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Si G, Lv X, Ge Y, Zhang R, Hao D, Chen X, Wang C, Li Y, Li X, Yuan X. Age at menarche and risk of non-alcoholic fatty liver disease: Insights from the NHANES 2017-2020 and Mendelian randomization analyses. Exp Gerontol 2025; 204:112748. [PMID: 40194671 DOI: 10.1016/j.exger.2025.112748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 03/31/2025] [Accepted: 04/03/2025] [Indexed: 04/09/2025]
Abstract
BACKGROUND This study aimed to explore the causal relationship between age at menarche (AAM) and non-alcoholic fatty liver disease (NAFLD), leveraging data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) alongside Mendelian randomization (MR) analyses. Notably, this research represents the first attempt to link AAM to NAFLD using genetic methodologies, thereby providing novel insights into the interplay between these two conditions. METHODS Cross-sectional data from 2730 participants were analyzed using logistic regression to evaluate the association between AAM and NAFLD risk. A two-sample MR study was performed to investigate causal relationships, utilizing genetic data from large-scale genome-wide association studies (GWASs). The inverse variance weighted (IVW) method served as the primary MR analysis approach. RESULTS A significant negative association between AAM and NAFLD was found in Model 3 (OR = 0.85, 95 % CI: 0.74-0.97). Participants in the highest AAM quintile exhibited a 68 % reduction of NAFLD prevalence compared to those in the lowest AAM quintile (OR = 0.32, 95 % CI: 0.11-0.97). MR analysis confirmed a potential negative causal association (discovery: OR = 0.81, 95 % CI: 0.73-0.90; validation: OR = 0.80, 95 % CI: 0.66-0.96). CONCLUSIONS Our findings indicate a potential causal association between AAM and NAFLD, suggesting that early AAM may serve as a potential risk marker for NAFLD. This highlights the importance of incorporating AAM into clinical risk assessment tools and developing targeted prevention strategies for at-risk populations. Further research is needed to clarify the underlying mechanisms and to explore the potential benefits of early intervention.
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Affiliation(s)
- Guifei Si
- School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, Shandong, China; Department of Gastroenterology, Linyi People's Hospital Affiliated to Shandong Second Medical University, Linyi 276000, Shandong, China
| | - Xiaopan Lv
- School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, Shandong, China; Department of Gastroenterology, Linyi People's Hospital Affiliated to Shandong Second Medical University, Linyi 276000, Shandong, China
| | - Yuxin Ge
- School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, Shandong, China; Department of Gastroenterology, Linyi People's Hospital Affiliated to Shandong Second Medical University, Linyi 276000, Shandong, China
| | - Rui Zhang
- School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, Shandong, China; Department of Gastroenterology, Linyi People's Hospital Affiliated to Shandong Second Medical University, Linyi 276000, Shandong, China
| | - Dongxiao Hao
- School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, Shandong, China; Department of Gastroenterology, Linyi People's Hospital Affiliated to Shandong Second Medical University, Linyi 276000, Shandong, China
| | - Xuemei Chen
- School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, Shandong, China; Department of Gastroenterology, Linyi People's Hospital Affiliated to Shandong Second Medical University, Linyi 276000, Shandong, China
| | - Changchun Wang
- Department of Internal Medicine, Feicheng Street Health Centre, Linyi 276000, Shandong, China
| | - Yuquan Li
- School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, Shandong, China; Department of Gastroenterology, Linyi People's Hospital Affiliated to Shandong Second Medical University, Linyi 276000, Shandong, China
| | - Xiuping Li
- Department of Gastroenterology, Linyi People's Hospital Affiliated to Shandong Second Medical University, Linyi 276000, Shandong, China
| | - Xuemin Yuan
- Department of Gastroenterology, Linyi People's Hospital Affiliated to Shandong Second Medical University, Linyi 276000, Shandong, China.
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Miao MY, Han WW, Lyu JQ, Liu ZY, Jiang W, Zhang Z, Zhu Z, Qin LQ, Chen GC. Female reproductive factors and metabolic dysfunction-associated steatotic liver disease: an integrated analysis of population cohort, liver imaging, and genetic data. Am J Obstet Gynecol 2025:S0002-9378(25)00212-1. [PMID: 40204176 DOI: 10.1016/j.ajog.2025.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 03/30/2025] [Accepted: 04/01/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Although premenopausal women are at lower risk for metabolic dysfunction-associated steatotic liver disease than men within the same age group, the sex advantage becomes minimal after menopause, suggesting a role for female hormones. OBJECTIVE This study aimed to elucidate the role of reproductive factors in the development of female metabolic dysfunction-associated steatotic liver disease, using an integrated analysis. STUDY DESIGN Up to 269,607 women without metabolic dysfunction-associated steatotic liver disease during baseline recruitment (2006-2010) of the UK Biobank were included. Among these, 21,017 women did not develop metabolic dysfunction-associated steatotic liver disease across the follow-up period (through December 2021) and had the measure of liver proton density fat fraction quantified by magnetic resonance imaging since 2014. Multivariable Cox regression models were applied to assess the prospective relationships of various reproductive factors with incident metabolic dysfunction-associated steatotic liver disease. Multiple linear regression models were used to explore the relationships of reproductive factors with liver proton density fat fraction. A 2-sample Mendelian randomization analysis was conducted to investigate causality in the relationships of certain reproductive factors with metabolic dysfunction-associated steatotic liver disease. RESULTS During a median of 12.65 years of follow-up, 3077 incident cases of metabolic dysfunction-associated steatotic liver disease were identified. Early menarche, a greater number of live births, younger age at first live birth, and oral contraceptives or hormone replacement therapy initiated at a young age were associated with an elevated risk of metabolic dysfunction-associated steatotic liver disease and higher levels of liver proton density fat fraction. Several other reproductive factors (ie, a greater number of miscarriages, surgical menopause at a young age, and prolonged use of hormone replacement therapy) were associated with incident metabolic dysfunction-associated steatotic liver disease but not with liver proton density fat fraction. In the Mendelian randomization analysis, genetically determined earlier age at menarche and younger age at first live birth were substantially associated with increased risk of metabolic dysfunction-associated steatotic liver disease. CONCLUSION Several reproductive factors were associated with the risk of and histologic features of metabolic dysfunction-associated steatotic liver disease, supporting the role of female hormones in the pathogenesis of metabolic dysfunction-associated steatotic liver disease.
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Affiliation(s)
- Meng-Yuan Miao
- Fourth Affiliated Hospital, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Medical College of Soochow University, Suzhou, China
| | - Wen-Wen Han
- Fourth Affiliated Hospital, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Medical College of Soochow University, Suzhou, China
| | - Jie-Qiong Lyu
- Fourth Affiliated Hospital, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Medical College of Soochow University, Suzhou, China
| | - Zhong-Yue Liu
- Fourth Affiliated Hospital, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Medical College of Soochow University, Suzhou, China
| | - Wei Jiang
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, China
| | - Zheng Zhang
- Centre of Child Health Management, Children's Hospital of Soochow University, Suzhou, China
| | - Zhengbao Zhu
- Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
| | - Li-Qiang Qin
- Fourth Affiliated Hospital, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Medical College of Soochow University, Suzhou, China
| | - Guo-Chong Chen
- Fourth Affiliated Hospital, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Medical College of Soochow University, Suzhou, China.
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3
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Meda C, Dolce A, Torre SD. Metabolic dysfunction-associated steatotic liver disease across women's reproductive lifespan and issues. Clin Mol Hepatol 2025; 31:327-332. [PMID: 39098816 PMCID: PMC11791579 DOI: 10.3350/cmh.2024.0419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 07/31/2024] [Accepted: 08/01/2024] [Indexed: 08/06/2024] Open
Affiliation(s)
- Clara Meda
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Arianna Dolce
- Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milan, Italy
| | - Sara Della Torre
- Department of Pharmaceutical Sciences, Università degli Studi di Milano, Milan, Italy
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Rakic R, Pavlica T, Havrljenko J, Bjelanovic J. Association of Age at Menarche with General and Abdominal Obesity in Young Women. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1711. [PMID: 39459498 PMCID: PMC11509626 DOI: 10.3390/medicina60101711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 10/07/2024] [Accepted: 10/14/2024] [Indexed: 10/28/2024]
Abstract
Background and Objectives: Age at menarche is related to various biological and socioeconomic factors in childhood. The aim of the study was to examine the association of age at menarche with general and abdominal obesity in young women. Materials and Methods: A transversal anthropometric survey was conducted with 102 females from 21 to 25 years of age. The surveyed traits included height, weight, waist circumference (WC) and hip circumference (HC). General obesity was assessed using the body mass index (BMI) and abdominal obesity by WC, waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). A retrospective method was used for collecting age at menarche data. Results: The average age at menarche is 12.80 years. Early menarcheal age (<12 years) is detected in 25.5% of young females, while late onset of menarche (>14 years) is recorded for 20.6% of subjects. Early menarche age subjects exhibit significantly higher BMI, WC and WHtR in comparison with their late menarche age peers. There is a significant negative correlation between BMI, WC and WHtR values and menarcheal age. Late age at menarche is associated with higher probability of underweight status (BMI < 18.5 and/or WHtR < 0.4). Conclusions: Age at menarche has a negative correlation with general and abdominal obesity. Young women with early age at menarche show statistically higher values of BMI, WC and WHtR, while those with late menarcheal age show greater susceptibility to becoming underweight.
