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Dong J, Liu C, Lu J, Wang L, Xie S, Ji L, Lu B. The relationship between sex hormone-binding protein and non-alcoholic fatty liver disease using Mendelian randomisation. Eur J Clin Invest 2024; 54:e14082. [PMID: 37605959 DOI: 10.1111/eci.14082] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 07/24/2023] [Accepted: 08/03/2023] [Indexed: 08/23/2023]
Abstract
BACKGROUND The incidence of non-alcohol fatty liver disease (NAFLD) has been increasing annually with the improvement of living standards. Numerous epidemiological observations have linked sex hormone-binding protein (SHBG) levels to NAFLD. However, evidence of the causal role of SHBG in the development and progression of NAFLD is still absent. Therefore, a systematic assessment of the causal relationship is needed. METHOD A two-sample Mendelian randomisation (MR) analysis was conducted. Genome-wide association study (GWAS) data for SHBG were obtained online from the IEU database (ebi-a-GCST90012111) as exposure. GWAS data from the NAFLD of the Finngen consortium were used for preliminary analysis, while NAFLD data from another GWAS involving 8434 participants were used for replication and meta-analyses. Causal effects were investigated with inverse variance weighted (IVW), weighted median and MR-Egger regression. Sensitivity analyses including Cochran's Q test, leave-one-out analysis and MR-Egger intercept analysis were simultaneously conducted to assess heterogeneity and pleiotropy. RESULTS After rigorous selection, 179 single-nucleotide polymorphisms (SNPs) were identified as strongly correlated instrumental variables. Preliminary analysis suggested a significant causal relationship between genetically determined serum SHBG levels and NAFLD [odds ratio (OR) IVW = .54, 95% confidence interval (CI) = .30-.98, p = .043], supported by the results of the replication analysis (ORIVW = .61, 95% CI = .46-.81, p = .0006) and further meta-analysis (OR = .59, 95% CI = .46-.77, p < .0001). CONCLUSION The genetic tendency to high levels of SHBG was causally correlated with a reduced risk of NAFLD, indicating that circulating high levels of SHBG was a protective factor for NAFLD.
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Affiliation(s)
- Jiaming Dong
- School of Medicine, Shaoxing University, Shaoxing, China
- Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing, China
| | - Chenming Liu
- Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing, China
- Zhejiang University School of Medicine, Hangzhou, China
| | - Jialiang Lu
- School of Medicine, Shaoxing University, Shaoxing, China
- Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing, China
| | - Luna Wang
- Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing, China
- Zhejiang University School of Medicine, Hangzhou, China
| | - Shisheng Xie
- School of Medicine, Shaoxing University, Shaoxing, China
- Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing, China
| | - Lichao Ji
- School of Medicine, Shaoxing University, Shaoxing, China
- Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing, China
| | - Baochun Lu
- Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing, China
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Smith SJ, Bekele D, Lopresti AL, Fairchild TJ. Examining the associations between testosterone and biomarkers as men age. Am J Hum Biol 2023; 35:e23942. [PMID: 37341438 DOI: 10.1002/ajhb.23942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 06/06/2023] [Accepted: 06/07/2023] [Indexed: 06/22/2023] Open
Abstract
OBJECTIVES Testosterone concentrations in men decline with advancing age. However, the cause of the decline is yet to be fully elucidated. Therefore, the aims of this study were to examine the associations between chronic diseases such as obesity and type 2 diabetes mellitus (T2DM) with total testosterone (TT) and sex hormone-binding globulin (SHBG), using a large nationally-representative data set (National Health and Nutrition Examination Survey; NHANES). METHODS NHANES is a cross-sectional survey, physical examination, and laboratory evaluation of a nationally-representative sample of a non-institutionalized United States population. Male participants aged ≥18 years during the NHANES 2013-2014 and NHANES 2015-2016 survey periods were selected for this analysis. The analysis included the following data: body mass index (BMI), oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA-IR), insulin, glucose, and age. RESULTS An overweight or obese condition was significantly inversely associated with TT and SHBG, even after adjusting for other variables. Several variables associated with T2DM (OGTT, HOMA-IR, insulin, and glucose) were also inversely associated with TT; however, only the associations between OGTT and insulin with TT remained significant after adjusting for the other variables. Insulin and HOMA-IR levels were significantly inversely associated with SHBG; however, only the association between SHBG and pre-diabetic HOMA-IR levels remained significant after adjusting for the other variables. OGTT became significantly associated with SHBG after adjusting for the other variables. Age was significantly inversely associated with TT, but positively associated with SHBG, even after adjusting for other variables. CONCLUSION The results of the present study, which is the largest to date, indicate that a marker of obesity, BMI, and some markers of T2DM are both independently and significantly inversely associated with TT and SHBG.
