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  • Abstract: Aging x
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Huiyuan Zhai Department of Pharmacy, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Dongxu Wang Department of Geriatrics, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Yong Wang Department of Pharmacy, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Hongwei Gu Central Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Juan Jv Department of Cardiology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Liangliang Yuan Department of Pharmacy, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Chao Wang Department of Pharmacy, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Leiyao Chen Department of Pharmacy, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China

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Chronic inflammation induced by obesity plays a crucial role in the pathogenesis of insulin resistance. The infiltration of macrophages into adipose tissues contributes to adipose tissue inflammation and insulin resistance. Kaempferol, a flavonoid present in various vegetables and fruits, has been shown to possess remarkable anti-inflammatory properties. In this study, we used leptin receptor-deficient obese mice (db/db) as an insulin-resistant model and investigated the effects of kaempferol treatment on obesity-induced insulin resistance. Our findings revealed that the administration of kaempferol (50 mg/kg/day, for 6 weeks) significantly reduced body weight, fat mass, and adipocyte size. Moreover, it effectively ameliorated abnormal glucose tolerance and insulin resistance in db/db mice. In the adipose tissue of obese mice treated with kaempferol, we observed a reduction in macrophage infiltration and a downregulation of mRNA expression of M1 marker genes TNF-α and IL-1β, accompanied by an upregulation of Arg1 and IL-10 mRNA expression. Additionally, kaempferol treatment significantly inhibited the STING/NLRP3 signaling pathway in adipose tissue. In vitro experiments, we further discovered that kaempferol treatment suppressed LPS-induced inflammation through the activation of NLRP3/caspase 1 signaling in RAW 264.7 macrophages. Our results suggest that kaempferol may effectively alleviate inflammation and insulin resistance in the adipose tissue of db/db mice by modulating the STING/NLRP3 signaling pathway.

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Sandra N Slagter Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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Robert P van Waateringe Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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André P van Beek Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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Melanie M van der Klauw Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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Bruce H R Wolffenbuttel Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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Jana V van Vliet-Ostaptchouk Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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Introduction

To evaluate the prevalence of metabolic syndrome (MetS) and its individual components within sex-, body mass index (BMI)- and age combined clusters. In addition, we used the age-adjusted blood pressure thresholds to demonstrate the effect on the prevalence of MetS and elevated blood pressure.

Subjects and methods

Cross-sectional data from 74,531 Western European participants, aged 18–79 years, were used from the Dutch Lifelines Cohort Study. MetS was defined according to the revised NCEP-ATPIII. Age-adjusted blood pressure thresholds were defined as recommended by the eight reports of the Joint National Committee (≥140/90 mmHg for those aged <60 years, and ≥150/90 mmHg for those aged ≥60 years).

Results

19.2% men and 12.1% women had MetS. MetS prevalence increased with BMI and age. Independent of BMI, abdominal obesity dominated MetS prevalence especially in women, while elevated blood pressure was already highly prevalent among young men. Applying age-adjusted blood pressure thresholds resulted in a 0.2–11.9% prevalence drop in MetS and 6.0–36.3% prevalence drop in elevated blood pressure, within the combined sex, BMI and age clusters.

Conclusions

We observed a gender disparity with age and BMI for the prevalence of MetS and, especially, abdominal obesity and elevated blood pressure. The strict threshold level for elevated blood pressure in the revised NCEP-ATPIII, results in an overestimation of MetS prevalence.

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Wentao Zhou The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Tiantao Kuang The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Xu Han Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Wenqi Chen Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Xuefeng Xu The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Wenhui Lou Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Dansong Wang The Research Institution of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Objectives

Systemic inflammation markers have been demonstrated to be associated with prognosis in various tumors. In this study, we aimed to assess the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index and the counts of lymphocyte, monocyte and neutrophil in predicting prognosis among patients with resected pancreatic neuroendocrine neoplasms (pNENs).

Methods

A total of 174 patients were included in the study. Univariate and multivariate analyses were performed to evaluate the predictive roles of inflammation markers for relapse-free survival (RFS) and overall survival (OS) in pNEN patients.

Results

The optimal cut-off values of NLR, LMR and lymphocyte count were 1.9, 5.0 and 1.4 × 109/L, respectively, determined by the X-tile software. RFS was found to be significantly longer in patients with NLR ≤1.9 (P = 0.041), LMR >5.0 (P < 0.001) and lymphocyte count >1.4 × 109/L (P = 0.002) in comparison to those with NLR >1.9, LMR ≤5.0 and lymphocyte count ≤1.4 × 109/L, respectively. Multivariate analysis revealed that LMR (hazard ratio 0.30, 95% CI 0.11–0.85, P = 0.023) was an independent predictor for RFS, but not NLR or lymphocyte count. For long-term survival analysis, patients with NLR ≤1.9 (P = 0.016) were found to be associated with favorable OS, but NLR was not an independent factor validated by multivariate analysis.

