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Devasia AG, Ramasamy A, Leo CH. Current Therapeutic Landscape for Metabolic Dysfunction-Associated Steatohepatitis. Int J Mol Sci 2025; 26:1778. [PMID: 40004240 PMCID: PMC11855529 DOI: 10.3390/ijms26041778] [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: 11/07/2024] [Revised: 01/31/2025] [Accepted: 02/11/2025] [Indexed: 02/27/2025] Open
Abstract
In recent years, "metabolic dysfunction-associated steatotic liver disease" (MASLD) has been proposed to better connect liver disease to metabolic dysfunction, which is the most common chronic liver disease worldwide. MASLD affects more than 30% of individuals globally, and it is diagnosed by the combination of hepatic steatosis and obesity, type 2 diabetes, or two metabolic risk factors. MASLD begins with the buildup of extra fat, often greater than 5%, within the liver, causing liver hepatocytes to become stressed. This can proceed to a more severe form, metabolic dysfunction-associated steatohepatitis (MASH), in 20-30% of people, where inflammation in the liver causes tissue fibrosis, which limits blood flow over time. As fibrosis worsens, MASH may lead to cirrhosis, liver failure, or even liver cancer. While the pathophysiology of MASLD is not fully known, the current "multiple-hits" concept proposes that dietary and lifestyle factors, metabolic factors, and genetic or epigenetic factors contribute to elevated oxidative stress and inflammation, causing liver fibrosis. This review article provides an overview of the pathogenesis of MASLD and evaluates existing therapies as well as pharmacological drugs that are currently being studied in clinical trials for MASLD or MASH.
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Affiliation(s)
- Arun George Devasia
- Science, Math & Technology, Singapore University of Technology & Design, Singapore 487372, Singapore;
- Genome Institute of Singapore (GIS), Agency for Science Technology and Research (A*STAR), 60 Biopolis Street, Singapore 138672, Singapore;
| | - Adaikalavan Ramasamy
- Genome Institute of Singapore (GIS), Agency for Science Technology and Research (A*STAR), 60 Biopolis Street, Singapore 138672, Singapore;
| | - Chen Huei Leo
- Department of Biomedical Engineering, College of Design & Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore
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Wang Q, Chen H, Deng H, Zhang M, Hu H, Ouyang H, Ma L, Liu R, Sun J, Hu G, Wang K. Association of daily sleep duration with risk of metabolic dysfunction-associated steatotic liver disease and adverse liver outcomes. DIABETES & METABOLISM 2025; 51:101628. [PMID: 39984033 DOI: 10.1016/j.diabet.2025.101628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 02/11/2025] [Accepted: 02/12/2025] [Indexed: 02/23/2025]
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, leading to substantial disease burden globally. Whether sleep duration is associated with the risk of MASLD, cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality remains underexplored. METHODS A total of 489,261 middle-aged and older adults from the UK Biobank without prior liver diseases were included. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, HCC, and liver-related mortality ascertained through linked hospital records and death registries. Sleep duration was self-reported at baseline survey and categorized into ≤ 5, 6, 7, 8 and ≥ 9 hours. RESULTS During a median (IQR) follow-up of 13.8 (1.5) years, 7,133 MASLD, 5,527 cirrhosis, 1,126 HCC, and 1,125 liver-related mortality cases were identified. After adjusting for potential confounders, the HRs [95% CIs] of MASLD were 1.44 [1.32;1.57], 1.17 [1.09;1.24], 1.00 (reference), 1.05 [0.99;1.11] and 1.35 [1.24;1.46] for ≤ 5, 6, 7, 8 and ≥ 9 hours of sleep duration, respectively. Similar trends were also observed for cirrhosis, HCC, and liver-related mortality. In addition, the U-shaped association between sleep duration and MASLD was more pronounced among participants without abnormal body mass index (overweight and obese), hypertension or insomnia (P for interaction <0.05). CONCLUSIONS Both short and long sleep duration are associated with an increased risk of MASLD, cirrhosis, HCC, and liver-related mortality. Maintaining a moderate sleep duration of 7 to 8 hours per day could be crucial to prevent against this escalating public health concern.
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Affiliation(s)
- Qian Wang
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Huiyi Chen
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Huiling Deng
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Minyi Zhang
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Haoyue Hu
- Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Haotong Ouyang
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Lien Ma
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Ruiyan Liu
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Jian Sun
- State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China; Guangdong Provincial Key Laboratory of Viral Hepatitis Research; Department of Infectious Diseases, Ministry of Education, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Guifang Hu
- Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
| | - Kaifeng Wang
- State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China; Guangdong Provincial Key Laboratory of Viral Hepatitis Research; Department of Infectious Diseases, Ministry of Education, Guangdong Provincial Clinical Research Center for Viral Hepatitis, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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Pirahesh K, Zarrinnia A, Nikniaz L, Nikniaz Z. Association between sleep duration and risk of nonalcoholic fatty liver disease: A systematic review and meta-analysis. Prev Med Rep 2025; 50:102968. [PMID: 39897736 PMCID: PMC11783128 DOI: 10.1016/j.pmedr.2025.102968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 01/06/2025] [Accepted: 01/07/2025] [Indexed: 02/04/2025] Open
Abstract
Introduction Considering that both long and short sleep duration may have an association with nonalcoholic fatty liver disease (NAFLD), in this meta-analysis, we analyzed the dose-response association between sleep duration and NAFLD along with meta-analyses of the differences in mean sleep duration between NAFLD patients and healthy controls, and linear meta-analysis of the association between sleep duration and NAFLD. Methods PubMed (665 articles), Scopus (442 articles), and Web of Sciences (200 articles) were searched from inception until November 2023. Observational studies were included if they assess the association between sleep duration and NAFLD or compare the mean sleep duration between patients with NAFLD and healthy population. All studies done in humans without restriction on sex, age, and language were included. The methological quality of studies was assessed by Joanna Briggs Institute (JBI) tools. The meta-analysis was conducted using STATA. Results Thirty-one studies that included 836,117 participants were included in this systematic review. The results indicated no significant differences between NAFLD patients and healthy controls regarding mean sleep duration [Mean difference: -7.08, 95 % CI: -20.10, 5.94]. The subgroup meta-analysis did not show any significant differences between groups. The long versus short sleep duration meta-analysis showed a significant association between sleep duration and NAFLD (OR: 0.8 [95 % CI, 0.74-0.91]). The results of the dose-response meta-analysis do not suggest a linear or nonlinear relationship between sleep duration and NAFLD (p-value = 0.9). Conclusion The highest category of sleep duration was associated with a lower risk of NAFLD. However, no dose-response association was observed.