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Affiliation(s)
- Rada Rakic
- Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovica 2, 21000 Novi Sad, Serbia; (R.R.); (J.H.)
| | - Tatjana Pavlica
- Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovica 2, 21000 Novi Sad, Serbia; (R.R.); (J.H.)
| | - Jelena Havrljenko
- Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovica 2, 21000 Novi Sad, Serbia; (R.R.); (J.H.)
| | - Jelena Bjelanovic
- Institute for Public Health of Vojvodina, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia;
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Jin B, Wu Z, Wang S, Yu Z, Ullah R, Liang X, Wu W, Huang K, Ni Y, Wang J, Dong G, Fu J. Gender differences in non-alcoholic fatty liver disease in obese children and adolescents: a large cross-sectional study. Hepatol Int 2024; 18:179-187. [PMID: 37861942 PMCID: PMC10858100 DOI: 10.1007/s12072-023-10596-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Accepted: 09/11/2023] [Indexed: 10/21/2023]
Abstract
OBJECTIVE Previous studies have reported sex differences in non-alcoholic fatty liver disease (NAFLD) among adults; however, little is known about its occurrence in children and adolescents. This study aims to examine the prevalence of NAFLD among them and investigate the relationship between sex hormones and NAFLD. METHOD This study included 2999 obese Chinese children aged 2-18 years. We examined the prevalence of NAFLD by sex, age, and Tanner stage. The regression model and principal component analysis were used to analyze the relationship between sex hormones and NAFLD. RESULTS The prevalence of NAFLD increased with age in both sexes, and the gender difference appeared before puberty. The prevalence in boys tended to stabilize at the age of 11 years, whereas girls reached their peak temporarily. NAFLD prevalence was positively associated with estradiol in boys (p = 0.011), but the opposite trend was observed in girls (p = 0.031). Testosterone levels decreased with the increase of NAFLD prevalence in boys (p < 0.001). Luteinizing hormone and prolactin were inversely associated with NAFLD prevalence in boys and girls, respectively. Results from the principal component analysis showed that sex hormone levels and fat distribution were important risk factors for the prevalence of NAFLD in obese children (p < 0.001). CONCLUSION The significant difference in NAFLD prevalence between genders in obese children begins in early childhood. This distinction emerges long before puberty onset and tends to stabilize during late adolescence. Sex hormones are associated with NAFLD prevalence and are influenced by the Tanner stages and fat distribution.
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Affiliation(s)
- Binghan Jin
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhaoyuan Wu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shan Wang
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhu Yu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Rahim Ullah
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xinyi Liang
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wei Wu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ke Huang
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yan Ni
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianbing Wang
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China
| | - Guanping Dong
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China.
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| | - Junfen Fu
- Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310051, China.
- National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Li K, Yin J, Qin Z, Ma B, He R, Zhuoma D, Wang Z, Liu Q, Zhao X. Age at menarche and metabolic dysfunction-associated fatty liver disease: Evidence from a large population-based epidemiological study in Southwest China. Prev Med 2023; 177:107776. [PMID: 37951543 DOI: 10.1016/j.ypmed.2023.107776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 10/29/2023] [Accepted: 11/08/2023] [Indexed: 11/14/2023]
Abstract
BACKGROUND The relationship between age at menarche and metabolic dysfunction-associated fatty liver disease remains largely not clear. The objective of this study was to examine the association between age at menarche (AAM) and metabolic dysfunction-associated fatty liver disease (MAFLD) in Chinese women and whether any observed associations were mediated by early adulthood adiposity. METHODS The cross-sectional study included 46,873 Chinese women, aged 30-79 from baseline data of the China Multi-Ethnic Cohort study. Logistic regression models were used to evaluate the association between AAM and MAFLD. Mediation analysis was adopted to examine whether early adulthood adiposity (around 25 years) mediated the association between AAM and MAFLD. RESULTS AAM was linearly and inversely associated with the risk of MAFLD (P for nonlinearity =0.743). In a multivariable-adjusted model, the odds ratios and 95% confidence interval (ORs (95% CI)) for MAFLD comparing menarche at <12, 12, 13, 15, 16, 17, ≥18 years to menarche at 14 years were 1.290 (1.082-1.537), 1.172 (1.068-1.285), 1.042 (0.960-1.131), 0.937 (0.861-1.020), 0.911(0.835-0.994), 0.868 (0.786-0.959), and 0.738 (0.670-0.814), respectively (P for trend <0.001). The 6.4% increased MAFLD risk was associated with each preceding year in AAM. The association between AAM and MAFLD was modified by age, ethnicity, and menopause. Early adulthood adiposity partially mediated this association. CONCLUSION The findings of this study suggest that obesity prevention strategies are needed from young adulthood in women who undergo early menarche to reduce the risk of MAFLD.
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Affiliation(s)
- Kehan Li
- Department of Health Behavior and Social Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jianzhong Yin
- Department of Nutrition and Food Hygiene, School of Public Health, Kunming Medical University, Kunming, Yunan, China; Baoshan College of Traditional Chinese Medicine, Baoshan, Yunan, China
| | - Zixiu Qin
- School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, China
| | - Bangjing Ma
- Qingbaijiang District Center for Disease Control and Prevention, Chengdu, Sichuan, China
| | - Ruifeng He
- Tibet Center for Disease Control and Prevention, Lhasa, Tibet, China
| | - Duoji Zhuoma
- School of Medicine, Tibet University, Lhasa, Tibet, China
| | - Zihao Wang
- Chongqing Municipal Center for Disease Control and Prevention, Chongqing, China
| | - Qiaolan Liu
- Department of Health Behavior and Social Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Xing Zhao
- Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
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Eng PC, Forlano R, Tan T, Manousou P, Dhillo WS, Izzi-Engbeaya C. Non-alcoholic fatty liver disease in women - Current knowledge and emerging concepts. JHEP Rep 2023; 5:100835. [PMID: 37771547 PMCID: PMC10522907 DOI: 10.1016/j.jhepr.2023.100835] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 05/26/2023] [Accepted: 06/05/2023] [Indexed: 09/30/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide, affecting up to 30% of adults. Progression to non-alcoholic steatohepatitis (NASH) is a key risk factor for cirrhosis, hepatocellular carcinoma and cardiovascular events. Alterations in reproductive hormones are linked to the development and/or progression of NAFLD/NASH in women. Women with polycystic ovary syndrome and those with oestrogen deficiency are at increased risk of NAFLD/NASH, with higher mortality rates in older women compared to men of similar ages. NAFLD/NASH is currently the leading indication for liver transplantation in women without hepatocellular carcinoma. Therefore, a better understanding of NAFLD in women is needed to improve outcomes. In this review, we discuss the hormonal and non-hormonal factors that contribute to NAFLD development and progression in women. Furthermore, we highlight areas of focus for clinical practice and for future research.
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Affiliation(s)
- Pei Chia Eng
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Diabetes and Endocrinology, Imperial College Healthcare NHS Trust, London, UK
| | - Roberta Forlano
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Hepatology, Imperial College Healthcare NHS Trust, London, UK
| | - Tricia Tan
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Diabetes and Endocrinology, Imperial College Healthcare NHS Trust, London, UK
| | - Pinelopi Manousou
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Hepatology, Imperial College Healthcare NHS Trust, London, UK
| | - Waljit S. Dhillo
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Diabetes and Endocrinology, Imperial College Healthcare NHS Trust, London, UK
| | - Chioma Izzi-Engbeaya
- Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
- Department of Diabetes and Endocrinology, Imperial College Healthcare NHS Trust, London, UK
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Kim C, Catov J, Schreiner PJ, Appiah D, Wellons MF, Siscovick D, Calderon‐Margalit R, Huddleston H, Ebong IA, Lewis CE. Women's Reproductive Milestones and Cardiovascular Disease Risk: A Review of Reports and Opportunities From the CARDIA Study. J Am Heart Assoc 2023; 12:e028132. [PMID: 36847077 PMCID: PMC10111436 DOI: 10.1161/jaha.122.028132] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
Abstract
In 1985 to 1986, the CARDIA (Coronary Artery Risk Development in Young Adults) study enrolled 5115 Black or White participants, including 2788 women, aged 18 to 30 years. Over the following 35 years, the CARDIA study amassed extensive longitudinal data on women's reproductive milestones, spanning menarche to menopause. Although not initially conceived as a study of women's health, >75 CARDIA study publications address relationships between reproductive factors and events with cardiovascular and metabolic risk factors, subclinical and clinical cardiovascular disease, and social determinants of health. The CARDIA study was one of the earliest population-based reports to note Black-White differences in age at menarche and associations with cardiovascular risk factors. Adverse pregnancy outcomes, particularly gestational diabetes and preterm birth, have been assessed along with postpartum behaviors, such as lactation. Existing studies have examined risk factors for adverse pregnancy outcomes and lactation, as well as their relationship to future cardiovascular and metabolic risk factors, diagnoses, and subclinical atherosclerosis. Ancillary studies examining components of polycystic ovary syndrome and ovarian biomarkers, such as anti-Müllerian hormone, have facilitated examination of reproductive health in a population-based cohort of young adult women. As the cohort transitioned through menopause, examination of the importance of premenopausal cardiovascular risk factors along with menopause has improved our understanding of shared mechanisms. The cohort is now aged in the 50s to mid-60s, and women will begin to experience a greater number of cardiovascular events as well as other conditions, such as cognitive impairment. Thus, in the next decade, the CARDIA study will provide a unique resource for understanding how the women's reproductive life course epidemiology informs cardiovascular risk, as well as reproductive and chronological aging.
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Affiliation(s)
- Catherine Kim
- Departments of Medicine, Obstetrics and Gynecology, and EpidemiologyUniversity of MichiganAnn ArborMI
| | - Janet Catov
- Department of Obstetrics, Gynecology and Reproductive SciencesUniversity of PittsburghPittsburghPA
| | - Pamela J. Schreiner
- Division of Epidemiology and Community HealthUniversity of MinnesotaMinneapolisMN
| | - Duke Appiah
- Department of Public Health, Graduate School of Biomedical SciencesTexas Tech UniversityLubbockTX
| | | | | | | | - Heather Huddleston
- Department of Obstetrics, Gynecology and Reproductive SciencesUniversity of California San FranciscoSan FranciscoCA
| | | | - Cora E. Lewis
- Department of EpidemiologyUniversity of Alabama at BirminghamBirminghamAL
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9
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Amiri M, Mousavi M, Azizi F, Ramezani Tehrani F. The relationship of reproductive factors with adiposity and body shape indices changes overtime: findings from a community-based study. J Transl Med 2023; 21:137. [PMID: 36814308 PMCID: PMC9948339 DOI: 10.1186/s12967-023-04000-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 02/16/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Studies focusing on the relationships of adiposity and body shape indices with reproductive factors have reported conflicting results. This study aimed to investigate the influence of reproductive factors on adiposity and body shape indices changes overtime. MATERIALS AND METHODS In this community-based prospective study, 1636 postmenopausal women were selected from Tehran Lipid and Glucose Study (TLGS). The unadjusted and adjusted Generalized Estimating Equation models (GEE) were applied to investigate secular longitudinal trends of adiposity and body shape indices. RESULTS According to the adjusted GEE models, mean changes in body mass index (BMI) in women with early menarche was 1.18 kg/m2 higher than those with normal menarche age (P = 0.030). Moreover, the mean changes in BMI overtime were 0.11 kg/m2 higher in women with premature/early menopausal age than those with normal menopausal age (P = 0.012). Mean changes of waist circumference (WC) in women with late menopause were 2.27 cm higher than those with normal menopausal age (P = 0.036). We also observed higher mean changes in a body shape index (ABSI) in women with late menopause (P = 0.037), compared to those with normal menopausal age. We found a marginal effect of parity on BMI and WC as well. CONCLUSIONS This study demonstrated higher BMI in females with earlier menarche age. We also showed higher values of BMI overtime in women with premature/ early menopause, whereas women with late menopausal age had higher WC and ABSI values. However, more longitudinal studies investigating body composition indices by adjusting all potential confounders are still required to confirm our study findings.
