Remzi Abali

Progression to impaired glucose tolerance or type 2 diabetes mellitus in polycystic ovary syndrome: a controlled follow-up study.

OBJECTIVE To investigate whether retesting with the oral glucose tolerance test (OGTT) is useful and necessary for all women with polycystic ovary syndrome (PCOS). DESIGN Follow-up study. SETTING Tertiary medical center. PATIENT(S) Eighty-four women with PCOS and 45 healthy controls. INTERVENTION(S) Peripheral venous blood sampling. MAIN OUTCOME MEASURE(S) We performed a 75-g 2-hour OGTT in women with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) at the time of the first test with and without PCOS. RESULT(S) The average follow-up period for women with PCOS was 2.6 years (range, 2-4.17 years). Seventy-eight of these women had NGT at baseline, 11.5% converted to IGT, with an annualized incidence rate of 4.5%. Of those women with IGT at baseline (n = 6), 33.3% converted to type 2 diabetes mellitus, with an annualized incidence rate of 10.4%. In the healthy subjects, the average follow-up period was 2.6 years (range, 2-4.08 years). Forty-two of these women had NGT at baseline, 2.3% converted to IGT, giving a progression of 0.9% per year. Among the three women with IGT at baseline, 33.3% reverted to NGT, and 66.6% had persistent IGT. CONCLUSION(S) Conversion rates from NGT to IGT or type 2 diabetes mellitus were accelerated in women with PCOS compared with healthy subjects. Women with PCOS should be tested regularly for early detection of abnormal glucose tolerance. In addition, the interval for periodic rescreening should be determined by further studies involving more women with PCOS.

Is subclinical hypothyroidism contributing dyslipidemia and insulin resistance in women with polycystic ovary syndrome

We aimed to analyze lipid parameters and determine the need for a 2-hour oral glucose tolerance test (OGTT) for the identification of IR and impaired glucose tolerance test (IGT) in subclinical hypothyroidism (SCH) women with and without polycystic ovary syndrome (PCOS). 20 patients with PCOS and SCH consisted of Group I and 39 patients with PCOS and normal thyroid function consisted of Group II and 53 healthy women with normal thyroid function consisted of Group III. Triglyceride levels were 143.26 ± 99.86 mg/dL in group 1 and 88.56 ± 37.56 mg/dL in group 2 and 83.71 ± 31.94 mg/dL in group 3 which were statistically significant. Total cholesterol, HDL- cholesterol, LDL-cholesterol were found similar between the groups. Fasting insulin levels were 12.45 ± 8.62 µU/mL in group 1 and 8.60 ± 5.35 µU/mL in group 2 and 7.04 ± 3.55 µU/mL in group 3 which were statistically significant (P = 0.027). HOMA-IR were 2.92 ± 2.34 in group 1 and 1.95 ± 1.52 in group 2 and 1.60 ± 0.86 in group 3 which were statistically significant (P = 0.046). This study showed that women with PCOS and subclinical hypothyroidism should be evaluated for dyslipidemia and Insulin resistance.

Assessment of impaired glucose tolerance prevalence with hemoglobin A1c and oral glucose tolerance test in 252 Turkish women with polycystic ovary syndrome: a prospective, controlled study