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Affiliation(s)
- Kasra Pirahesh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Zarrinnia
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Students` Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Leila Nikniaz
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zeinab Nikniaz
- Tabriz Health Services Management Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Tian T, Zeng J, Li YC, Wang J, Zhang DF, Wang DG, Pan HF, Fan JG, Ni J. Joint effects of sleep disturbance and renal function impairment on incident new-onset severe metabolic dysfunction-associated steatotic liver disease. Diabetes Obes Metab 2024; 26:4724-4733. [PMID: 39118216 DOI: 10.1111/dom.15841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 07/09/2024] [Accepted: 07/15/2024] [Indexed: 08/10/2024]
Abstract
AIM To elucidate the effects of sleep parameters and renal function on the risk of developing new-onset severe metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS The primary analysis involved a cohort of 305 257 participants. Multivariable Cox models were employed to calculate hazard ratios and 95% confidence intervals. Traditional mediation and two-step Mendelian randomization (MR) analyses were conducted to assess the associations and mediating roles of renal function indicators between sleep and new-onset severe MASLD. RESULTS Poor sleep score and renal function biomarker score (RFS) were associated with an increased risk of new-onset severe MASLD (all ptrend <0.001). Participants with poor sleep patterns and the highest RFS had a 5.45-fold higher risk of new-onset severe MASLD, compared to those with healthy sleep patterns and the lowest RFS (p < 0.001). The RFS could explain 10.08% of the correlations between poor sleep score and risk of new-onset severe MASLD. Additionally, MR analyses supported a causal link between insomnia and new-onset severe MASLD and revealed a mediating role of chronic kidney disease in the connection between insomnia and new-onset severe MASLD risk. CONCLUSIONS This study highlights the independent and combined associations of sleep parameters and renal function indicators with new-onset severe MASLD, underscoring the bidirectional communication of the liver-kidney axis and providing modifiable strategies for preventing MASLD.
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Affiliation(s)
- Tian Tian
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, China
- Department of Central Research Laboratory, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medicine Sciences and Peking Union Medical College, Nanjing, China
| | - Jing Zeng
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuan-Cheng Li
- Department of Central Research Laboratory, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medicine Sciences and Peking Union Medical College, Nanjing, China
| | - Jing Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, China
| | - Dan-Feng Zhang
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, China
- Department of Nephrology, The Second Hospital of Anhui Medical University, Hefei, China
| | - De-Guang Wang
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, China
- Department of Nephrology, The Second Hospital of Anhui Medical University, Hefei, China
| | - Hai-Feng Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, China
| | - Jian-Gao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Ni
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
- Institute of Kidney Disease, Inflammation & Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, China
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Bu LF, Xiong CY, Zhong JY, Xiong Y, Li DM, Hong FF, Yang SL. Non-alcoholic fatty liver disease and sleep disorders. World J Hepatol 2024; 16:304-315. [PMID: 38577533 PMCID: PMC10989311 DOI: 10.4254/wjh.v16.i3.304] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 01/11/2024] [Accepted: 02/18/2024] [Indexed: 03/27/2024] Open
Abstract
Studies have shown that non-alcoholic fatty liver disease (NAFLD) may be associated with sleep disorders. In order to explore the explicit relationship between the two, we systematically reviewed the effects of sleep disorders, especially obstructive sleep apnea (OSA), on the incidence of NAFLD, and analyzed the possible mechanisms after adjusting for confounding factors. NAFLD is independently associated with sleep disorders. Different sleep disorders may be the cause of the onset and aggravation of NAFLD. An excessive or insufficient sleep duration, poor sleep quality, insomnia, sleep-wake disorders, and OSA may increase the incidence of NAFLD. Despite that some research suggests a unidirectional causal link between the two, specifically, the onset of NAFLD is identified as a result of changes in sleep characteristics, and the reverse relationship does not hold true. Nevertheless, there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD. Further research is needed to establish a clear relationship between NAFLD and sleep disorders. This will lay the groundwork for earlier identification of potential patients, which is crucial for earlier monitoring, diagnosis, effective prevention, and treatment of NAFLD.
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Affiliation(s)
- Lu-Fang Bu
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China
| | - Chong-Yu Xiong
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China
| | - Jie-Yi Zhong
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China
| | - Yan Xiong
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China
| | - Dong-Ming Li
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China
| | - Fen-Fang Hong
- Experimental Center of Pathogen Biology, College of Medicine, Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Shu-Long Yang
- Department of Physiology, Fuzhou Medical College, Nanchang University, Fuzhou 344000, Jiangxi Province, China
- Key Laboratory of Chronic Diseases, Fuzhou Medical University, Fuzhou 344000, Jiangxi Province, China
- Technology Innovation Center of Chronic Disease Research in Fuzhou City, Fuzhou Science and Technology Bureau, Fuzhou 344000, Jiangxi Province, China.
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Sayed Ahmed HA, Abo El-Ela SG, Joudeh AI, Moawd SM, El Hayek S, Shah J, Eldahshan NA. Prevalence and Correlates of Night Eating Syndrome, Insomnia, and Psychological Distress in Primary Care Patients with Obesity: A Cross-Sectional Study. Obes Facts 2024; 17:274-285. [PMID: 38484714 PMCID: PMC11149973 DOI: 10.1159/000538341] [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: 06/11/2023] [Accepted: 03/05/2024] [Indexed: 06/06/2024] Open
Abstract
INTRODUCTION Management of obesity is challenging for both patients and healthcare workers. Considering the low success rate of current interventions, this study aimed to explore the prevalence and associated factors of night eating syndrome (NES), insomnia, and psychological distress among individuals with obesity in order to plan comprehensive obesity management interventions. METHODS A cross-sectional study on a convenient sample from five primary healthcare centers in Port Said, Egypt, was conducted from November 2020 to March 2021. Sociodemographic and clinical characteristics were collected in addition to the assessment of NES, insomnia, and psychological distress using the Arabic versions of the Night Eating Diagnostic Questionnaire (NEQ), the Insomnia Severity Index (ISI), and the Patient Health Questionnaire-4 (PHQ-4) scales, respectively. Associations of NES, insomnia, and psychological distress were assessed by multiple regression analysis. We performed Bonferroni adjustments for multiple comparisons. RESULTS We included 425 participants with obesity with a mean age of 45.52 ± 6.96 years. In all, 54.4% were females and the mean body mass index (BMI) was 35.20 ± 4.41 kg/m2. The prevalence rates of NES, insomnia, and psychological distress were 21.6% (95% CI: 17.7-25.6%), 15.3% (95% CI: 11.9-18.7%), and 18.8% (95% CI: 15.1-22.6%), respectively. NES was significantly associated with younger age (OR 0.974, p = 0.016), physical inactivity (OR 0.485, p = 0.010), insomnia (OR 2.227, p = 0.014), and psychological distress (OR 2.503, p = 0.002). Insomnia showed strong associations with NES (OR 2.255, p = 0.015) and psychological distress (OR 5.990, p < 0.001). Associated factors of psychological distress symptoms included insomnia (OR 6.098, p < 0.001) and NES (OR 2.463, p = 0.003). CONCLUSION The prevalence rates of NES, insomnia, and psychological distress were high among primary care patients with obesity, and these conditions were interrelated. Optimal obesity management necessitates individualized and targeted multidisciplinary care plans that take into consideration individual patients' mental, behavioral, and dietary habits needs.
