Effects of vitamin D supplementation on metabolic parameters of women with polycystic ovary syndrome: a randomized controlled trial

Effects of vitamin D supplementation on metabolic parameters of women with polycystic ovary syndrome: a randomized controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of vitamin D supplementation on metabolic parameters of women with polycystic ovary syndrome: a randomized controlled trial Xinling Wen, Fen Li, Xuewen Yu, Li Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3996462/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Jul, 2024 Read the published version in Journal of Ovarian Research → Version 1 posted 10 You are reading this latest preprint version Abstract Objective Polycystic ovary syndrome (PCOS) is a common reproductive endocrine and metabolic disease. The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters of PCOS women. Methods A total of 60 PCOS women with vitamin D deficiency or insufficiency were enrolled in this randomized controlled trial. Participants were randomized to vitamin D group (2000 IU/day) or control group. The observational parameters were measured at baseline and after treatment (4 weeks, 8 weeks and 12 weeks), including body mass index (BMI), waist to hip ratio (WHR), blood pressure, oral glucose tolerance test (OGTT) and insulin release test, and lipid metabolism parameters. Results The serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group ( P < 0.05). In addition, with the extension of treatment time, the serum 25(OH)D concentration gradually increased. The BMI, WHR, insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in women of Vitamin D group after 12 weeks of treatment were significantly lower than that in women of control group ( P < 0.05). Additionally, The serum insulin concentrations and HOMA-IR at different time points of OGTT, serum TG, TC and LDL-C concentrations in women of vitamin D group (obesity) were significantly lower than that in control group (obesity) ( P < 0.05). The BMI, WHR, TG, TC and LDL-C concentration in women of vitamin D group (IR) were significantly lower compared with control group (IR) ( P 0.05), and these differences of metabolic parameters were also not observed between vitamin D group (non-IR) and control group (non-IR) ( P > 0.05). Conclusion The findings of this study supported that vitamin D supplementation had beneficial effects on metabolic parameters of PCOS women, especially in women with obesity or IR. vitamin D supplementation polycystic ovary syndrome vitamin D deficiency vitamin D insufficiency metabolic parameters insulin resistance Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Polycystic ovary syndrome (PCOS) is the most common reproductive, endocrine, and metabolic disorders affecting 6–10% of reproductive-age women all over the world [ 1 ]. Women with PCOS are often identified with symptoms of menstrual disorder, infertility due to ovulation dysfunction, hirsutism, acne and metabolic disorder. Previous studies have confirmed that PCOS is associated with metabolic disorders, such as type 2 diabetes (T2DM), dyslipidemia, cardiovascular disease (CVD), atherosclerosis, metabolic syndrome (MS), nonalcoholic fatty liver disease (NAFLD), and ultimately cirrhosis [ 2 , 3 ]. In recent years, these metabolic problems in PCOS women attracted the attention of scholars worldwide. A systematic review and meta-analysis showed that 40–50% of women suffering from PCOS have impaired glucose tolerance (IGT), insulin resistance (IR) and compensatory hyperinsulinaemia (HI) and that approximately 10% of these women will develop T2DM [ 4 ]. Additionally, PCOS women are prone to dyslipidemia, including higher levels of triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) than healthy women [ 5 – 7 ]. The molecular action of vitamin D is involved in maintaining the normal resting levels of reactive oxygen species (ROS) and Ca 2+ , not only in pancreatic β-cells, but also in insulin responsive tissues. Vitamin D prevents epigenetic alterations associated with IR, and vitamin D deficiency is one of the factors accelerating IR formation [ 8 ]. Additionally, studies have confirmed that vitamin D supplementation reduce the level of metabolic parameters such as TC, LDL-C, TG, glycated hemoglobin (HbA1c), as well as decreases HOMA-IR in patients with T2DM [ 9 – 10 ]. Multiple epidemiological data worldwide have confirmed that vitamin D deficiency and insufficiency are common in women with PCOS, especially in those with obesity or IR [ 11 – 13 ]. A recent meta-analysis displayed that 67–85% PCOS women had vitamin D deficiency [ 14 ]. However, the effects of vitamin D supplementation on metabolic parameters of women with PCOS are controversial. Some of studies shown beneficial effects of vitamin D supplementation on glucose metabolism, IR, dyslipidemia, cardiovascular risk factors, liver markers, metabolic profiles and NAFLD [ 15 – 16 ]. Nevertheless, other studies suggested that vitamin D supplementation had no significant effect on metabolic and endocrine parameters in PCOS women [ 17 ]. In recent years, the therapeutic schedule for PCOS women are improvement of patient’s clinical symptoms and treatment of infertility. However, this may not be completely effective in preventing long-term complications, such as metabolic disorders, DM, dyslipidemia, CVD, NAFLD and endometrial carcinoma. These long-term complications can seriously affect women's health and quality of life. The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters of women with PCOS. Materials and methods Study design and participants We conducted a randomized controlled trial (RCT) study on PCOS patients with vitamin D deficiency or insufficiency in the First Affiliated Hospital of Xi’an Jiaotong University from January 2021 to June 2023. All participants gave written informed consent on the basis of procedures granted by the Ethics Committee of The First Affiliated Hospital of Medical College of Xi’an Jiaotong University (XJTU1AF2021LSK-207). This study has been registered on China’s clinical trials registration: www.chictr.org.cn (ChiCTR2100048736). Sixty-eight PCOS women were enrolled in this study. All patients were aged 21–34 years. The diagnostic criteria of PCOS was based on a modified Rotterdam criteria: menstrual abnormalities (oligomenorrhea, amenorrhea, or irregular uterine bleeding), combined with either hyperandrogenaemia or polycystic ovarian morphology (PCO) [ 18 ]. Hyperandrogenaemia was identified as either clinical manifestations or laboratory evidence. Laboratory evidence was defined as an abnormally increased testosterone level. Clinical manifestations included hirsutism or acne. Hirsutism was defined as a modified Ferriman-Gallwey score of more than 3 at the time of physical examination. PCO was identified as the presence of 12 or more follicles in unilateral ovary or bilateral ovaries measuring 2–9 mm in diameter, and/or ovarian volume ≥ 10 ml. Ovarian volume = 0.5 × length diameter × transverse diameter × anteroposterior diameter. Participants who were diagnosed with tumor secreting androgens, thyroid dysfunction, hyperprolactinemia, hypothalamic amenorrhea, Cushing’s syndrome, congenital adrenal hyperplasia (CAH), premature ovarian insufficiency (POI), premature ovarian failure (POF), hypercalcemia, malabsorption disorders and diabetes mellitus were excluded. In addition, participants who used corticosteroids, hypolipidemic agents, calcium supplements, or any other drugs known to affect vitamin D metabolism were also excluded from the study. The baseline data of PCOS women were collected by questionnaire in a face-to-face interview, such as age, body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, marital status, gravidity, parity, employment status, family history and outdoor exercise. BMI ≥ 30.0 kg/m 2 was defined as obesity [ 19 ]. Sixty-eight PCOS women were enrolled initially in this RCT study, 8 women with normal serum vitamin D level were excluded. Then, sixty PCOS women with vitamin D deficiency or insufficiency were randomly divided into vitamin D group or control group, and 30 participants in each group. Two participants in the vitamin D group and 1 participant in the control group were lost to follow-up. Finally, 57 participants (vitamin D group, n = 28. control group, n = 29) completed the 12 weeks study period (Fig. 1 ). Measurement of serum vitamin D 25-hydroxyvitamin D3 [ 25(OH)D ] is the primary circulating form of vitamin D, which is the most abundant vitamin D metabolite and considered as the best parameter of vitamin D status within the human body. Therefore, serum 25(OH)D was detected by chemiluminescence method. According to the Institute of Medicine (IOM) and World Health Organization (WHO), vitamin D deficiency was defined as serum 25 (OH) D concentration lower than 20 ng/mL, and vitamin D insufficiency was defined as a concentration of 20– < 30 ng/mL. Serum 25(OH)D concentration of 30–50 ng/mL were regarded as normal [ 20 ]. Detection of biochemical indicators All biochemical indicators in this study were detected in the clinical laboratory of our hospital. The basic sex hormone concentrations and anti-Mullerian hormone (AMH) concentration were tested during 2–4 days of natural menstrual cycle or progesterone withdrawal bleeding using chemiluminescence method. Sex hormone included follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E 2 ), progesterone (P) and testosterone (T). All participants were given 83 g oral glucose for oral glucose tolerance test (OGTT) and insulin release test. The blood glucose was detected by hexokinase method. Serum insulin level was detected through radioimmunoassay. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to evaluate IR. HOMA-IR = [fasting glucose (mmol/L) × fasting insulin (mU/L)]/22.5. A HOMA-IR > 3.0 was defined as IR, and an insulin level after oral glucose powder intake 10 times higher than the fasting level was also defined as IR [ 21 ]. At the same time, the blood lipids were detected using automatic biochemical analyzer, including TC, TG, LDL-C and high-density lipoprotein cholesterol (HDL-C). Sample size Sample size was calculated provided that serum 25(OH)D concentration and glucose metabolism and lipid metabolism indicators were the primary outcomes. According to the method reported in previous literatures, sample size was calculated with the following parameters: probability of type one error (α) of 0.05 and type two error (β) of 0.20 (power = 80%), difference between two means to be detected was 0.52, expected background standard deviation was 1. Based on this, we needed 27 participants in each group. Considering a follow-up rate of 3 participants per group, we needed to have 30 participants in each group. Randomization and intervention All participants were randomly divided into vitamin D group or control group by means of computer-generated random numbers. Participants in vitamin D group received basic treatment combined with vitamin D supplementation (2000 IU/day). Basic treatment included a proper diet and aerobic exercise outdoors at least three times per week. Each aerobic exercise lasted at least 30 minutes. Participants in control group were only given basic treatment. Outcome measures The primary outcomes were the serum 25(OH)D concentration, glucose metabolism, insulin concentration and lipid metabolism indicators. The secondary outcomes were general metabolic parameters, including BMI, WHR and blood pressure. Statistical analysis Statistical analyses were performed using SPSS version 20.0 (IBM, Armonk, NY, USA). The continuous variables were presented as mean ± standard deviation, and were performed by the Student’s t -test or variance analysis. Differences in dichotomous outcomes were given as number and percentage (%), which were compared by chi-square test. P < 0.05 was considered statistically significant. Results Baseline data Table 1 shows the baseline data of women between the two groups. No significant difference was found when comparing the baseline data between the two groups ( P > 0.05). Table 1 Baseline data of women between the two groups. Characteristics Vitamin D group (n = 28) Control group (n = 29) P- value a Age (years) 26.7 ± 9.3 25.3 ± 8.6 0.764 BMI (kg/m 2 ) 25.2 ± 7.4 24.9 ± 7.9 0.812 WHR 0.9 ± 0.3 0.9 ± 0.4 0.978 SBP (mm Hg) 109.5 ± 12.3 107.6 ± 11.9 0.714 DBP (mm Hg) 78.4 ± 6.5 75.1 ± 7.0 0.256 Marital status 0.705 Single 12 (42.9) 11 (37.9) Married 16 (57.1) 18 (62.1) Gravidity (number) 3.6 ± 1.2 3.3 ± 1.1 0.798 Parity (number) 1.3 ± 0.6 1.2 ± 0.5 0.609 Employment status 0.561 Working 23 (82.1) 22 (75.9) Non-working 5 (17.9) 7 (24.1) Family history DM 3 (10.7) 4 (13.8) 0.723 CVD 4 (14.3) 4 (13.8) 0.957 Thyroid diseases 2 (7.1) 3 (10.3) 0.669 Outdoor exercise 0.561 Never 5 (17.9) 7 (24.1) ≥ 1 times daily 23 (82.1) 22 (75.9) Basal concentration FSH (mIU/mL) 6.1 ± 1.5 6.9 ± 1.6 0.568 LH (mIU/mL) 15.6 ± 4.9 17.1 ± 4.5 0.609 PRL (ng/mL) 14.8 ± 6.2 15.3 ± 5.9 0.544 E 2 (pmol/L) 122.3 ± 17.5 136.4 ± 15.8 0.312 T (nmol/L) 2.1 ± 0.6 1.9 ± 0.5 0.377 P (nmol/L) 1.2 ± 0.4 1.0 ± 0.3 0.459 AMH (ng/mL) 5.6 ± 1.5 5.3 ± 1.7 0.780 Serum 25(OH)D detection time 0.974 Spring 8 (28.6) 9 (31.0) Summer 9 (32.1) 9 (31.0) Autumn 5 (17.9) 6 (20.7) Winter 6 (21.4) 5 (17.2) Serum 25(OH)D concentrations (ng/mL) 12.3 ± 4.6 13.0 ± 4.9 0.517 Vitamin D status 0.786 Deficiency 23 (82.1) 23 (79.3) Insufficiency 5 (17.9) 6 (20.7) BGC (mmol/L) Fasting 4.1 ± 0.9 4.2 ± 0.8 0.879 1 hour after OGTT 9.2 ± 1.3 9.8 ± 1.4 0.776 2 hour after OGTT 6.7 ± 1.0 7.2 ± 1.1 0.564 3 hour after OGTT 4.3 ± 0.8 4.2 ± 0.7 0.902 Insulin level (mIU/L) Fasting 27.7 ± 5.8 29.4 ± 8.9 0.213 1 hour after OGTT 312.5 ± 56.4 297.6 ± 49.0 0.204 2 hour after OGTT 206.8 ± 44.3 187.5 ± 40.2 0.290 3 hour after OGTT 61.5 ± 10.4 58.3 ± 11.2 0.576 HOMA IR Fasting 5.0 ± 0.6 5.5 ± 0.7 0.145 1 hour after OGTT 127.8 ± 19.7 130.1 ± 21.6 0.690 2 hour after OGTT 61.2 ± 15.2 60.1 ± 13.9 0.887 3 hour after OGTT 11.8 ± 3.9 10.9 ± 3.2 0.468 TG (mmol/L) 1.9 ± 0.3 1.7 ± 0.4 0.443 TC (mmol/L) 5.6 ± 1.4 5.8 ± 1.3 0.865 LDL-C (mmol/L) 3.42 ± 1.09 3.58 ± 1.12 0.409 HDL-C (mmol/L) 1.3 ± 0.5 1.5 ± 0.6 0.357 a T-test or chi-square test. Data given as mean ± SD or number (%). SBP: systolic blood pressure, DBP: diastolic blood pressure. Serum vitamin D concentrations The data in Table 2 illustrate that the serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group ( P < 0.05). In addition, with the extension of treatment time, the serum 25(OH)D concentration gradually increased. Table 2 The serum 25(OH)D concentrations at baseline and different times after treatment (ng/mL). Vitamin D group (n = 28) Control group (n = 29) P- value a Baseline 12.3 ± 4.6 13.0 ± 4.9 0.517 4 weeks after treatment 21.2 ± 5.4 14.8 ± 5.3 0.032 8 weeks after treatment 32.8 ± 6.9 15.9 ± 6.2 0.021 12 weeks after treatment 44.2 ± 9.3 13.6 ± 5.9 0.008 a T-test. Data given as mean ± SD. Effects of vitamin D supplementation on general metabolic parameters Table 3 demonstrates the general metabolic parameters between the two groups. The data reveal that BMI and WHR of women in Vitamin D group 12 weeks of treatment were significantly reduced compared with baseline ( P < 0.05). In addition, the above parameters 12 weeks of treatment in vitamin D group were also significant lower than that in women of control group ( P = 0.045, P = 0.048). However, no significant difference was found when comparing SBP and DPB between baseline and different times after treatment ( P > 0.05). These significant differences after treatment were also not observed between vitamin D group and control group ( P = 0.675, P = 0.326). Table 3 The effects on general metabolic parameters between the two groups. Characteristics Vitamin D group (n = 28) Control group (n = 29) Baseline 12 weeks Change P- value a Baseline 12 weeks Change P- value a BMI (kg/m 2 ) 25.2 ± 7.4 23.1 ± 6.5 ▲ -2.1 ± 0.9 0.041 24.9 ± 7.9 24.6 ± 7.4 -0.3 ± 0.1 0.219 WHR 0.9 ± 0.3 0.7 ± 0.3 ▲ -0.2 ± 0.0 0.043 0.9 ± 0.4 0.8 ± 0.3 -0.1 ± 0.0 0.307 SBP (mm Hg) 109.5 ± 12.3 106.4 ± 11.5 -3.1 ± 0.9 0.431 107.6 ± 11.9 105.9 ± 10.3 -1.7 ± 0.8 0.685 DPB (mm Hg) 78.4 ± 6.5 76.7 ± 6.2 -1.7 ± 0.6 0.309 75.1 ± 7.0 73.8 ± 6.5 -1.3 ± 0.7 0.443 a T-test. Data given as mean ± SD. ▲ Vitamin D group vs. Control group after 12 weeks of treatment, P < 0.05. Effects of vitamin D supplementation on biochemical metabolic parameters The biochemical metabolic parameters at 12 weeks after treatment were detected between the two groups. The serum insulin concentrations at fasting, 1 h, 2 h and 3h after OGTT in women of Vitamin D group were significantly lower than that in control group ( P = 0.046, P = 0.029, P = 0.035, P = 0.041). The HOMA-IR at the above time point were also lower compared with control group ( P = 0.048, P = 0.021, P = 0.033, P = 0.047). Moreover, the TG, TC and LDL-C concentrations in women of vitamin D group were significantly lower than that in control group ( P = 0.031, P = 0.027, P = 0.034). However, no significant difference was found when comparing blood glucose concentrations at different time points of OGTT and HDL-C concentration between the two groups ( P = 0.342–0.835) (Fig. 2 ). All participants were divided into four groups according to BMI: vitamin D group (obesity) (n = 8), vitamin D group (non-obesity) (n = 20), control group (obesity) (n = 10), control group (non-obesity) (n = 19). The biochemical metabolic parameters at baseline and 12 weeks after treatment were detected among the four groups. The serum insulin concentrations at fasting, 1 h, 2 h and 3h after OGTT in women of vitamin D group (obesity) were significantly lower than that in control group (obesity) ( P = 0.041, P = 0.022, P = 0.030, P = 0.043). Additionally, the HOMA-IR at the above time point OGTT, TG concentration, TC concentration and LDL-C concentration were also significantly reduced in vitamin D group (obesity) compared with women in control group (obesity) ( P = 0.018–0.049). Nevertheless, no significant difference was observed of the biochemical metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity) ( P = 0.317–0.806) (Fig. 3 ). In addition, all participants were divided into four groups according to HOMA-IR: vitamin D group (IR) (n = 17), vitamin D group (non-IR) (n = 11), control group (IR) (n = 19), control group (non-IR) (n = 10). The BMI, WHR, TG concentration, TC concentration and LDL-C concentration in women of vitamin D group (IR) were significantly lower than that in control group (IR) ( P = 0.022–0.047). However, no significant difference was seen observed when comparing the above parameters between vitamin D group (non-IR) and control group (non-IR) ( P = 0.257–0.913). In addition, no significant difference was observed in SBP and DPB among the four groups ( P = 0.897, P = 0.926) (Fig. 4 ). Discussion PCOS is a multiple metabolic