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Affiliation(s)
- Mina Amiri
- grid.411600.2Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 24 Parvaneh, Yaman Street, Velenjak, P. O. Box 19395-4763, 1985717413 Tehran, I. R. of Iran
| | - Maryam Mousavi
- grid.411600.2Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 24 Parvaneh, Yaman Street, Velenjak, P. O. Box 19395-4763, 1985717413 Tehran, I. R. of Iran ,grid.412266.50000 0001 1781 3962Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Fereidoun Azizi
- grid.411600.2Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, I. R. of Iran
| | - Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 24 Parvaneh, Yaman Street, Velenjak, P. O. Box 19395-4763, 1985717413, Tehran, I. R. of Iran.
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10
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Deng P, Yu Q, Tang H, Lu Y, He Y. Age at Menarche Mediating Visceral Adipose Tissue's Influence on Pre-eclampsia: A Mendelian Randomization Study. J Clin Endocrinol Metab 2023; 108:405-413. [PMID: 36184738 PMCID: PMC9844965 DOI: 10.1210/clinem/dgac566] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 09/19/2022] [Indexed: 01/22/2023]
Abstract
CONTEXT The association between visceral adipose tissue (VAT) and pre-eclampsia (PE) shows inconsistent results and the underlying mediator remains unknown. OBJECTIVE We aimed to explore the causal effect of VAT on PE risks and the mediation role of age at menarche (AAM) in explaining this relationship. METHODS Summary data for PE were obtained from the FinnGen genome-wide association study (3556 cases and 114 735 controls). For exposure data, 70 genetic variants associated with the predicted VAT in 161 149 European women from UK Biobank were used as instrumental variables. Inverse variance weighted and multiple sensitivity analyses were applied. We also conducted multivariable Mendelian randomization (MR) analyses to test the association between VAT-associated single-nucleotide variations and PE. Next, mediation analyses were performed to study whether the association between VAT and PE was mediated via AAM. RESULTS In univariable MR analysis, higher volume of VAT was associated with the advancement of AAM and increased PE risk (beta = -0.33; 95% CI, -0.49 to -0.16 for AAM; odds ratio 1.65, 95% CI, 1.23 to 2.20 for PE). After adjusting for waist circumference, waist to hip ratio, and hip circumference, the multivariable MR results presented the consistent positive causality of VAT on PE. Two-step MR analysis proved an estimated 14.3% of the positive effect of VAT on PE was mediated by AAM. CONCLUSION Our findings provided evidence of the causal relationship between VAT and PE and proved VAT could accelerate AAM and then contribute to the risk of incident PE.
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Affiliation(s)
- Peizhi Deng
- Clinical Research Center, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Qingwei Yu
- Clinical Research Center, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Haibo Tang
- Clinical Research Center, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Yao Lu
- Clinical Research Center, The Third Xiangya Hospital, Central South University, Changsha 410013, China
- Faculty of Life Sciences and Medicine, King's College London, London WC2R2ls, UK
| | - Yingdong He
- Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China
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11
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Pafili K, Paschou SA, Armeni E, Polyzos SA, Goulis DG, Lambrinoudaki I. Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones. J Endocrinol Invest 2022; 45:1609-1623. [PMID: 35303270 DOI: 10.1007/s40618-022-01766-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 02/09/2022] [Indexed: 12/12/2022]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) differs between various stages of the female lifespan. The aim of this review is to summarize current evidence on the association of NAFLD and circulating sex hormones and to explore the pathogenesis of NAFLD within the context of (1) sex hormone changes during the reproductive, post-reproductive female life and beyond and (2) the in vitro and in vivo evidence on pharmacological modulation in women on menopausal hormone treatment (MHT) or endocrine therapy after breast cancer. The fluctuation in estrogen concentrations, the relative androgen excess, and the age-related reduction in sex hormone-binding globulin are related to increased NAFLD risk. Moreover, the peri-menopausal changes in body composition and insulin resistance might contribute to the increased NAFLD risk. Whether MHT prevents or improves NAFLD in this population remains an open question. Studies in women with breast cancer treated with tamoxifen or non-steroidal aromatase inhibitors point to their adverse effects on NAFLD development, although a more pronounced effect of tamoxifen is reported. Future studies focusing on the underlying pathogenesis should identify subgroups with the highest risk of NAFLD development and progression into more aggressive forms, as well as elucidate the role of hormone therapies, such as MHT.
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Affiliation(s)
- K Pafili
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, Munich-Neuherberg, Germany
- Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - S A Paschou
- Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Menopause Unit, 2nd Department of Obstetrics and Gynecology, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - E Armeni
- Menopause Unit, 2nd Department of Obstetrics and Gynecology, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - S A Polyzos
- First Laboratory of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloníki, Greece
| | - D G Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloníki, Greece
| | - I Lambrinoudaki
- Menopause Unit, 2nd Department of Obstetrics and Gynecology, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
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12
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Quek SXZ, Tan EXX, Ren YP, Muthiah M, Loo EXL, Tham EH, Siah KTH. Factors early in life associated with hepatic steatosis. World J Hepatol 2022; 14:1235-1247. [PMID: 35978672 PMCID: PMC9258263 DOI: 10.4254/wjh.v14.i6.1235] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/01/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) mirrors the obesity epidemic. NAFLD is insidious but may gradually progress from simple steatosis to steatohepatitis, fibrosis and cirrhosis and/or hepatocellular carcinoma. Intervention strategies to ameliorate developmental programming of NAFLD may be more efficacious during critical windows of developmental plasticity.
AIM To review the early developmental factors associated with NAFLD.
METHODS Databases MEDLINE via PubMed, and EMBASE and Reference Citation Analysis were searched and relevant publications up to April 30, 2021 were assessed. Original research studies that included risk factors associated with early development of NAFLD in human subjects were included. These factors include: Maternal factors, intrauterine and prenatal factors, post-natal factors, genetic and ethnic predisposition, childhood and adolescence environmental factors. Studies were excluded if they were review articles or animal studies, case reports or conference abstracts, or if NAFLD was not clearly defined and assessed radiologically.
RESULTS Of 1530 citations identified by electronic search, 420 duplicates were removed. Of the 1110 citations screened from title and abstract, 80 articles were included in the final analysis. Genetic polymorphisms such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) and membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) were associated with increased risk of NAFLD. Familial factors such as maternal obesogenic environment and parental history of hepatic steatosis was associated with offspring NAFLD. Longer duration of exclusive breastfeeding in infancy was associated with a lower risk of developing NAFLD later in life while metabolic dysfunction and/or obesity in adolescence was associated with increased risk of NAFLD. Studies relating to socioeconomic factors and its association with NAFLD reported confounding results.
CONCLUSION Maternal metabolic dysfunction during pregnancy, being exclusively breastfed for a longer time postnatally, diet and physical activity in childhood and adolescence are potential areas of intervention to decrease risk of NAFLD.
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Affiliation(s)
- Sabrina Xin Zi Quek
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Eunice Xiang-Xuan Tan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Yi Ping Ren
- Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Evelyn Xiu Ling Loo
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore 119228, Singapore
- Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore 117609, Singapore
| | - Elizabeth Huiwen Tham
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore 119228, Singapore
| | - Kewin Tien Ho Siah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
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Carrieri L, Osella AR, Ciccacci F, Giannelli G, Scavo MP. Premenopausal Syndrome and NAFLD: A New Approach Based on Gender Medicine. Biomedicines 2022; 10:1184. [PMID: 35625920 PMCID: PMC9138606 DOI: 10.3390/biomedicines10051184] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/18/2022] [Accepted: 05/19/2022] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition that affects 25% of the world's population. There is a clear difference in both geographical distribution and sex in childbearing age. These differences are reduced when women become older and senescence begins. The factors that affect the likelihood of developing NAFLD in a premenopausal woman are an imbalance of sex hormones (especially in estradiol and androgen), microbiome dysregulation, insulin resistance, early menarche, the length of time that the woman breastfeeds for and polycystic ovarian syndrome (PCOS). The aim of this review is to identify various physical ailments that may not appear to be serious to young women but that then affect the onset of NAFLD in perimenopause and can degenerate into NASH. These conditions should also be considered in future clinical management, as well as in research opportunities, in order to customize the monitoring and treatment of NAFLD, considering gender medicine for those women who had early metabolic symptoms that were not considered to be significant at the time.
