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Hamidreza Mani Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, UK
Department of Diabetes and Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK

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Yogini Chudasama Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, UK

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Michelle Hadjiconstantinou Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, UK

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Danielle H Bodicoat Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, UK

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Charlotte Edwardson Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, UK
The Leicester Biomedical Research Centre, Leicester and Loughborough, UK

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Miles J Levy Department of Diabetes and Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK

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Laura J Gray Department of Health Sciences, University of Leicester, Leicester, UK

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Janette Barnett Department of Diabetes and Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK

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Heather Daly Leicester Medical Group, Thurmaston Health Centre, Leicester, UK

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Trevor A Howlett Department of Diabetes and Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK

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Kamlesh Khunti Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, UK

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Melanie J Davies Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Leicester, UK

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Objective

To evaluate the effectiveness of a structured education programmes in women with polycystic ovary syndrome (PCOS).

Methods

Single-centre, randomised controlled trial, testing a single exposure to a group-based, face-to-face, structured education programme. Inclusion criteria were women with PCOS, aged 18–49 years inclusive and body mass index ≥23 kg/m2 for black and minority ethnicities or ≥25 kg/m2 for white Europeans. Primary outcome was step-count/day at 12 months. Secondary outcomes included indices of physical activity, cardiovascular risk factors, quality of life (QoL) and illness perception (IP).

Results

161 women were included (78 control, 83 intervention); 69% white; mean age 33.4 (s.d. 7.6) years, of whom 100 (48 intervention; 52 control) attended their 12-month visit (38% attrition). 77% of the intervention arm attended the education programme. No significant change in step-count was observed at 12 months (mean difference: +351 steps/day (95% confidence interval −481, +1183); P = 0.40). No differences were found in biochemical or anthropometric outcomes. The education programme improved participants’ IP in 2 dimensions: understanding their PCOS (P < 0.001) and sense of control (P < 0.01) and improved QoL in 3 dimensions: emotions (P < 0.05), fertility (P < 0.05), weight (P < 0.01) and general mental well-being (P < 0.01).

Discussion

A single exposure to structured education programme did not increase physical activity or improve biochemical markers in overweight and obese women with PCOS. However, providing a structured education in parallel to routine medical treatment can be beneficial for participants’ understanding of their condition, reducing their anxiety and improving their QoL.

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Angela Köninger Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany

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Antonella Iannaccone Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany

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Ensar Hajder Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany

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Mirjam Frank Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany

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Boerge Schmidt Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany

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Ekkehard Schleussner Department of Obstetrics, Jena University Hospital, Jena, Germany

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Rainer Kimmig Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany

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Alexandra Gellhaus Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany

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Hans Dieplinger Division of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria

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Background

Patients suffering from polycystic ovary syndrome (PCOS) are often insulin resistant and at elevated risk for developing gestational diabetes mellitus (GDM). The aim of this study was to explore afamin, which can be determined preconceptionally to indicate patients who will subsequently develop GDM. Serum concentrations of afamin are altered in conditions of oxidative stress like insulin resistance (IR) and correlate with the gold standard of IR determination, the HOMA index.

Methods

Afamin serum concentrations and the HOMA index were analyzed post hoc in 63 PCOS patients with live births. Patients were treated at Essen University Hospital, Germany, between 2009 and 2018. Mann–Whitney U test, T test, Spearman’s correlation, linear regression models and receiver-operating characteristic (ROC) analyses were performed for statistical analysis.

Results

Patients who developed GDM showed significantly higher HOMA and serum afamin values before their pregnancy (P < 0.001, respectively). ROCs for afamin concentrations showed an area under the curve of 0.78 (95% confidence interval (CI) 0.65–0.90) and of 0.77 (95% CI 0.64–0.89) for the HOMA index. An afamin threshold of 88.6 mg/L distinguished between women who will develop GDM and those who will not with a sensitivity of 79.3% and a specificity of 79.4%. A HOMA index of 2.5 showed a sensitivity of 65.5% and a specificity of 88.2%.

Conclusion

The HOMA index and its surrogate parameter afamin are able to identify pre-pregnant PCOS patients who are at risk to develop GDM. Serum afamin concentrations are independent of fasting status and therefore an easily determinable biomarker.

