OR24-04 High Prevalence Of Elevated ALT In Adolescent Females With Obesity And PCOS

Abnormal aminotransferase activity in women with polycystic ovary syndrome

A variant in the fibrillin-3 gene is associated with TGF-β and inhibin B levels in women with polycystic ovary syndrome

Rosiglitazone treatment alleviates inflammation and improves liver function in overweight women with polycystic ovary syndrome: a randomized placebo-controlled study

IL-22 and its interaction with amino acid and glycolipid metabolite in polycystic ovary syndrome (PCOS) patients

This Month in Gastroenterology

Polycystic ovary syndrome (PCOS) increases non-alcoholic fatty liver disease (NAFLD) risk and severity in adults, but data in adolescents with diverse backgrounds are limited. We evaluated NAFLD prevalence and characterized NAFLD risk factors in overweight/obese adolescents by PCOS status. Retrospective study of overweight (n=52)/obese (n=271) female adolescents (12-18 years old), evaluated clinically 2012-2020, was conducted comparing PCOS patients to age-matched non-PCOS controls. NAFLD was defined as ALT≥44U/L x2 and/or≥80U/L x1, hepatic steatosis on imaging, or NAFLD on biopsy, in absence of other liver disease. Metabolic comorbidities were captured. Log-binomial regression models estimated prevalence risk ratios (PR). NAFLD prevalence was 19.1% in adolescents with PCOS (n=161), similar to those without (n=162) (16.8%, p=0.6). Adolescents with PCOS were more likely to have insulin resistance, hypercholesterolemia, and higher triglycerides (p<0.05). Those with PCOS and concomitant type 2 diabetes (T2DM) did have increased NAFLD risk (PR 2.5, p=0.04), but those with PCOS without T2DM did not (PR 0.9, p=0.8). Adolescents with PCOS and NAFLD, compared to those with PCOS without NAFLD, had a higher prevalence of metabolic comorbidities including hypercholesterolemia (77 vs. 48 %), T2DM (29 vs. 8 %), and hypertriglyceridemia (65 vs. 37 %) (p<0.01). Almost 1 in 5 overweight/obese female adolescents had NAFLD, but PCOS did not increase NAFLD risk in this diverse cohort. Among young women with PCOS, concomitant T2DM did increase the risk for NAFLD. Closer monitoring of obesity comorbidities in adolescents with PCOS is essential for optimizing health and merits updating current guidelines.

Does elevated alanine aminotransferase predict components of the metabolic syndrome in polycystic ovarian syndrome?

Implications of Elevated Serum Alanine Aminotransferase Levels: Think Outside the Liver

Improvement in quality-of-life questionnaire measures in obese adolescent females with polycystic ovary syndrome treated with lifestyle changes and oral contraceptives, with or without metformin

Women with polycystic ovary syndrome (PCOS) have been implicated to have higher levels of alanine aminotransferase (ALT) because of the high prevalence of obesity. Our aim was to investigate the relationship between elevated ALT and aspartate aminotransferase (AST) activity and characteristic hyperandrogenism in women with PCOS. We conducted a cross-sectional case-control study in a reproductive endocrinology clinic and voluntary annual medical health check-up program of the health management center in a tertiary medical center. A total of 279 women with PCOS and 279 age-frequency-matched healthy women were studied. There were no interventions. All subjects underwent anthropometric measurement, clinical history recorded by questionnaires, and biochemical tests after an overnight fast. The prevalence of elevated ALT and AST levels was significantly higher in women with PCOS than healthy control subjects. Multivariate regression analysis for women revealed that the presence of PCOS was significantly associated with elevated ALT but not AST after adjustment for age, obesity, and dyslipidemia. The level of androgenicity represented by free androgen index in women with PCOS was significantly related to elevated ALT and AST levels in multivariate regression models. Women with PCOS who had the highest quartile of free androgen index level had the highest risk of elevated ALT level after adjustment for age, obesity, insulin resistance, and dyslipidemia. The risk of elevated ALT level is significantly higher in women with PCOS than those without, independent of obesity. The elevated ALT levels in women with PCOS were associated with the increased androgen levels, independent of obesity, insulin resistance, and dyslipidemia.