disorders syndrome characterized by obesity, IR, dyslipidemia and other metabolic abnormalities. Studies have confirmed that PCOS women are prone to obesity, IGT, IR, and about 10% of them will progresses to T2DM. In addition, women with PCOS also have an increased risk of cardiovascular disease, hypertension (3 to 5 times higher than normal women, with increased SBP), NAFLD, abnormal lipid metabolism (increased TG and LDL-C levels) and MS [ 21 ]. IR occurs in women with PCOS, is significantly associated with different metabolic disorders including increased aromatase activity, elevated androgen secretion, and damaged progesterone synthesis in granulosa cells [ 16 ]. Accumulating evidence suggests that vitamin D deficiency and insufficiency are important factors in the pathogenesis of IR, metabolic disorders and CVD in PCOS [ 9 ]. Indeed, a high prevalence of vitamin D deficiency is observed among PCOS women, especially in those women with obesity or IR [ 11 ]. It has been proven that insulin secretion is a calcium-dependent process, so vitamin D may affect pancreatic β-cells through the regulation of calcium concentrations [ 22 ]. Also, a beneficial effect of combined vitamin D and calcium on glucose metabolism and lipid profiles in patients with T2DM has previously been reported [ 23 ]. However, the effects of vitamin D supplementation on metabolic parameters of women with PCOS are controversial. The data in our study demonstrated that significant increases in vitamin D concentrations were shown at different time points after vitamin D supplementation. Furthermore, with the extension of treatment time, the serum 25(OH)D concentration gradually increased. The BMI, WHR, serum insulin concentrations and HOMA-IR in women of vitamin D group were significantly lower than that in control group. Although IR is not within any of the diagnostic criteria of PCOS in different countries, it occurs in most lean and overweight women with PCOS, who have a form of IR intrinsic and the compensatory hyperinsulinaemia drives many of the phenotypic features of PCOS. Additionally, compared with lean PCOS women, women with obesity are more likely to accompany IR. In fact, obesity and IR interact with each other and form a vicious cycle, which are also difficult to treat clinically. Vitamin D dramatically improves glucose metabolism by increasing insulin production, insulin receptor expression and reducing pro-inflammatory cytokines [ 24 ]. Findings from the current study revealed that the serum insulin concentrations and HOMA-IR at different time points of OGTT in women of vitamin D group (obesity) were significantly lower than that in control group (obesity). Moreover, the BMI, WHR, TG concentration, TC concentration and LDL-C concentration in women of vitamin D group (IR) were significantly lower than that in control group (IR). Nevertheless, no significant difference was seen in metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity), as well as between vitamin D group (non-IR) and control group (non-IR). A systematic review and meta-analysis of RCT reported that PCOS women with continuous low dose of vitamin D supplementation improve fasting glucose concentration and HOMA-IR, but the meta-analysis included studies of vitamin D in combination with other micronutrients [ 25 ]. Similarly, Menichini et al. confirmed that vitamin D supplementation (4000 IU/day) for a period of at least 12 weeks lead to improvement in terms of glucose level, insulin sensitivity, hyperlipidemia, and hormonal functionality in PCOS women [ 26 ]. The mechanism for vitamin D improving IR includes the following aspects: (a) Vitamin D receptor (VDR) is a key modulator of inflammation and β cell survival, whihc restored β cell function and ameliorate hyperglycemia in murine T2D models [ 27 ]. (b) Vitamin D increases insulin responsiveness for glucose transport through the binding of 1,25(OH)2D-VDR complex to the vitamin D response element of the insulin receptor [ 28 ]. (c) Vitamin D regulates the extracellular and intracellular calcium concentration, which is important for the mediation of glucose transport in the target tissues [ 29 ]. Nevertheless, Trummer et al. reported that Vitamin D supplementation had no significant effect on metabolic and endocrine parameters in PCOS [ 17 ]. Similarly, Ardabili et al. displayed that the fasting serum insulin and glucose levels, the insulin sensitivity and HOMA-IR did not change significantly by the end of the study [ 30 ]. The different results may be explained by different types of studies, dose and time of vitamin D supplementation, treatment with vitamin D alone or with other micronutrients, participants with pre-processed or not, lifestyles of the participants, place of residence and so on. Our findings demonstrated that compared to control group, vitamin D supplementation significantly improved dyslipidemia in PCOS women with vitamin D deficiency and insufficiency, including reduced the serum TG, TC and LDL-C concentrations. Additionally, the serum TG, TC and LDL-C concentrations in women of vitamin D group (obesity) were significantly lower than that in control group (obesity). Similarly, some studies shown that vitamin D supplementation plus Calcium for eight weeks among vitamin D deficient women with PCOS had beneficial effects on serum TG and VLDL-cholesterol levels, but it did not affect other lipid profiles [ 31 ]. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that control lipid homeostasis. Asano et al. screened a chemical library of endogenous molecules and identified 25-hydroxyvitamin D (25OHD) as an inhibitor of SREBPs activation. They found that vitamin D may regulate lipoprotein lipase gene expression and therefore, might decrease serum TC concentration [ 32 ]. However, the beneficial effect of vitamin D supplementation on lipid profiles was not found in other studies [ 33 ]. Different study designs and dosages of vitamin D supplementation, baseline data of participants might provide explanation for different results. Several mechanisms can explain the effects of vitamin D supplementation on serum TG and VLDL-cholesterol levels. On the one hand, 1,25-dihydroxy-cholecalciferol represses the expression of the apolipoprotein A-I (apo A-I) gene in hepatocytes, and vitamin D receptor modulators in hepatocytes and intestinal cells differentially regulate expression of the apo A-I gene [ 34 ]. On the other hand, the increased intracellular Calcium due to vitamin D supplementation in liver leads to stimulating microsomal triglycerides transfer protein (MTP), which is implicated in the formation and secretion of VLDL, and then results in decreased serum TG and VLDL-cholesterol levels [ 35 ]. However, the effect of vitamin D supplementation on lipid profiles in PCOS patients and its specific mechanism still needs further exploration. Some limitations must be considered in this study. First, this was a single-centre RCT study in the city of Xi’an in Shaanxi, China. Second, the metabolic parameters observed in this study were relatively limited, and androgen metabolic parameters and inflammatory indicators were not observed. Therefore, future studies are required to confirm the effectiveness of vitamin D on metabolic parameters of PCOS women, and the specific regulation mechanism are also need to be further explored. Conclusion This study provides evidence that vitamin D supplementation significantly increased serum vitamin D concentration in PCOS women with vitamin D deficiency and insufficiency. Furthermore, this RCT study supports beneficial effects of vitamin D supplementation on metabolic parameters of PCOS women, including significant improvements in BMI, WHR, serum insulin concentrations and HOMA-IR, lipid metabolism parameters, especially in women with obesity or IR. Declarations Conflicts of Interest No potential conflict of interest was reported by the authors. Funding This research was funded by the social development project of key research and development plan of Shaanxi province, China (No. 2022SF-163). Author Contribution Li Wang conceived the study and wrote the manuscript. Xinling Wen, Fen Li and Xuewen Yu provided participants and collated data. All authors have given final approval of the article to be published. 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J Cell Biochem. 2019;120(6):10337–41. Zhao H, Zhang J, Cheng X, et al. Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment. J Ovarian Res. 2023;16:9. Jamka M, Woźniewicz M, Walkowiak J, et al. The effect of vitamin D supplementation on selected inflammatory biomarkers in obese and overweight subjects: a systematic review with meta-analysis. Eur J Nutr. 2016;55:2163–76. Gagnon C, Daly RM, Carpentier A, et al. Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and β-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: a pilot randomized, placebo-controlled trial. PLoS ONE. 2014;9:e109607. Mohan A, Haider R, Fakhor H, et al. Vitamin D and polycystic ovary syndrome (PCOS): a review. Ann Med Surg. 2023;85(7):3506–11. Lagowska K, Bajerska J, Jamka M. The role of vitamin D oral supplementation in insulin resistance in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2018;10:1637. Menichini D, Facchinetti F. Effects of vitamin D supplementation in women with polycystic ovary syndrome: a review. Gynecol Endocrinol. 