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  • Author: Barbara R Obermayer-Pietsch x
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Elisabeth Wehr, Olivia Trummer, Albrecht Giuliani, Hans-Jürgen Gruber, Thomas R Pieber and Barbara Obermayer-Pietsch

Introduction

Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances including insulin resistance (IR), which might be related to vitamin D metabolism. We aimed to investigate the association of polymorphisms in the vitamin D receptor (VDR) gene as well as vitamin D level-associated genes with metabolic and endocrine parameters in PCOS women. Moreover, we examined whether there are associations with PCOS susceptibility.

Methods

Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed in 545 PCOS and 145 control women. Genotyping of VDR (Cdx2, Bsm-I, Fok-I, Apa-I, and Taq-I), GC, DHCR7, and CYP2R1 polymorphisms was performed.

Results

25-Hydroxyvitamin D (25(OH)D) levels showed significant negative correlation with IR and positive correlation with insulin sensitivity (P<0.05 for all) in PCOS women. In PCOS women, the VDR Cdx2 ‘AA’ genotype was associated with lower fasting insulin (P=0.039) and homeostatic model assessment-IR (P=0.041) and higher quantitative insulin-sensitivity check index (P=0.012) and MATSUDA index (P=0.003). The VDR Apa-I ‘AA’ genotype was associated with lower testosterone (P=0.028) levels. In PCOS women, 170 women (31.2%) presented with 25(OH)D levels <20 ng/ml. PCOS women carrying the GC ‘GG’ genotype and the DHCR7 ‘GG’ genotype had a significantly higher risk for 25(OH)D levels <20 ng/ml (OR 2.53 (1.27–5.06), P=0.009, and OR 2.66 (1.08–6.55), P=0.033 respectively) compared with PCOS women carrying the GC ‘TT’ genotype and DHCR ‘TT’ genotype in multivariate analyses. We observed no association of genetic variations and PCOS susceptibility.

Conclusion

VDR and vitamin D level-related variants are associated with metabolic and endocrine parameters including 25(OH)D levels in PCOS women.

Free access

Elisabeth Lerchbaum, Hans-Jürgen Gruber, Verena Schwetz, Albrecht Giuliani, Reinhard Möller, Thomas R Pieber and Barbara Obermayer-Pietsch

Introduction

Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances and might be affected by hepatic steatosis. The fatty liver index (FLI) was developed as a simple and accurate predictor of hepatic steatosis. We aimed to analyze the association of FLI with endocrine and metabolic parameters in a cohort of PCOS and control women.

Methods

FLI was calculated using body mass index (BMI), waist circumference, triglycerides, and gamma-glutamyl transferase in 611 PCOS and 139 BMI-matched control women within the same age range. Elevated FLI was defined as >60. Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed.

Results

PCOS women had significantly higher FLI levels than control women in age-adjusted analyses (11.4 (4.3–48.8) and 8.8 (3.9–35.0), respectively, P=0.001), whereas fibrosis indices were similar (aspartate amino transferase-to-platelet ratio index) or lower (FIB-4) respectively. In binary logistic regression analysis adjusted for age, odds ratio (OR) for elevated FLI was 2.52 (1.31–4.85), P=0.006, for PCOS women when compared with controls. PCOS women with high FLI levels had an adverse anthropometric, metabolic, and endocrine risk profile. The prevalence of elevated FLI was 88.7% in PCOS women with metabolic syndrome (MS) and 11.3% in PCOS women without MS (P<0.001). In control women, elevated FLI was present in 66.7% of women with MS and 30.8% of women without MS.

Conclusion

High FLI levels are a common finding in obese PCOS women and are closely linked to MS. FLI calculation might be a useful tool for identifying PCOS patients at high risk for metabolic and hepatic disturbances.

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Paul Lips, Kevin D Cashman, Cje Lamberg-Allardt, Heike Annette Bischoff-Ferrari, Barbara R Obermayer-Pietsch, Ml Bianchi, Jan Stepan, Ghada El-Hajj Fuleihan and Roger Bouillon

Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) < 50 nmol/l or 20 ng/ml), is common in Europe and the Middle East. It occurs in < 20 % of the population in Northern Europe, in 30-60% in Western, Southern and Eastern Europe and up to 80 % in Middle East countries. Severe deficiency (serum 25(OH)D < 30 nmol/l or 12 ng/ml) is found in > 10 % of Europeans. The ECTS advises that the measurement of serum 25(OH)D be standardized e.g. by the Vitamin D Standardization Program. Risk groups include young children, adolescents, pregnant women, older people, especially the institutionalized, and non-western immigrants. Consequences of vitamin D deficiency include mineralization defects and lower bone mineral density causing fractures. Extra-skeletal consequences may be muscle weakness, falls and acute respiratory infection, and are the subject of large ongoing clinical trials. The ECTS advises to improve vitamin D status by food fortification and the use of vitamin D supplements in risk groups. Fortification of foods by adding vitamin D to dairy products, bread and cereals can improve the vitamin D status of the whole population, but quality assurance monitoring is needed to prevent intoxication. Specific risk groups such as infants and children up to 3 years, pregnant women, older persons and non-western immigrants should routinely receive vitamin D supplements. Future research should include genetic studies to better define individual vulnerability for vitamin D deficiency, and Mendelian randomization studies to address the effect of vitamin D deficiency on long term non-skeletal outcomes such as cancer.