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Affiliation(s)
- Hazem A Sayed Ahmed
- Department of Family Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Sohila G Abo El-Ela
- Department of Family Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Anwar I Joudeh
- Internal Medicine Department, Al-Khor Hospital, Hamad Medical Corporation, Doha, Qatar
- Internal Medicine Department, College of Medicine, University of Qatar, Doha, Qatar
| | - Sally M Moawd
- Department of Family Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Samer El Hayek
- Medical Department, Erada Center for Treatment and Rehabilitation in Dubai, Dubai, United Arab Emirates
| | - Jaffer Shah
- Weill Cornell Medicine, New York, New York, USA
| | - Nahed Amen Eldahshan
- Department of Family Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
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Yang J, Zhang K, Xi Z, Ma Y, Shao C, Wang W, Tang YD. Short sleep duration and the risk of nonalcoholic fatty liver disease/metabolic associated fatty liver disease: a systematic review and meta-analysis. Sleep Breath 2023; 27:1985-1996. [PMID: 36544011 PMCID: PMC9771780 DOI: 10.1007/s11325-022-02767-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/02/2022] [Accepted: 12/08/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE It is unclear whether or not nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated fatty liver disease (MAFLD) is related to short sleep duration. A meta-analysis was conducted to determine if inadequate sleep time increased the risk of NAFLD/MAFLD. METHODS A comprehensive systematic literature review was conducted in the Embase, PubMed, and Cochrane Library databases from inception to August 1, 2022. Studies examining the correlation between inadequate sleep time and the risk of NAFLD/MAFLD were included. We pooled the odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. RESULTS This meta-analysis included fifteen studies involving a total of 261,554 participants. In the pooled analysis, short sleep duration was found to be strongly correlated with an increased risk of NAFLD/MAFLD (OR, 1.15; 95% CI, 1.04-1.28; P = 0.01), with a moderate degree of heterogeneity between studies (I2 = 71.92%, Q = 49.87, P < 0.01). The sensitivity analysis suggested that the primary outcome was robust, and there was no significant publication bias. CONCLUSION This meta-analysis indicates that inadequate sleep duration is strongly correlated with an elevated risk of NAFLD/MAFLD. The findings suggest that obtaining an adequate amount of sleep may be useful for preventing NAFLD/MAFLD, which is especially important given the low rate of response to pharmacotherapy.
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Affiliation(s)
- Jie Yang
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037 China
| | - Kuo Zhang
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037 China
| | - Ziwei Xi
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037 China
| | - Yue Ma
- Department of Cardiology and Institute of Vascular Medicine, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Third Hospital, No. 49 Huayuanbei Road, Beijing, 100191 China
| | - Chunli Shao
- Department of Cardiology and Institute of Vascular Medicine, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Third Hospital, No. 49 Huayuanbei Road, Beijing, 100191 China
| | - Wenyao Wang
- Department of Cardiology and Institute of Vascular Medicine, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Third Hospital, No. 49 Huayuanbei Road, Beijing, 100191 China
| | - Yi-Da Tang
- Department of Cardiology and Institute of Vascular Medicine, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Third Hospital, No. 49 Huayuanbei Road, Beijing, 100191 China
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Lo YJ, Mishra VK, Lo HY, Dubey NK, Lo WC. Clinical Spectrum and Trajectory of Innovative Therapeutic Interventions for Insomnia: A Perspective. Aging Dis 2023; 14:1038-1069. [PMID: 37163444 PMCID: PMC10389812 DOI: 10.14336/ad.2022.1203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 12/03/2022] [Indexed: 05/12/2023] Open
Abstract
Increasing incidences of insomnia in adults, as well as the aging population, have been reported for their negative impact on the quality of life. Insomnia episodes may be associated with neurocognitive, musculoskeletal, cardiovascular, gastrointestinal, renal, hepatic, and metabolic disorders. Epidemiological evidence also revealed the association of insomnia with oncologic and asthmatic complications, which has been indicated as bidirectional. Two therapeutic approaches including cognitive behavioral therapy (CBT) and drugs-based therapies are being practiced for a long time. However, the adverse events associated with drugs limit their wide and long-term application. Further, Traditional Chinese medicine, acupressure, and pulsed magnetic field therapy may also provide therapeutic relief. Notably, the recently introduced cryotherapy has been demonstrated as a potential candidate for insomnia which could reduce pain, by suppressing oxidative stress and inflammation. It seems that the synergistic therapeutic approach of cryotherapy and the above-mentioned approaches might offer promising prospects to further improve efficacy and safety. Considering these facts, this perspective presents a comprehensive summary of recent advances in pathological aetiologies of insomnia including COVID-19, and its therapeutic management with a greater emphasis on cryotherapy.
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Affiliation(s)
| | | | | | - Navneet Kumar Dubey
- Victory Biotechnology Co., Ltd., Taipei 114757, Taiwan.
- ShiNeo Technology Co., Ltd., New Taipei City 24262, Taiwan.
| | - Wen-Cheng Lo
- Department of Surgery, Division of Neurosurgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Department of Neurosurgery, Taipei Medical University Hospital, Taipei 11031, Taiwan.
- Taipei Neuroscience Institute, Taipei Medical University, Taipei 11031, Taiwan.
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Sun Z, Ji J, Zuo L, Hu Y, Wang K, Xu T, Wang Q, Cheng F. Causal relationship between nonalcoholic fatty liver disease and different sleep traits: a bidirectional Mendelian randomized study. Front Endocrinol (Lausanne) 2023; 14:1159258. [PMID: 37334291 PMCID: PMC10272397 DOI: 10.3389/fendo.2023.1159258] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 05/19/2023] [Indexed: 06/20/2023] Open
Abstract
Background and aims Non-alcoholic fatty liver disease(NAFLD) is common worldwide and has previously been reported to be associated with sleep traits. However, it is not clear whether NAFLD changes sleep traits or whether the changes in sleep traits lead to the onset of NAFLD. The purpose of this study was to investigate the causal relationship between NAFLD and changes in sleep traits using Mendelian randomization. Methods We proposed a bidirectional Mendelian randomization (MR) analysis and performed validation analyses to dissect the association between NAFLD and sleep traits. Genetic instruments were used as proxies for NAFLD and sleep. Data of genome-wide association study(GWAS) were obtained from the center for neurogenomics and cognitive research database, Open GWAS database and GWAS catalog. Three MR methods were performed, including inverse variance weighted method(IVW), MR-Egger, weighted median. Results In total,7 traits associated with sleep and 4 traits associated with NAFLD are used in this study. A total of six results showed significant differences. Insomnia was associated with NAFLD (OR(95% CI)= 2.25(1.18,4.27), P = 0.01), Alanine transaminase levels (OR(95% CI)= 2.79(1.70, 4.56), P =4.71×10-5) and percent liver fat(OR(95% CI)= 1.31(1.03,1.69), P = 0.03). Snoring was associated with percent liver fat (1.15(1.05,1.26), P =2×10-3), alanine transaminase levels (OR(95% CI)= 1.27(1.08,1.50), P =0.04).And dozing was associated with percent liver fat(1.14(1.02,1.26), P =0.02).For the remaining 50 outcomes, no significant or definitive association was yielded in MR analysis. Conclusion Genetic evidence suggests putative causal relationships between NAFLD and a set of sleep traits, indicating that sleep traits deserves high priority in clinical practice. Not only the confirmed sleep apnea syndrome, but also the sleep duration and sleep state (such as insomnia) deserve clinical attention. Our study proves that the causal relationship between sleep characteristics and NAFLD is the cause of the change of sleep characteristics, while the onset of non-NAFLD is the cause of the change of sleep characteristics, and the causal relationship is one-way.