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Affiliation(s)
- Livianna Carrieri
- Personalized Medicine Laboratory, National Institute of Gastroenterology IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy;
| | - Alberto Ruben Osella
- Laboratory of Epidemiology and Biostatistics, National Institute of Gastroenterology IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy;
| | - Fausto Ciccacci
- UniCamillus Saint Camillus International, University of Health Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy;
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy;
| | - Maria Principia Scavo
- Personalized Medicine Laboratory, National Institute of Gastroenterology IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, Italy;
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14
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Zhong L, Wu C, Li Y, Zeng Q, Lai L, Chen S, Tang S. Nonalcoholic fatty liver disease and health outcomes: An umbrella review of systematic reviews and meta-analyses. Ther Adv Chronic Dis 2022; 13:20406223221083508. [PMID: 35620184 PMCID: PMC9127863 DOI: 10.1177/20406223221083508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 02/09/2022] [Indexed: 11/17/2022] Open
Abstract
Purpose: A large number of systemic reviews and meta-analyses have explored the relationship between nonalcoholic fatty liver disease (NAFLD) and multiple health outcomes. The aim of this study is to conduct an umbrella review to assess the strength and evidence for the association between NAFLD and health outcomes. Methods: We systematically identified the present meta-analyses of observational studies reporting an association between NAFLD and health outcomes. For each meta-analysis, we assessed the quality with AMSTAR2 and graded the epidemiologic evidence. Results: Fifty-four articles comprising 111 unique meta-analyses were included in this study. Eighty-five unique outcomes showed significant associations ( P ← 0.05), whereas 26 unique outcomes showed insignificant associations, and we cannot assess the epidemiologic evidence. For 85 significant health outcomes, four outcomes (carotid intima-media thickness (C-IMT), peak A velocity, left ventricle end-diastolic diameter, incident chronic kidney disease (CKD) in adult patients) was graded as high quality of evidence, 23 outcomes were graded as the moderate quality of evidence, and the remaining 58 outcomes were graded as weak quality of evidence. Fourty-seven (87.03%) studies showed critically low methodological quality. Conclusion: In this umbrella review, only four statistically significant health outcomes showed high epidemiologic evidence. NAFLD seems to relate to an increased risk of C-IMT, peak A velocity, left ventricle end-diastolic diameter, and incident CKD in adult patients.
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Affiliation(s)
- Lixian Zhong
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, P.R. China
| | - Chutian Wu
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, P.R. China
| | - Yuting Li
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, P.R. China
| | - Qiuting Zeng
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, P.R. China
| | - Leizhen Lai
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, P.R. China
| | - Sisi Chen
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, P.R. China
| | - Shaohui Tang
- Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
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Della Torre S. Beyond the X Factor: Relevance of Sex Hormones in NAFLD Pathophysiology. Cells 2021; 10:2502. [PMID: 34572151 PMCID: PMC8470830 DOI: 10.3390/cells10092502] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/12/2021] [Accepted: 09/14/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, being frequently associated with obesity, unbalanced dietary regimens, and reduced physical activity. Despite their greater adiposity and reduced physical activity, women show a lower risk of developing NAFLD in comparison to men, likely a consequence of a sex-specific regulation of liver metabolism. In the liver, sex differences in the uptake, synthesis, oxidation, deposition, and mobilization of lipids, as well as in the regulation of inflammation, are associated with differences in NAFLD prevalence and progression between men and women. Given the major role of sex hormones in driving hepatic sexual dimorphism, this review will focus on the role of sex hormones and their signaling in the regulation of hepatic metabolism and in the molecular mechanisms triggering NAFLD development and progression.
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Affiliation(s)
- Sara Della Torre
- Department of Pharmaceutical Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy
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16
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Czarnecka K, Pilarz A, Rogut A, Maj P, Szymańska J, Olejnik Ł, Szymański P. Aspartame-True or False? Narrative Review of Safety Analysis of General Use in Products. Nutrients 2021; 13:1957. [PMID: 34200310 PMCID: PMC8227014 DOI: 10.3390/nu13061957] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 05/27/2021] [Accepted: 06/03/2021] [Indexed: 12/14/2022] Open
Abstract
Aspartame is a sweetener introduced to replace the commonly used sucrose. It was discovered by James M. Schlatter in 1965. Being 180-200 times sweeter than sucrose, its intake was expected to reduce obesity rates in developing countries and help those struggling with diabetes. It is mainly used as a sweetener for soft drinks, confectionery, and medicines. Despite its widespread use, its safety remains controversial. This narrative review investigates the existing literature on the use of aspartame and its possible effects on the human body to refine current knowledge. Taking to account that aspartame is a widely used artificial sweetener, it seems appropriate to continue research on safety. Studies mentioned in this article have produced very interesting results overall, the current review highlights the social problem of providing visible and detailed information about the presence of aspartame in products. The studies involving the impact of aspartame on obesity, diabetes mellitus, children and fetus, autism, neurodegeneration, phenylketonuria, allergies and skin problems, its cancer properties and its genotoxicity were analyzed. Further research should be conducted to ensure clear information about the impact of aspartame on health.
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Affiliation(s)
- Kamila Czarnecka
- Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland; (A.P.); (A.R.); (P.M.); (J.S.); (Ł.O.)
- Department of Radiobiology and Radiation Protection, Military Institute of Hygiene and Epidemiology, 4 Kozielska St., 01-163 Warsaw, Poland
| | - Aleksandra Pilarz
- Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland; (A.P.); (A.R.); (P.M.); (J.S.); (Ł.O.)
| | - Aleksandra Rogut
- Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland; (A.P.); (A.R.); (P.M.); (J.S.); (Ł.O.)
| | - Patryk Maj
- Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland; (A.P.); (A.R.); (P.M.); (J.S.); (Ł.O.)
| | - Joanna Szymańska
- Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland; (A.P.); (A.R.); (P.M.); (J.S.); (Ł.O.)
| | - Łukasz Olejnik
- Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland; (A.P.); (A.R.); (P.M.); (J.S.); (Ł.O.)
| | - Paweł Szymański
- Department of Pharmaceutical Chemistry, Drug Analyses and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland; (A.P.); (A.R.); (P.M.); (J.S.); (Ł.O.)
- Department of Radiobiology and Radiation Protection, Military Institute of Hygiene and Epidemiology, 4 Kozielska St., 01-163 Warsaw, Poland
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Wang J, Wu AH, Stanczyk FZ, Porcel J, Noureddin M, Terrault NA, Wilkens LR, Setiawan VW. Associations Between Reproductive and Hormone-Related Factors and Risk of Nonalcoholic Fatty Liver Disease in a Multiethnic Population. Clin Gastroenterol Hepatol 2021; 19:1258-1266.e1. [PMID: 32801014 PMCID: PMC7878579 DOI: 10.1016/j.cgh.2020.08.012] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 08/04/2020] [Accepted: 08/09/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Despite apparent differences between men and women in the prevalence and incidence of nonalcoholic fatty liver disease (NAFLD), there are limited epidemiologic data regarding the associations of reproductive and hormone-related factors with NAFLD. We examined the associations of these factors and exogenous hormone use with NAFLD risk in African American, Japanese American, Latino, Native Hawaiian, and white women. METHODS We conducted a nested case-control study (1861 cases and 17,664 controls) in the Multiethnic Cohort Study. NAFLD cases were identified using Medicare claims data; controls were selected among participants without liver disease and individually matched to cases by birth year, ethnicity, and length of Medicare enrollment. Reproductive and hormone-related factors and covariates were obtained from the baseline questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs. RESULTS Later age at menarche was associated inversely with NAFLD (Ptrend = .01). Parity, regardless of number of children or age at first birth, was associated with increased risk of NAFLD (OR, 1.25; 95% CI, 1.05-1.48). Oral contraceptive use also was linked to increased risk of NAFLD (OR, 1.14; 95% CI, 1.01-1.29; duration of use Ptrend = .04). Compared with women with natural menopause, those with oophorectomy (OR, 1.41; 95% CI, 1.18-1.68) or hysterectomy (OR, 1.33; 95% CI, 1.11-1.60) had an increased risk of NAFLD. A longer duration of menopause hormone therapy (only estrogen therapy) was linked with an increasing risk of NAFLD (OR per 5 years of use, 1.08, 95% CI, 1.01-1.15). CONCLUSIONS Findings from a large multiethnic study support the concept that menstrual and reproductive factors, as well as the use of exogenous hormones, are associated with the risk of NAFLD.
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Affiliation(s)
- Jun Wang
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA,Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA
| | - Anna H. Wu
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA,Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA
| | - Frank Z. Stanczyk
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA,Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Jacqueline Porcel
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Mazen Noureddin
- Division of Gastroenterology and Hepatology, Department of Medicine, and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Norah A. Terrault
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Lynne R. Wilkens
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI
| | - Veronica Wendy Setiawan
- Department of Preventive Medicine; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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Di Sessa A, Grandone A, Marzuillo P, Umano GR, Cirillo G, Miraglia Del Giudice E. Early menarche is associated with insulin-resistance and non-alcoholic fatty liver disease in adolescents with obesity. J Pediatr Endocrinol Metab 2021; 34:607-612. [PMID: 33823088 DOI: 10.1515/jpem-2020-0684] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 02/12/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVES Recent evidence linked early menarche to a higher risk of insulin-resistance (IR) and nonalcoholic fatty liver disease (NAFLD) in adulthood. We aimed to evaluate the impact of early menarche on glucose derangements and NAFLD in a sample of Italian adolescents with obesity. METHODS Anthropometric and biochemical evaluations were conducted in all the enrolled 318 obese patients (mean age 12.31 ± 2.95 years). NAFLD was defined by the presence of ultrasound detected liver steatosis and/or alanine transaminase (ALT) levels >40 IU/L. RESULTS Patients with early menarche showed both higher homeostasis model assessment of insulin-resistance (HOMA-IR) (p=0.008) and ALT (p=0.02) values, an increased prevalence of NAFLD (p=0.001), and lower Matsuda and Insulinogenic Index (IGI) values than the other obese patients. The association between early menarche and both ALT and Matsuda Index remained significant in General Linear Models (GLMs) in which respectively body mass index standard deviation score (BMI-SDS) and Matsuda Index, and BMI-SDS were included as covariates. Patients with early menarche also showed a higher risk of both HOMA-IR>3 (OR 1.69, CI 1.05-2.70, p=0.02) and NAFLD (OR 1.10, CI 1.01-1.21, p=0.03). CONCLUSIONS Girls with obesity presenting early menarche showed higher HOMA-IR levels, lower Matsuda Index and IGI values, and higher risk of NAFLD compared to girls without early menarche.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Anna Grandone
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Grazia Cirillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy
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Kim H, Choe SA, Lee SJ, Sung J. Causal relationship between the timing of menarche and young adult body mass index with consideration to a trend of consistently decreasing age at menarche. PLoS One 2021; 16:e0247757. [PMID: 33635908 PMCID: PMC7909625 DOI: 10.1371/journal.pone.0247757] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 02/12/2021] [Indexed: 02/08/2023] Open
Abstract
Younger age at menarche (AAM) is associated with higher body mass index (BMI) for young women. Considering that continuous trends in decreasing AAM and increasing BMI are found in many countries, we attempted to assess whether the observed negative association between AAM and young adult BMI is causal. We included 4,093 women from the Korean Genome and Epidemiology Study (KoGES) and Healthy twin Study (HTS) with relevant epidemiologic data and genome-wide marker information. To mitigate the remarkable differences in AAM across generations, we converted the AAM to a generation-standardized AAM (gsAAM). To test causality, we applied the Mendelian randomization (MR) approach, using a genetic risk score (GRS) based on 14 AAM-associated single nucleotide polymorphisms (SNPs). We constructed MR models adjusting for education level and validated the results using the inverse-variance weighted (IVW), weighted median (WM), MR-pleiotropy residual sum and outliers test (MR-PRESSO), and MR-Egger regression methods. We found a null association using observed AAM and BMI level (conventional regression; -0.05 [95% CIs -0.10-0.00] per 1-year higher AAM). This null association was replicated when gsAAM was applied instead of AAM. Using the two-stage least squares (2SLS) approach employing a univariate GRS, the association was also negated for both AAM and gsAAM, regardless of model specifications. All the MR diagnostics suggested statistically insignificant associations, but weakly negative trends, without evidence of confounding from pleiotropy. We did not observe a causal association between AAM and young adult BMI whether we considered the birth cohort effect or not. Our study alone does not exclude the possibility of existing a weak negative association, considering the modest power of our study design.