2020;36:1–5. Wei Z, Yoshihara E, He N, et al. Vitamin D switches BAF complexes to protect β Cells. Cell. 2018;173:1135–49. Dong B, Zhou Y, Wang W, et al. Vitamin D receptor activation in liver macrophages ameliorates hepatic inflammation, steatosis, and insulin resistance in mice. Hepatology. 2020;71:1559–74. Gupta T, Rawat M, Gupta N, et al. Study of effect of vitamin D supplementation on the clinical, hormonal and metabolic profile of the PCOS women. J Obstet Gynaecol India. 2017;67:349–55. Ardabili HR, Gargari BP, Farzadi L. Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency. Nutr Res. 2012;32:195–201. Asemi Z, Foroozanfard F, Hashemi T, et al. Calcium plus vitamin D supplementation affects glucose metabolism and lipid concentrations in overweight and obese vitamin D deficient women with polycystic ovary syndrome. Clin Nutr. 2015;34:586–92. Asano L, Watanabe M, Ryoden Y, et al. Vitamin D metabolite, 25-Hydroxyvitamin D, regulates lipid metabolism by inducing degradation of SREBP/SCAP. Cell Chem Biol. 2017;24:207–17. Zhu W, Cai D, Wang Y, et al. Calcium plus vitamin D3 supplementation facilitated fat loss in overweight and obese college students with very-low calcium consumption: a randomized controlled trial. Nutr J. 2013;12:8. Wehmeier KR, Mazza A, Hachem S, et al. Differential regulation of apolipoprotein A-I gene expression by vitamin D receptor modulators. Biochim Biophys Acta. 2008;1780:264–73. Cho HJ, Kang HC, Choi SA, et al. The possible role of Ca2 + on the activation of microsomal triglyceride transfer protein in rat hepatocytes. Biol Pharm Bull. 2005;28:1418–23. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 16 Jul, 2024 Read the published version in Journal of Ovarian Research → Version 1 posted Editorial decision: Revision requested 26 Jun, 2024 Reviews received at journal 26 Jun, 2024 Reviewers agreed at journal 24 Jun, 2024 Reviews received at journal 11 May, 2024 Reviewers agreed at journal 18 Apr, 2024 Reviewers agreed at journal 06 Mar, 2024 Reviewers invited by journal 05 Mar, 2024 Editor assigned by journal 29 Feb, 2024 Submission checks completed at journal 29 Feb, 2024 First submitted to journal 28 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3996462","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":275806253,"identity":"660fc689-f74a-4364-8eb4-809fc53266da","order_by":0,"name":"Xinling Wen","email":"","orcid":"","institution":"The First Affiliated Hospital of Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Xinling","middleName":"","lastName":"Wen","suffix":""},{"id":275806254,"identity":"aada1e3b-14c5-45be-9d14-f26914bfa536","order_by":1,"name":"Fen Li","email":"","orcid":"","institution":"The First Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Fen","middleName":"","lastName":"Li","suffix":""},{"id":275806255,"identity":"3c7dd99c-ff5e-4f79-bd22-f98c10760f56","order_by":2,"name":"Xuewen Yu","email":"","orcid":"","institution":"The First Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Xuewen","middleName":"","lastName":"Yu","suffix":""},{"id":275806256,"identity":"56379577-422b-42cd-8eec-74801e905c64","order_by":3,"name":"Li Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIie3PsQrCMBCA4SuBdAm6KhV9hZNCcAj2VQqFuATpI/QBBFcfw0coBnVRXDs4FARxcIibg4OtnVzajoL5t4P74A7AZvvVchSMErI3BsW0HQlRDjoulc4qllFLAloMu4wTZjZO0rSN+6O+hbEsDgN+EZgScPV2XUsOczkJP7/AzFd47gCTMqsjPFUci19KknoKrwR6jNeT070kuiBO4k1QO0kjyZSfV4RQD9qQILtzqA6jZLxAGdGmX/pL5RvzEsFoeXrkz5eYdl29qyVFtPc9NqyXEdNiyWaz2f65N56dRSMaVgT8AAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":true,"prefix":"","firstName":"Li","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-02-28 11:07:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3996462/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3996462/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13048-024-01473-6","type":"published","date":"2024-07-16T16:05:18+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":52042907,"identity":"64113988-042b-4262-82fd-a08b836e3d90","added_by":"auto","created_at":"2024-03-05 18:47:10","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":120782,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of study participation\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3996462/v1/76ad3376311917b393f6af65.jpg"},{"id":52042905,"identity":"e1cf90c6-688a-4cc4-8eed-31df71fb4c21","added_by":"auto","created_at":"2024-03-05 18:47:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":93629,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of biochemical metabolic parameters between the two groups (A: Blood glucose concentrations at different time points of OGTT, B: Serum insulin concentrations at different time points of OGTT, C: HOMA-IRat different time points of OGTT, D: Blood lipid parameters. * \u003cem\u003eP \u0026lt; \u003c/em\u003e0.05)\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3996462/v1/3457bf24e2e52e362f5ef03f.jpg"},{"id":52042906,"identity":"1dfe3c33-55f2-4f58-8ff8-4d7cd96ea489","added_by":"auto","created_at":"2024-03-05 18:47:09","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":129554,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of biochemical metabolic parameters among the four groups (A: Blood glucose concentrations at different time points of OGTT, B: Blood insulin concentrations at different time points of OGTT, C: HOMA-IRat different time points of OGTT, D: Blood lipid parameters. * \u003cem\u003eP \u0026lt; \u003c/em\u003e0.05)\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3996462/v1/efba1765046608767300d737.jpg"},{"id":52042903,"identity":"346f5bb5-040d-4eee-a0ac-83b576d8d833","added_by":"auto","created_at":"2024-03-05 18:47:08","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":104709,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of metabolic parameters among the four groups (A: BMI, B: WHR, C: SBP and DPB, D: Blood lipid parameters. * \u003cem\u003eP \u0026lt; \u003c/em\u003e0.05)\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3996462/v1/f038945ede3ba0cd401835ac.jpg"},{"id":61595108,"identity":"0b6069a9-b4e0-4d97-a8af-3360e505be7c","added_by":"auto","created_at":"2024-08-01 17:20:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1155169,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3996462/v1/7e190a4d-9d3a-4a1d-9fbc-9f46ca51674b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of vitamin D supplementation on metabolic parameters of women with polycystic ovary syndrome: a randomized controlled trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePolycystic ovary syndrome (PCOS) is the most common reproductive, endocrine, and metabolic disorders affecting 6\u0026ndash;10% of reproductive-age women all over the world [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Women with PCOS are often identified with symptoms of menstrual disorder, infertility due to ovulation dysfunction, hirsutism, acne and metabolic disorder. Previous studies have confirmed that PCOS is associated with metabolic disorders, such as type 2 diabetes (T2DM), dyslipidemia, cardiovascular disease (CVD), atherosclerosis, metabolic syndrome (MS), nonalcoholic fatty liver disease (NAFLD), and ultimately cirrhosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In recent years, these metabolic problems in PCOS women attracted the attention of scholars worldwide. A systematic review and meta-analysis showed that 40\u0026ndash;50% of women suffering from PCOS have impaired glucose tolerance (IGT), insulin resistance (IR) and compensatory hyperinsulinaemia (HI) and that approximately 10% of these women will develop T2DM [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Additionally, PCOS women are prone to dyslipidemia, including higher levels of triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) than healthy women [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe molecular action of vitamin D is involved in maintaining the normal resting levels of reactive oxygen species (ROS) and Ca\u003csup\u003e2+\u003c/sup\u003e, not only in pancreatic β-cells, but also in insulin responsive tissues. Vitamin D prevents epigenetic alterations associated with IR, and vitamin D deficiency is one of the factors accelerating IR formation [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Additionally, studies have confirmed that vitamin D supplementation reduce the level of metabolic parameters such as TC, LDL-C, TG, glycated hemoglobin (HbA1c), as well as decreases HOMA-IR in patients with T2DM [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMultiple epidemiological data worldwide have confirmed that vitamin D deficiency and insufficiency are common in women with PCOS, especially in those with obesity or IR [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. A recent meta-analysis displayed that 67\u0026ndash;85% PCOS women had vitamin D deficiency [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, the effects of vitamin D supplementation on metabolic parameters of women with PCOS are controversial. Some of studies shown beneficial effects of vitamin D supplementation on glucose metabolism, IR, dyslipidemia, cardiovascular risk factors, liver markers, metabolic profiles and NAFLD [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Nevertheless, other studies suggested that vitamin D supplementation had no significant effect on metabolic and endocrine parameters in PCOS women [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn recent years, the therapeutic schedule for PCOS women are improvement of patient\u0026rsquo;s clinical symptoms and treatment of infertility. However, this may not be completely effective in preventing long-term complications, such as metabolic disorders, DM, dyslipidemia, CVD, NAFLD and endometrial carcinoma. These long-term complications can seriously affect women's health and quality of life. The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters of women with PCOS.