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Rizzo M, Colletti A, Penson PE, Katsiki N, Mikhailidis DP, Toth PP, Gouni-Berthold I, Mancini J, Marais D, Moriarty P, Ruscica M, Sahebkar A, Vinereanu D, Cicero AFG, Banach M, Al-Khnifsawi M, Alnouri F, Amar F, Atanasov AG, Bajraktari G, Banach M, Gouni-Berthold I, Bhaskar S, Bielecka-Dąbrowa A, Bjelakovic B, Bruckert E, Bytyçi I, Cafferata A, Ceska R, Cicero AF, Chlebus K, Collet X, Daccord M, Descamps O, Djuric D, Durst R, Ezhov MV, Fras Z, Gaita D, Gouni-Berthold I, Hernandez AV, Jones SR, Jozwiak J, Kakauridze N, Kallel A, Katsiki N, Khera A, Kostner K, Kubilius R, Latkovskis G, John Mancini G, David Marais A, Martin SS, Martinez JA, Mazidi M, Mikhailidis DP, Mirrakhimov E, Miserez AR, Mitchenko O, Mitkovskaya NP, Moriarty PM, Mohammad Nabavi S, Nair D, Panagiotakos DB, Paragh G, Pella D, Penson PE, Petrulioniene Z, Pirro M, Postadzhiyan A, Puri R, Reda A, Reiner Ž, Radenkovic D, Rakowski M, Riadh J, Richter D, Rizzo M, Ruscica M, Sahebkar A, Serban MC, Shehab AM, Shek AB, Sirtori CR, Stefanutti C, Tomasik T, Toth PP, Viigimaa M, Valdivielso P, Vinereanu D, Vohnout B, von Haehling S, Vrablik M, Wong ND, Yeh HI, Zhisheng J, Zirlik A. Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP). Pharmacol Res 2023; 189:106679. [PMID: 36764041 DOI: 10.1016/j.phrs.2023.106679] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 01/25/2023] [Accepted: 01/26/2023] [Indexed: 02/11/2023]
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.
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Affiliation(s)
- Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Via del Vespro 141, 90127 Palermo, Italy.
| | - Alessandro Colletti
- Department of Science and Drug Technology, University of Turin, Turin, Italy
| | - Peter E Penson
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Liverpool Centre for Cardiovascular Science, Liverpool, UK
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece; School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Campus, Medical School, University College London (UCL), London, UK
| | - Peter P Toth
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, IL, USA
| | - Ioanna Gouni-Berthold
- Department of Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany
| | - John Mancini
- Department of Medicine, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada
| | - David Marais
- Chemical Pathology Division of the Department of Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa
| | - Patrick Moriarty
- Division of Clinical Pharmacology, Division of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Dragos Vinereanu
- Cardiology Department, University and Emergency Hospital, Bucharest, Romania, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
| | - Arrigo Francesco Giuseppe Cicero
- Hypertension and Cardiovascular disease risk research center, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy; IRCCS Policlinico S. Orsola-Malpighi, Bologna, Italy
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.
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Zarean E, Looha MA, Amini P, Ahmadi A, Dugué PA. Sleep characteristics of middle-aged adults with non-alcoholic fatty liver disease: findings from the Shahrekord PERSIAN cohort study. BMC Public Health 2023; 23:312. [PMID: 36774488 PMCID: PMC9922458 DOI: 10.1186/s12889-023-15251-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 02/09/2023] [Indexed: 02/13/2023] Open
Abstract
BACKGROUND Several studies have reported short sleep duration in people with non-alcoholic fatty liver disease (NAFLD) but other sleep characteristics have been less studied. We aimed to assess the cross-sectional association of NAFLD with sleep duration and quality in an Iranian population sample. METHODS We used data from 9,151 participants in the Shahrekord Prospective Epidemiological Research Studies in Iran (PERSIAN) Cohort Study, including 1,320 that were diagnosed with NAFLD. Log-binomial regression models sequentially adjusted for sociodemographic, lifestyle, clinical and biological variables were used to estimate relative risks (RR) and 95% confidence intervals (95% CI) for the association between NAFLD and sleep characteristics. RESULTS Participants with NAFLD had shorter sleep duration, later wake-up time and bedtime, worse sleep efficiency, and more frequent daytime napping and use of sleeping pills, in age- and sex-adjusted models. After controlling for sociodemographic, lifestyle, clinical, and biological variables the associations remained strong for sleep efficiency (per 10%, RR = 0.92, 95%CI: 0.88-0.96) and use of sleeping pills (RR = 1.48, 95%CI: 1.17-1.88). The association between NAFLD and sleep efficiency was stronger in participants aged > 60 years (RR = 0.81, 0.70-0.93) and 40-60 years (RR = 0.87, 0.82-0.94), compared with those aged < 40 years (P-heterogeneity < 0.001). More frequent daytime napping in participants with NAFLD, compared with non-NAFLD, was observed in males but not females (P-heterogeneity = 0.007), and in those with body mass index (BMI) < 30 but not in obese participants (P-heterogeneity < 0.001). CONCLUSIONS Diagnosis of NAFLD is associated with several poor sleep characteristics in middle-aged Iranians. Although longitudinal studies would help to clarify the direction of causality, our study shows that poor sleep is an important aspect of NAFLD.