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Affiliation(s)
- Hakyung Kim
- Genome and Health Big Data Laboratory, Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Seung-Ah Choe
- Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea
| | - Soo Ji Lee
- Genome and Health Big Data Laboratory, Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea
- Institute of Health & Environment, Seoul National University, Seoul, Korea
| | - Joohon Sung
- Genome and Health Big Data Laboratory, Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea
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20
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Kim JH, Lim JS. Early menarche and its consequence in Korean female: reducing fructose intake could be one solution. Clin Exp Pediatr 2021; 64:12-20. [PMID: 32403898 PMCID: PMC7806406 DOI: 10.3345/cep.2019.00353] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 12/27/2019] [Accepted: 02/28/2020] [Indexed: 12/31/2022] Open
Abstract
The mean age at menarche (AAM) of Korean females has been rapidly decreasing over the last 50 years; currently, the prevalence of early menarche (<12 years) is 22.3%. Female adolescents who experience early menarche are known to be at greater risk of psychosocial and behavioral problems along with several physical health problems such as menstrual problems. They also tend to achieve a shorter final height and develop obesity. Population-based Korean studies have shown a strong association between early menarche and the risk of obesity, insulin resistance, metabolic syndrome, nonalcoholic fatty liver disease, diabetes, breast cancer, and cardiovascular disease in adulthood. Although the exact mechanism of how early menarche causes cardiometabolic derangement in later adulthood is unknown, childhood obesity and insulin resistance might be major contributors. Recent studies demonstrated that an excessive consumption of fructose might underlie the development of obesity and insulin resistance along with an earlier AAM. A positive association was observed between sugar-sweetened beverages (a major source of fructose) intake and obesity, metabolic syndrome, insulin resistance, and cardiometabolic risk in Korean females. In pediatrics, establishing risk factors is important in preventing disease in later life. In this regard, early menarche is a simple and good marker for the management of cardiometabolic diseases in adulthood. Decreasing one's fructose intake might prevent early menarche as well as the development of obesity, insulin resistance, and cardiometabolic diseases.
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Affiliation(s)
- Ji Hyun Kim
- Department of Pediatrics, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Jung Sub Lim
- Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea
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21
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Mueller NT, Liu T, Mitchel EB, Yates KP, Suzuki A, Behling C, Lavine JE. Sex Hormone Relations to Histologic Severity of Pediatric Nonalcoholic Fatty Liver Disease. J Clin Endocrinol Metab 2020; 105:5896884. [PMID: 32840311 PMCID: PMC7494240 DOI: 10.1210/clinem/dgaa574] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 08/18/2020] [Indexed: 01/09/2023]
Abstract
CONTEXT Sex hormones have been linked with presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults, but it is unknown if they affect severity of pediatric NAFLD. OBJECTIVE To examine associations of circulating SHBG, estrogens, and androgens with key histologic features of pediatric, biopsy-confirmed NAFLD. DESIGN Baseline assessment of longitudinal cohorts and randomized clinical trials. SETTING Nonalcoholic Steatohepatitis Clinical Research Network. PATIENTS Children and adolescents ≤18 years with liver biopsy-confirmed NAFLD in the United States. MAIN OUTCOME MEASURES We assayed SHBG, estrone, estradiol, dehydroepiandrosterone (DHEAS), androstenedione, and testosterone in relation to grade/stage of steatosis, portal inflammation, hepatic ballooning, fibrosis, and nonalcoholic steatohepatitis (NASH) severity using linear regression. RESULTS Mean age of 573 children at the time of biopsy was 13.1 years (SD 2.8). Lower SHBG was inversely associated with steatosis severity in boys and girls (P = 0.001), and with portal inflammation in girls only (P for sex interaction <0.001). Higher testosterone was related to improved features of steatosis and fibrosis (P for sex interaction = 0.003 and 0.01, respectively) in boys, but detrimental in girls. In boys and girls, higher estrone, estradiol, and testosterone were associated with lower portal inflammation grade; higher estradiol was positively associated with hepatic ballooning severity; DHEAS was inversely associated with hepatic ballooning and NASH severity (all P < 0.05). Androstenedione was not associated with NAFLD features. CONCLUSIONS Largely consistent with findings in adults, sex hormones are associated with distinct histologic features of NAFLD in children and adolescents. These hormone levels relate to differences with gender and pubertal change.
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Affiliation(s)
- Noel T Mueller
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
- Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA
| | - Tiange Liu
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Elana B Mitchel
- Department of Pediatrics, Columbia Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Katherine P Yates
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Ayako Suzuki
- Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Cynthia Behling
- Department of Pathology, Sharp Memorial Hospital, San Diego, California, USA
| | - Joel E Lavine
- Department of Pediatrics, Columbia Vagelos College of Physicians and Surgeons, New York, New York, USA
- Correspondence and Reprint Requests: Joel E. Lavine, MD, PhD, 622 W. 168th St, PH17-105H, Department of Pediatrics, Columbia Vagelos College of Physicians and Surgeons, New York, NY 10032. E-mail:
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Della Torre S. Non-alcoholic Fatty Liver Disease as a Canonical Example of Metabolic Inflammatory-Based Liver Disease Showing a Sex-Specific Prevalence: Relevance of Estrogen Signaling. Front Endocrinol (Lausanne) 2020; 11:572490. [PMID: 33071979 PMCID: PMC7531579 DOI: 10.3389/fendo.2020.572490] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 08/20/2020] [Indexed: 12/11/2022] Open
Abstract
There is extensive evidence supporting the interplay between metabolism and immune response, that have evolved in close relationship, sharing regulatory molecules and signaling systems, to support biological functions. Nowadays, the disruption of this interaction in the context of obesity and overnutrition underlies the increasing incidence of many inflammatory-based metabolic diseases, even in a sex-specific fashion. During evolution, the interplay between metabolism and reproduction has reached a degree of complexity particularly high in female mammals, likely to ensure reproduction only under favorable conditions. Several factors may account for differences in the incidence and progression of inflammatory-based metabolic diseases between females and males, thus contributing to age-related disease development and difference in life expectancy between the two sexes. Among these factors, estrogens, acting mainly through Estrogen Receptors (ERs), have been reported to regulate several metabolic pathways and inflammatory processes particularly in the liver, the metabolic organ showing the highest degree of sexual dimorphism. This review aims to investigate on the interaction between metabolism and inflammation in the liver, focusing on the relevance of estrogen signaling in counteracting the development and progression of non-alcoholic fatty liver disease (NAFLD), a canonical example of metabolic inflammatory-based liver disease showing a sex-specific prevalence. Understanding the role of estrogens/ERs in the regulation of hepatic metabolism and inflammation may provide the basis for the development of sex-specific therapeutic strategies for the management of such an inflammatory-based metabolic disease and its cardio-metabolic consequences.
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Affiliation(s)
- Sara Della Torre
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
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Yuan L, Kardashian A, Sarkar M. NAFLD in women: Unique pathways, biomarkers and therapeutic opportunities. ACTA ACUST UNITED AC 2020; 18:425-432. [PMID: 32523869 DOI: 10.1007/s11901-019-00495-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Purpose of review In this review article we evaluate sex differences in the natural history of NAFLD and highlight distinct risk profiles of women with NAFLD, as well as unique treatment considerations and research gaps. Summary of findings Reproductive factors, such as menopausal status should be considered when evaluating NAFLD risk in women, as well as additional reproductive risk factors such as age at menarche, presence of polycystic ovary syndrome, and gestational diabetes. Women do appear to have lower risk for hepatocellular carcinoma from NASH, as well as lower mortality from NASH cirrhosis than men, although among women, NASH is now the leading indication for liver transplant. Data on sex differences in biomarker development and clinical trials are lacking, and researchers should be encouraged to evaluate biomarker performance by sex, and specifically report clinical trial endpoints in women.
