B, Kelishadi R & Kermani N 2011. The prevalence of metabolic syndrome and insulin resistance according to the phenotypic subgroups of polycystic ovary syndrome in a representative sample of Iranian females. Jjournal of Isfahan University of medical sciences. 16 (6): 763-769.
38. Miranda E & Dey C 2004. Effect of chromium and zinc on insulin signaling in skeletal muscle cells. Biological trace element research. 101 (1): 19-36.
39. Mirmiran P, Esfahani FH, Mehrabi Y, Hedayati M & Azizi F 2010. Reliability and relative validity of an FFQ for nutrients in the Tehran lipid and glucose study. Public health nutrition. 13 (5): 654-662.
40. Moran L & Teede H 2009. Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Human reproduction update. 15 (4): 477-488.
41. Norman R, Dewailly D, Legro R, Hickey T & 370:685–697. L 2007. Polycystic ovary syndrome. Lancet. 9588 (9588): 685-697.
42. Ramezani Tehrani F, Rashidi H, Bahri Khomami M, Tohidi M & Azizi F 2014. The prevalence of metabolic disorders in various phenotypes of polycystic ovary syndrome: a community based study in Southwest of Iran. Reproductive biology and endocrinology. 12 (89): 1-6.
43. Rayman M 2012. Selenium and human health. Lancet. 379 (9822): 1256-1268.
44. Salehpour S 2011. Evaluation of homocysteine levels in patients with polycystic ovarian syndrome. International journal of fertility & sterility. 4 (4): 168.
45. Schorge J, et al. 2008. Williams gynecology. McGraw-Hill Medical: New York.
46. Shishehgar F, et al. 2016. Comparison of dietary intake between polycystic ovary syndrome women and controls. Global journal of health science. 8 (9): 302.
47. Sirmans SM & Pate KA 2014. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical epidemiology. 6: 1-13.
48. Sugiura M, et al. 2006. The homeostasis model assessment-insulin resistance index is inversely associated with serum carotenoids in non-diabetic subjects. Journal of epidemiology. 16 (2): 71-78.
49. Taghdir M, et al. 2009. XML Relationship Between Serum Zinc and Insulin Concentration, Insulin Resistance and Oxidative Stress in Postmenopausal Diabetic Women. Iranian journal of endocrinology and metabolism. 11 (5): 485-596.
50. Teede H, Deeks A & Moran L 2010. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC medicine. 8 (1): 1-10.
51. Thomson RL, Spedding S & Buckley JD 2012. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clinical endocrinology. 77 (3): 343-350.
52. Vincent J 2018. The nutritional biochemistry of chromium (III). Elsevier.
53. Wallace T, Levy J & Matthews D 2004. Use and abuse of HOMA modeling. Diabetes care. 27 (6): 1487-1495.
54. Wang Y, et al. 2017. High dietary selenium intake is associated with less insulin resistance in the Newfoundland population. PloS one. 12 (4): e0174149.
55. Woodside J, McCall D, McGartland C & Young I 2005. Micronutrients: dietary intake v. supplement use. Proceedings of the nutrition society. 64 (4): 543-553.
56. Wright C, Zborowski J, Talbott E, McHugh-Pemu K & Youk A 2004. Dietary intake, physical activity, and obesity in women with polycystic ovary syndrome. International journal of obesity. 28 (8): 1026-1032.
57. Yildizhan R, et al. 2009. Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Archives of gynecology and obstetrics. 280 (4): 559-563.
58. Ylönen K, et al. 2003. Dietary intakes and plasma concentrations of carotenoids and tocopherols in relation to glucose metabolism in subjects at high risk of type 2 diabetes: the Botnia Dietary Study. American journal of clinical nutrition. 77 (6): 1434-1441.
59. Zeng H 2009. Selenium as an essential micronutrient: roles in cell cycle and apoptosis. Molecules. 14 (3): 1263-1278.
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