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eWe conducted a randomized controlled trial (RCT) study on PCOS patients with vitamin D deficiency or insufficiency in the First Affiliated Hospital of Xi\u0026rsquo;an Jiaotong University from January 2021 to June 2023. All participants gave written informed consent on the basis of procedures granted by the Ethics Committee of The First Affiliated Hospital of Medical College of Xi\u0026rsquo;an Jiaotong University (XJTU1AF2021LSK-207). This study has been registered on China\u0026rsquo;s clinical trials registration: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.chictr.org.cn\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.chictr.org.cn\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (ChiCTR2100048736).\u003c/p\u003e \u003cp\u003eSixty-eight PCOS women were enrolled in this study. All patients were aged 21\u0026ndash;34 years. The diagnostic criteria of PCOS was based on a modified Rotterdam criteria: menstrual abnormalities (oligomenorrhea, amenorrhea, or irregular uterine bleeding), combined with either hyperandrogenaemia or polycystic ovarian morphology (PCO) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Hyperandrogenaemia was identified as either clinical manifestations or laboratory evidence. Laboratory evidence was defined as an abnormally increased testosterone level. Clinical manifestations included hirsutism or acne. Hirsutism was defined as a modified Ferriman-Gallwey score of more than 3 at the time of physical examination. PCO was identified as the presence of 12 or more follicles in unilateral ovary or bilateral ovaries measuring 2\u0026ndash;9 mm in diameter, and/or ovarian volume\u0026thinsp;\u0026ge;\u0026thinsp;10 ml. Ovarian volume\u0026thinsp;=\u0026thinsp;0.5 \u0026times; length diameter \u0026times; transverse diameter \u0026times; anteroposterior diameter. Participants who were diagnosed with tumor secreting androgens, thyroid dysfunction, hyperprolactinemia, hypothalamic amenorrhea, Cushing\u0026rsquo;s syndrome, congenital adrenal hyperplasia (CAH), premature ovarian insufficiency (POI), premature ovarian failure (POF), hypercalcemia, malabsorption disorders and diabetes mellitus were excluded. In addition, participants who used corticosteroids, hypolipidemic agents, calcium supplements, or any other drugs known to affect vitamin D metabolism were also excluded from the study.\u003c/p\u003e \u003cp\u003eThe baseline data of PCOS women were collected by questionnaire in a face-to-face interview, such as age, body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, marital status, gravidity, parity, employment status, family history and outdoor exercise. BMI\u0026thinsp;\u0026ge;\u0026thinsp;30.0 kg/m\u003csup\u003e2\u003c/sup\u003e was defined as obesity [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSixty-eight PCOS women were enrolled initially in this RCT study, 8 women with normal serum vitamin D level were excluded. Then, sixty PCOS women with vitamin D deficiency or insufficiency were randomly divided into vitamin D group or control group, and 30 participants in each group. Two participants in the vitamin D group and 1 participant in the control group were lost to follow-up. Finally, 57 participants (vitamin D group, n\u0026thinsp;=\u0026thinsp;28. control group, n\u0026thinsp;=\u0026thinsp;29) completed the 12 weeks study period (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of serum vitamin D\u003c/h2\u003e \u003cp\u003e25-hydroxyvitamin D3 [ 25(OH)D ] is the primary circulating form of vitamin D, which is the most abundant vitamin D metabolite and considered as the best parameter of vitamin D status within the human body. Therefore, serum 25(OH)D was detected by chemiluminescence method. According to the Institute of Medicine (IOM) and World Health Organization (WHO), vitamin D deficiency was defined as serum 25 (OH) D concentration lower than 20 ng/mL, and vitamin D insufficiency was defined as a concentration of 20\u0026ndash;\u003cem\u003e\u0026lt;\u003c/em\u003e30 ng/mL. Serum 25(OH)D concentration of 30\u0026ndash;50 ng/mL were regarded as normal [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eDetection of biochemical indicators\u003c/h2\u003e \u003cp\u003eAll biochemical indicators in this study were detected in the clinical laboratory of our hospital. The basic sex hormone concentrations and anti-Mullerian hormone (AMH) concentration were tested during 2\u0026ndash;4 days of natural menstrual cycle or progesterone withdrawal bleeding using chemiluminescence method. Sex hormone included follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E\u003csub\u003e2\u003c/sub\u003e), progesterone (P) and testosterone (T). All participants were given 83 g oral glucose for oral glucose tolerance test (OGTT) and insulin release test. The blood glucose was detected by hexokinase method. Serum insulin level was detected through radioimmunoassay. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to evaluate IR. HOMA-IR = [fasting glucose (mmol/L) \u0026times; fasting insulin (mU/L)]/22.5. A HOMA-IR\u0026thinsp;\u0026gt;\u0026thinsp;3.0 was defined as IR, and an insulin level after oral glucose powder intake 10 times higher than the fasting level was also defined as IR [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. At the same time, the blood lipids were detected using automatic biochemical analyzer, including TC, TG, LDL-C and high-density lipoprotein cholesterol (HDL-C).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eSample size\u003c/h2\u003e \u003cp\u003eSample size was calculated provided that serum 25(OH)D concentration and glucose metabolism and lipid metabolism indicators were the primary outcomes. According to the method reported in previous literatures, sample size was calculated with the following parameters: probability of type one error (α) of 0.05 and type two error (β) of 0.20 (power\u0026thinsp;=\u0026thinsp;80%), difference between two means to be detected was 0.52, expected background standard deviation was 1. Based on this, we needed 27 participants in each group. Considering a follow-up rate of 3 participants per group, we needed to have 30 participants in each group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eRandomization and intervention\u003c/h2\u003e \u003cp\u003eAll participants were randomly divided into vitamin D group or control group by means of computer-generated random numbers. Participants in vitamin D group received basic treatment combined with vitamin D supplementation (2000 IU/day). Basic treatment included a proper diet and aerobic exercise outdoors at least three times per week. Each aerobic exercise lasted at least 30 minutes. Participants in control group were only given basic treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcome measures\u003c/h2\u003e \u003cp\u003eThe primary outcomes were the serum 25(OH)D concentration, glucose metabolism, insulin concentration and lipid metabolism indicators. The secondary outcomes were general metabolic parameters, including BMI, WHR and blood pressure.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using SPSS version 20.0 (IBM, Armonk, NY, USA). The continuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and were performed by the Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test or variance analysis. Differences in dichotomous outcomes were given as number and percentage (%), which were compared by chi-square test. \u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eBaseline data\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the baseline data of women between the two groups. No significant difference was found when comparing the baseline data between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline data of women between the two groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVitamin D group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.764\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.812\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e109.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107.6\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.714\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.256\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarital status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.705\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (37.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (62.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGravidity (number)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.798\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity (number)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.609\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmployment status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.561\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWorking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (82.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (75.