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Affiliation(s)
- Liyun Yuan
- University of Southern California, Division of GI/Hepatology
| | - Ani Kardashian
- University of California, San Francisco, Division of GI/Hepatology
| | - Monika Sarkar
- University of California, San Francisco, Division of GI/Hepatology
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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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Xiong M, Li J, Yang S, Zeng F, Ji Y, Liu J, Wu Q, He Q, Jiang R, Zhou F, Wen W, Chen J, Hou J. Influence of Gender and Reproductive Factors on Liver Fibrosis in Patients With Chronic Hepatitis B Infection. Clin Transl Gastroenterol 2019; 10:e00085. [PMID: 31651450 PMCID: PMC6884344 DOI: 10.14309/ctg.0000000000000085] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Accepted: 08/16/2019] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION The role of reproductive factors in the development of chronic hepatitis B (CHB) remains unknown. We assessed the potential contributions of gender, menopausal status, and menarche age to liver fibrosis in CHB. METHODS A cross-sectional prospective study included 716 women and 716 age-matched men with CHB who were not currently receiving antiviral therapy. Liver stiffness measurement using transient elastography was used to stage liver fibrosis as F0-F1 (<7.2 kPa), F ≥ 2 (7.2 kPa), F ≥ 3 (9.4 kPa), and F = 4 (12.2 kPa). Female patients were asked regarding their age at menarche and menopausal status using a questionnaire. RESULTS Of the 716 women, 121 (16.9%) were postmenopausal, and 80 (11.2%) had advanced liver fibrosis. Multivariate logistic regression analysis showed that the postmenopausal status compared with the premenopausal status (odds ratio [OR] = 3.65-8.83; P < 0.05) and age at menarche of >14 years compared with <13 years (OR = 2.85-3.95; P < 0.05) were significantly associated with advanced fibrosis. Compared with premenopausal women, age-matched men had a higher OR for advanced fibrosis (P < 0.05). Compared with postmenopausal women, age-matched men did not show a significant difference in the degree of liver fibrosis (P > 0.05). Longitudinal data analysis showed that postmenopausal women (n = 31) were significantly less likely to undergo regression of liver fibrosis after antiviral treatment vs premenopausal women (n = 19) (26.3% vs 74.2%, respectively; P < 0.001). DISCUSSION Menopause and late menarche aggravated liver fibrosis in untreated CHB, besides menopause delayed fibrosis regression under antiviral therapy. The protective effect of female gender against fibrosis was lost for postmenopausal women. TRANSLATIONAL IMPACT It is important to consider menopausal status and age at menarche in establishing surveillance strategies among CHB females. Postmenopausal estrogen therapy may be considered for the prevention or treatment of liver fibrosis.
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Affiliation(s)
- Ming Xiong
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Junying Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shuling Yang
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fansen Zeng
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Infectious Diseases, Guangzhou Women and Children's Medical Center, Guangzhou, China
| | - Yali Ji
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jiang Liu
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qiaoping Wu
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qingjun He
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ronglong Jiang
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fuyuan Zhou
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Weiqun Wen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jinjun Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jinlin Hou
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Granados A, Gebremariam A, Gidding SS, Terry JG, Carr JJ, Steffen LM, Jacobs DR, Lee JM. Association of abdominal muscle composition with prediabetes and diabetes: The CARDIA study. Diabetes Obes Metab 2019; 21:267-275. [PMID: 30159995 PMCID: PMC6329642 DOI: 10.1111/dom.13513] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 08/13/2018] [Accepted: 08/21/2018] [Indexed: 12/28/2022]
Abstract
AIM To evaluate the relationship of abdominal muscle lean tissue and adipose tissue volumes with prediabetes and diabetes. RESEARCH DESIGN AND METHODS We measured abdominal muscle composition in 3170 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent computed tomography (CT) at Year 25 of follow-up (ages, 43-55 years). Multinomial regression analysis was used to evaluate the associations of CT-measured intermuscular adipose tissue (IMAT), lean muscle tissue (lean) and visceral adipose tissue (VAT) volumes with diabetes at any point during the CARDIA study, newly detected prediabetes, prior history of prediabetes, and normal glucose tolerance. Models were adjusted for potential confounding factors: age, sex, race, height, smoking status, hypertension, hyperlipidaemia, cardiorespiratory fitness and study centre. RESULTS Higher IMAT, lean and VAT volumes were all separately associated with a higher prevalence of prediabetes and diabetes. Inclusion of VAT volume in models with both IMAT volume and lean volume attenuated the association of IMAT with both prediabetes and diabetes, but higher lean volume retained its association with prediabetes and diabetes. Individuals in the highest IMAT quartile, coupled with VAT in its lower three quartiles, had a higher prevalence of diabetes, but not of prediabetes, than those with both IMAT and VAT in their respective lower three quartiles. Adjusting for cardiorespiratory fitness did not substantially change the findings. CONCLUSION Higher IMAT volume was associated with a higher prevalence of diabetes even after adjustment for VAT volume. However, further study is warranted to understand the complicated relationship between abdominal muscle and adipose tissues.
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Affiliation(s)
- Andrea Granados
- Department of Pediatrics, Pediatric Endocrinology, Washington University, St Louis, Missouri
| | - Achamyeleh Gebremariam
- Child Health Evaluation and Research Center (CHEAR), University of Michigan, Ann Arbor, Michigan
| | - Samuel S Gidding
- Nemours Cardiac Center, A. I. DuPont Hospital for Children, Wilmington, Delaware
| | - James G Terry
- Department of Radiology and Vanderbilt Translational and Clinical Cardiovascular Research Center (VTRACC), Vanderbilt University Medical Center, Nashville, Tennessee
| | - John Jeffrey Carr
- Department of Radiology and Vanderbilt Translational and Clinical Cardiovascular Research Center (VTRACC), Vanderbilt University Medical Center, Nashville, Tennessee
| | - Lyn M Steffen
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota
| | - David R Jacobs
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota
| | - Joyce M Lee
- Child Health Evaluation and Research Center (CHEAR), University of Michigan, Ann Arbor, Michigan
- Department of Pediatric Endocrinology, University of Michigan, Ann Arbor, Michigan
- Department of Nutrition, School of Public Health, University of Minnesota, Minneapolis, Minnesota
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27
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Schwimmer JB, Ugalde-Nicalo P, Welsh JA, Angeles JE, Cordero M, Harlow KE, Alazraki A, Durelle J, Knight-Scott J, Newton KP, Cleeton R, Knott C, Konomi J, Middleton MS, Travers C, Sirlin CB, Hernandez A, Sekkarie A, McCracken C, Vos MB. Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A Randomized Clinical Trial. JAMA 2019; 321:256-265. [PMID: 30667502 PMCID: PMC6440226 DOI: 10.1001/jama.2018.20579] [Citation(s) in RCA: 182] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
IMPORTANCE Pediatric guidelines for the management of nonalcoholic fatty liver disease (NAFLD) recommend a healthy diet as treatment. Reduction of sugary foods and beverages is a plausible but unproven treatment. OBJECTIVE To determine the effects of a diet low in free sugars (those sugars added to foods and beverages and occurring naturally in fruit juices) in adolescent boys with NAFLD. DESIGN, SETTING, AND PARTICIPANTS An open-label, 8-week randomized clinical trial of adolescent boys aged 11 to 16 years with histologically diagnosed NAFLD and evidence of active disease (hepatic steatosis >10% and alanine aminotransferase level ≥45 U/L) randomized 1:1 to an intervention diet group or usual diet group at 2 US academic clinical research centers from August 2015 to July 2017; final date of follow-up was September 2017. INTERVENTIONS The intervention diet consisted of individualized menu planning and provision of study meals for the entire household to restrict free sugar intake to less than 3% of daily calories for 8 weeks. Twice-weekly telephone calls assessed diet adherence. Usual diet participants consumed their regular diet. MAIN OUTCOMES AND MEASURES The primary outcome was change in hepatic steatosis estimated by magnetic resonance imaging proton density fat fraction measurement between baseline and 8 weeks. The minimal clinically important difference was assumed to be 4%. There were 12 secondary outcomes, including change in alanine aminotransferase level and diet adherence. RESULTS Forty adolescent boys were randomly assigned to either the intervention diet group or the usual diet group (20 per group; mean [SD] age, 13.0 [1.9] years; most were Hispanic [95%]) and all completed the trial. The mean decrease in hepatic steatosis from baseline to week 8 was significantly greater for the intervention diet group (25% to 17%) vs the usual diet group (21% to 20%) and the adjusted week 8 mean difference was -6.23% (95% CI, -9.45% to -3.02%; P < .001). Of the 12 prespecified secondary outcomes, 7 were null and 5 were statistically significant including alanine aminotransferase level and diet adherence. The geometric mean decrease in alanine aminotransferase level from baseline to 8 weeks was significantly greater for the intervention diet group (103 U/L to 61 U/L) vs the usual diet group (82 U/L to 75 U/L) and the adjusted ratio of the geometric means at week 8 was 0.65 U/L (95% CI, 0.53 to 0.81 U/L; P < .001). Adherence to the diet was high in the intervention diet group (18 of 20 reported intake of <3% of calories from free sugar during the intervention). There were no adverse events related to participation in the study. CONCLUSIONS AND RELEVANCE In this study of adolescent boys with NAFLD, 8 weeks of provision of a diet low in free sugar content compared with usual diet resulted in significant improvement in hepatic steatosis. However, these findings should be considered preliminary and further research is required to assess long-term and clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02513121.
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Affiliation(s)
- Jeffrey B. Schwimmer
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla
- Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, California
| | - Patricia Ugalde-Nicalo
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla
| | - Jean A. Welsh
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia
- Children’s Healthcare of Atlanta, Atlanta, Georgia
- Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, Georgia
| | - Jorge E. Angeles
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla
| | - Maria Cordero
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia
| | - Kathryn E. Harlow
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla
- Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, California
| | - Adina Alazraki
- Department of Radiology, Children’s Healthcare of Atlanta, Atlanta, Georgia
| | - Janis Durelle
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla
| | - Jack Knight-Scott
- Department of Radiology, Children’s Healthcare of Atlanta, Atlanta, Georgia
| | - Kimberly P. Newton
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla
- Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, California
| | - Rebecca Cleeton
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia
| | - Cynthia Knott
- Altman Clinical and Translational Research Institute, School of Medicine, University of California, San Diego, La Jolla
| | - Juna Konomi
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia
| | - Michael S. Middleton
- Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla
| | - Curtis Travers
- Pediatric Biostatistics Core, Department of Pediatrics, Emory University, Atlanta, Georgia
| | - Claude B. Sirlin
- Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla
| | - Albert Hernandez
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia
| | - Ahlia Sekkarie
- Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, Georgia
| | - Courtney McCracken
- Children’s Healthcare of Atlanta, Atlanta, Georgia
- Pediatric Biostatistics Core, Department of Pediatrics, Emory University, Atlanta, Georgia
| | - Miriam B. Vos
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia
- Children’s Healthcare of Atlanta, Atlanta, Georgia
- Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, Georgia
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Parikh NI, Kapphahn K, Hedlin H, Olgin JE, Allison MA, Magnani JW, Ryckman KR, Waring ME, Perez MV, Howard BV. Effects of reproductive period duration and number of pregnancies on midlife ECG indices: a secondary analysis from the Women's Health Initiative Clinical Trial. BMJ Open 2018; 8:e019129. [PMID: 30121588 PMCID: PMC6104755 DOI: 10.1136/bmjopen-2017-019129] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVES Pregnancy, menses and menopause are related to fluctuations in endogenous sex hormones in women, which cumulatively may alter cardiac electrical conduction. Therefore, we sought to study the association between number of pregnancies and reproductive period duration (RD, time from menarche to menopause) with ECG intervals in the Women's Health Initiative Clinical Trials. DESIGN Secondary analysis of multicentre clinical trial. SETTING USA. PRIMARY OUTCOME MEASURES ECGintervals: PR interval, P-wave duration, P-wave dispersion, QTc interval. PARTICIPANTS n=40 687 women (mean age=62 years) participating in the Women's Health Initiative Clinical Trials. 82.5% were white, 9.3% black, 4% Hispanic and 2.7% Asian. METHODS In primary analysis, we employed multivariable linear regression models relating number of pregnancies and RD with millisecond changes in intervals from enrolment ECG. We studied effect modification by hormone therapy use. RESULTS Among participants, 5+ live births versus 0 prior pregnancies was associated with a 1.32 ms increase in PR interval (95% CI 0.25 to 2.38), with a graded association with longer QTc interval (ms) (none (prior pregnancy, no live births)=0.66 (-0.56 to 1.88), 1=0.15 (-0.71 to 1.02), 2-4=0.25 (-0.43 to 0.94) and 5+ live births=1.15 (0.33 to 1.98), p=0.008). RD was associated with longer PR interval and maximum P-wave duration (but not P-wave dispersion) among never users of hormone therapy: (PR (ms) per additional RD year: 0.10 (0.04 to 0.16); higher P-wave duration (ms): 0.09 (0.06 to 0.12)). For every year increase in reproductive period, QTc decreased by 0.04 ms (-0.07 to -0.01). CONCLUSIONS An increasing number of live births is related to increased and RD to decreased ventricular repolarisation time. Both grand multiparity and longer RD are related to increased atrial conduction time. Reproductive factors that alter midlife cardiac electrical conduction system remodelling in women may modestly influence cardiovascular disease risk in later life. TRIAL REGISTRATION NUMBER NCT00000611; Post-results.