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Feifei Cheng Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Noel Yat Hey Ng Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Claudia Ha Ting Tam Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Yuying Zhang Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Cadmon King Poo Lim Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Guozhi Jiang Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Alex Chi Wai Ng Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Tiffany Tse Ling Yau Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Lai Ping Cheung Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong

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Aimin Xu Department of Medicine, Li Ka Shing (LKS) Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong
State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, Hong Kong
Department of Pharmacy and Pharmacology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong

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Juliana C N Chan Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, Hong Kong
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong
Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, Hong Kong, Hong Kong

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Ronald C W Ma Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, Hong Kong
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong
Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, Hong Kong, Hong Kong

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Women with polycystic ovary syndrome (PCOS) have an increased risk of developing type 2 diabetes. FGF19, FGF21 and lipocalin-2 have emerged as important markers of metabolic risk. This study aims to compare the levels of FGF19, FGF21 and lipocalin-2 between subjects with or without PCOS, and to investigate the relationship between proteins and diabetes progression. In this nested case–control cohort study, 128 Chinese PCOS women and 128 controls were recruited and followed-up. All subjects underwent the oral glucose tolerance test for the evaluation of glycaemic status. Baseline serum protein levels were measured using ELISA. Compared with controls, PCOS subjects had higher levels of FGF19 (P < 0.001) and FGF21 (P = 0.022), but had lower lipocalin-2 (P < 0.001). In total, 20.8% of PCOS and 9.2% of controls developed diabetes over a mean duration of 10.4 ± 1.2 and 11.3 ± 0.5 years, respectively. Logistic regression analyses suggested FGF19 was positively associated with diabetes progression in controls, after adjusting for age, follow-up duration, waist and fasting glucose (P = 0.026, odds ratio (OR) (95% CI): 7.4 (1.3–43.6)), and the positive relationship between FGF21 and diabetes progression in controls was attenuated by adjusting for age and follow-up duration (P = 0.183). Lipocalin-2 was positively correlated with diabetes progression in PCOS group (P = 0.026, OR (95% CI)): 2.5 (1.1–5.6)); however, this became attenuated after adjusting for waist and fasting glucose (P = 0.081). In conclusion, there is differential expression of FGF19, FGF21, and lipocalin-2 in PCOS. The serum level of FGF19, and FGF21 is associated with diabetes progression in women without PCOS, while lipocalin-2 was related to diabetes progression in PCOS women.

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Malin Nylander Department of Obstetrics and Gynecology, Herlev Gentofte Hospital, Herlev, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Signe Frøssing Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Internal Medicine, Endocrine Unit, Herlev Gentofte Hospital, Herlev, Denmark

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Caroline Kistorp Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Internal Medicine, Endocrine Unit, Herlev Gentofte Hospital, Herlev, Denmark

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Jens Faber Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Internal Medicine, Endocrine Unit, Herlev Gentofte Hospital, Herlev, Denmark

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Sven O Skouby Department of Obstetrics and Gynecology, Herlev Gentofte Hospital, Herlev, Denmark
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Polycystic ovary syndrome (PCOS) is associated with increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) in later life. We aimed to study the effect of liraglutide intervention on markers of VTE and CVD risk, in PCOS. In a double-blind, placebo-controlled, randomized trial, 72 overweight and/or insulin-resistant women with PCOS were randomized, in a 2:1 ratio, to liraglutide or placebo 1.8 mg/day. Endpoints included between-group difference in change (baseline to follow-up) in plasminogen activator inhibitor-1 levels and in thrombin generation test parameters: endogenous thrombin potential, peak thrombin concentration, lag time and time to peak. Mean weight loss was 5.2 kg (95% CI 3.0–7.5 kg, P < 0.001) in the liraglutide group compared with placebo. We detected no effect on endogenous thrombin potential in either group. In the liraglutide group, peak thrombin concentration decreased by 16.71 nmol/L (95% CI 2.32–31.11, P < 0.05) and lag time and time to peak increased by 0.13 min (95% CI 0.01–0.25, P < 0.05) and 0.38 min (95% CI 0.09–0.68, P < 0.05), respectively, but there were no between-group differences. There was a trend toward 12% (95% CI 0–23, P = 0.05) decreased plasminogen activator inhibitor-1 in the liraglutide group, and there was a trend toward 16% (95% CI −4 to 32, P = 0.10) reduction, compared with placebo. In overweight women with PCOS, liraglutide intervention caused an approximate 5% weight loss. In addition, liraglutide affected thrombin generation, although not significantly differently from placebo. A concomitant trend toward improved fibrinolysis indicates a possible reduction of the baseline thrombogenic potential. The findings point toward beneficial effects of liraglutide on markers of VTE and CVD risk, which should be further pursued in larger studies.