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Affiliation(s)
- Stephen J Smith
- Clinical Research Australia, Perth, Western Australia, Australia
- The Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, Western Australia, Australia
| | - Daniel Bekele
- College of Natural and Computational Sciences, Dire Dawa University, Dire Dawa, Ethiopia
| | - Adrian L Lopresti
- Clinical Research Australia, Perth, Western Australia, Australia
- The Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, Western Australia, Australia
| | - Timothy J Fairchild
- The Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, Western Australia, Australia
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Huang R, Wang Y, Yan R, Ding B, Ma J. Sex Hormone Binding Globulin is an Independent Predictor for Insulin Resistance in Male Patients with Newly Diagnosed Type 2 Diabetes Mellitus. Diabetes Ther 2023; 14:1627-1637. [PMID: 37462840 PMCID: PMC10499719 DOI: 10.1007/s13300-023-01445-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 06/30/2023] [Indexed: 09/14/2023] Open
Abstract
INTRODUCTION This study explored the correlation between sex hormones, sex hormone binding globulin (SHBG), and insulin resistance in male patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS A total of 48 male patients with newly diagnosed T2DM were enrolled in this study between March 2022 and December 2022. Clinical characteristics, sex hormones, and SHBG levels were collected. All enrolled subjects received intensive hypoglycemic treatment with insulin pump for 1 week to achieve glycemic control, then the steady-state glucose infusion rate (GIR), an indicator of insulin sensitivity, was determined by the hyperinsulinemic-euglycemic clamp. Correlation analysis and multivariate logistic regression analysis were performed to explore the association of clinical characteristics, sex hormones, and SHBG with insulin sensitivity. The optimal cutoff value to predict insulin resistance was calculated using receiver operating characteristic (ROC) curve. RESULTS According to the GIR cut-point value of 5.700 mg/(kg min), there were 40 patients with insulin resistance (IR group) and 8 patients without (non-IR group). The IR group exhibited lower testosterone and SHBG levels than the non-IR group (all p < 0.050). Correlation analysis showed that insulin sensitivity was positively associated with testosterone and SHBG, while negatively associated with body mass index, fasting blood glucose, alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, and apolipoprotein B (all p < 0.050). Multivariate logistic regression analysis demonstrated that SHBG is an independent predictor for insulin resistance (p = 0.029). Further ROC curve analysis revealed that the optimal cutoff value of SHBG to predict insulin resistance is 17.200 nmol/L, with the corresponding area under the curve (AUC) and its 95% confidence interval (CI) being 0.813 and 0.691-0.934. CONCLUSIONS SHBG is an independent predictor for insulin resistance in male patients with newly diagnosed T2DM. TRIAL REGISTRATION NUMBER KY20220314-01.
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Affiliation(s)
- Rong Huang
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, No.32 Gongqingtuan Road, Nanjing, 210012, China
| | - Ying Wang
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, No.32 Gongqingtuan Road, Nanjing, 210012, China
| | - Rengna Yan
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, No.32 Gongqingtuan Road, Nanjing, 210012, China
| | - Bo Ding
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, No.32 Gongqingtuan Road, Nanjing, 210012, China.
| | - Jianhua Ma
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, No.32 Gongqingtuan Road, Nanjing, 210012, China.
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Biernacka-Bartnik A, Kocełak P, Owczarek AJ, Choręza PS, Markuszewski L, Madej P, Puzianowska-Kuźnicka M, Chudek J, Olszanecka-Glinianowicz M. The cut-off value for HOMA-IR discriminating the insulin resistance based on the SHBG level in women with polycystic ovary syndrome. Front Med (Lausanne) 2023; 10:1100547. [PMID: 36968815 PMCID: PMC10037532 DOI: 10.3389/fmed.2023.1100547] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 02/20/2023] [Indexed: 03/12/2023] Open
Abstract
INTRODUCTION The study aimed to estimate the cut-off value for homeostatic model assessment for insulin resistance (HOMA-IR) discriminating the insulin resistance based on the sex hormones binding globulin (SHBG) level in women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS Data from medical records of 854 Caucasian women diagnosed with PCOS were analyzed. Anthropometric data, fasting plasma glucose, insulin and SHBG levels were measured. HOMA-IR was calculated with a standard formula. The cut-off value was calculated using receiver-operating characteristics. RESULTS Circulating SHBG levels below the normal range (26.1 nmol/L) were found in 25.4% of study participants. This subgroup had a significantly higher BMI, fasting glucose and insulin concentrations and HOMA-IR values. Empirical optimal cut-off values for HOMA-IR corresponding to low SHBG levels was ≥2.1 [area under the curve (AUC) 0.73, accuracy 0.65, sensitivity 72.3%, specificity 63.1%, positive predictive value (PPV) 40.0%, negative predictive value (NPV) 87.0%]. CONCLUSIONS Our study suggests that the cut-off point for HOMA-IR discriminating the insulin resistance based on the SHBG level, in young Caucasian women with polycystic ovary syndrome is 2.1, and is consistent with the cut-off value adopted by the European Group for the Study of Insulin Resistance (above 2.0).