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-working\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.723\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.957\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyroid diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.669\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutdoor exercise\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.561\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1 times daily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (82.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (75.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasal concentration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH (mIU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.568\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLH (mIU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.609\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePRL (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.544\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE\u003csub\u003e2\u003c/sub\u003e (pmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136.4\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.312\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT (nmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.377\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP (nmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.459\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAMH (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.780\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum 25(OH)D detection time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.974\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpring\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSummer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (32.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutumn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (20.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWinter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum 25(OH)D\u003c/p\u003e \u003cp\u003econcentrations (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.517\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin D status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.786\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (82.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (79.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsufficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (20.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBGC (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFasting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.879\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 hour after OGTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.776\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2 hour after OGTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 hour after OGTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.902\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin level (mIU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFasting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 hour after OGTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e312.5\u0026thinsp;\u0026plusmn;\u0026thinsp;56.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e297.6\u0026thinsp;\u0026plusmn;\u0026thinsp;49.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.204\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2 hour after OGTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e206.8\u0026thinsp;\u0026plusmn;\u0026thinsp;44.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e187.5\u0026thinsp;\u0026plusmn;\u0026thinsp;40.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.290\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 hour after OGTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.3\u0026thinsp;\u0026plusmn;\u0026thinsp;11.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.576\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHOMA IR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFasting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.145\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 hour after OGTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e127.8\u0026thinsp;\u0026plusmn;\u0026thinsp;19.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130.1\u0026thinsp;\u0026plusmn;\u0026thinsp;21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.690\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2 hour after OGTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.2\u0026thinsp;\u0026plusmn;\u0026thinsp;15.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.887\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 hour after OGTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.468\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTG (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.443\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTC (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.865\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL-C (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.409\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL-C (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.357\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003ea\u003c/sup\u003e T-test or chi-square test. Data given as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or number (%).\u003c/p\u003e \u003cp\u003eSBP: systolic blood pressure, DBP: diastolic blood pressure.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSerum vitamin D concentrations\u003c/h2\u003e \u003cp\u003eThe data in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e illustrate that the serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In addition, with the extension of treatment time, the serum 25(OH)D concentration gradually increased.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe serum 25(OH)D concentrations at baseline and different times after treatment (ng/mL).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVitamin D group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e12.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e13.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.517\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 weeks after treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e21.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8 weeks after treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e32.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12 weeks after treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e44.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e13.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003ea\u003c/sup\u003e T-test. Data given as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEffects of vitamin D supplementation on general metabolic parameters\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e demonstrates the general metabolic parameters between the two groups. The data reveal that BMI and WHR of women in Vitamin D group 12 weeks of treatment were significantly reduced compared with baseline (\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05). In addition, the above parameters 12 weeks of treatment in vitamin D group were also significant lower than that in women of control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048). However, no significant difference was found when comparing SBP and DPB between baseline and different times after treatment (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). These significant differences after treatment were also not observed between vitamin D group and control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.675, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.326).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe effects on general metabolic parameters between the two groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eVitamin D group (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 weeks\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eChange\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12 weeks\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eChange\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e23.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003csup\u003e▲\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e24.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e24.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003csup\u003e▲\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-0.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.307\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e109.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e106.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.431\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e107.6\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e105.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.685\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDPB (mm Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e78.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e76.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e-1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.309\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c7\"\u003e \u003cp\u003e75.