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Dorte Glintborg Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Hanne Mumm Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Jens Juul Holst Department of Biomedical Sciences and NNF Centre for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

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Marianne Andersen Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Context

Insulin resistance in polycystic ovary syndrome (PCOS) may increase the risk of reactive hypoglycaemia (RH) and decrease glucagon-like peptide-1 (GLP-1) secretion. The possible effects of treatment with oral contraceptives (OCP) and/or metformin on GLP-1 secretion and risk of RH in PCOS is undetermined.

Setting

Outpatient clinic.

Patients and interventions

Randomized, controlled clinical trial. Ninety women with PCOS were randomized to 12-month treatment with OCP (150 mg desogestrel + 30 mg ethinylestradiol), metformin (2 g/day) or metformin + OCP. Five-hour oral glucose tolerance tests (5-h OGTT) measuring fasting and area under the curve (AUC) for GLP-1, glucose, insulin and C-peptide were performed before and after the intervention period. Sixty-five women completed the study and 34 weight-matched healthy women were included as controls.

Main outcome measures

Changes in GLP-1, glucose, insulin and C-peptide during 5-h OGTT.

Results

Fasting GLP-1 levels increased during metformin + OCP vs OCP treatment, whereas AUC GLP-1 levels were unchanged during medical treatment. The prevalence of reactive hypoglycemia increased from 9/65 to 14/65 after intervention (P < 0.01) and was more common after treatment with metformin + OCP (increase from 3/23 to 6/23, P = 0.01). Reactive hypoglycaemia was associated with higher insulin and C-peptide levels during 5-h OGTT, but was unassociated with BMI and AUC GLP-1. GLP-1 levels were comparable in PCOS vs controls. AUC GLP-1 levels were significantly lower in obese vs lean patients and were inversely associated with BMI.

Conclusions

AUC GLP-1 levels were unchanged during treatment. Increased risk of hypoglycemia during metformin + OCP could be associated with increased insulin secretion.

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Sarantis Livadas Endocrine Unit, Athens Medical Centre, Athens, Greece

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Christina Bothou Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zurich, Zurich, Switzerland

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Justyna Kuliczkowska-Płaksej Department of Endocrinology, Diabetology and Isotope Therapy, University of Medicine, Wrocław, Poland

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Ralitsa Robeva Ushate ‘acad. IV. Penchev’, Department of Endocrinology, Faculty of Medicine, Medical University-Sofia, Sofia, Bulgaria

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Andromahi Vryonidou Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece

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Jelica Bjekic Macut Department of Endocrinology, UMC Bežanijska Kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Ioannis Androulakis Endocrine Unit, Athens Medical Centre, Athens, Greece

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Milica Opalic Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Zadalla Mouslech 1st Medical Propedeutic, Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Andrej Milewicz Department of Endocrinology, Diabetology and Isotope Therapy, University of Medicine, Wrocław, Poland

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Alessandra Gambineri Department of Medical and Surgical Science-DIMEC Endocrinology Unit, University of Bologna – S. Orsola-Mapighi Hospital, Italy

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Dimitrios Panidis Gynaecological Endocrinology Infirmary of the Second Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Djuro Macut Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Background

Polycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear.

Aim of the study

To determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk.

Subjects and methods

The oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI.

Results

Dysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice.

Conclusions

One-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported.