Polycystic ovary syndrome (PCOS) is a recognized risk factor for nonalcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence and factors associated with NAFLD in women with PCOS and evaluate noninvasive indices of hepatic fibrosis in patients with PCOS and NAFLD. Patients with PCOS (n = 87) and women without PCOS (n = 40; controls) were included. NAFLD was diagnosed by abdominal ultrasonography after exclusion of alcohol consumption and viral or autoimmune liver disease. Anthropometric, clinical and metabolic variables, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid accumulation product (LAP), FIB-4 index, NAFLD score, and transient elastography (TE; FibroScan) were obtained in subsets of patients with PCOS and NAFLD. A total of 87 patients with PCOS were included (mean age: 34.4 ± 5.7 years, mean body mass index [BMI]: 34.7 ± 4.7 kg/m 2 ). NAFLD was present in 67 (77.0%) patients with PCOS versus 21 of 40 (52.5%) controls (p = 0.005). Women with PCOS and liver steatosis, compared with their NAFLD-free counterparts, had higher values of BMI, waist circumference, triglycerides, total cholesterol, alanine and aspartate aminotransferases, and γ-glutamyltransferase, along with higher frequencies of obesity, metabolic syndrome, and insulin resistance. NAFLD was independently associated with waist circumference, serum triglycerides, and alanine aminotransferase levels. The FIB-4 index was not compatible with advanced fibrosis in any of the evaluated patients, while NAFLD score and TE were compatible with advanced liver fibrosis in 1 of 26 (3.8%) and 3 of 25 (12%) patients, respectively. Women with PCOS had a high risk of NAFLD, and a combination of both was associated with central obesity, dyslipidemia, insulin resistance, and metabolic syndrome. Noninvasive methods suggested low rates of severe hepatic fibrosis in Brazilian women with PCOS. Arch Endocrinol Metab. 2020;64(3):235-42.

Objective To explore the incidence of insulin resistance (IR) in patients with obese polycystic ovary syndrome (PCOS) and its relationship with body composition including body fat (BF) and visceral fat area (VFA). Methods In the period from April 2013 to December 2014, in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, 62 patients with obese PCOS who were in the weight loss program in the Department of Clinical Nutrition were selected, and 19 obesity subjects without PCOS, matching with the obsess PCOS group in age and body mass index (BMI), were selected as controls. In the cases and controls, we used Biospace Inbody720 body composition analyzer to determine their body composition, measured serum lipid profile, conducted 75 g oral glucose tolerance test and insulin release test, and calculated homeostasis model assessment of insulin resistance (HOMA-IR). Results Blood lipids, insulin level, and HOMA-IR were not significantly different between the obese PCOS and the control groups (all P>0.05). Both groups showed IR (defined as HOMA-IR≥2.69), and HOMA-IR in the obese PCOS group was higher than that in the control group, but with no significant difference(6.17 ± 3.15 vs. 5.00±2.18, t= 1.515, P= 0.134). The mean alanine aminotransferase (ALT) level in the obese PCOS group was higher than normal, and the ALT values and the proportion of patients with ALT> 40 U/L were higher than those in the control group, but with no significant difference (P= 0.106 and P= 0.134). Those with nonalcoholic fatty liver disease (NAFLD) accounted for 27/62 in the obese PCOS group, also higher than the 6/19 in the control group(χ2 = 0.863, P= 0.353). BF in the obese PCOS group was lower than that in the control group [(36.28±6.16)kg vs. (39.56±6.13)kg, t=-2.032, P=0.046], so was VFA after adjusting for waist-to-hip ratio [(150.39±22.86)cm2vs. (161.74±20.77)cm2,OR=0.963, P=0.040]. Linear regression analysis showed that HOMA-IR was not correlated with BF, VFA or other body composition indexes in the obese PCOS patients (all P>0.05). Conclusions Obesity PCOS patients have significant IR, but HOMA-IR seems to be not correlated with BF, VFA, and other body composition indexes in this population. Studies with larger sample size and exploring relevant mechanisms are still needed. Key words: Obesity; Polycystic ovary syndrome; Insulin resistance index; Inbody720 body composition analyzer; Visceral fat area

