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Milica Popovic Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland

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Fahim Ebrahimi Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland

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Sandrine Andrea Urwyler Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland

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Marc Yves Donath Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
Department of Biomedicine, University of Basel, Basel, Switzerland

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Mirjam Christ-Crain Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland

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Arginine vasopressin (AVP) was suggested to contribute to cardiovascular risk and type 2 diabetes in patients with metabolic syndrome. The proinflammatory cytokine interleukin (IL)-1 is able to induce AVP secretion and plays a causal role in cardiovascular mortality and type 2 diabetes. We investigated in two studies whether copeptin levels – the surrogate marker for AVP – are regulated by IL-1-mediated chronic inflammation in patients with metabolic syndrome. Study A was a prospective, interventional, single-arm study (2014–2016). Study B was a randomized, placebo-controlled, double-blind study (2016–2017). n = 73 (Study A) and n = 66 (Study B) adult patients with metabolic syndrome were treated with 100 mg anakinra or placebo (only in study B) twice daily for 1 day (study A) and 28 days (study B). Fasting blood samples were drawn at day 1, 7, and 28 of treatment for measurement of serum copeptin. Patients with chronic low-grade inflammation (C-reactive protein levels ≥2 mg/L) and BMI >35 kg/m2 had higher baseline copeptin levels (7.7 (IQR 4.9–11.9) vs 5.8 (IQR 3.9–9.3) pmol/L, P inflamm = 0.009; 7.8 (IQR 5.4–11.7) vs 4.9 (IQR 3.7–9.8) pmol/L, P BMI = 0.008). Copeptin levels did not change either in the anakinra or in the placebo group and remained stable throughout the treatment (P = 0.44). Subgroup analyses did not reveal effect modifications. Therefore, we conclude that, although IL-1-mediated inflammation is associated with increased circulating copeptin levels, antagonizing IL-1 does not significantly alter copeptin levels in patients with metabolic syndrome.

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Ru-Xuan Zhao Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Ting-Ting Shi Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Sha Luo Department of Nuclear Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Yun-Fu Liu Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Zhong Xin Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Jin-Kui Yang Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Background

Graves’ orbitopathy (GO) is an autoimmune disease with mechanical impairment of orbital muscles and lacrimal gland dysfunction. The frequently used methods of assessing GO activity include Clinical Activity Score (CAS), CT, and MRI. These approaches are mainly associated with orbital muscles; however, there are not many studies that focus on the lacrimal gland inflammation of GO patients.

Objective

The aim of this study is to assess the usefulness of 99mTc-DTPA single-photon emission (SPE) CT/CT in evaluating the lacrimal gland inflammation in GO, as compared with other methods.

Methods

A retrospective analysis of 48 patients with active GO compared with 33 controls was conducted. All subjects underwent clinical–endocrinological analyses, CAS evaluation, CT scans, and SPECT/CT examination. Lacrimal gland dimensions were determined and analyzed.

Results

The lacrimal glands in patients with GO were significantly larger in all measured dimensions (P  < 0.001) on CT scans relative to those in controls. Increased lacrimal gland diethylene triamine pentaacetic acid (DTPA) uptake ratios (P  < 0.001) were displayed in active GO patients compared to controls and were also correlated with thyrotropin receptor antibody levels. The cut-off value for discriminating active and inactive disease was calculated to be 1.735, with specificity of 82.6% and sensitivity of 74.2%. SPECT/CT uptake ratios and CAS values were positively correlated in all GO patients. SPECT/CT uptake ratios were also positively correlated with CT measurements including lacrimal gland volume and coronal width in GO patients.

Conclusions

These data indicated that lacrimal gland SPECT/CT images can serve as a good tool for assessing the inflammation and disease activity of GO.

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Xiao-Shan Huang Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Ning Dai Zhejiang Chinese Medical University, Hangzhou, China

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Jian-Xia Xu Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Jun-Yi Xiang Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Xiao-Zhong Zheng Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Tian-Yu Ke Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Lin-Ying Ma Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Qi-Hao Shi Zhejiang Chinese Medical University, Hangzhou, China

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Shu-Feng Fan Department of Radiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

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Objective

Hashimoto’s thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis.

Methods

Forty patients with Hashimoto’s thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months.

Results

After 6 months of a low-carbohydrate diet, patients with Hashimoto’s thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63–614.62) vs 89.45 (15.9–215.67); TgAb: 17.05 (1.47–81.64) vs 4.1 (0.51–19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto’s thyroiditis following a normal diet after 6 months (P < 0.05).

Conclusion

Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto’s thyroiditis.