STUDY QUESTION What is the prevalence of abnormalities in glucose metabolism in patients with polycystic ovary syndrome (PCOS) and controls in a Turkish population? SUMMARY ANSWER The total prevalence of glucose abnormalities in PCOS patients was 16.3% [impaired glucose tolerance (IGT) 14.3%; type 2 diabetes mellitus (T2DM) 2%] and was higher than in healthy subjects (IGT 8.5%; T2DM 0%, respectively). WHAT IS KNOWN ALREADY One of the most common markers of chronic glycemia is hemoglobin Alc (HbA1c). However, little is known about whether the use of HbA1c results in diagnosis of more cases of glucose intolerance in the PCOS population than the oral glucose tolerance test (OGTT) alone. STUDY DESIGN, SIZE, DURATION This was a prospective study, including 252 women with PCOS and 117 control women without PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was carried out in the gynecological outpatient department of Namik Kemal University Hospital, Turkey, between 2010 and 2012. Women with PCOS (n = 252) were diagnosed according to Rotterdam criteria. The control group included 117 women (aged 17-45 years) who were selected randomly. BMI of participants ranged between 15.6 and 47.9 kg/m(2). MAIN RESULTS AND THE ROLE OF CHANCE Patients with PCOS were comparable to controls in terms of age (24.8 versus 25.9 years, respectively) and had higher BMI (26.1 versus 24.9 kg/m(2), respectively). Of 252 patients with PCOS, 41 had glucose intolerance (IGT 14.3%; T2DM 2%) when compared with 10 of the 117 control patients (IGT 8.5%; T2DM 0%; odds ratios = 2.08; P = 0.045) during the OGTT. When an HbA1c value ≥ 5.6% was used to divide the total population, the prevalence of abnormal glucose metabolism was 7.9% in the patients with PCOS, below the value detected in the control patients (8.5%), which showed that 20 of 41 patients with abnormal glucose tolerance would not have been diagnosed, if the HbA1c alone had been used. When compared with the OGTT results, HbA1c provided 52.4% sensitivity, 74.4% specificity, 67.1% positive and 60.9% negative predictive values with a threshold value of 5.6% in abnormal glucose tolerance. The receiver operating characteristic analysis suggested a threshold value of 5.35% in HbA1c (75.6% sensitivity and 52.6% specificity) for the prediction of abnormal glucose tolerance. LIMITATIONS, REASONS FOR CAUTION This study did not involve weight-matched healthy subjects, which may cause a difference in prevalence of abnormal glucose metabolism between the groups, and the results are limited to an unselected population of patients who have the full PCOS phenotype. In addition, the incidence of T2DM among the first-degree relatives and 2-h insulin levels could not be reported in full. WIDER IMPLICATIONS OF THE FINDINGS Further investigation of the efficacy of HbA1c for the prediction of abnormal glucose tolerance should be undertaken in long-term prospective studies and in different geographic populations. At present, the only way to reliably detect abnormal glucose metabolism in Turkish women with PCOS appears to be using the OGTT. STUDY FUNDING/COMPETING INTEREST(S) No financial support. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER Not applicable.

Omentin and chemerin and their association with obesity in women with polycystic ovary syndrome

Abstract We aimed to investigate whether overweight/obesity is associated with omentin and chemerin. The study group consisted of 81 women with Polycystic ovarian syndrome (PCOS) (41 lean, BMI < 25 kg/m2 and 40 overweight or obese, BMI > 25 kg/m2) and 61 healthy subjects (31 lean, BMI < 25 kg/m2 and 30 overweight or obese, BMI > 25 kg/m2; control group). The clinical, endocrine, metabolic parameters, plasma omentin and chemerin levels were measured in patients and compared to control. In all subjects with PCOS (n = 80), serum chemerin levels were higher compared with those of the controls (n = 58) (7.71 ± 1.78 ng/mL versus 6.94 ± 0.82 ng/mL, p = 0.003). However, serum omentin levels were not significantly different between the PCOS subjects and the controls (1.55 ± 0.43 ng/mL versus 1.69 ± 0.37 ng/mL, p = 0.056). The mean chemerin concentrations were significantly elevated in the obese PCOS group compared with the obese control subjects (8.98 ± 1.45 ng/mL versus 7.02 ± 0.67 ng/mL, p = 0.000) and the nonobese PCOS group compared with the obese control subjects (6.57 ± 1.17 ng/mL versus 7.02 ± 0.67 ng/mL, p = 0.000). In conclusion, fat mass seems to be the main determinant factor of increased chemerin and decreased omentin in women with PCOS.