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Affiliation(s)
- Aleksandra Biernacka-Bartnik
- Department of Gynecological Endocrinology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| | - Piotr Kocełak
- Pathophysiology Unit, Department of Pathophysiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| | - Aleksander Jerzy Owczarek
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| | - Piotr Stanisław Choręza
- Department of Statistics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland
| | - Leszek Markuszewski
- Faculty of Medical Sciences and Health Sciences, University of Humanities and Technology in Radom, Radom, Poland
| | - Paweł Madej
- Department of Gynecological Endocrinology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| | - Monika Puzianowska-Kuźnicka
- Department of Human Epigenetics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
- Department of Geriatrics and Gerontology, Medical Center of Postgraduate Education, Warsaw, Poland
| | - Jerzy Chudek
- Pathophysiology Unit, Department of Pathophysiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
- Department of Internal Medicine and Oncological Chemotherapy, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| | - Magdalena Olszanecka-Glinianowicz
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
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Urbano F, Chiarito M, Lattanzio C, Messa A, Ferrante M, Francavilla M, Mehmeti I, Lassandro G, Giordano P, Faienza MF. Sex Hormone-Binding Globulin (SHBG) Reduction: The Alarm Bell for the Risk of Non-Alcoholic Fatty Liver Disease in Adolescents with Polycystic Ovary Syndrome. CHILDREN (BASEL, SWITZERLAND) 2022; 9:1748. [PMID: 36421197 PMCID: PMC9689249 DOI: 10.3390/children9111748] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/02/2022] [Accepted: 11/10/2022] [Indexed: 08/30/2023]
Abstract
Polycystic ovary syndrome (PCOS) represents an endocrine condition affecting 5-18% of adolescents, frequently in association with obesity, metabolic alterations, and liver dysfunction. In this study, we aimed to evaluate the prevalence and risk factors for developing non-alcoholic fatty liver disease (NAFLD) in a cohort of PCOS adolescents. Thirty-two girls were assessed for anthropometric and biochemical markers: total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT). In addition, LH, FSH, 17β-Estradiol (E2), prolactin, testosterone (T), free testosterone, delta 4-androstenedione (D4 A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding protein (SHBG) were also evaluated. All subjects underwent liver ultrasound to detect NAFLD. Our data demonstrated that PCOS adolescents complicated with NAFLD accounted for 37.5%, and those with obesity and lower SHBG were more predisposed to developing NAFLD. Moreover, SHBG showed a negative correlation with several parameters such as blood pressure, body mass index, waist circumference, insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR). Our results demonstrated that the assessment of SHBG may allow the identification of PCOS adolescents at risk for developing NAFLD and metabolic alterations.
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Affiliation(s)
- Flavia Urbano
- Pediatric Unit, Giovanni XXIII Pediatric Hospital, 70126 Bari, Italy
| | | | | | - Angela Messa
- Pediatric Unit, Giovanni XXIII Pediatric Hospital, 70126 Bari, Italy
| | - Marco Ferrante
- Pediatric Unit, Giovanni XXIII Pediatric Hospital, 70126 Bari, Italy
| | | | - Irsida Mehmeti
- Faculty of Pharmacy, Catholic University “Our Lady of Good Counsel”, 1000 Tirana, Albania
| | | | - Paola Giordano
- Pediatric Unit, Department of Interdisciplinary Medicine, University of Bari “A. Moro”, 70124 Bari, Italy
| | - Maria Felicia Faienza
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari “A. Moro”, 70124 Bari, Italy
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Yang X, Chen X, Xu H, Deng H, Yao B, Xu W, Lin Q. Relations Between Body Fat Mass and Insulin Resistance in Non-Obese Patients with Idiopathic Hypogonadotropic Hypogonadism and Normal Glucose Tolerance. Horm Metab Res 2022; 54:671-676. [PMID: 36206760 DOI: 10.1055/a-1933-3009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
The purpose of this study was to investigate the relationship between body fat mass and insulin resistance in non-obese patients with idiopathic hypogonadotropic hypogonadism (IHH) and normal glucose tolerance. A total of 42 patients with IHH and normal glucose tolerance, and BMI lower than 28 kg/m2 were recruited. Patients were required to have a normal glucose tolerance test for inclusion in the study. Ten Healthy subjects were recruited as control group. Laboratory studies included fasting insulin, testosterone, and lipids. Waist circumference (WC), weight, and body fat mass were measured, and waist-to-hip ratio (WHR), body mass index (BMI), HOMA-IR, and logHOMA-B were calculated. Data were compared between groups, and linear regression was used to determine relations. Blood pressure, fasting glucose, BMI, WHR, and lipids were similar between the groups. Fasting insulin levels (15.61±7.66 mIU/l vs. 7.60±3.84 mIU/l), logHOMA-B (2.39±0.29 vs. 2.03±0.21), HOMA-IR (3.38±1.71 vs. 1.64±0.91), and body fat mass (30.49±9.46% vs. 21.11±4.31%) were significantly greater in the IHH group compared with those in control group (all p<0.05). Multivariable linear regression showed that in IHH patients body fat mass was an independent predictor of fasting insulin level (β=0.71, p<0.01), logHOMA-B (β=0.02, p<0.05), and HOMA-IR (β=0.14, p<0.05). Body fat mass is an independent predictor of insulin resistance in non-obese IHH patients with normal glucose tolerance.
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Affiliation(s)
- Xubin Yang
- Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xueyan Chen
- Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Huan Xu
- Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Hongrong Deng
- Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Bin Yao
- Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Wen Xu
- Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Qiongyan Lin
- Department of Endocrinology, Jieyang People's Hospital, Jieyang, China
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Aljabban J, Rohr M, Syed S, Khorfan K, Borkowski V, Aljabban H, Segal M, Mukhtar M, Mohammed M, Panahiazar M, Hadley D, Spengler R, Spengler E. Transcriptome changes in stages of non-alcoholic fatty liver disease. World J Hepatol 2022; 14:1382-1397. [PMID: 36158924 PMCID: PMC9376779 DOI: 10.4254/wjh.v14.i7.1382] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/29/2022] [Accepted: 06/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and globally. The currently understood model of pathogenesis consists of a ‘multiple hit’ hypothesis in which environmental and genetic factors contribute to hepatic inflammation and injury.