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c8\"\u003e \u003cp\u003e73.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c9\"\u003e \u003cp\u003e-1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.443\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003ea\u003c/sup\u003e T-test. Data given as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e \u003cp\u003e \u003csup\u003e▲\u003c/sup\u003eVitamin D group vs. Control group after 12 weeks of treatment, \u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eEffects of vitamin D supplementation on biochemical metabolic parameters\u003c/h2\u003e \u003cp\u003eThe biochemical metabolic parameters at 12 weeks after treatment were detected between the two groups. The serum insulin concentrations at fasting, 1 h, 2 h and 3h after OGTT in women of Vitamin D group were significantly lower than that in control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.046, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041). The HOMA-IR at the above time point were also lower compared with control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.033, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047). Moreover, the TG, TC and LDL-C concentrations in women of vitamin D group were significantly lower than that in control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034). However, no significant difference was found when comparing blood glucose concentrations at different time points of OGTT and HDL-C concentration between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.342\u0026ndash;0.835) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAll participants were divided into four groups according to BMI: vitamin D group (obesity) (n\u0026thinsp;=\u0026thinsp;8), vitamin D group (non-obesity) (n\u0026thinsp;=\u0026thinsp;20), control group (obesity) (n\u0026thinsp;=\u0026thinsp;10), control group (non-obesity) (n\u0026thinsp;=\u0026thinsp;19). The biochemical metabolic parameters at baseline and 12 weeks after treatment were detected among the four groups. The serum insulin concentrations at fasting, 1 h, 2 h and 3h after OGTT in women of vitamin D group (obesity) were significantly lower than that in control group (obesity) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.043). Additionally, the HOMA-IR at the above time point OGTT, TG concentration, TC concentration and LDL-C concentration were also significantly reduced in vitamin D group (obesity) compared with women in control group (obesity) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018\u0026ndash;0.049). Nevertheless, no significant difference was observed of the biochemical metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.317\u0026ndash;0.806) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn addition, all participants were divided into four groups according to HOMA-IR: vitamin D group (IR) (n\u0026thinsp;=\u0026thinsp;17), vitamin D group (non-IR) (n\u0026thinsp;=\u0026thinsp;11), control group (IR) (n\u0026thinsp;=\u0026thinsp;19), control group (non-IR) (n\u0026thinsp;=\u0026thinsp;10). The BMI, WHR, TG concentration, TC concentration and LDL-C concentration in women of vitamin D group (IR) were significantly lower than that in control group (IR) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022\u0026ndash;0.047). However, no significant difference was seen observed when comparing the above parameters between vitamin D group (non-IR) and control group (non-IR) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.257\u0026ndash;0.913). In addition, no significant difference was observed in SBP and DPB among the four groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.897, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.926) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePCOS is a multiple metabolic disorders syndrome characterized by obesity, IR, dyslipidemia and other metabolic abnormalities. Studies have confirmed that PCOS women are prone to obesity, IGT, IR, and about 10% of them will progresses to T2DM. In addition, women with PCOS also have an increased risk of cardiovascular disease, hypertension (3 to 5 times higher than normal women, with increased SBP), NAFLD, abnormal lipid metabolism (increased TG and LDL-C levels) and MS [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. IR occurs in women with PCOS, is significantly associated with different metabolic disorders including increased aromatase activity, elevated androgen secretion, and damaged progesterone synthesis in granulosa cells [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Accumulating evidence suggests that vitamin D deficiency and insufficiency are important factors in the pathogenesis of IR, metabolic disorders and CVD in PCOS [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Indeed, a high prevalence of vitamin D deficiency is observed among PCOS women, especially in those women with obesity or IR [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIt has been proven that insulin secretion is a calcium-dependent process, so vitamin D may affect pancreatic β-cells through the regulation of calcium concentrations [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Also, a beneficial effect of combined vitamin D and calcium on glucose metabolism and lipid profiles in patients with T2DM has previously been reported [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, the effects of vitamin D supplementation on metabolic parameters of women with PCOS are controversial. The data in our study demonstrated that significant increases in vitamin D concentrations were shown at different time points after vitamin D supplementation. Furthermore, with the extension of treatment time, the serum 25(OH)D concentration gradually increased. The BMI, WHR, serum insulin concentrations and HOMA-IR in women of vitamin D group were significantly lower than that in control group. Although IR is not within any of the diagnostic criteria of PCOS in different countries, it occurs in most lean and overweight women with PCOS, who have a form of IR intrinsic and the compensatory hyperinsulinaemia drives many of the phenotypic features of PCOS. Additionally, compared with lean PCOS women, women with obesity are more likely to accompany IR. In fact, obesity and IR interact with each other and form a vicious cycle, which are also difficult to treat clinically. Vitamin D dramatically improves glucose metabolism by increasing insulin production, insulin receptor expression and reducing pro-inflammatory cytokines [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Findings from the current study revealed that the serum insulin concentrations and HOMA-IR at different time points of OGTT in women of vitamin D group (obesity) were significantly lower than that in control group (obesity). Moreover, the BMI, WHR, TG concentration, TC concentration and LDL-C concentration in women of vitamin D group (IR) were significantly lower than that in control group (IR). Nevertheless, no significant difference was seen in metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity), as well as between vitamin D group (non-IR) and control group (non-IR). A systematic review and meta-analysis of RCT reported that PCOS women with continuous low dose of vitamin D supplementation improve fasting glucose concentration and HOMA-IR, but the meta-analysis included studies of vitamin D in combination with other micronutrients [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Similarly, Menichini et al. confirmed that vitamin D supplementation (4000 IU/day) for a period of at least 12 weeks lead to improvement in terms of glucose level, insulin sensitivity, hyperlipidemia, and hormonal functionality in PCOS women [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe mechanism for vitamin D improving IR includes the following aspects: (a) Vitamin D receptor (VDR) is a key modulator of inflammation and β cell survival, whihc restored β cell function and ameliorate hyperglycemia in murine T2D models [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. (b) Vitamin D increases insulin responsiveness for glucose transport through the binding of 1,25(OH)2D-VDR complex to the vitamin D response element of the insulin receptor [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. (c) Vitamin D regulates the extracellular and intracellular calcium concentration, which is important for the mediation of glucose transport in the target tissues [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Nevertheless, Trummer et al. reported that Vitamin D supplementation had no significant effect on metabolic and endocrine parameters in PCOS [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Similarly, Ardabili et al. displayed that the fasting serum insulin and glucose levels, the insulin sensitivity and HOMA-IR did not change significantly by the end of the study [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The different results may be explained by different types of studies, dose and time of vitamin D supplementation, treatment with vitamin D alone or with other micronutrients, participants with pre-processed or not, lifestyles of the participants, place of residence and so on.