Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency
Introduction
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Polycystic ovary syndrome is characterized by hyperandrogenism and chronic anovulation [1]. The prevalence of PCOS in women of reproductive age is estimated to be 6.4% to 6.8% worldwide [2]. Currently, PCOS is defined by the presence of having at least 2 of the following criteria: irregular or absent ovulation, elevated levels of androgenic hormones, and enlarged ovaries containing at least 12 follicles each [3]. Of women with PCOS, 50% to 70% are insulin resistant [4]. Current evidence shows that insulin resistance has a central role in the etiology of PCOS [1]. It appears that insulin resistance and compensatory hyperinsulinemia cause hyperandrogenism [5] and obesity [6], and in addition, insulin resistance is a risk factor for impaired glucose tolerance and type 2 diabetes mellitus [7].
There is some evidence that vitamin D deficiency is related to impaired glucose clearance and insulin secretion in animal [8] and human models [9]. Vitamin D has different functions and potential effects in addition to calcium homeostasis. Vitamin D receptors exist in tissues, such as pancreatic islet cells and the ovaries. These findings show the complex effect of vitamin D on human metabolism [10]. Liu et al [11] showed that the plasma 25-hydroxyvitamin D (25 [OH] D) concentration is inversely associated with the fasting blood glucose level and insulin resistance. One recent prospective study demonstrated an inverse association between the baseline serum 25 (OH) D level and the 10-year risk for hyperglycemia and insulin resistance [12]. Pittas et al [13] confirmed that patients with impaired fasting glucose who used cholecalciferol plus calcium supplementation for 3 years had a lower increase in insulin resistance in comparison with a control group.
It has been suggested that a vitamin D deficiency is a problem in patients with PCOS [14], [15]. A recent study confirmed that increased body weight has a negative effect on serum 25 (OH) D concentrations [16], as well as parathyroid hormone (PTH) levels [17], in women with PCOS.
It should be mentioned that there have only been 2 small intervention studies with vitamin D supplementation on glucose metabolism in PCOS patients [14], [18]. With attention to the scarcity of the data on the subject, the aim of the current study was to determine the effect of oral cholecalciferol administration on insulin sensitivity and glucose metabolism indices in women with PCOS who are vitamin D deficient in a randomized, placebo-controlled, double-blinded model. We hypothesized that vitamin D supplementation would lower glucose levels and insulin resistance in women with PCOS who are vitamin D deficient. To test this hypothesis, we administered 3 doses of cholecalciferol to women with PCOS and vitamin D deficiency, and the serum glucose, insulin, PTH, and 25 (OH) D levels and insulin resistance were measured before and after supplementation.
Section snippets
Study participants
Women with PCOS were recruited from the academic outpatient clinic at Alzahra Hospital of the Tabriz University of Medical Sciences. Of 170 patients with PCOS, 60 vitamin D–deficient women were selected for the study. The sample size calculation showed that 25 subjects would be required for each arm of the trial to detect a change of 1.2 in the homeostasis model assessment of insulin resistance (HOMA-IR) with 80% power and 5% significance. The standard deviation (SD) was assumed to be 1.48 [18]
Results
Of 80 patients who met the selection criteria, 60 were accepted to participate in the study. Fifty patients completed the study (vitamin D group, n = 24; placebo group, n = 26). The details of the study design and subjects lost to follow-up are illustrated in Fig. 1.
The mean ± SD for age, BMI, and 25 (OH) D level of the 50 patients were 26.9 ± 4.2 years, 28.7 ± 4.1 kg/m2, and 7.4 ± 2.8 ng/mL, respectively. At the beginning of the study, 25 (OH) D was undetectable (<4 ng/mL) in 4 subjects (2
Discussion
In the current study, 3 oral doses of cholecalciferol (1250 μg [50 000 IU]) for 2 months did not demonstrate any improvement in insulin resistance and insulin sensitivity in women with PCOS and vitamin D deficiency. However, the HOMA-B increased significantly in the supplemented group compared with baseline, although the changes were not significant in comparison with the placebo group.
Several epidemiologic studies have shown a negative association between serum 25 (OH) D levels and
Acknowledgment
This article was written based on a dataset of MS thesis, registered in Tabriz University of Medical Sciences. The present study was funded by Nutritional Research Center (grant number: 5/71/479, 1389/5/24) and vice chancellor of research (grant number: 5/4/4151, 1389/6/4) of Tabriz University of Medical Sciences, Tabriz, Iran. There is no conflict of interest.
References (36)
- et al.
Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome
Fertil Steril
(2009) What is the optimal vitamin D status for health?
Prog Biophys Mol Biol
(2006)Geographic location and vitamin D synthesis
Mol Aspects Med
(2008)- et al.
Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus
Am J Clin Nutr
(1994) - et al.
Glucose tolerance and vitamin D: effects of treating vitamin D deficiency
Nutrition
(2008) - et al.
Validation of the insulin sensitivity index (ISI (0,120)): comparison with other measures
Diabetes Res Clin Pract
(2000) Polycystic ovary syndrome
N Engl J Med
(1995)- et al.
The prevalence and features of the polycystic ovary syndrome in an unselected population
J Clin Endocrinol Metab
(2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome
Hum Reprod
(2004)- et al.
Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls
Obstet Gynecol Surv
(2004)
Insulin resistance and polycystic ovary syndrome
Curr Diab Rep
Molecular mechanisms of insulin resistance in polycystic ovary syndrome
Trends Mol Med
Insulin resistance in PCOS
Endocrine
Influence of vitamin D3 deficiency and 1, 25 dihydroxyvitamin D3 on de novo insulin biosynthesis in the islets of the rat endocrine pancreas
J Endocrinol
The vitamin D receptor gene variant and physical activity predicts fasting glucose levels in healthy young men
Diabet Med
Vitamin D and diabetes mellitus
Endocrine
Plasma 25-hydroxyvitamin D is associated with markers of the insulin resistant phenotype in nondiabetic adults
J Nutr
Baseline serum 25-hydroxyvitamin D is predictive of future glycemic status and insulin resistance. The Medical Research Council Ely Prospective Study 1990-2000
Diabetes
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