AIM To examine the genetic expression of NAFLD and non-alcoholic steatohepatitis (NASH) tissue samples to identify common pathways that contribute to NAFLD and NASH pathogenesis.
METHODS We employed the Search Tag Analyze Resource for Gene Expression Omnibus platform to search the The National Center for Biotechnology Information Gene Expression Omnibus to elucidate NAFLD and NASH pathology. For NAFLD, we conducted meta-analysis of data from 58 NAFLD liver biopsies and 60 healthy liver biopsies; for NASH, we analyzed 187 NASH liver biopsies and 154 healthy liver biopsies.
RESULTS Our results from the NAFLD analysis reinforce the role of altered metabolism, inflammation, and cell survival in pathogenesis and support recently described contributors to disease activity, such as altered androgen and long non-coding RNA activity. The top upstream regulator was found to be sterol regulatory element binding transcription factor 1 (SREBF1), a transcription factor involved in lipid homeostasis. Downstream of SREBF1, we observed upregulation in CXCL10, HMGCR, HMGCS1, fatty acid binding protein 5, paternally expressed imprinted gene 10, and downregulation of sex hormone-binding globulin and insulin-like growth factor 1. These molecular changes reflect low-grade inflammation secondary to accumulation of fatty acids in the liver. Our results from the NASH analysis emphasized the role of cholesterol in pathogenesis. Top canonical pathways, disease networks, and disease functions were related to cholesterol synthesis, lipid metabolism, adipogenesis, and metabolic disease. Top upstream regulators included pro-inflammatory cytokines tumor necrosis factor and IL1B, PDGF BB, and beta-estradiol. Inhibition of beta-estradiol was shown to be related to derangement of several cellular downstream processes including metabolism, extracellular matrix deposition, and tumor suppression. Lastly, we found riciribine (an AKT inhibitor) and ZSTK-474 (a PI3K inhibitor) as potential drugs that targeted the differential gene expression in our dataset.
CONCLUSION In this study we describe several molecular processes that may correlate with NAFLD disease and progression. We also identified ricirbine and ZSTK-474 as potential therapy.
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Affiliation(s)
- Jihad Aljabban
- Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI 53792, United States
| | - Michael Rohr
- Department of Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, United States
| | - Saad Syed
- Department of Medicine, Northwestern Memorial Hospital, Chicago, IL 60611, United States
| | - Kamal Khorfan
- Department of Gastroenterology and Hepatology, University of California San Francisco-Fresno , Fresno, CA 93701, United States
| | - Vincent Borkowski
- Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI 53792, United States
| | - Hisham Aljabban
- Department of Medicine, Barry University, Miami, FL 33161, United States
| | - Michael Segal
- Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI 53792, United States
| | - Mohamed Mukhtar
- Department of Medicine, Michigan State University College of Human Medicine, East Lansing, MI 49503, United States
| | - Mohammed Mohammed
- Department of Medicine, Windsor University School of Medicine, Saint Kitts 1621, Cayon, Saint Kitts and Nevis
| | - Maryam Panahiazar
- Department of Surgery, University of California San Francisco, San Francisco, CA 94305, United States
| | - Dexter Hadley
- Department of Artificial Intelligence, Pathology, University of Central Florida College of Medicine , Orlando, FL 32827, United States
| | - Ryan Spengler
- Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI 53792, United States
| | - Erin Spengler
- Department of Gastroenterology and Hepatology, University of Wisconsin Hospital and Clinics, Madison, WI 53792, United States
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Sex hormone binding globulin as a potential drug candidate for liver-related metabolic disorders treatment. Biomed Pharmacother 2022; 153:113261. [PMID: 35738176 DOI: 10.1016/j.biopha.2022.113261] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 05/30/2022] [Accepted: 06/06/2022] [Indexed: 11/29/2022] Open
Abstract
Sex hormone binding globulin (SHBG) is a hepatokine that binds to circulating steroid hormones (testosterone, oestradiol) to regulate their concentration in the bloodstream. Recently SHBG was recognized as an essential biomarker for metabolic syndrome (MetS) and hepatic steatosis development. At the hepatic level, the production of SHBG is mainly regulated by sex steroids and thyroxine. Studies of various research groups, including ours, showed that SHBG could be considered a reliable marker of insulin resistance and, therefore, can serve as a predictor of type 2 diabetes. Moreover, increased levels of circulating pro-inflammatory mediators strongly correlate with lowered serum levels of SHBG. This review paper emphasizes the role of SHBG as a potential drug candidate in the course of various metabolic dysfunctions, including non-alcoholic fatty liver disease (NAFLD), obesity, diabetes mellitus and insulin resistance. The studies related to SHBG and its role in the course of metabolic disorders are very limited. Here, we have summarized the most current knowledge about SHBG and its mechanism of action, indicating a novel concept for its possible therapeutic application in the management framework of commonly occurring metabolic dysfunctions.