\u003c/p\u003e \u003cp\u003eOur findings demonstrated that compared to control group, vitamin D supplementation significantly improved dyslipidemia in PCOS women with vitamin D deficiency and insufficiency, including reduced the serum TG, TC and LDL-C concentrations. Additionally, the serum TG, TC and LDL-C concentrations in women of vitamin D group (obesity) were significantly lower than that in control group (obesity). Similarly, some studies shown that vitamin D supplementation plus Calcium for eight weeks among vitamin D deficient women with PCOS had beneficial effects on serum TG and VLDL-cholesterol levels, but it did not affect other lipid profiles [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that control lipid homeostasis. Asano et al. screened a chemical library of endogenous molecules and identified 25-hydroxyvitamin D (25OHD) as an inhibitor of SREBPs activation. They found that vitamin D may regulate lipoprotein lipase gene expression and therefore, might decrease serum TC concentration [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, the beneficial effect of vitamin D supplementation on lipid profiles was not found in other studies [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Different study designs and dosages of vitamin D supplementation, baseline data of participants might provide explanation for different results. Several mechanisms can explain the effects of vitamin D supplementation on serum TG and VLDL-cholesterol levels. On the one hand, 1,25-dihydroxy-cholecalciferol represses the expression of the apolipoprotein A-I (apo A-I) gene in hepatocytes, and vitamin D receptor modulators in hepatocytes and intestinal cells differentially regulate expression of the apo A-I gene [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. On the other hand, the increased intracellular Calcium due to vitamin D supplementation in liver leads to stimulating microsomal triglycerides transfer protein (MTP), which is implicated in the formation and secretion of VLDL, and then results in decreased serum TG and VLDL-cholesterol levels [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. However, the effect of vitamin D supplementation on lipid profiles in PCOS patients and its specific mechanism still needs further exploration.\u003c/p\u003e \u003cp\u003eSome limitations must be considered in this study. First, this was a single-centre RCT study in the city of Xi\u0026rsquo;an in Shaanxi, China. Second, the metabolic parameters observed in this study were relatively limited, and androgen metabolic parameters and inflammatory indicators were not observed. Therefore, future studies are required to confirm the effectiveness of vitamin D on metabolic parameters of PCOS women, and the specific regulation mechanism are also need to be further explored.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study provides evidence that vitamin D supplementation significantly increased serum vitamin D concentration in PCOS women with vitamin D deficiency and insufficiency. Furthermore, this RCT study supports beneficial effects of vitamin D supplementation on metabolic parameters of PCOS women, including significant improvements in BMI, WHR, serum insulin concentrations and HOMA-IR, lipid metabolism parameters, especially in women with obesity or IR.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflicts of Interest\u003c/h2\u003e \u003cp\u003eNo potential conflict of interest was reported by the authors.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research was funded by the social development project of key research and development plan of Shaanxi province, China (No. 2022SF-163).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eLi Wang conceived the study and wrote the manuscript. Xinling Wen, Fen Li and Xuewen Yu provided participants and collated data. All authors have given final approval of the article to be published.\u003c/p\u003e\u003ch2\u003eData availability statement\u003c/h2\u003e \u003cp\u003eAll datasets generated for this study are included in the article. Further inquiries can be directed to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTeede HJ, Tay CT, Laven JJE, et al. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. J Clin Endocrinol Metab. 2023;108(10):2447\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenham JL, Goldberg A, Teede H, et al. Polycystic ovary syndrome: associations with cardiovascular disease. Climacteric. 2024;27(1):47\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWimalawansa SJ. Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome. 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Calcium plus vitamin D3 supplementation facilitated fat loss in overweight and obese college students with very-low calcium consumption: a randomized controlled trial. Nutr J. 2013;12:8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWehmeier KR, Mazza A, Hachem S, et al. Differential regulation of apolipoprotein A-I gene expression by vitamin D receptor modulators. Biochim Biophys Acta. 2008;1780:264\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho HJ, Kang HC, Choi SA, et al. The possible role of Ca2\u003csup\u003e+\u003c/sup\u003e on the activation of microsomal triglyceride transfer protein in rat hepatocytes. Biol Pharm Bull. 2005;28:1418\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"vitamin D supplementation, polycystic ovary syndrome, vitamin D deficiency, vitamin D insufficiency, metabolic parameters, insulin resistance","lastPublishedDoi":"10.21203/rs.3.rs-3996462/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3996462/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003ePolycystic ovary syndrome (PCOS) is a common reproductive endocrine and metabolic disease. The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters of PCOS women.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 60 PCOS women with vitamin D deficiency or insufficiency were enrolled in this randomized controlled trial. Participants were randomized to vitamin D group (2000 IU/day) or control group. The observational parameters were measured at baseline and after treatment (4 weeks, 8 weeks and 12 weeks), including body mass index (BMI), waist to hip ratio (WHR), blood pressure, oral glucose tolerance test (OGTT) and insulin release test, and lipid metabolism parameters.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In addition, with the extension of treatment time, the serum 25(OH)D concentration gradually increased. The BMI, WHR, insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in women of Vitamin D group after 12 weeks of treatment were significantly lower than that in women of control group (\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05). Additionally, The serum insulin concentrations and HOMA-IR at different time points of OGTT, serum TG, TC and LDL-C concentrations in women of vitamin D group (obesity) were significantly lower than that in control group (obesity) (\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05). The BMI, WHR, TG, TC and LDL-C concentration in women of vitamin D group (IR) were significantly lower compared with control group (IR) (\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05). No significant difference was seen in metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), and these differences of metabolic parameters were also not observed between vitamin D group (non-IR) and control group (non-IR) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe findings of this study supported that vitamin D supplementation had beneficial effects on metabolic parameters of PCOS women, especially in women with obesity or IR.\u003c/p\u003e","manuscriptTitle":"Effects of vitamin D supplementation on metabolic parameters of women with polycystic ovary syndrome: a randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-05 18:47:02","doi":"10.21203/rs.3.rs-3996462/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-26T05:47:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-26T04:33:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"251028572483223606202857399352484862507","date":"2024-06-24T12:34:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-11T22:53:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"9d158d25-f954-47d7-a287-15fc3cbd9718","date":"2024-04-18T08:46:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"0070d96b-a169-4436-861a-d2476b9a924c","date":"2024-03-06T14:44:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-05T06:58:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-01T02:34:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-29T12:39:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Ovarian Research","date":"2024-02-28T11:04:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"49ccee9f-ba26-4356-8e59-34914673b377","owner":[],"postedDate":"March 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-01T16:18:10+00:00","versionOfRecord":{"articleIdentity":"rs-3996462","link":"https://doi.org/10.1186/s13048-024-01473-6","journal":{"identity":"journal-of-ovarian-research","isVorOnly":false,"title":"Journal of Ovarian Research"},"publishedOn":"2024-07-16 16:05:18","publishedOnDateReadable":"July 16th, 2024"},"versionCreatedAt":"2024-03-05 18:47:02","video":"","vorDoi":"10.1186/s13048-024-01473-6","vorDoiUrl":"https://doi.org/10.1186/s13048-024-01473-6","workflowStages":[]},"version":"v1","identity":"rs-3996462","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3996462","identity":"rs-3996462","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}