Conclusions

Preoperative LMR is an independent systemic inflammation marker to predict relapses in pNEN patients who underwent curative resections, whose clinical value needs to be verified in further large sample-based prospective studies.

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Zhiwei Zhang Department of Obstetrics and Gynecology, Liaocheng People’s Hospital, Liaocheng, Shandong, China

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Hui Zhao Department of Obstetrics and Gynecology, Liaocheng People’s Hospital, Liaocheng, Shandong, China

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Aixia Wang Department of Obstetrics and Gynecology, Liaocheng People’s Hospital, Liaocheng, Shandong, China

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Background

Gestational diabetes mellitus (GDM) has a high incidence rate among pregnant women. The objective of the study was to assess the effect of plant-derived oleuropein in attenuating inflammatory and oxidative stress of GDM.

Methods

Oleuropein was administered to GDM mice at the doses of 5 or 10 mg/kg/day. Body weight, blood glucose, insulin and hepatic glycogen levels were recorded. To evaluate the effect of oleuropein in reducing oxidative stress, ELISA was used to measure the hepatic oxidative stress markers. The inflammation levels of GDM mice were evaluated by measuring serum levels of IL-6 and TNF-α by ELISA and mRNA levels of IL-1β, TNF-α and IL-6 by real-time PCR (RT-PCR). The AMP-activated protein kinase (AMPK) signaling pathway was assessed by Western blot. Gestational outcome was analyzed through comparing litter size and birth weight.

Results

Oleuropein attenuated the elevated body weight of GDM mice and efficiently reduced blood glucose, insulin and hepatic glycogen levels. Oxidative stress and inflammation were alleviated by oleuropein treatment. The AMPK signaling was activated by oleuropein in GDM mice. Gestational outcome was markedly improved by oleuropein treatment.

Conclusions

Our study suggests that oleuropein is effective in alleviating symptoms of GDM and improving gestational outcome in the mouse model. This effect is achieved by attenuating oxidative stress and inflammation, which is mediated by the activation of the AMPK signaling pathway.

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Shaomin Shi Division of Nephrology, The First Affiliated Hospital of Yangtze University, Jingzhou, China

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Xinghua Chen Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China

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Wen Yu Department of Immunology, School of Medicine, Yangtze University, Jingzhou, China

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Xiaolan Ke Division of Nephrology, The First Affiliated Hospital of Yangtze University, Jingzhou, China

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Tean Ma Division of Nephrology, The First Affiliated Hospital of Yangtze University, Jingzhou, China

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Protection of podocytes is one of the important means to delay the progression of diabetic nephropathy (DN), and glucagon-like peptide-1 (GLP-1) has been shown to have a protective effect on the kidney in DN models, but whether it has a protective effect on podocytes and the potential mechanisms of action remain largely unknown. In the present study, we established a type 2 diabetes mellitus (T2DM) mouse model by high-fat diet feeding combined with streptozotocin (STZ) induction and administered the intervention for 14 weeks. We found that liraglutide significantly ameliorated podocyte injury in DN mice. Mechanistically, we detected glucagon-like peptide-1 receptor (GLP-1R) protein expression levels in kidney tissues by immunohistochemical staining, immunofluorescence staining, and western blotting and found that podocytes could express GLP-1R and liraglutide treatment could restore GLP-1R expression in the kidney tissues of DN mice. Furthermore, we found that NLRP3-induced inflammation and pyroptosis were positively correlated with podocyte injury in DN mice, and liraglutide inhibited the expression of NLRP3-induced inflammation and pyroptosis-related proteins. Our results suggest that liraglutide protects DN mouse podocytes by regulating GLP-1R in renal tissues and by regulating NLRP3-induced inflammation and pyroptosis.

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Sebastião Freitas de Medeiros Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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Márcia Marly Winck Yamamoto Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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Matheus Antônio Souto de Medeiros Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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Bruna Barcelo Barbosa Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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José Maria Soares Junior Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Edmund Chada Baracat Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Objective

To verify whether aging can modify the clinical and biochemical characteristics of women with polycystic ovary syndrome (PCOS).