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Khanlarkhani N, Azizi E, Amidi F, Khodarahmian M, Salehi E, Pazhohan A, Farhood B, Mortezae K, Goradel NH, Nashtaei MS. Metabolic risk factors of ovarian cancer: a review. JBRA Assist Reprod 2022; 26:335-347. [PMID: 34751020 PMCID: PMC9118962 DOI: 10.5935/1518-0557.20210067] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 08/29/2021] [Indexed: 11/20/2022] Open
Abstract
Ovarian cancer continues to be the leading cause of death from gynecological cancers. Despite inconsistent results, patients with metabolic abnormalities, including obesity and diabetes mellitus (DM), have poorer outcomes, showing a correlation with ovarian cancer incidence and ovarian cancer survival. Since ovarian cancer is the most common cancer in women, and considering the increasing prevalence of obesity and DM, this paper reviews the literature regarding the relationship between the aforementioned metabolic derangements and ovarian cancer, with a focus on ovarian cancer incidence, mortality, and likely mechanisms behind them. Several systematic reviews and meta-analyses have shown that obesity is associated with a higher incidence and poorer survival in ovarian cancer. Although more studies are required to investigate the etiological relation of DM and ovarian cancer, sufficient biological evidence indicates poorer outcomes and shorter survival in DM women with ovarian cancer. A variety of pathologic factors may contribute to ovarian cancer risk, development, and survival, including altered adipokine expression, increased levels of circulating growth factors, altered levels of sex hormones, insulin resistance, hyperinsulinemia, and chronic inflammation. Thus, obesity and DM, as changeable risk factors, can be targeted for intervention to prevent ovarian cancer and improve its outcomes.
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Affiliation(s)
- Neda Khanlarkhani
- Department of Physiology and Pharmacology, Karolinska Institute, Sweden
| | - Elham Azizi
- Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fardin Amidi
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahshad Khodarahmian
- Infertility department, Arash Women's Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Ensieh Salehi
- Department of Gynecology, School of Medicine, Fertility and Infertility Research Center, Dr. Ali Shariati Hospital, Shahid Mohammadi Hospital, Hormozgan University of Medical Sciences, Hormozgan, Iran
| | - Azar Pazhohan
- Infertility Center, Academic Center for Education, Culture and Research, East Azarbaijan, Tabriz, Iran. / Department of Midwifery, Urmia Branch, Islamic Azad University, Urmia, Iran
| | - Bagher Farhood
- Departments of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Keywan Mortezae
- Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Nasser Hashemi Goradel
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Shabani Nashtaei
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. / Infertility Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Mo MQ, Huang ZC, Yang ZH, Liao YH, Xia N, Pan L. Relationship between total testosterone, sex hormone-binding globulin levels and the severity of non-alcoholic fatty liver disease in males: a meta-analysis. Ther Adv Endocrinol Metab 2022; 13:20420188221106879. [PMID: 35785018 PMCID: PMC9240586 DOI: 10.1177/20420188221106879] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 05/25/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND In recent years, many studies have reported the relationship between non-alcoholic fatty liver disease (NAFLD) and sex hormones, especially total testosterone (TT) and sex hormone-binding globulin (SHBG). However, the relationship between sex hormones and the severity of NAFLD is still unclear. METHODS PubMed, Embase, Cochrane Library, Web of Science, WanFang, China National Knowledge Infrastructure and VIP databases were searched for relevant studies from inception to 31 August 2021. Values of weighted mean differences (WMDs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined by Stata 12.0 software to evaluate the relationship between TT, SHBG and the severity of NAFLD in males. RESULTS A total of 2995 patients with NAFLD from 10 published cross-sectional studies were included for further analysis. The meta-analysis indicated that the moderate-severe group had a lower TT than the mild group in males with NAFLD (WMD: -0.35 ng/ml, 95% CI = -0.50 to -0.20). TT and SHBG were important risk factors of moderate-severe NAFLD in males (ORTT = 0.79, 95% CI = 0.73 to 0.86; ORSHBG = 0.22, 95% CI = 0.12 to 0.39; p < 0.001). Moreover, when the analysis was limited to men older than age 50, SHBG levels were lower in those with moderate-severe disease (WMD: -11.32 nmol/l, 95% CI = -14.23 to -8.40); while for men with body mass index (BMI) >27 kg/m2, moderate-severe NAFLD had higher SHBG levels than those with mild disease (WMD: 1.20 nmol/l, 95% CI = -2.01 to 4.42). CONCLUSION The present meta-analysis shows that lower TT is associated with the severity of NAFLD in males, while the relationship between SHBG and severity of NAFLD is still to be further verified.