Protective effect of infliximab on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation

OBJECTIVE The aim of this study was to investigate the effect of infliximab on experimentally induced ovarian ischemia/reperfusion injury (IRi). STUDY DESIGN A total of 42 female rats were equally divided into 6 experimental groups; group 1: sham operation, group 2: 3-h ischemia, group 3 and 4: 3-h ischemia, 3-h reperfusion, group 5 and 6: 3-h ischemia, 24h reperfusion. In group 4 and group 6, 30 min before reperfusion, infliximab was administered intraperitoneally at a dose of 5mg/kg. Bilateral ovaries were removed for histopathologic and biochemical analysis. Serum MDA (sMDA), tissue MDA (tMDA), serum NO (sNO), tissue NO (tNO) and serum catalase concentrations were analyzed. Tissue damage of ovarian tissue was scored by histological examination. RESULTS The infliximab administration significantly lowered the sNO, tNO and sMDA concentrations in group 4 compared to group 3 (p=0.041, p=0.025 and p=0.035, respectively). sNO, tNO and sMDA concentrations were also lower in group 6 when compared to group 5, but this differences were not significant (p>0.05). On the other hand, tMDA concentrations were lower in infliximab-applied groups when compared to ischemia/reperfusion groups (group 3 vs. 4 and 5 vs. 6) (p=0.045 and p=0.048, respectively). Moreover, histopathologic tissue damage scores in infliximab administration groups were significantly lower than in ischemia/reperfusion groups (p<0.001). CONCLUSION Infliximab attenuates I/R-induced ovarian tissue injury in rats subjected to ischemia/reperfusion.

Implications of circulating irisin and Fabp4 levels in patients with polycystic ovary syndrome

abstract The aim of the study was to evaluate the fatty acid-binding protein-4 (FABP4) and irisin concentrations in women with polycystic ovary syndrome (PCOS). Forty-nine women with PCOS, diagnosed according to Rotterdam criteria and 39 healthy women matched for body mass index (BMI) and age. Serum irisin and plasma FABP4 concentrations were measured in both groups. The association of irisin and FABP4 concentrations with metabolic parameters were also tested. Women with PCOS had significantly lower mean serum irisin concentrations than control subjects (158.5 ± 123.3 versus 222.9 ± 152.2 ng/ml, p < 0.05). Concentrations of FABP4 in PCOS and control groups were not significantly different (10.5 ± 4.4 versus 10.9 ± 4.2 ng/ml, p > 0.05). FABP4 concentrations were correlated with BMI, waist–hip ratio (WHR) and HOMA-IR (r = 0.57, p = 0.001; r = 0.26, p = 0.03; r = 0.26, p = 0.03, respectively). No associations between irisin and all the others parameters except serum levels of LH were found. Serum irisin concentrations of women with PCOS were lower compared to the controls. Moreover, there were no difference in plasma FABP4 concentrations between women with PCOS and controls.

Decreased ovarian reserve in female Sprague-Dawley rats induced by isotretinoin (retinoic acid) exposure.

Isotretinoin is a retinoid widely used for the treatment of severe nodulocystic acne. Although it has broad side effects, there is no well-designed study about its effects on the ovary. This study investigated possible toxic effects of isotretinoin on female gonads. A total of 30 female rats were randomly divided into three equal groups according to the dose of isotretinoin they were administered: 0 mg/kg/day (group 1), 7.5 mg/kg/day (group 2) or 15 mg/kg/day (group 3). Thirty days after the treatment, the effects of isotretinoin on the ovaries were evaluated with serum anti-Müllerian hormone (AMH) concentrations, apoptosis by TUNEL assay and immunohistochemical observations by proliferating cell nuclear antigen (PCNA). The percentage of atretic follicles was calculated for each stage of folliculogenesis. The serum AMH concentrations were found to be lower in both isotretinoin groups. The percentage of atretic follicles in both isotretinoin groups was higher than the control. The number of PCNA-positive granulosa cells was decreased in the isotretinoin groups. The number of ovarian follicles with apoptotic granulosa cells was increased in the experimental groups. These data are the first to identify that exposure of isotretinoin may be responsible for decreased ovarian reserve and toxic effects on rat ovaries.

