Улогата на адипонектинот, лептинот и резистинот кај жени со полицистичен овариjaлен синдром и нивната корелација со инсулинската резистенција

Abstract

Introduction Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. PCOS is often connected with obesity and insulin resistance. In obesity, fat accumulation causes dysregulation of adipokine production that strongly contributes to the onset of obesity-related diseases. Dysfunction of adipose tissue has been implicated in the pathophysiology of PCOS. Increasing evidence shows that the dysregulated expression of adipokines, the secreted products of adipose tissue, plays an important role in the pathology of PCOS. However, they are also involved in other functions in the organism including reproductive functions. Aim The primary purpose of this thesis was to evaluate whether the levels of adipocytokines (adiponectin, resistin and leptin) are different between women with PCOS and healthy group of women. Furthermore, we want to evaluate the possible correlations with other metabolic parameters, such as anthropometric measures, indexes of insulin resistance, lipid and inflammatory markers. Moreover, we compared the values of adiponectin, leptin and resistin between normal weight PCOS women and obese PCOS women, and on the base of presence of insulin resistance, and tried to determine which of the examined factors have the greatest impact on their serum levels. Study subjects and methods The study included 89 women diagnosed with PCOS set by the Rotterdam criteria and 60 healthy women. Serum levels of adiponectin, resistin and leptin had been taken from morning fasting blood sample in all woman involved in this study. Obesity measurements (weight, waist and hip circumference) were also determined during the visit. Two measures for insulin resistance (insulin/ glucose and HOMA- IR) were calculated based on fasting insulin and glucose levels. We compared levels of adiponectin, resistin and leptin with biochemical parameters of insulin resistance (insulin, insulin/ glucose, HOMA- IR); anthropometric measures as well as lipid parameters, hs-CRP and homocysteine. Furthermore, we compared the values of this adipokines between PCOS women, divided in two groups based on their BMI, and based of presence of insulin resistance and tried to determine which of the examined factors have the greatest impact on their serum levels. Results We found statistically significant differences among adiponectin and leptin levels between PCOS women and healthy controls (p<0.001). Serum resistin levels did not differ between PCOS women and control group. Women with PCOS presented higher, triglyceride, and LDL and hs-CRP levels than women without PCOS (p<0.001). There were a significant difference in adiponectin and leptin serum levels between normal weight (BMI ≤25) and overweight (BMI >25) PCOS patients (p<0.001). A significant negative correlation for adiponectin, and significant positive correlation for leptin and resistin was found with BMI, and waist circumference (p<0.001). A significant positive correlation for leptin was found with indexes of insulin resistance (p<0.001). A significant negative correlation was obtained between adiponectin and insulin (p<0.032), insulin/ glucose (p<0.044), and HOMA-IR (p<0.034). A significant alteration in A/L, A/R and A/R ratio was found in PCOS group when compared with healthy group of women. Women with PCOS have significantly elevated leptin levels and significantly lower adiponectin than healthy women. The reversal reactions between adiponectin and leptin were very clear, but the impact of resistin on women’s health remains a controversy. Conclusion Given the abnormal adipokine profile in women with PCOS irrespective of the presence or absence of obesity, PCOS may reciprocally influence the secretion of adipokines. Adipokines may thus serve as an endocrine link between obesity and PCOS. Our current understanding of the role for adipokines in PCOS is far from complete. The heterogeneity of clinical manifestations of PCOS patients makes this syndrome even challenging in the field of endocrinology, metabolism, and reproduction. Further work will thus be necessary for better understanding the role of adipokines in reproductive functions that may act as a link between obesity and PCOS. This study is only the beginning of this type of research in our population. Identification of women with altered adipokine expression as putative markers of possible metabolic and cardiovascular complications would be useful for setting up preventive strategies by life-style changes and/or use of insulin- sensitizing agents.