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Affiliation(s)
- Nisha I Parikh
- Division of Cardiology, University of California San Francisco, San Francisco, California, USA
| | - Kristopher Kapphahn
- Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Haley Hedlin
- Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Jeffrey E Olgin
- Division of Cardiology, University of California San Francisco, San Francisco, California, USA
| | - Matthew A Allison
- Department of Family Medicine, University of California, San Diego, San Diego, California, USA
| | - Jared W Magnani
- Division of Cardiology, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Kelli R Ryckman
- Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USA
| | - Molly E Waring
- Division of Epidemiology of Chronic Diseases and Vulnerable Populations, Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, USA
| | - Marco Valentin Perez
- Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Barbara V Howard
- MedStar Health Research Institute, Hyattsville, Maryland, USA
- Georgetown and Howard Universities Center for Clinical and Translational Science, Washington, District of Columbia, USA
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Harreiter J, Kautzky-Willer A. Sex and Gender Differences in Prevention of Type 2 Diabetes. Front Endocrinol (Lausanne) 2018; 9:220. [PMID: 29780358 PMCID: PMC5945816 DOI: 10.3389/fendo.2018.00220] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 04/18/2018] [Indexed: 12/25/2022] Open
Abstract
Lifestyle intervention programs are effective in the prevention of type 2 diabetes mellitus (T2DM) in high risk populations. However, most studies only give limited information about the influence of sex and/or gender effectiveness of these interventions. So far, similar outcome was reported for diabetes progression and weight loss. Nevertheless, long-term data on cardiovascular outcome are sparse but favoring women regarding all-cause and cardiovascular mortality. In both men and women, sex hormone imbalances and reproductive disorders are associated with a higher risk of T2DM development. Diabetes prevention approaches are reported for polycystic ovary syndrome, gestational diabetes mellitus, and erectile dysfunction and are presented in this review. In the surgical treatment options for morbid obese patients, sex and gender differences are present. Choices and preferences of adherence to lifestyle and pharmacological interventions, expectations, treatment effects, and complications are influenced by sex or gender. In general, bariatric surgery is performed more often in women seeking medical/surgical help to lose weight. Men are older and have higher comorbidities and mortality rates and worse follow-up outcome after bariatric surgery. A more gender-sensitive clinical approach, as well as consideration of ethnicity may improve quality of life and increase health and life expectancy in men and women with a high risk for subsequent progression to T2DM.
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Yi KH, Hwang JS, Lim SW, Lee JA, Kim DH, Lim JS. Early menarche is associated with non-alcoholic fatty liver disease in adulthood. Pediatr Int 2017; 59:1270-1275. [PMID: 28892211 DOI: 10.1111/ped.13422] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 09/26/2016] [Accepted: 08/30/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND The aim of this study was to examine the association between early menarche (<12 years) and non-alcoholic fatty liver disease (NAFLD) in premenopausal women and to explore whether it is mediated by adult obesity and insulin resistance. METHODS We analyzed data of premenopausal women, aged ≥15 years, from the Korea National Health and Nutrition Examination Survey (2007-2009). We divided the women into three groups: early menarche, reference (12.00-15.99 years), and late menarche. The presence of NAFLD was determined using hepatic steatosis index >36.0. RESULTS Of the 4,387 women evaluated, 673 (15.4%) met the criteria for NAFLD. The prevalence of NAFLD was higher in both women with early and late menarche compared with the reference (early, 23.4%; reference, 14.0%; late, 19.9%, P < 0.001). After adjustment of confounders including age, the OR for NAFLD in early menarche compared with the reference was 3.04 (95%CI: 1.99-4.65). Further adjustment of mediators, such as central obesity or insulin resistance, attenuated the association to 1.91-2.17. There was no association, however, between late menarche and NAFLD after adjustment of confounders. CONCLUSIONS Early menarche was associated with an increased risk of NAFLD in young and middle-aged premenopausal Korean women.
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Affiliation(s)
- Kyung Hee Yi
- Department of Pediatrics, Sanbon Medical Center, Wonkwang University, Sanbon, Korea
| | - Jin Soon Hwang
- Department of Pediatrics, Ajou University School of Medicine, Ajou University Hospital, Suwon, Korea
| | - Se Won Lim
- Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea
| | - Jun Ah Lee
- Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea
| | - Dong Ho Kim
- Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea
| | - Jung Sub Lim
- Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea
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31
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Xing C, Huang Z, Li J, Li M, Xu L, Tao J, Fu L, Fang Y. Interactions of physical activity and body mass index with age at menarche: A school-based sample of Chinese female adolescents. Eur J Obstet Gynecol Reprod Biol 2017; 218:68-72. [DOI: 10.1016/j.ejogrb.2017.09.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 09/14/2017] [Accepted: 09/18/2017] [Indexed: 11/16/2022]
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Ballestri S, Nascimbeni F, Baldelli E, Marrazzo A, Romagnoli D, Lonardo A. NAFLD as a Sexual Dimorphic Disease: Role of Gender and Reproductive Status in the Development and Progression of Nonalcoholic Fatty Liver Disease and Inherent Cardiovascular Risk. Adv Ther 2017; 34:1291-1326. [PMID: 28526997 PMCID: PMC5487879 DOI: 10.1007/s12325-017-0556-1] [Citation(s) in RCA: 392] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) spans steatosis through nonalcoholic steatohepatis, cirrhosis, and hepatocellular carcinoma (HCC) associated with striking systemic features and excess cardiovascular and liver-related mortality. The pathogenesis of NAFLD is complex and multifactorial. Endocrine derangements are closely linked with dysmetabolic traits. For example, in animal and human studies, female sex is protected from dysmetabolism thanks to young individuals' ability to partition fatty acids towards ketone body production rather than very low density lipoprotein (VLDL)-triacylglycerol, and to sex-specific browning of white adipose tissue. Ovarian senescence facilitates both the development of massive hepatic steatosis and the fibrotic progression of liver disease in an experimental overfed zebrafish model. Consistently, estrogen deficiency, by potentiating hepatic inflammatory changes, hastens the progression of disease in a dietary model of nonalcoholic steatohepatitis (NASH) developing in ovariectomized mice fed a high-fat diet. In humans, NAFLD more often affects men; and premenopausal women are equally protected from developing NAFLD as they are from cardiovascular disease. It would be expected that early menarche, definitely associated with estrogen activation, would produce protection against the risk of NAFLD. Nevertheless, it has been suggested that early menarche may confer an increased risk of NAFLD in adulthood, excess adiposity being the primary culprit of this association. Fertile age may be associated with more severe hepatocyte injury and inflammation, but also with a decreased risk of liver fibrosis compared to men and postmenopausal status. Later in life, ovarian senescence is strongly associated with severe steatosis and fibrosing NASH, which may occur in postmenopausal women. Estrogen deficiency is deemed to be responsible for these findings via the development of postmenopausal metabolic syndrome. Estrogen supplementation may at least theoretically protect from NAFLD development and progression, as suggested by some studies exploring the effect of hormonal replacement therapy on postmenopausal women, but the variable impact of different sex hormones in NAFLD (i.e., the pro-inflammatory effect of progesterone) should be carefully considered.
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Affiliation(s)
- Stefano Ballestri
- Azienda USL di Modena, Pavullo Hospital, Pavullo nel Frignano, Italy
| | - Fabio Nascimbeni
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
| | - Enrica Baldelli
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandra Marrazzo
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Dante Romagnoli
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Amedeo Lonardo
- Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
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Brittain EL, Nwabuo C, Xu M, Gupta DK, Hemnes AR, Moreira HT, De Vasconcellos HD, Terry JG, Carr JJ, Lima JAC. Echocardiographic Pulmonary Artery Systolic Pressure in the Coronary Artery Risk Development in Young Adults (CARDIA) Study: Associations With Race and Metabolic Dysregulation. J Am Heart Assoc 2017; 6:JAHA.116.005111. [PMID: 28360228 PMCID: PMC5533013 DOI: 10.1161/jaha.116.005111] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Background The determinants of pulmonary artery systolic pressure (PASP) are not fully understood. It is unknown whether racial differences in PASP exist or if other population characteristics are associated with pulmonary pressure in humans. We examined echocardiographically estimated PASP in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a middle‐aged, biracial community‐based cohort. Methods and Results At the CARDIA year‐25 examination, 3469 participants underwent echocardiography, including measurement of tricuspid regurgitant jet velocity to estimate PASP. Clinical features, laboratory values, pulmonary function tests, and measurement of adipose depot volume were analyzed for association with PASP. PASP was estimated in 1311 individuals (61% female, 51% white). Older age, higher blood pressure, and higher body mass index were associated with higher PASP. Black race was associated with higher PASP after adjustment for demographics and left and right ventricular function (β 0.94, 95% CI 0.24‐1.64; P=0.009), but this association was no longer significant after further adjustment for lung volume (β 0.42, 95% CI −0.68 to 0.96; P=0.74). Insulin resistance, inflammation (C‐reactive protein and interleukin‐6), and visceral adipose volume were independently associated with higher PASP after adjustment for relevant covariates. PASP rose with worsening diastolic function (ratio of early transmitral Doppler velocity to average mitral annular tissue Doppler velocity [E/e′] and left atrial volume index). Conclusions In a large biracial cohort of middle‐aged adults, we identified associations among black race, insulin resistance, and diastolic dysfunction with higher echocardiographically estimated PASP. Further studies are needed to examine racial differences in PASP and whether insulin resistance directly contributes to pulmonary vascular disease in humans.