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Fang Lv Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China

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Xiaoling Cai Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China

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Chu Lin Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China

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Tianpei Hong Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China

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Xiaomei Zhang Department of Endocrinology, Peking University International Hospital, Beijing, China

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Zhufeng Wang Department of Endocrinology and Metabolism, China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China

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Huifang Xing Department of Endocrinology and Metabolism, Beijing Mentougou Hospital, Beijing, China

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Guizhi Zong Department of Endocrinology and Metabolism, Beijing Jingmei Group General hospital, Beijing, China

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Juming Lu Department of Endocrinology, Chinese PLA General Hospital, Beijing, China

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Xiaohui Guo Department of Endocrinology, Peking University First Hospital, Beijing, China

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Jing Wu Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China

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Leili Gao Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China

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Xianghai Zhou Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China

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Xueyao Han Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China

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Linong Ji Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China

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Aims

To estimate the sex differences in the prevalence of overweight and obesity aged 20–89 in Chinese patients with type 2 diabetes (T2D).

Methods

811,264 patients with T2D from six hospital-based, cross-sectional studies, and 46,053 subjects from the general population were included in our analysis. Prevalence of underweight, overweight, obesity were calculated in each sex.

Results

In patients with T2D, the standardized prevalence of underweight (BMI <18.5 kg/m2), overweight (24 kg/m2 ≤ BMI < 28 kg/m2), and general obesity (BMI ≥28 kg/m2) were 2.2%, 43.2%, and 11.6%, respectively. Similar trend patterns of the prevalence of underweight and overweight were observed in general and T2D population, in males and females with T2D (all P for trend <0.01). In patients with T2D, patients at a younger age and older age were more likely to be underweight. The prevalence of overweight increased first, then stabilized or decreased with age. However, different trend patterns of the prevalence of obesity in males and females were found. In males, the prevalence of obesity decreased first, and then stabilized after 60 years of age. In females, the prevalence of obesity decreased first, then increased after 50 years of age. In the general population, the prevalence of obesity increased with age in females, while, the trend of prevalence of obesity with age in males was not obvious.

Conclusion

Different trends in the prevalence of obesity with age in different sex were found in Chinese patients with T2D.

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Andrea Mazurat Section of Surgical Oncology, Department of Surgery, CancerCare Manitoba, University of Manitoba, GF440 A, 820 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1R9

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Andrea Torroni Section of Surgical Oncology, Department of Surgery, CancerCare Manitoba, University of Manitoba, GF440 A, 820 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1R9

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Jane Hendrickson-Rebizant Section of Surgical Oncology, Department of Surgery, CancerCare Manitoba, University of Manitoba, GF440 A, 820 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1R9

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Harbinder Benning Section of Surgical Oncology, Department of Surgery, CancerCare Manitoba, University of Manitoba, GF440 A, 820 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1R9

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Richard W Nason Section of Surgical Oncology, Department of Surgery, CancerCare Manitoba, University of Manitoba, GF440 A, 820 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1R9

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K Alok Pathak Section of Surgical Oncology, Department of Surgery, CancerCare Manitoba, University of Manitoba, GF440 A, 820 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1R9

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Well-differentiated thyroid carcinoma (WDTC) represents a group of thyroid cancers with excellent prognosis. Age, a well-recognized risk factor for WDTC, has been consistently included in various prognostic scoring systems. An age threshold of 45 years is currently used by the American Joint Cancer Committee-TNM staging system for the risk stratification of patients. This study analyzes the relationship between the patients' age at diagnosis and thyroid cancer-specific survival in a population-based thyroid cancer cohort of 2115 consecutive patients with WDTC, diagnosed during 1970–2010, and evaluates the appropriateness of the currently used age threshold. Oncological outcomes of patients in terms of disease-specific survival (DSS) and disease-free survival (DFS) were calculated by the Kaplan–Meier method, while multivariable analysis was done by the Cox proportional hazard model and proportional hazards regression for sub-distribution of competing risks to assess the independent influence of various prognostic factors. The mean age of the patients was 47.3 years, 76.6% were female and 83.3% had papillary carcinoma. The median follow-up of the cohort was 122.4 months. The DSS and DFS were 95.4 and 92.8% at 10 years and 90.1 and 87.6% at 20 years, respectively. Multivariable analyses confirmed patient's age to be an independent risk factor adversely affecting the DSS but not the DFS. Distant metastasis, incomplete surgical resection, T3/T4 stages, Hürthle cell histology, and male gender were other independent prognostic determinants. The DSS was not independently influenced by age until the age of 55 years. An age threshold of 55 years is better than that of 45 years for risk stratification.