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Affiliation(s)
- Elaheh Zarean
- grid.440801.90000 0004 0384 8883Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran ,grid.1002.30000 0004 1936 7857Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC Australia
| | - Mehdi Azizmohammad Looha
- grid.411600.2Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Payam Amini
- grid.411746.10000 0004 4911 7066Department of Biostatistics, School of Public Health, IRAN University of Medical Sciences, Tehran, Iran
| | - Ali Ahmadi
- Department of Epidemiology and Biostatistics, School of Health and, Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Pierre-Antoine Dugué
- grid.1002.30000 0004 1936 7857Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC Australia ,Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC Australia ,grid.1008.90000 0001 2179 088XCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC Australia
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Larion S, Padgett CA, Butcher JT, Mintz JD, Fulton DJ, Stepp DW. The biological clock enhancer nobiletin ameliorates steatosis in genetically obese mice by restoring aberrant hepatic circadian rhythm. Am J Physiol Gastrointest Liver Physiol 2022; 323:G387-G400. [PMID: 35997288 PMCID: PMC9602907 DOI: 10.1152/ajpgi.00130.2022] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 07/13/2022] [Accepted: 08/03/2022] [Indexed: 01/31/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with disruption of homeostatic lipid metabolism, but underlying processes are poorly understood. One possible mechanism is impairment in hepatic circadian rhythm, which regulates key lipogenic mediators in the liver and whose circadian oscillation is diminished in obesity. Nobiletin enhances biological rhythms by activating RAR-related orphan receptor nuclear receptor, protecting against metabolic syndrome in a clock-dependent manner. The effect of nobiletin in NAFLD is unclear. In this study, we investigate the clock-enhancing effects of nobiletin in genetically obese (db/db) PER2::LUCIFERASE reporter mice with fatty liver. We report microarray expression data suggesting hepatic circadian signaling is impaired in db/db mice with profound hepatic steatosis. Circadian PER2 activity, as assessed by mRNA and luciferase assay, was significantly diminished in liver of db/db PER2::LUCIFERASE reporter mice. Continuous animal monitoring systems and constant dark studies suggest the primary circadian defect in db/db mice lies within peripheral hepatic oscillators and not behavioral rhythms or the master clock. In vitro, nobiletin restored PER2 amplitude in lipid-laden PER2::LUCIFERASE reporter macrophages. In vivo, nobiletin dramatically upregulated core clock gene expression, hepatic PER2 activity, and ameliorated steatosis in db/db PER2::LUCIFERASE reporter mice. Mechanistically, nobiletin reduced serum insulin levels, decreased hepatic Srebp1c, Acaca1, Tnfα, and Fgf21 expression, but did not improve Plin2, Plin5, or Cpt1, suggesting nobiletin attenuates steatosis in db/db mice via downregulation of hepatic lipid accumulation. These data suggest restoring endogenous rhythm with nobiletin resolves steatosis in obesity, proposing that hypothesis that targeting the biological clock may be an attractive therapeutic strategy for NAFLD.NEW & NOTEWORTHY NAFLD is the most common chronic liver disease, but underlying mechanisms are unclear. We show here that genetically obese (db/db) mice with fatty liver have impaired hepatic circadian rhythm. Hepatic Per2 expression and PER2 reporter activity are diminished in db/db PER2::LUCIFERASE mice. The biological clock-enhancer nobiletin restores hepatic PER2 in db/db PER2::LUCIFERASE mice, resolving steatosis via downregulation of Srebp1c. These studies suggest targeting the circadian clock may be beneficial strategy in NAFLD.
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Affiliation(s)
- Sebastian Larion
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia
- Department of Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia
| | - Caleb A Padgett
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia
| | - Joshua T Butcher
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia
| | - James D Mintz
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia
| | - David J Fulton
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia
- Department of Pharmacology, Medical College of Georgia, Augusta University, Augusta, Georgia
| | - David W Stepp
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, Georgia
- Department of Pharmacology, Medical College of Georgia, Augusta University, Augusta, Georgia
- Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia
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Yang J, Luo S, Li R, Ju J, Zhang Z, Shen J, Sun M, Fan J, Xia M, Zhu W, Liu Y. Sleep Factors in Relation to Metabolic Dysfunction-Associated Fatty Liver Disease in Middle-Aged and Elderly Chinese. J Clin Endocrinol Metab 2022; 107:2874-2882. [PMID: 35900115 DOI: 10.1210/clinem/dgac428] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Indexed: 11/19/2022]
Abstract
CONTEXT Accumulating evidence implies that sleep disturbance is involved in metabolic disorders. OBJECTIVE We comprehensively evaluated the association between various dimensions of sleep behaviors and the risk for metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS In this cross-sectional study of 5011 participants with self-reported sleep behaviors and radiologically diagnosed MAFLD, a comprehensive healthy sleep score was generated to evaluate the associations between sleep behaviors and MAFLD risk using multivariate logistic regression adjusting for demographics, lifestyles, medication, and metabolic comorbidities. Furthermore, mediation analysis was utilized to assess the extent to which obesity explains the effect of sleep quality on MAFLD risk. RESULTS Late bedtime, snoring, and daytime napping for over 30 minutes significantly associated with an increased risk of MAFLD, with odds ratios (OR) of 1.37 (95% CI 1.10, 1.70), 1.59 (95% CI 1.33, 1.91), and 1.17 (95% CI 1.02, 1.35), respectively, after full adjustments including obesity. Participants with disturbance in nighttime sleep and prolonged daytime napping showed the highest risk for MAFLD (OR 2.38, 95% CI 1.73, 3.27). Each additional increase of healthy sleep score was associated with a 16% reduction in MAFLD risk. Further stratified analysis revealed that people with a sedentary lifestyle and central obesity experienced more prominent adverse effects from poor sleep quality than others. Moreover, obesity accounted for only 20.77% of the total effect of sleep quality on MAFLD risk. CONCLUSIONS Sleep behaviors, both cumulatively and individually, are associated with MAFLD risk. Public health awareness and strategies should be encouraged to curb MAFLD.