The relationship between copper, homocysteine and early vascular disease in lean women with polycystic ovary syndrome

Abstract This study investigates copper (Cu) levels and vascular dysfunction in lean women with polycystic ovary syndrome (PCOS). 44 subjects with PCOS, diagnosed according to Rotterdam criteria, and 42 healthy subjects matched for body mass index and age. Comparison of serum Cu, homocysteine, carotid intima-media thickness (CIMT), brachial artery flow mediated dilation (FMD) was carried out between PCOS patients and the control group. Clinical study was done in Namik Kemal University School of Medicine. The CIMT and concentration of Cu in PCOS patients was significantly higher than the healthy controls. FMD levels in PCOS patients were significantly lower than those in controls. In PCOS patients, CIMT was correlated with estrogen and Cu levels. However, FMD was correlated with age and Cu levels. Among these contributing factors, Cu levels were correlated with a change in CIMT and FMD. CIMT and FMD in PCOS patients were related to Cu levels as well as several cardiovascular risk factors. Thus, increased Cu levels may be responsible for the increased risk of early vascular disease in women with PCOS.

Tear Osmolarity and Ocular Surface Changes in Patient with Polycystic Ovary Syndrome

Purpose: To evaluate the tear osmolarity and ocular surface changes in patients with polycystic ovary syndrome (PCOS). Materials and Methods: Forty-eight patients with recently diagnosed PCOS and thirty-three control volunteers were enrolled in this prospective, observational study. Ocular surface disease index (OSDI) score was calculated. Tear osmolarity was measured using the TearLab Osmolarity System (Tearlab, San Diego, CA, USA). All subjects also underwent the following ophthalmologic evaluation: Schirmer I test, tear-film breakup time (TBUT), ocular surface flourescein staining, and conjunctival impression cytology. Results: Mean OSDI score was significantly higher in patients with PCOS than control subjects (P = 0.001). Tear osmolarity was similar in both groups (P = 0.404). There were no significant differences between groups in Schirmer I test results, TBUT, and ocular surface flourescein staining scores (P > 0.05). Compared to control group, a statistically significant squamous metaplasia was observed in temporal bulbar conjunctival impression cytology specimens in PCOS group (P = 0.032). Conclusions: In patients with recently diagnosed PCOS, tear volume and osmolarity are not affected but, conjunctival morphology may be affected, though on a limited scale.

The serum protein α2-Heremans-Schmid glycoprotein/fetuin-a concentration and carotid intima-media thickness in women with polycystic ovary syndrome.

OBJECTIVE To investigate fetuin-A concentrations and its association with metabolic and sonographic cardiovascular markers in women with polycystic ovary syndrome (PCOS) and healthy subjects. STUDY DESIGN Thirty-five women with PCOS and 37 healthy control women were matched for body mass index (BMI) and age. Serum fetuin-A concentrations, and reproductive and adrenal hormones were measured, and insulin resistance and carotid intima media thickness (CIMT) were evaluated in both groups. The correlations between cardiovascular risk factors, CIMT and fetuin-A concentrations were tested. RESULTS Mean fetuin-A concentrations were significantly elevated in the PCOS group compared with control subjects (101.2 ng/ml ± 33.55 vs. 82.5 ng/ml ± 32.65, P=0.019). CIMT was also higher in women with PCOS than in control subjects (0.51 ± 0.05 mm vs. 0.44 ± 0.05 mm, P<0.01). Serum lipid parameters were correlated to serum fetuin-A concentrations in the PCOS group, but no correlation was found between fetuin-A and CIMT (rPCOS=0.244, pPCOS=0.158; rcontrol=-0.002, pcontrol=0.988). CONCLUSION In this, the first study of fetuin-A concentrations in PCOS, the results showed that fetuin-A concentrations were increased in euglycemic patients with PCOS.