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Liangming Li Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sport University, Guangzhou, China
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Yuan Wei Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sport University, Guangzhou, China
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Chunlu Fang Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sport University, Guangzhou, China
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Shujing Liu Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sport University, Guangzhou, China
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Fu Zhou Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Ge Zhao Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Yaping Li Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Yuan Luo Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Ziyi Guo Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Weiqun Lin Department of Clinical Nutrition, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China

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Wenqi Yang Center for Scientific Research and Institute of Exercise and Health, Guangzhou Sport University, Guangzhou, China
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, China

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Exercise has been recommended as an important strategy to improve glucose metabolism in obesity. Adipose tissue fibrosis is associated with inflammation and is implicated in glucose metabolism disturbance and insulin resistance in obesity. However, the effect of exercise on the progression of adipose tissue fibrosis is still unknown. The aim of the present study was to investigate whether exercise retarded the progression of adipose tissue fibrosis and ameliorated glucose homeostasis in diet-induced obese mice. To do so, obesity and adipose tissue fibrosis in mice were induced by high-fat diet feeding for 12 weeks and the mice subsequently received high-fat diet and exercise intervention for another 12 weeks. Exercise alleviated high-fat diet-induced glucose intolerance and insulin resistance. Continued high-fat diet feeding exacerbated collagen deposition and further increased fibrosis-related gene expression in adipose tissue. Exercise attenuated or reversed these changes. Additionally, PPARγ, which has been shown to inhibit adipose tissue fibrosis, was observed to be increased following exercise. Moreover, exercise decreased the expression of HIF-1α in adipose fibrosis, and adipose tissue inflammation was inhibited. In conclusion, our data indicate that exercise attenuates and even reverses the progression of adipose tissue fibrosis, providing a plausible mechanism for its beneficial effects on glucose metabolism in obesity.

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Stefano Mangiola Bioinformatics Division, Walter and Eliza Hall Institute, Parkville, Victoria, Australia
Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia
Department of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Ryan Stuchbery Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia

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Patrick McCoy Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia
Department of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Ken Chow Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia
Department of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Natalie Kurganovs Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia
Australian Prostate Cancer Research Centre Epworth, Richmond, Victoria, Australia
Ontario Institute for Cancer Research, Toronto, Canada
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada

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Michael Kerger Australian Prostate Cancer Research Centre Epworth, Richmond, Victoria, Australia

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Anthony Papenfuss Bioinformatics Division, Walter and Eliza Hall Institute, Parkville, Victoria, Australia
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
Department of Mathematics and Statistics, University of Melbourne, Melbourne, Victoria, Australia

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Christopher M Hovens Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia
Department of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia

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Niall M Corcoran Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia
Department of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia
Department of Urology, Frankston Hospital, Frankston, Victoria, Australia

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Prostate cancer is a leading cause of morbidity and cancer-related death worldwide. Androgen deprivation therapy (ADT) is the cornerstone of management for advanced disease. The use of these therapies is associated with multiple side effects, including metabolic syndrome and truncal obesity. At the same time, obesity has been associated with both prostate cancer development and disease progression, linked to its effects on chronic inflammation at a tissue level. The connection between ADT, obesity, inflammation and prostate cancer progression is well established in clinical settings; however, an understanding of the changes in adipose tissue at the molecular level induced by castration therapies is missing. Here, we investigated the transcriptional changes in periprostatic fat tissue induced by profound ADT in a group of patients with high-risk tumours compared to a matching untreated cohort. We find that the deprivation of androgen is associated with a pro-inflammatory and obesity-like adipose tissue microenvironment. This study suggests that the beneficial effect of therapies based on androgen deprivation may be partially counteracted by metabolic and inflammatory side effects in the adipose tissue surrounding the prostate.

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T L C Wolters Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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C D C C van der Heijden Division of Experimental Internal Medicine, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
Division of Vascular Medicine, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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N van Leeuwen Department of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

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B T P Hijmans-Kersten Department of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

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M G Netea Division of Experimental Internal Medicine, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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J W A Smit Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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D H J Thijssen Department of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK

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A R M M Hermus Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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N P Riksen Division of Vascular Medicine, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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R T Netea-Maier Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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Objective

Acromegaly is characterized by an excess of growth hormone (GH) and insulin-like growth factor 1 (IGF1). Cardiovascular disease (CVD) risk factors are common in acromegaly and often persist after treatment. Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Therefore, we hypothesized that inflammation persists in treated acromegaly and may contribute to CVD risk.