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Jie Yang J Yang, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Min Lin M Lin, Reproductive Medicine Center, The First People's Hospital of Yulin, Yulin, China

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Xiaoyan Tian X Tian, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Chujun Li C Li, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Haocun Wu H Wu, Department of Clinical Laboratory, Shunde Hospital of Southern Medical University, Foshan, China

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Ling Deng L Deng, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Xuelan Li X Li, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Xin Chen X Chen, Reproductive Medicine Center, Shunde Hospital of Southern Medical University, Foshan, China

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Purpose: Our study aimed to assess the relationship between serum adipokines and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS), as well as explore the predictive value of adipokines on IR in PCOS.

Methods: This was a prospective cross-sectional study. 154 women with PCOS were included from July 2021 to September 2022 who underwent gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test and homeostasis model assessment (HOMA)-IR. Adiponectin (APN), leptin and secreted frizzled-related protein (Sfrp5) were measured by immunoturbidimetry and enzyme-linked immunosorbent assay. Women with PCOS were categorised based on the presence of IR.

Results: Women with PCOS with IR (n=99) had significantly lower APN level and APN to leptin ratio (A/L ratio) than those without IR (n=55), whereas serum levels of leptin and Sfrp5 were similar between the two groups. In multivariable linear regression analysis, serum log (APN) and log (A/L ratio) were associated with log(HOMA-IR), the association was statistically significant after adjusting for body mass index (BMI) and free androgen index. The area under the ROC curve (95% CI) for APN and A/L ratio were 0.726 (0.644–0.807; P<0.001) and 0.660(0.569–0.751; P<0.01), with cutoff values of 5.225 mg/L (Youden index ¼ 0.364) and 1.438 (Youden index ¼ 0.265) respectively.

Conclusion: Our study demonstrated that serum APN was negatively related to IR. Serum APN may be useful as a clinical marker for IR in women with PCOS. Our findings warrant further investigations into the function of APN in the pathogenesis of IR in women with PCOS.

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M von Wolff Division of Gynaecological Endocrinology and Reproductive Medicine, University Women’s Hospital, Bern University Hospital, University of Bern, Bern, Switzerland

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C T Nakas University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Laboratory of Biometry, University of Thessaly, Volos, Greece

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M Tobler Division of Gynaecological Endocrinology and Reproductive Medicine, University Women’s Hospital, Bern University Hospital, University of Bern, Bern, Switzerland
Division of Pneumology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

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T M Merz Division of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

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M P Hilty Intensive Care Unit, University Hospital, Zurich, Switzerland

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J D Veldhuis Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, Centre for Translational Science Activities, Mayo Clinic, Rochester, New York, USA

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A R Huber Centre for Laboratory Medicine, Cantonal Hospital, Aarau, Switzerland

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J Pichler Hefti Division of Pneumology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

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Humans cannot live at very high altitude for reasons, which are not completely understood. Since these reasons are not restricted to cardiorespiratory changes alone, changes in the endocrine system might also be involved. Therefore, hormonal changes during prolonged hypobaric hypoxia were comprehensively assessed to determine effects of altitude and hypoxia on stress, thyroid and gonadal hypothalamus–pituitary hormone axes. Twenty-one male and 19 female participants were examined repetitively during a high-altitude expedition. Cortisol, prolactin, thyroid-stimulating hormone (TSH), fT4 and fT3 and in males follicle-stimulating hormone (FSH), luteinizing hormone (LH) and total testosterone were analysed as well as parameters of hypoxemia, such as SaO2 and paO2 at 550 m (baseline) (n = 40), during ascent at 4844 m (n = 38), 6022 m (n = 31) and 7050 m (n = 13), at 4844 m (n = 29) after acclimatization and after the expedition (n = 38). Correlation analysis of hormone concentrations with oxygen parameters and with altitude revealed statistical association in most cases only with altitude. Adrenal, thyroid and gonadal axes were affected by increasing altitude. Adrenal axis and prolactin were first supressed at 4844 m and then activated with increasing altitude; thyroid and gonadal axes were directly activated or suppressed respectively with increasing altitude. Acclimatisation at 4844 m led to normalization of adrenal and gonadal but not of thyroid axes. In conclusion, acclimatization partly leads to a normalization of the adrenal, thyroid and gonadal axes at around 5000 m. However, at higher altitude, endocrine dysregulation is pronounced and might contribute to the physical degradation found at high altitude.