Material and methods

This observational cross-sectional study was conducted at the reproductive endocrinology clinics of Julio Muller University Hospital and Tropical Institute of Reproductive Medicine in Cuiabá, MT, Brazil, between 2003 and 2017. Both, 796 PCOS and 444 non-PCOS normal cycling women underwent the same examination. PCOS was diagnosed using the Rotterdam criteria as recommended for adolescent and adult subjects. Anthropometric, metabolic, and endocrinological modifications with aging were initially examined in the two groups: control and PCOS. Further analyses were performed after a 5-year age stratification of data throughout the reproductive period. All participants signed a consent form approved by the local ethical committee.

Results

Biomarkers of adiposity were more remarkable in African descendant PCOS women. Body weight, waist/hip ratio, fat mass, and BMI were higher in PCOS women and tended to increase at all 5 age-strata, between ≤19 and 35 years of age. Serum androgen levels decreased with aging, markedly in PCOS subjects (P < 0.01 for all age-strata comparisons), but remained elevated when compared with the levels found in controls. Carbohydrate markers, triglycerides, and total cholesterol tended to increase over time in PCOS (P < 0.01 for all age-strata comparisons). Total cholesterol also tended to increase with age in non-PCOS women (P = 0.041).

Conclusion

The present study has shown that the advancing age influences many features of PCOS women. Biochemical hyperandrogenism, the core criterion recommended in the current systems to define the syndrome, showed statistically significant tendencies to decrease with aging progression but did not normalize. The use of age-adjusted features for the diagnosis of PCOS are recommended.

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Tingting Jia Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

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Ya-nan Wang Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

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Dongjiao Zhang Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

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Xin Xu Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

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Diabetes-induced advanced glycation end products (AGEs) overproduction would result in compromised osseointegration of titanium implant and high rate of implantation failure. 1α,25-dihydroxyvitamin D3 (1,25VD3) plays a vital role in osteogenesis, whereas its effects on the osseointegration and the underlying mechanism are unclear. The purpose of this study was to investigate that 1,25VD3 might promote the defensive ability of osseointegration through suppressing AGEs/RAGE in type 2 diabetes mellitus. In animal study, streptozotocin-induced diabetic rats accepted implant surgery, with or without 1,25VD3 intervention for 12 weeks. After killing, the serum AGEs level, bone microarchitecture and biomechanical index of rats were measured systematically. In vitro study, osteoblasts differentiation capacity was analyzed by alizarin red staining, alkaline phosphatase assay and Western blotting, after treatment with BSA, AGEs, AGEs with RAGE inhibitor and AGEs with 1,25VD3. And the expression of RAGE protein was detected to explore the mechanism. Results showed that 1,25VD3 could reverse the impaired osseointegration and mechanical strength, which possibly resulted from the increased AGEs. Moreover, 1,25VD3 could ameliorate AGEs-induced damage of cell osteogenic differentiation, as well as downregulating the RAGE expression. These data may provide a theoretical basis that 1,25VD3 could work as an adjuvant treatment against poor osseointegration in patients with type 2 diabetes mellitus.

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Luca Boeri Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
Department of Urology, Foundation IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

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Paolo Capogrosso Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Walter Cazzaniga Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Edoardo Pozzi Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Luigi Candela Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Federico Belladelli Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Davide Oreggia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Eugenio Ventimiglia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Nicolò Schifano Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Giuseppe Fallara Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Marina Pontillo Laboratory Medicine Service, IRCCS Ospedale San Raffaele, Milan, Italy

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Costantino Abbate Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Emanuele Montanari Department of Urology, Foundation IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

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Francesco Montorsi Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Andrea Salonia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Objective:

We aimed to test the association between age, BMI and sex-hormone–binding globulin (SHBG) in a homogenous cohort of white-European men presenting for primary couple’s infertility.

Design:

Retrospective study.

Methods:

Data from 1547 infertile men were analysed. Health-significant comorbidities were scored with the Charlson comorbidity index (CCI). Fasting serum hormones were measured in every patient. Age was considered according to quartile groups (<33, 33-41, >41 years) and BMI as normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obesity (>30 kg/m2). Descriptive statistics and linear regression analysis tested the associations between age, BMI and SHBG.

Results:

Median SHBG levels increased across quartiles of age and decreased along with BMI increases (all P < 0.001). For each year increase in age, SHBG increased 0.32 nmol/L; conversely, for each unit increase in BMI, SHBG decreased by 1.1 nmol/L (all P < 0.001). SHBG levels decline with increasing BMI was greater than SHBG progressive increase with age. Overall, BMI explained 3.0 times more of the variability in SHBG than did ageing. At multivariate linear model, age and BMI were the most significant factors influencing SHBG concentration (all P < 0.001), after accounting for CCI, albumin levels and smoking status.

Conclusions:

We found a wide distribution of SHBG concentrations across age and BMI values in primary infertile men. The association between BMI and lowered SHBG levels seems to be greater than the association of ageing with increased SHBG.

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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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