Methods

In this cross-sectional study, we assessed cardiovascular structure and function, and inflammatory parameters in treated acromegaly patients. Immune cell populations and inflammatory markers were assessed in peripheral blood from 71 treated acromegaly patients (with controlled or uncontrolled disease) and 41 matched controls. Whole blood (WB) was stimulated with Toll-like receptor ligands. In a subgroup of 21 controls and 33 patients with controlled disease, vascular ultrasound measurements were performed.

Results

Leukocyte counts were lower in patients with controlled acromegaly compared to patients with uncontrolled acromegaly and controls. Circulating IL18 concentrations were lower in patients; concentrations of other inflammatory mediators were comparable with controls. In stimulated WB, cytokine production was skewed toward inflammation in patients, most pronounced in those with uncontrolled disease. Vascular measurements in controlled patients showed endothelial dysfunction as indicated by a lower flow-mediated dilatation/nitroglycerine-mediated dilatation ratio. Surprisingly, pulse wave analysis and pulse wave velocity, both markers of endothelial dysfunction, were lower in patients, whereas intima-media thickness did not differ.

Conclusions

Despite treatment, acromegaly patients display persistent inflammatory changes and endothelial dysfunction, which may contribute to CVD risk and development of CVD.

Open access
Fernando Aprile-Garcia Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina
Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina

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María Antunica-Noguerol Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina
Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina

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Maia Ludmila Budziñski Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina

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Ana C Liberman Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina

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Eduardo Arzt Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina
Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina

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Inflammatory responses are elicited after injury, involving release of inflammatory mediators that ultimately lead, at the molecular level, to the activation of specific transcription factors (TFs; mainly activator protein 1 and nuclear factor-κB). These TFs propagate inflammation by inducing the expression of cytokines and chemokines. The neuroendocrine system has a determinant role in the maintenance of homeostasis, to avoid exacerbated inflammatory responses. Glucocorticoids (GCs) are the key neuroendocrine regulators of the inflammatory response. In this study, we describe the molecular mechanisms involved in the interplay between inflammatory cytokines, the neuroendocrine axis and GCs necessary for the control of inflammation. Targeting and modulation of the glucocorticoid receptor (GR) and its activity is a common therapeutic strategy to reduce pathological signaling. Poly (ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes the addition of PAR on target proteins, a post-translational modification termed PARylation. PARP1 has a central role in transcriptional regulation of inflammatory mediators, both in neuroendocrine tumors and in CNS cells. It is also involved in modulation of several nuclear receptors. Therefore, PARP1 and GR share common inflammatory pathways with antagonic roles in the control of inflammatory processes, which are crucial for the effective maintenance of homeostasis.

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Ferdinand Roelfsema Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Diana van Heemst Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

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Ali Iranmanesh Endocrine Section, Medical Service, Salem Veterans Affairs Medical Center, Salem, Virginia, USA

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Paul Takahashi Primary Care Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA

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Rebecca Yang Endocrine Research Unit, Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota, USA

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Johannes D Veldhuis Endocrine Research Unit, Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota, USA

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Context

Studies on 24-h cortisol secretion are rare. The impact of sex, age and adiposity on cortisol levels, often restricted to one or a few samples, are well recognized, but conflicting.

Objective

To investigate cortisol dynamics in 143 healthy men and women, spanning 7 decades and with a 2-fold body mass index (BMI) range with different analytic tools.

Setting

Clinical Research Unit.

Design

Cortisol concentrations in 10-min samples collected for 24 h. Outcomes were mean levels, deconvolution parameters, approximate entropy (ApEn, regularity statistic) and 24-h rhythms.

Results

Total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. Mean 24-h cortisol concentrations were lower in premenopausal women than those in men of comparable age (176 ± 8.2 vs 217 ± 9.4 nmol/L, P = 0.02), but not in subjects older than 50 years. This was due to lower daytime levels in women, albeit similar in the quiescent overnight period. Aging increased mean cortisol by 10 nmol/L per decade during the quiescent secretory phase and advanced the acrophase of the diurnal rhythm by 24 min/decade. However, total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. ApEn of 24-h profiles was higher (more random) in premenopausal women than those in men (1.048 ± 0.025 vs 0.933 ± 0.023, P = 0.001), but not in subjects older than 50 years. ApEn peaked during the daytime.

Conclusion

Sex and age jointly determine the 24-h cortisol secretory profile. Sex effects are largely restricted to age <50 years, whereas age effects elevate concentrations in the late evening and early night and advance the timing of the peak diurnal rhythm.

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