Polycystic Ovary Syndrome (PCOS) affects 12 to 21% of Australian reproductive-aged women and is a major public health concern (1-5). Whilst reproductive features (anovulation, infertility) are prominent, PCOS also has major metabolic [obesity, metabolic syndrome, type 2 diabetes (T2DM), cardiovascular disease risk factors] and psychological features (6-8). Obesity is a major chronic disease, with rising prevalence and diverse health impacts. The interplay between PCOS and weight contributes to the long-term consequences of PCOS, but is not well understood. Women with PCOS demonstrate insulin resistance (IR), which leads to adverse health consequences, both independent of and exacerbated by obesity. Here, I explore the poorly understood interplay between PCOS, IR, metabolic complications and weight. My clinical research aims to assess prevalence and severity of IR in PCOS and explore novel markers of IR: Pigment Epithelium-Derived Factor (PEDF) and vitamin D. Women with PCOS were more insulin resistant than body mass index (BMI)-matched controls. IR was present in 75% of lean women with PCOS, 62% of overweight controls and 95% of overweight women with PCOS. IR was exacerbated by increased BMI. PEDF was not elevated in PCOS, was not associated with IR and was not reduced by exercise training, despite improved IR. It was mainly obesity related and is not a useful marker of IR. Despite similar adiposity, vitamin D levels were lower in overweight women with PCOS compared with overweight controls. Vitamin D was associated with IR in PCOS, but not in the non-PCOS group. PCOS is an insulin resistant state with intrinsic IR, exacerbated by lifestyle/obesity mediated extrinsic IR. Measurement of IR remains a challenge; novel simple markers of IR are needed. New interventions to manage IR, including potentially vitamin D, need to be studied. My epidemiological research examines the natural history of PCOS and the relationship between PCOS, weight and complications. Extensive data from the Australian Longitudinal Study on Women’s Health (ALSWH) was analysed to explore the prevalence of PCOS, the impact of obesity and relationship to reproductive and metabolic complications. We found that weight, body mass index (BMI) and weight gain over 10 years was higher in women reporting PCOS compared to those not reporting PCOS. BMI was the key predictor of PCOS status. Women with PCOS reported less contraception use and higher rates of trying to conceive, higher rates of infertility and use of fertility treatment including ovulation induction, but not increased in-vitro fertilisation. Reported pregnancy loss was higher in PCOS (related to fertility treatment and BMI, but not PCOS per se). The number of children per woman was similar in PCOS and non-PCOS groups, albeit with higher rates of fertility treatment. After conception and delivery, high BMI was negatively correlated with breastfeeding, suggesting the need for greater lactation support for overweight women. PCOS alone does not appear to impact on breastfeeding. PCOS was associated with higher prevalence of gestational diabetes and T2DM, independent of BMI. This suggests that all women with PCOS should be screened pre-conception or early in pregnancy, during pregnancy and in non-pregnant states for gestational diabetes and T2DM. PCOS status was not associated with hypertension, however BMI was, highlighting the need for blood pressure monitoring in overweight and obese women. This thesis addresses key gaps in our understanding of the natural history of PCOS. It provides important insight into aetiology and natural history of PCOS and advances the area by providing greater understanding of the interplay between BMI and PCOS and related complications.

Introduction:Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women in reproductive age that is associated with insulin resistance (IR) and metabolic abnormalities which are also a part of metabolic syndrome (Met S). This study was aimed to determine the prevalence of nonalcoholic fatty liver disease (NAFLD) women diagnosed with PCOS based on the Rotterdam criteria from January 2013 to June 2014.Methods:In this cross-sectional study, 75 women with PCOS and 75 healthy controls were enrolled. Anthropometric parameters, biochemical and hormonal investigation, were measured in all women. IR was calculated by homeostasis model assessment. Abdominal ultrasonography and biochemical tests were used to determine the NAFLD.Results:The level of triglyceride, cholesterol, low-density lipoprotein, aspartate aminotransferase, alkalin phosphatase, fasting insulin, and homeostatic model assessment index in women with PCOS were significantly higher than women without PCOS. High-density lipoprotein and alanine aminotransferase (ALT) in women with PCOS were significantly lower. The frequency of IR women with or without PCOS was 53.3% and 29.3%, respectively (P = 0.003). The frequency of Met S in women with PCOS was 33.3% and in other was 10.7% (P = 0.001). The prevalence of fatty liver in women with or without PCOS was 38.7% and 18.7%, respectively (0.008). In women with PCOS, body mass index (BMI) (odds ratio [OR] = 4.25; P = 0.046), ALT (OR = 1.62; P = 0.005), fasting insulin (OR = 1.32; P = 0.032), and IR (OR = 58.17; P = 0.025) were associated with a higher fatty liver.Conclusions:NAFLD is frequent in patients with PCOS with combination with other metabolic derangements. BMI, ALT, fasting insulin, and IR are the risk factors for high prevalence of NAFLD in women with PCOS.

Lower serum apelin levels in women with polycystic ovary syndrome