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Affiliation(s)
| | | | - Zhen-Hua Yang
- Department of Nephrology, The First Affiliated
Hospital of Guangxi Medical University, Nanning, China
| | - Yun-Hua Liao
- Department of Nephrology, The First Affiliated
Hospital of Guangxi Medical University, Nanning, China
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11
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Cai J, Lin C, Lai S, Liu Y, Liang M, Qin Y, Liang X, Tan A, Gao Y, Lu Z, Wu C, Huang S, Yang X, Zhang H, Kuang J, Mo Z. Waist-to-height ratio, an optimal anthropometric indicator for metabolic dysfunction associated fatty liver disease in the Western Chinese male population. Lipids Health Dis 2021; 20:145. [PMID: 34706716 PMCID: PMC8549212 DOI: 10.1186/s12944-021-01568-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 09/23/2021] [Indexed: 12/24/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) has been entitled as metabolic-dysfunction associated fatty liver disease (MAFLD). Therefore anthropometric indicators of adiposity may provide a non-invasive predictive and diagnostic tool for this disease. This study intended to validate and compare the MAFLD predictive and diagnostic capability of eight anthropometric indicators. Methods The study involved a population-based retrospective cross-sectional design. The Fangchenggang area male health and examination survey (FAMHES) was used to collect data of eight anthropometric indicators, involving body mass index (BMI), waist-to-height ratio (WHtR), waist-hip ratio (WHR), body adiposity index (BAI), cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and abdominal volume index (AVI). Receiver operating characteristics (ROC) curves and the respective areas under the curves (AUCs) were utilized to compare the diagnostic capacity of each indicator for MAFLD and to determine the optimal cutoff points. Binary logistic regression analysis was applied to identify the odds ratios (OR) with 95% confidence intervals (95% CI) for all anthropometric indicators and MAFLD. The Spearman rank correlation coefficients of anthropometric indicators, sex hormones, and MAFLD were also calculated. Results All selected anthropometric indicators were significantly associated with MAFLD (P < 0.001), with an AUC above 0.79. LAP had the highest AUC [0.868 (95% CI, 0.853–0.883)], followed by WHtR [0.863 (95% CI, 0.848–0.879)] and AVI [0.859 (95% CI, 0.843–0.874)]. The cutoff values for WHtR, LAP and AVI were 0.49, 24.29, and 13.61, respectively. WHtR [OR 22.181 (95% CI, 16.216–30.340)] had the strongest association with MAFLD, regardless of potential confounders. Among all the anthropometric indicators, the strongest association was seen between LAP and sex hormones. Conclusion All anthropometric indicators were associated with MAFLD. WHtR was identified as the strongest predictor of MAFLD in young Chinese males, followed by LAP and AVI. The strongest association was found between LAP and sex hormones. Supplementary Information The online version contains supplementary material available at 10.1186/s12944-021-01568-9.
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Affiliation(s)
- Jinwei Cai
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.,Department of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.,Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Cuiting Lin
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, China.,Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Shuiqing Lai
- Department of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Yingshan Liu
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.,Department of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
| | - Min Liang
- Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yingfen Qin
- Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Xinghuan Liang
- Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Aihua Tan
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Yong Gao
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Zheng Lu
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Chunlei Wu
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Shengzhu Huang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.,Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.,Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Xiaobo Yang
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Haiying Zhang
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Jian Kuang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China. .,Department of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
| | - Zengnan Mo
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.,Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.,Guangxi Key Laboratory of Genomic and Personalized Medicine, Nanning, Guangxi Zhuang Autonomous Region, China.,Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi Zhuang Autonomous Region, China
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12
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Zan G, Li L, Cheng H, Huang L, Huang S, Luo X, Xiao L, Liu C, Zhang H, Mo Z, Yang X. Mediated relationships between multiple metals exposure and fasting blood glucose by reproductive hormones in Chinese men. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 278:116791. [PMID: 33684679 DOI: 10.1016/j.envpol.2021.116791] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 02/16/2021] [Accepted: 02/17/2021] [Indexed: 06/12/2023]
Abstract
Previous studies have reported metals exposure contribute to the change of fasting blood glucose (FBG) level. However, the roles of reproductive hormones in their associations have not been fully elucidated. The aim of the study is to investigate the associations of multiple serum metals with reproductive hormones, and to further explore potential roles of reproductive hormones in relationships between metals exposure and FBG level. A total of 1911 Chinese Han men were analyzed by a cross-sectional study. We measured serum levels of 22 metals by inductively coupled plasma mass spectrometer (ICP-MS). FBG, total testosterone (TT), estradiol (E2), follicle stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) levels were determined. Least absolute shrinkage and selection operator (LASSO) regression models were conducted to select important metals, and restricted cubic spline models were then used to estimate dose-response relationships between selected metals and reproductive hormones. We also conducted mediation analyses to evaluate whether reproductive hormones played mediating roles in the associations between metals and FBG. We found significant inverse dose-dependent trends of copper, tin and zinc with E2; zinc with SHBG; copper and nickel with TT, while significant positive dose-dependent trend of iron with E2, respectively. Moreover, approximately inverted U-shaped associations existed between lead and SHBG, iron and TT. In addition, E2, SHBG and TT were negatively associated with FBG level. In mediation analyses, the association of copper with FBG was mediated by E2 and TT, with a mediation ratio of 10.4% and 22.1%, respectively. Furthermore, E2 and SHBG mediated the relationship of zinc with FBG, with a mediation ratio of 7.8% and 14.5%, respectively. E2 mediated 11.5% of positive relationship between tin with FBG. Our study suggested that the associations of metals exposure with FBG may be mediated by reproductive hormones.
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Affiliation(s)
- Gaohui Zan
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Longman Li
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Hong Cheng
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Lulu Huang
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Sifang Huang
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Xiaoyu Luo
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Lili Xiao
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Chaoqun Liu
- Department of Nutrition and Food Hygiene, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Haiying Zhang
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Zengnan Mo
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China
| | - Xiaobo Yang
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China; Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Key Laboratory for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi, China; Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, Guangxi, China; Department of Public Health, School of Medicine, Guangxi University of Science and Technology, Liuzhou, Guangxi, China.