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Affiliation(s)
- Jialu Yang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Shiyun Luo
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Rui Li
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Jingmeng Ju
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Zhuoyu Zhang
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Jichuan Shen
- Department of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou, China
| | - Minying Sun
- Department of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou, China
| | - Jiahua Fan
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Min Xia
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Wei Zhu
- Department of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou, China
| | - Yan Liu
- Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou, China
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
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Zhang H, Wang Y, Chen C, Wang B, Chen J, Tan X, Xia F, Zhang J, Lu Y, Wang N. Non-alcoholic fatty liver disease, sleep behaviors, and incident type 2 diabetes. J Gastroenterol Hepatol 2022; 37:1633-1640. [PMID: 35499342 DOI: 10.1111/jgh.15877] [Citation(s) in RCA: 6] [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: 03/07/2022] [Revised: 04/19/2022] [Accepted: 04/24/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Non-alcoholic fatty liver disease (NAFLD) is associated with incident type 2 diabetes; however, the extent to which NAFLD may confer its risk remains uncertain, especially in Europeans. Emerging evidence suggests that sleep behaviors are linked to NAFLD and diabetes. We aimed to measure whether sleep behaviors modified the association between NAFLD and incident type 2 diabetes. METHODS This prospective cohort study included 365 339 participants without type 2 diabetes at baseline in UK Biobank data. Five sleep behaviors, including sleep duration, insomnia, snoring, chronotype, and daytime sleepiness, were collected from the questionnaire. Overall sleep patterns were created by summing the five scores. Liver steatosis was based on the fatty liver index. RESULTS During a median follow up of 11.0 years, we documented 8774 patients with incident type 2 diabetes. NAFLD was significantly associated with increased diabetes risk. Sleeping 7-8 h/day, no insomnia, no self-reported snoring, and no frequent daytime sleepiness were independently associated with incident type 2 diabetes, with a 20%, 18%, 16%, and 31% lower risk, respectively. About 33.8% and 33.5% of type 2 diabetes events in this cohort could be attributed to NAFLD and poor sleep pattern, respectively. Participants with NAFLD and poor sleep pattern showed the highest risk of type 2 diabetes (relative risk 3.17, 95% confidence interval 2.80, 3.59). Sleep pattern (healthy, intermediate, and poor) did not significantly modify the association between NAFLD and type 2 diabetes. However, when studying separately, we found a significant interaction between NAFLD and insomnia on the risk of incident type 2 diabetes (P for interaction = 0.003). CONCLUSION In this large prospective study, both NAFLD and some sleep behaviors were risk factors for type 2 diabetes. Although overall sleep pattern did not modify the association between NAFLD and type 2 diabetes, certain sleep behavior, especially insomnia, showed the modification effect.
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Affiliation(s)
- Haojie Zhang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Yuying Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Chi Chen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Bin Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Jie Chen
- Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Xiao Tan
- Department of Neuroscience, Uppsala University, Uppsala, Sweden
- Department of Clinical Neuroscience, Karolinska Institute, Solna, Sweden
| | - Fangzhen Xia
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Jihui Zhang
- Guangdong Mental Health Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yingli Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Ningjian Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
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Fan H, Liu Z, Zhang X, Yuan H, Zhao X, Zhao R, Shi T, Wu S, Xu Y, Suo C, Chen X, Zhang T. Investigating the Association Between Seven Sleep Traits and Nonalcoholic Fatty Liver Disease: Observational and Mendelian Randomization Study. Front Genet 2022; 13:792558. [PMID: 35656325 PMCID: PMC9152285 DOI: 10.3389/fgene.2022.792558] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 03/28/2022] [Indexed: 11/13/2022] Open
Abstract
Background and Aim: Aberrant sleep parameters are associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, existing information is inconsistent among studies and involves reverse causation. Therefore, we aimed to investigate the observational associations and causations between sleep traits and NAFLD. Methods: We performed multivariable regression to assess observational associations of seven sleep traits (sleep duration, easiness of getting up in the morning, chronotype, nap during day, snoring, insomnia, and narcolepsy), and NAFLD in the UK Biobank (1,029 NAFLD). The Cox proportional hazards model was applied to derive hazard ratios and 95% confidence intervals (CIs). Furthermore, a bidirectional two-sample Mendelian randomization (MR) approach was used to explore the causal relationships between sleep traits and NAFLD. Results: In the multivariable regression model adjusted for potential confounders, getting up in the morning not at all easy (HR, 1.51; 95% CI, 1.27-1.78) and usually insomnia (HR, 1.46; 95% CI, 1.21-1.75) were associated with the risk of NAFLD. Furthermore, the easiness of getting up in the morning and insomnia showed a dose-response association with NAFLD (Ptrend <0.05). MR analysis found consistent causal effects of NAFLD on easiness of getting up in the morning (OR, 0.995; 95% CI, 0.990-0.999; p = 0.033) and insomnia (OR, 1.006; 95% CI, 1.001-1.011; p = 0.024). These results were robust to weak instrument bias, pleiotropy, and heterogeneity. Conclusions: Findings showed consistent evidence of observational analyses and MR analyses that trouble getting up in the morning and insomnia were associated with an increased risk of NAFLD. Bidirectional MR demonstrated causal effects of NAFLD on sleep traits.
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Affiliation(s)
- Hong Fan
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Zhenqiu Liu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
| | - Xin Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Huangbo Yuan
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Xiaolan Zhao
- Department of Chronic Diseases Prevention, Taizhou Center for Disease Control and Prevention, Jiangsu, China
| | - Renjia Zhao
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tingting Shi
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Sheng Wu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Yiyun Xu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Chen Suo
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Xingdong Chen
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China.,State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.,Department of Chronic Diseases Prevention, Taizhou Center for Disease Control and Prevention, Jiangsu, China.,Human Phenome Institute, Fudan University, Shanghai, China
| | - Tiejun Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China.,Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, China.,Fudan University Taizhou Institute of Health Sciences, Taizhou, China
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16
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McCarthy M, Murphy P, Rosenberg R, Orford C. The overlooked vital sign: The importance of measuring sleep in drug development studies. Drug Discov Today 2021; 27:690-696. [PMID: 34896625 DOI: 10.1016/j.drudis.2021.12.003] [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: 06/01/2021] [Revised: 08/30/2021] [Accepted: 12/04/2021] [Indexed: 11/26/2022]
Abstract
Sleep is rarely considered in drug development studies. Pre-existing sleep problems or changes in sleep parameters in response to therapeutics have the potential to diminish the true utility of the agent under development. Sleep is integral to human health and affects virtually every disease. We present evidence that indicates how sleep quality and quantity can be predictive of disease risk, progression, remission, and recurrence. Supporting the premise that we should conceptualize sleep as a 'vital sign' and measure sleep as an integral component in drug development. We highlight the emergence of digital health technologies that have enabled the capture of this 'vital sign' and ask the question: why is sleep still largely ignored in drug development studies?
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17
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Cerebrovascular alterations in NAFLD: Is it increasing our risk of Alzheimer's disease? Anal Biochem 2021; 636:114387. [PMID: 34537182 DOI: 10.1016/j.ab.2021.114387] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/27/2021] [Accepted: 09/15/2021] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease, which has been classified as an emerging epidemic not only confined to liver-related morbidity and mortality. It is also becoming apparent that NAFLD is associated with moderate cerebral dysfunction and cognitive decline. A possible link between NAFLD and Alzheimer's disease (AD) has only recently been proposed due to the multiple shared genes and pathological mechanisms contributing to the development of these conditions. Although AD is a progressive neurodegenerative disease, the exact pathophysiological mechanism remains ambiguous and similarly to NAFLD, currently available pharmacological therapies have mostly failed in clinical trials. In addition to the usual suspects (inflammation, oxidative stress, blood-brain barrier alterations and ageing) that could contribute to the NAFLD-induced development and progression of AD, changes in the vasculature, cerebral perfusion and waste clearance could be the missing link between these two diseases. Here, we review the most recent literature linking NAFLD and AD, focusing on cerebrovascular alterations and the brain's clearance system as risk factors involved in the development and progression of AD, with the aim of promoting further research using neuroimaging techniques and new mechanism-based therapeutic interventions.