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M Boering Isala, Diabetes Centre, Zwolle, The Netherlands

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P R van Dijk Isala, Diabetes Centre, Zwolle, The Netherlands
Isala, Department of Internal Medicine, Zwolle, The Netherlands

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S J J Logtenberg Diakonessenhuis, Department of Internal Medicine, Utrecht, The Netherlands
Langerhans Medical Research group, Zwolle, The Netherlands

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K H Groenier Isala, Diabetes Centre, Zwolle, The Netherlands
Department of General Practice, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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B H R Wolffenbuttel Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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R O B Gans Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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N Kleefstra Isala, Diabetes Centre, Zwolle, The Netherlands
Langerhans Medical Research group, Zwolle, The Netherlands
Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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H J G Bilo Isala, Diabetes Centre, Zwolle, The Netherlands
Isala, Department of Internal Medicine, Zwolle, The Netherlands
Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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Aims

Elevated sex hormone-binding globulin (SHBG) concentrations have been described in patients with type 1 diabetes mellitus (T1DM), probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII), or subcutaneous (SC), influences SHBG concentrations among T1DM patients.

Methods

Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13) years, diabetes duration 23 (±11) years, and hemoglobin A1c (HbA1c) 8.7 (±1.1) (72 (±12) mmol/mol). As secondary outcomes, testosterone, 17-β-estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were analyzed.

Results

Estimated mean change in SHBG was −10.3nmol/L (95% CI: −17.4, −3.2) during CIPII and 3.7nmol/L (95% CI: −12.0, 4.6) during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was −6.6nmol/L (95% CI: −17.5, 4.3); −12.7nmol/L (95% CI: −25.1, −0.4) for males and −1.7nmol/L (95% CI: −24.6, 21.1) for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; −15.8nmol/L (95% CI: −24.2, −7.5) and −8.3nmol/L (95% CI: −14.4, −2.2), respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2) among males.

Conclusions

SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

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Liza Haqq School of Science and Technology, University of New England, Armidale, New South Wales 2351, Australia

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James McFarlane School of Science and Technology, University of New England, Armidale, New South Wales 2351, Australia

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Gudrun Dieberg School of Science and Technology, University of New England, Armidale, New South Wales 2351, Australia

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Neil Smart School of Science and Technology, University of New England, Armidale, New South Wales 2351, Australia

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Polycystic ovarian syndrome (PCOS) affects 18–22% of women at reproductive age. We conducted a systematic review and meta-analysis evaluating the expected benefits of lifestyle (exercise plus diet) interventions on the reproductive endocrine profile in women with PCOS. Potential studies were identified by systematically searching PubMed, CINAHL and the Cochrane Controlled Trials Registry (1966–April 30, 2013) systematically using key concepts of PCOS. Significant improvements were seen in women receiving lifestyle intervention vs usual care in follicle-stimulating hormone (FSH) levels, mean difference (MD) 0.39 IU/l (95% CI 0.09 to 0.70, P=0.01), sex hormone-binding globulin (SHBG) levels, MD 2.37 nmol/l (95% CI 1.27 to 3.47, P<0.0001), total testosterone levels, MD −0.13 nmol/l (95% CI −0.22 to −0.03, P=0.008), androstenedione levels, MD −0.09 ng/dl (95% CI −0.15 to −0.03, P=0.005), free androgen index (FAI) levels, MD −1.64 (95% CI −2.94 to −0.35, P=0.01) and Ferriman–Gallwey (FG) score, MD −1.01 (95% CI −1.54 to −0.48, P=0.0002). Significant improvements were also observed in women who received exercise-alone intervention vs usual care in FSH levels, MD 0.42 IU/l (95% CI 0.11 to 0.73, P=0.009), SHBG levels, MD 3.42 nmol/l (95% CI 0.11 to 6.73, P=0.04), total testosterone levels, MD −0.16 nmol/l (95% CI −0.29 to −0.04, P=0.01), androstenedione levels, MD −0.09 ng/dl (95% CI −0.16 to −0.03, P=0.004) and FG score, MD −1.13 (95% CI −1.88 to −0.38, P=0.003). Our analyses suggest that lifestyle (diet and exercise) intervention improves levels of FSH, SHBG, total testosterone, androstenedione and FAI, and FG score in women with PCOS.

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