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13
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Sun M, Sun B, Qiao S, Feng X, Li Y, Zhang S, Lin Y, Hou L. Elevated maternal androgen is associated with dysfunctional placenta and lipid disorder in newborns of mothers with polycystic ovary syndrome. Fertil Steril 2021; 113:1275-1285.e2. [PMID: 32482257 DOI: 10.1016/j.fertnstert.2020.02.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 01/24/2020] [Accepted: 02/09/2020] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To investigate the placental morphology alterations and identify the clinical characteristics of women with polycystic ovary syndrome (PCOS) and their newborns. Pregnant women with PCOS (n = 12) and pregnant women without PCOS (n = 11) were recruited. Then, the placenta, maternal blood and cord blood were collected after delivery. DESIGN Clinical observational study. SETTING Not applicable. PATIENT(S) In the present study, pregnant women with PCOS and healthy pregnant women were recruited from the clinic of the Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, China, between February 2015 and October 2015. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) A proteomic analysis was performed on the placenta in women with PCOS and healthy women. RESULT(S) The maternal testosterone, androstenedione, dehydroepiandrosterone sulfate, free androgen index, cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A-I levels were significantly higher in the PCOS group than in the control group, and the offspring in the PCOS group had higher dehydroepiandrosterone sulfate, high-density lipoprotein, and cholesterol levels, when compared with the control group. The placenta in the PCOS group demonstrated infarction, calcification, and a greater intervillous space, when compared with the control group. A higher level of estrogen receptor-β protein was observed in the placenta of women with PCOS, when compared with women without PCOS. A total of 258 proteins in the placenta were identified to be significantly different, when the PCOS and control groups were compared, and fibronectin 1 exhibited the closest relationship with other differential proteins. CONCLUSION(S) The overexposure to hyperandrogenism and hyperlipidemia affects the functions of the placenta, which are associated with the development of metabolic disorders in newborns.
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Affiliation(s)
- Miao Sun
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China
| | - Bo Sun
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Grafton, Auckland, New Zealand
| | - Shicong Qiao
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China; Department of Gynecology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People's Republic of China
| | - Xiaoling Feng
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China
| | - Yan Li
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China
| | - Shuwen Zhang
- Department of Animal Sciences, Washington State University, Pullman, Washington
| | - Yuhan Lin
- Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Lihui Hou
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, People's Republic of China.
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Venetsanaki V, Polyzos SA. Menopause and Non-Alcoholic Fatty Liver Disease: A Review Focusing on Therapeutic Perspectives. Curr Vasc Pharmacol 2020; 17:546-555. [PMID: 29992886 DOI: 10.2174/1570161116666180711121949] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Revised: 06/05/2018] [Accepted: 06/14/2018] [Indexed: 02/06/2023]
Abstract
There is increasing evidence that menopause is associated with the progression and severity of non-alcoholic fatty liver disease (NAFLD). Estrogen deficiency worsens non-alcoholic steatohepatitis (NASH) in mice models with fatty liver. The prevalence of NAFLD seems to be higher in postmenopausal compared with premenopausal women. Although more data are needed, lower serum estradiol levels are associated with NASH in postmenopausal women. Apart from estrogen deficiency, relative androgen excess and decrease in sex hormone-binding protein are observed in postmenopausal women. These hormonal changes seem to interplay with an increase in abdominal adipose mass, also observed in postmenopausal women, and aging, which are both closely related to the severity and progressive forms of NAFLD. NAFLD adds extra morbidity to postmenopausal women, possibly increasing the risk of type 2 diabetes mellitus and cardiovascular disease. Improving parameters of the metabolic syndrome via modifications in diet and physical exercise may reduce the risk of NAFLD and its related morbidity. Limited studies have shown a beneficial effect of hormone replacement therapy (HRT) on NAFLD, although adverse hepatic effects have been attributed to progesterone in one study. Phytoestrogens may be alternatives to HRT, but their long-term efficacy and safety remain to be shown. The aim of this review was to summarize evidence linking menopause with NAFLD with a special focus on potential therapeutic perspectives.
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Affiliation(s)
- Vasiliki Venetsanaki
- Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stergios A Polyzos
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
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15
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Nonalcoholic Fatty Liver Disease, Male Sexual Dysfunction, and Infertility: Common Links, Common Problems. Sex Med Rev 2020; 8:274-285. [DOI: 10.1016/j.sxmr.2019.01.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 12/28/2018] [Accepted: 01/14/2019] [Indexed: 12/18/2022]
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16
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Hassanabad MF, Fatehi M. Androgen Therapy in Male Patients Suffering from Type 2 Diabetes: A Review of Benefits and Risks. Curr Diabetes Rev 2020; 16:189-199. [PMID: 30073928 DOI: 10.2174/1573399814666180731125724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 07/23/2018] [Accepted: 07/29/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND The current estimated numbers of patients with Type 2 Diabetes (T2D) is believed to be close to 10% of the whole populations of many geographical regions, causing serious concerns over the resulting elevated morbidity and mortality as well as the impact on health care systems around the world. In addition to negatively affecting the quality of life, diabetes is associated with cardiovascular and cerebrovascular complications, indicating that appropriate drug therapy should not only deal with metabolic dysfunction but also protect the vascular system, kidney function and skeletal muscle mass from the effects of the epigenetic changes induced by hyperglycaemia. OBJECTIVE To provide an insight into the management of hypogonadism associated with T2D, this review focuses on clinical observations related to androgen therapy in qualified diabetic patients, and discusses the lines of evidence for its benefits and risks. The potential interactions of testosterone with medicines used by patients with T2D will also be discussed. CONCLUSION From recent clinical findings, it became evident that a considerable percentage of patients suffering from T2D manifested low serum testosterone and experienced diminished sexual activity, as well as reduced skeletal muscle mass and lower bone density. Although there are some controversies, Testosterone Replacement Therapy (TRT) for this particular population of patients appears to be beneficial overall only if it is implemented carefully and monitored regularly.