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Affiliation(s)
- Evan L Brittain
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN .,Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Chike Nwabuo
- Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD.,Harvard Medical School, Mount Auburn Hospital, Cambridge, MA
| | - Meng Xu
- Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN
| | - Deepak K Gupta
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN.,Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Anna R Hemnes
- Division of Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN
| | - Henrique T Moreira
- Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD.,Division of Cardiology, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | | | - James G Terry
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN
| | - Jeffrey J Carr
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN
| | - Joao A C Lima
- Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD
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Brief Report: Maternal Age of Menarche and Adiposity: Evidence from Hong Kong's "Children of 1997" Birth Cohort. Epidemiology 2017; 27:433-7. [PMID: 26808596 DOI: 10.1097/ede.0000000000000448] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Earlier age of menarche predicts chronic diseases. Earlier maternal age of menarche is also associated with higher body mass index (BMI) and height into childhood. METHODS We used generalized estimating equations in Hong Kong's "Children of 1997" birth cohort to examine the adjusted association of maternal age of menarche with BMI and height z score, and whether associations varied by maternal birthplace. RESULTS Earlier maternal age of menarche was not associated with infant BMI but was associated subsequently with higher BMI in childhood and at puberty. Maternal age of menarche was negatively associated with height in children of Hong Kong-born mothers, but positively associated with infant length for children with mothers born in China (P value for interaction 0.02). CONCLUSION These different patterns suggest drivers of adiposity and linear growth differ, and are more influential in some circumstances. Understanding these drivers may indicate setting-specific interventions to prevent childhood obesity.
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Werneck AO, Silva DRP, Souza MF, Christofaro DGD, Tomeleri CM, Fernandes RA, Ronque ER, Coelho‐e‐Silva MJ, Sardinha LB, Cyrino ES. Correlates of Blood Pressure According to Early, On Time, and Late Maturation in Adolescents. J Clin Hypertens (Greenwich) 2016; 18:424-30. [PMID: 26408345 PMCID: PMC8032168 DOI: 10.1111/jch.12699] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 07/28/2015] [Accepted: 07/30/2015] [Indexed: 11/29/2022]
Abstract
The aim of this study was to estimate the prevalence and correlates of blood pressure (BP) according to somatic maturation in Southern Brazilian adolescents. A total of 1321 adolescents participated in the study (732 girls), aged between 10 and 16 years, enrolled in public schools. The assessment of BP was performed using oscillometric equipment. Measurements of body weight, height, waist circumference, and skinfold thickness were performed. Somatic maturation was estimated by the age at peak height velocity. Behavioral and hereditary variables were obtained using a questionnaire. Early-maturing adolescents had the highest prevalence of high BP (28%; 95% confidence interval, 24.6-33.5) compared with other maturational groups (P=.003). In late-maturing adolescents, the variables associated with BP were paternal hypertension (systolic BP: β=4.9; diastolic BP: β=5.3) and early physical activity (systolic BP: β=-4.0; diastolic DBP: β=-3.6). In average-maturing adolescents, waist circumference (systolic BP: β=0.3), body mass index (diastolic BP: β=0.5), and mother's hypertension (diastolic BP: β=1.8) were positively related to BP. In early-maturing adolescents, only waist circumference (systolic BP: β=0.3; diastolic BP: β=0.3) was associated with BP. The authors conclude that the prevalence of high BP is greater in adolescents with early maturity and the outcome appears to be related to biological indicators in this group. On the other hand, in late-maturing adolescents, behavioral and hereditary variables are more related to BP.
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Affiliation(s)
- André O. Werneck
- Study and Research Group in Metabolism, Nutrition, and Exercise – GEPEMENELondrina State University (UEL)LondrinaBrazil
| | - Danilo R. P. Silva
- Study and Research Group in Metabolism, Nutrition, and Exercise – GEPEMENELondrina State University (UEL)LondrinaBrazil
| | - Mariana F. Souza
- Study and Research Group in Metabolism, Nutrition, and Exercise – GEPEMENELondrina State University (UEL)LondrinaBrazil
| | - Diego G. D. Christofaro
- Scientific Research Group Related to Physical Activity (GICRAF)Laboratory of Investigation in Exercise (LIVE)Department of Physical EducationSão Paulo State University (UNESP)Presidente PrudenteBrazil
| | - Crisieli M. Tomeleri
- Study and Research Group in Metabolism, Nutrition, and Exercise – GEPEMENELondrina State University (UEL)LondrinaBrazil
| | - Rômulo A. Fernandes
- Scientific Research Group Related to Physical Activity (GICRAF)Laboratory of Investigation in Exercise (LIVE)Department of Physical EducationSão Paulo State University (UNESP)Presidente PrudenteBrazil
| | - Enio R.V. Ronque
- Study and Research Group in Metabolism, Nutrition, and Exercise – GEPEMENELondrina State University (UEL)LondrinaBrazil
| | | | - Luís B. Sardinha
- Exercise and Health LaboratoryCIPERFaculty of Human KineticsUniversity of LisbonLisbonPortugal
| | - Edilson S. Cyrino
- Study and Research Group in Metabolism, Nutrition, and Exercise – GEPEMENELondrina State University (UEL)LondrinaBrazil
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Mueller NT, Jacobs DR, MacLehose RF, Demerath EW, Kelly SP, Dreyfus JG, Pereira MA. Consumption of caffeinated and artificially sweetened soft drinks is associated with risk of early menarche. Am J Clin Nutr 2015; 102:648-54. [PMID: 26178725 PMCID: PMC4548172 DOI: 10.3945/ajcn.114.100958] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Accepted: 06/12/2015] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Early menarche has been linked to risk of several chronic diseases. Prospective research on whether the intake of soft drinks containing caffeine, a modulator of the female reproductive axis, is associated with risk of early menarche is sparse. OBJECTIVE We examined the hypothesis that consumption of caffeinated soft drinks in childhood is associated with higher risk of early menarche. DESIGN The National Heart, Lung, and Blood Institute Growth and Health Study recruited and enrolled 2379 (1213 African American, 1166 Caucasian) girls aged 9-10 y (from Richmond, CA; Cincinnati, OH; and Washington, DC) and followed them for 10 y. After exclusions were made, there were 1988 girls in whom we examined prospective associations between consumption of caffeinated and noncaffeinated sugar- and artificially sweetened soft drinks and early menarche (defined as menarche age <11 y). We also examined associations between intakes of caffeine, sucrose, fructose, and aspartame and early menarche. RESULTS Incident early menarche occurred in 165 (8.3%) of the girls. After adjustment for confounders and premenarcheal percentage body fat, greater consumption of caffeinated soft drinks was associated with a higher risk of early menarche (RR for 1 serving/d increment: 1.47; 95% CI: 1.22, 1.79). Consumption of artificially sweetened soft drinks was also positively associated with risk of early menarche (RR for 1 serving/d increment: 1.43; 95% CI: 1.08, 1.88). Consumption of noncaffeinated soft drinks was not significantly associated with early menarche (RR for 1 serving/d increment: 0.88; 95% CI: 0.62, 1.25); nor was consumption of sugar-sweetened soft drinks (RR for 1 serving/d increment: 1.15; 95% CI: 0.95, 1.39). Consistent with the beverage findings, intakes of caffeine (RR for 1-SD increment: 1.22; 95% CI: 1.08, 1.37) and aspartame (RR for 1-SD increment: 1.20; 95% CI: 1.10, 1.31) were positively associated with risk of early menarche. CONCLUSION Consumption of caffeinated and artificially sweetened soft drinks was positively associated with risk of early menarche in a US cohort of African American and Caucasian girls.
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Affiliation(s)
- Noel T Mueller
- Department of Epidemiology, Mailman School of Public Health and Institute of Human Nutrition and Department of Medicine, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY;
| | - David R Jacobs
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; and
| | - Richard F MacLehose
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; and
| | - Ellen W Demerath
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; and
| | - Scott P Kelly
- Department of Epidemiology and Biostatistics, George Washington University, Washington, DC
| | - Jill G Dreyfus
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; and
| | - Mark A Pereira
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; and
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Day FR, Perry JRB, Ong KK. Genetic Regulation of Puberty Timing in Humans. Neuroendocrinology 2015; 102:247-255. [PMID: 25968239 PMCID: PMC6309186 DOI: 10.1159/000431023] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Accepted: 04/28/2015] [Indexed: 12/11/2022]
Abstract
Understanding the regulation of puberty timing has relevance to developmental and human biology and to the pathogenesis of various diseases. Recent large-scale genome-wide association studies on puberty timing and adult height, body mass index (BMI) and central body shape provide evidence for shared biological mechanisms that regulate these traits. There is a substantial genetic overlap between age at menarche in women and BMI, with almost invariable directional consistency with the epidemiological associations between earlier menarche and higher BMI. By contrast, the genetic loci identified for age at menarche are largely distinct from those identified for central body shape, while alleles that confer earlier menarche can be associated with taller or shorter adult height. The findings of population-based studies on age at menarche show increasing relevance for other studies of rare monogenic disorders and enrich our understanding of the mechanisms that regulate the timing of puberty and reproductive function.
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Affiliation(s)
- Felix R Day
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
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