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Chu X, Liu L, Ye J, Wen Y, Li P, Cheng B, Cheng S, Zhang L, Qi X, Ma M, Liang C, Kafle OP, Wu C, Wang S, Wang X, Ning Y, Zhang F. Insomnia affects the levels of plasma bilirubin and protein metabolism: an observational study and GWGEIS in UK Biobank cohort. Sleep Med 2021; 85:184-190. [PMID: 34343768 DOI: 10.1016/j.sleep.2021.05.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/11/2021] [Accepted: 05/31/2021] [Indexed: 10/21/2022]
Abstract
STUDY OBJECTIVES We aim to explore the mechanism of relationship between insomnia and liver metabolism by examining the gene × insomnia interactions. METHODS Individual level genotypic and phenotypic data were obtained from the UK Biobank cohort. Regression analysis was first conducted to test the association of insomnia with plasma total bilirubin (TBil; n = 186,793), direct bilirubin (DBil; n = 159,854) and total protein (TP; n = 171,574) in UK Biobank cohort. Second, genome-wide gene-environment interaction study (GWGEIS) was conducted by PLINK 2.0, and FUMA platform was used to identify enriched pathway terms. RESULTS In UK Biobank cohort, we found that TP (P < 2.00 × 10-16), DBil (P = 1.72 × 10-3) and TBil (P = 3.38 × 10-5) were significantly associated with insomnia. GWGEIS of both DBil and TBil observed significant G × INSOMNIA effects between insomnia and UDP Glucuronosyltransferase Family 1 (rs6431558, P = 6.26 × 10-11) gene. GWGEIS of TP also detected several significant genes interacting with insomnia, such as KLF15, (rs70940816, P = 6.77 × 10-10) and DOK7, (rs2344205, P = 1.37 × 10-9). Multiple gene ontology (GO) terms were identified for bilirubin, such as GO_URONIC_ACID_METABOLIC_PROCESS (adjusted P = 4.15 × 10-26). CONCLUSION Our study results suggested negative associations between insomnia and DBil and TBil; and a positive association between insomnia and TP.
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Affiliation(s)
- Xiaomeng Chu
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Li Liu
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Jing Ye
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Yan Wen
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Ping Li
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Bolun Cheng
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Shiqiang Cheng
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Lu Zhang
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Xin Qi
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Mei Ma
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Chujun Liang
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Om Prakash Kafle
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Cuiyan Wu
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Sen Wang
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Xi Wang
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Yujie Ning
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Feng Zhang
- Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
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Zhang Y, Yang G, Wang X, Ni G, Cui Z, Yan Z. Sagittaria trifolia tuber: bioconstituents, processing, products, and health benefits. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2021; 101:3085-3098. [PMID: 33270242 DOI: 10.1002/jsfa.10977] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 11/12/2020] [Accepted: 12/03/2020] [Indexed: 06/12/2023]
Abstract
Sagittaria trifolia is an aquatic plant that is distributed worldwide. The edible tuber part of S. trifolia is a very common and popular vegetable in China. The aim of the present review is to discuss the discovery of nutraceuticals from S. trifolia tuber by reviewing its major constituents, food processing, food products, and health-promoting benefits. Sagittaria trifolia tuber comprises a series of nutritional and bioactive constituents, including dietary fibers, amino acids, minerals, starches, non-starch polysaccharides, diterpenoids, colchicine, phenols, and organic acids. Food processing affects its flavor, biocomponents, and bioactivity. Numerous S. trifolia tuber-based food products and nutraceuticals have been developed, but new categories of products and the anticipated functions still need to be explored. The non-starch polysaccharides could be the central ingredients that contribute to the plant's antioxidant, hepatoprotective, hypoglycemic, lipid-regulating, and immunostimulatory properties. Of these, antioxidant and hepatoprotective effects have been thoroughly investigated. Procedures for the extraction and purification of polysaccharides influence their health-promoting actions. Overall, S. trifolia tuber is an underutilized aquatic vegetable species that is an emerging subject for nutraceutical research. © 2020 Society of Chemical Industry.
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Affiliation(s)
- Yang Zhang
- School of Biology and Food Engineering, Changshu Institute of Technology, Changshu, China
| | - Guihong Yang
- School of Biology and Food Engineering, Changshu Institute of Technology, Changshu, China
| | - Xinyu Wang
- School of Biology and Food Engineering, Changshu Institute of Technology, Changshu, China
| | - Gaoyang Ni
- School of Biology and Food Engineering, Changshu Institute of Technology, Changshu, China
| | - Zhumei Cui
- School of Biology and Food Engineering, Changshu Institute of Technology, Changshu, China
| | - Zhaowei Yan
- Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, China
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20
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Shah NM, Malhotra AM, Kaltsakas G. Sleep disorder in patients with chronic liver disease: a narrative review. J Thorac Dis 2020; 12:S248-S260. [PMID: 33214928 PMCID: PMC7642630 DOI: 10.21037/jtd-cus-2020-012] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Sleep disturbance is a common feature of chronic liver disease (CLD) with impact on health-related quality of life; 60-80% of patients with CLD report subjective poor sleep; frequent presentations of sleep disturbance include insomnia, reduced sleep efficiency, increased sleep latency, reduced time in rapid eye movement (REM) sleep, restless leg syndrome and excessive daytime sleepiness (EDS). Key contributors to sleep disturbance include hepatic encephalopathy (HE) and circadian rhythm imbalance due to altered melatonin metabolism. Specific conditions causing CLD, such as non-alcoholic fatty liver disease (NAFLD), chronic viral hepatitis and primary biliary cholangitis (PBC) result in different types of sleep disturbance, and the treatment of these conditions can often also lead to sleep disturbance. There are currently limited management options for sleep disturbance in CLD. Obstructive sleep apnoea (OSA) is a common condition that causes chronic intermittent hypoxia due to airway collapse during sleep. This chronic intermittent hypoxia appears to contribute to the development of NAFLD. The presence of reactive oxygen species and the overexpression of hypoxia inducible factor 1-alpha secondary to hypoxia may be responsible for the second 'hit' of the 'two-hit' hypothesis of NAFLD. Treatment of the intermittent hypoxia with continuous positive airway pressure therapy has limited efficacy against liver dysfunction. There remain many outstanding areas of investigation in the management of sleep disturbance in CLD, and of liver dysfunction in OSA.