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Affiliation(s)
- Mortaza F Hassanabad
- Alberta Institute of Diabetes and Department of Pharmacology, Faculty of Sciences, University of Alberta, Edmonton, Canada
| | - Mohammad Fatehi
- Alberta Institute of Diabetes and Department of Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, Canada
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17
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Park B, Lee YJ. Inverse association of testosterone and sex hormone binding globulin levels with leukocyte count in middle-aged and elderly men. Aging Male 2018; 21:176-181. [PMID: 29863448 DOI: 10.1080/13685538.2018.1477934] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
OBJECTIVE The inverse associations of testosterone and sex hormone-binding globulin (SHBG) levels with cardiometabolic diseases are well established and are increasingly viewed as inflammatory diseases. This study aimed to examine the associations of testosterone and SHBG levels with leukocyte count in 451 Korean men aged ≥50 years. METHODS Serum testosterone and SHBG levels were categorized into tertiles. High leukocyte count was defined as ≥7340 cells/μl, which corresponded to the 75th percentile of the current sample. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for high leukocyte count were calculated across testosterone and SHBG tertiles using multiple logistic regression analysis. RESULTS The mean leukocyte counts significantly decreased with increasing testosterone and SHBG tertiles. The ORs (95% CIs) of high leukocyte count for the first tertile of testosterone and SHBG were 3.27 (1.34-7.95) and 2.38 (1.05-5.96), respectively, compared with the referent third tertile, after adjusting for age, smoking status, alcohol drinking, regular exercise, body mass index, blood pressure, fasting plasma glucose, triglyceride, and high-density lipoprotein (HDL) cholesterol level. CONCLUSION We found inversely graded associations of low testosterone and SHBG levels with leukocyte count. These findings suggest that low testosterone and SHBG levels may be interpreted as a state of low-grade inflammation.
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Affiliation(s)
- Byoungjin Park
- a Department of Family Medicine, Yonsei University College of Medicine , Seoul , Korea
- b Department of Medicine, Graduate School of Medicine , Yonsei University, Seoul , Korea
| | - Yong-Jae Lee
- a Department of Family Medicine, Yonsei University College of Medicine , Seoul , Korea
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18
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Mohammadghasemi F, Abbasi M, Rudkhaneei K, Aghajany-Nasab M. Beneficial effect of apple vinegar on reproductive parameters in male rat model of nonalcoholic fatty liver disease. Andrologia 2018; 50:e13065. [DOI: 10.1111/and.13065] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Revised: 04/18/2018] [Accepted: 05/06/2018] [Indexed: 12/17/2022] Open
Affiliation(s)
- Fahimeh Mohammadghasemi
- Cellular & Molecular Research Center; School Of Medicine; Guilan University of Medical Sciences; Rasht Iran
| | - Masumeh Abbasi
- Department Of Anatomy; School Of Medicine; Guilan University of Medical Sciences; Rasht Iran
| | - Kamran Rudkhaneei
- Department Of Anatomy; School Of Medicine; Guilan University of Medical Sciences; Rasht Iran
| | - Monireh Aghajany-Nasab
- Cellular & Molecular Research Center; School Of Medicine; Guilan University of Medical Sciences; Rasht Iran
- Department Of Biochemistry & Biophysic; School Of Medicine; Guilan University of Medical Sciences; Rasht Iran
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Abstract
Hepatic steatosis is an underlying feature of nonalcoholic fatty liver disease (NAFLD), which is the most common form of liver disease and is present in up to ∼70% of individuals who are overweight. NAFLD is also associated with hypertriglyceridaemia and low levels of HDL, glucose intolerance, insulin resistance and type 2 diabetes mellitus. Hepatic steatosis is a strong predictor of the development of insulin resistance and often precedes the onset of other known mediators of insulin resistance. This sequence of events suggests that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle. Hepatokines are proteins that are secreted by hepatocytes, and many hepatokines have been linked to the induction of metabolic dysfunction, including fetuin A, fetuin B, retinol-binding protein 4 (RBP4) and selenoprotein P. In this Review, we describe the factors that influence the development of hepatic steatosis, provide evidence of strong links between hepatic steatosis and insulin resistance in non-hepatic tissues, and discuss recent advances in our understanding of how steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication.
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Affiliation(s)
- Ruth C R Meex
- Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program and the Department of Physiology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
- Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
| | - Matthew J Watt
- Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program and the Department of Physiology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
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