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Affiliation(s)
- Neeraj Mukesh Shah
- Lane Fox Respiratory Service, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Lane Fox Clinical Respiratory Physiology Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Centre for Human and Applied Physiological Sciences (CHAPS), King's College London, London, UK
| | - Akanksha Mimi Malhotra
- Lane Fox Respiratory Service, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Georgios Kaltsakas
- Lane Fox Respiratory Service, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Lane Fox Clinical Respiratory Physiology Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Centre for Human and Applied Physiological Sciences (CHAPS), King's College London, London, UK
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21
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Ge L, Guyatt G, Tian J, Pan B, Chang Y, Chen Y, Li H, Zhang J, Li Y, Ling J, Yang K. Insomnia and risk of mortality from all-cause, cardiovascular disease, and cancer: Systematic review and meta-analysis of prospective cohort studies. Sleep Med Rev 2019; 48:101215. [PMID: 31630016 DOI: 10.1016/j.smrv.2019.101215] [Citation(s) in RCA: 106] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 09/05/2019] [Accepted: 09/10/2019] [Indexed: 12/15/2022]
Abstract
Growing evidence indicates that insomnia may be associated with mortality. However, these findings have been inconsistent. We systematically searched MEDLINE and EMBASE to identify prospective cohort studies that assessed the association between insomnia disorder/individual insomnia symptoms and the risk of mortality among adults aged ≥18 yrs. We addressed this association using summary hazard ratios (HRs) and 95% confidence intervals (CIs) calculated using random-effects meta-analysis, and the GRADE approach to rate the certainty of evidence. Twenty-nine cohorts including 1,598,628 individuals (55.3% men; mean age 63.7 yrs old) with a median follow-up duration of 10.5 yrs proved eligible. Difficulty falling asleep (DFA) and non-restorative sleep (NRS) were associated with an increased risk of all-cause mortality (DFA: HR = 1.13, 95%CI 1.03 to 1.23, p = 0.009, moderate certainty; NRS: HR = 1.23, 95%CI 1.07 to 1.42, p = 0.003, high certainty) and cardiovascular disease mortality (DFA: 1.20, 95%CI: 1.01, 1.43; p = 0.04, moderate certainty; NRS: HR = 1.48, 95%CI 1.06 to 2.06, p = 0.02, moderate certainty). Convincing associations between DFA and all-cause mortality were restricted to the mid to older-aged population (moderate credibility). Insomnia disorder, difficulty maintaining sleep, and early morning awakening proved to be unassociated with all-cause and cardiovascular disease mortality. No insomnia symptoms proved to be associated with cancer-related mortality.
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Affiliation(s)
- Long Ge
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, 730000, China; Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China; Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, 730000, China; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, L8S 4L8, Canada; Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Gordon Guyatt
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, L8S 4L8, Canada
| | - Jinhui Tian
- Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China; Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, 730000, China
| | - Bei Pan
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Yaping Chang
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, L8S 4L8, Canada
| | - Yajing Chen
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Huijuan Li
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Junmei Zhang
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Yahong Li
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Juan Ling
- Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China; Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, 730000, China
| | - Kehu Yang
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou, 730000, China; Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China; Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, 730000, China.
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22
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Jiang T, Chen X, Xia C, Liu H, Yan H, Wang G, Wu Z. Association between Helicobacter pylori infection and non-alcoholic fatty liver disease in North Chinese: a cross-sectional study. Sci Rep 2019; 9:4874. [PMID: 30890750 PMCID: PMC6425019 DOI: 10.1038/s41598-019-41371-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 03/07/2019] [Indexed: 12/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. Previous studies on the association between Helicobacter pylori (HP) infection and NAFLD are inconsistent. Our study was aimed to find out the relationship between HP infection and NAFLD. We performed a large cross-sectional study in northern Chinese adults in 2015. 13C-urea breath tests were used to determine HP infection status. Abdominal ultrasonography was performed to diagnose NAFLD. Multivariable logistic regression was conducted to identify the association between HP infection and NAFLD. A total of 4081 individuals were included in this study; 2137 (52.36%) participants were HP-positive, and 1022 (47.82%) were diagnosed with NAFLD in HP-positive individuals. The odds ratios (OR) and 95% confidence intervals (CI) of participants with HP infection for NAFLD were 1.20 (1.06–1.36) in crude model and 1.27 (1.07–1.50) in fully adjusted model. When stratified by sex and dyslipidemia, the fully adjusted OR and 95% CI for NAFLD were 1.22 (1.10–1.80) in females and 1.44 (1.18–1.75) in subjects with dyslipidemia. There were not significant increased OR for NAFLD when stratified by age. The study indicate that HP infection is associated with NAFLD, particularly in females and patients with dyslipidemia, suggesting that HP eradication might be an alternative method for the prevention or treatment of NAFLD treatment.
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Affiliation(s)
- Tian Jiang
- Research Center for Translational Medicine, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, 317500, Zhejiang, China
| | - Xia Chen
- Department of Gastroenterology, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, 317500, Zhejiang, China
| | - Chenmei Xia
- Department of Gastroenterology, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, 317500, Zhejiang, China
| | - Huamin Liu
- School of Public Health, Taishan Medical University, Tai'an, 271000, China
| | - Haifan Yan
- Department of Gastroenterology, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, 317500, Zhejiang, China
| | - Guoping Wang
- Department of Gastroenterology, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, 317500, Zhejiang, China
| | - Zhongbiao Wu
- Department of Urology, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, 317500, Zhejiang, China.
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23
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Nutraceutical Approach to Non-Alcoholic Fatty Liver Disease (NAFLD): The Available Clinical Evidence. Nutrients 2018; 10:nu10091153. [PMID: 30142943 PMCID: PMC6163782 DOI: 10.3390/nu10091153] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Revised: 08/15/2018] [Accepted: 08/21/2018] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a clinical condition characterized by lipid infiltration of the liver, highly prevalent in the general population affecting 25% of adults, with a doubled prevalence in diabetic and obese patients. Almost 1/3 of NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), and this can lead to fibrosis and cirrhosis of the liver. However, the main causes of mortality of patients with NAFLD are cardiovascular diseases. At present, there are no specific drugs approved on the market for the treatment of NAFLD, and the treatment is essentially based on optimization of lifestyle. However, some nutraceuticals could contribute to the improvement of lipid infiltration of the liver and of the related anthropometric, haemodynamic, and/or biochemical parameters. The aim of this paper is to review the available clinical data on the effect of nutraceuticals on NAFLD and NAFLD-related parameters. Relatively few nutraceutical molecules have been adequately studied for their effects on NAFLD. Among these, we have analysed in detail the effects of silymarin, vitamin E, vitamin D, polyunsaturated fatty acids of the omega-3 series, astaxanthin, coenzyme Q10, berberine, curcumin, resveratrol, extracts of Salvia milthiorriza, and probiotics. In conclusion, Silymarin, vitamin E and vitamin D, polyunsaturated fatty acids of the omega-3 series, coenzyme Q10, berberine and curcumin, if well dosed and administered for medium–long periods, and associated to lifestyle changes, could exert positive effects on NAFLD and NAFLD-related parameters.
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