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Kim A, Jeon E, Lee H, Heo H, Woo K. Risk factors for prediabetes in community-dwelling adults: A generalized estimating equation logistic regression approach with natural language processing insights. Res Nurs Health 2024; 47:620-634. [PMID: 38961672 DOI: 10.1002/nur.22413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 05/11/2024] [Accepted: 06/22/2024] [Indexed: 07/05/2024]
Abstract
The global prevalence of prediabetes is expected to reach 8.3% (587 million people) by 2045, with 70% of people with prediabetes developing diabetes during their lifetimes. We aimed to classify community-dwelling adults with a high risk for prediabetes based on prediabetes-related symptoms and to identify their characteristics, which might be factors associated with prediabetes. We analyzed homecare nursing records (n = 26,840) of 1628 patients aged over 20 years. Using a natural language processing algorithm, we classified each nursing episode as either low-risk or high-risk for prediabetes based on the detected number and category of prediabetes-symptom words. To identify differences between the risk groups, we employed t-tests, chi-square tests, and data visualization. Risk factors for prediabetes were identified using multiple logistic regression models with generalized estimating equations. A total of 3270 episodes (12.18%) were classified as potentially high-risk for prediabetes. There were significant differences in the personal, social, and clinical factors between groups. Results revealed that female sex, age, cancer coverage as part of homecare insurance coverage, and family caregivers were significantly associated with an increased risk of prediabetes. Although prediabetes is not a life-threatening disease, uncontrolled blood glucose can cause unfavorable outcomes for other major diseases. Thus, medical professionals should consider the associated symptoms and risk factors of prediabetes. Moreover, the proposed algorithm may support the detection of individuals at a high risk for prediabetes. Implementing this approach could facilitate proactive monitoring and early intervention, leading to reduced healthcare expenses and better health outcomes for community-dwelling adults.
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Affiliation(s)
- Aeri Kim
- College of Nursing, Seoul National University, Seoul, South Korea
| | - Eunjoo Jeon
- Technology Research, Samsung SDS, Seoul, South Korea
| | - Hana Lee
- College of Nursing, Seoul National University, Seoul, South Korea
| | - Hyunsook Heo
- Seoul National University Hospital, Seoul, South Korea
| | - Kyungmi Woo
- College of Nursing, Seoul National University, Seoul, South Korea
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Cao L, An Y, Liu H, Jiang J, Liu W, Zhou Y, Shi M, Dai W, Lv Y, Zhao Y, Lu Y, Chen L, Xia Y. Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis. BMC Med 2024; 22:101. [PMID: 38448943 PMCID: PMC10919055 DOI: 10.1186/s12916-024-03315-0] [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: 08/01/2023] [Accepted: 02/23/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.
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Affiliation(s)
- Limin Cao
- The Third Central Hospital of Tianjin, Tianjin, China
| | - Yu An
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Huiyuan Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Jinguo Jiang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Wenqi Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yuhan Zhou
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Mengyuan Shi
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Wei Dai
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yanling Lv
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yuhong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China
| | - Yanhui Lu
- School of Nursing, Peking University, 38 Xueyuan Rd, Haidian District, Beijing, 100191, China.
| | - Liangkai Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Yang Xia
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning, 110004, China.
- Liaoning Key Laboratory of Precision Medical Research On Major Chronic Disease, Liaoning Province, Shenyang, China.
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Chan KE, Ong EYH, Chung CH, Ong CEY, Koh B, Tan DJH, Lim WH, Yong JN, Xiao J, Wong ZY, Syn N, Kaewdech A, Teng M, Wang JW, Chew N, Young DY, Know A, Siddiqui MS, Huang DQ, Tamaki N, Wong VWS, Mantzoros CS, Sanyal A, Noureddin M, Ng CH, Muthiah M. Longitudinal Outcomes Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-analysis of 129 Studies. Clin Gastroenterol Hepatol 2024; 22:488-498.e14. [PMID: 37775028 DOI: 10.1016/j.cgh.2023.09.018] [Citation(s) in RCA: 34] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 08/30/2023] [Accepted: 09/01/2023] [Indexed: 10/01/2023]
Abstract
BACKGROUND & AIMS The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted. METHODS To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated. RESULTS One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD. CONCLUSIONS The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.
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Affiliation(s)
- Kai En Chan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Elden Yen Hng Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Charlotte Hui Chung
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Christen En Ya Ong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Benjamin Koh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Zhen Yu Wong
- Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Margaret Teng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Jiong-Wei Wang
- Department of Surgery, Cardiovascular Research Institute (CVRI), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Nanomedicine Translational Research Programme, Centre for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Nicholas Chew
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Cardiology, National University Heart Centre, National University Hospital, Singapore
| | - Dan Yock Young
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Alfred Know
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, National University Hospital Singapore, Singapore
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Christos S Mantzoros
- Division of Endocrinology, Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts
| | - Arun Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia
| | | | - Cheng Han Ng
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore.
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Andreozzi F, Mancuso E, Mazza E, Mannino GC, Fiorentino TV, Arturi F, Succurro E, Perticone M, Sciacqua A, Montalcini T, Pujia A, Sesti G. One-hour post-load glucose levels are associated with hepatic steatosis assessed by transient elastography. Diabetes Obes Metab 2024; 26:682-689. [PMID: 37953652 DOI: 10.1111/dom.15358] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 10/11/2023] [Accepted: 10/19/2023] [Indexed: 11/14/2023]
Abstract
AIM To examine the association between 1-hour plasma glucose (PG) concentration and markers of non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE). METHODS We performed TE in 107 metabolically well-characterized non-diabetic White individuals. Controlled attenuation parameter (CAP) was used to quantify liver steatosis, while liver stiffness marker (LS) was used to evaluate fibrosis. RESULTS Controlled attenuation parameter correlated significantly with 1-hour PG (r = 0.301, P < 0.01), fasting insulin (r = 0.285, P < 0.01), 2-hour insulin (r = 0.257, P < 0.02), homeostasis model assessment index of insulin resistance (r = 0.252, P < 0.01), high-density lipoprotein cholesterol (r = -0.252, P < 0.02), body mass index (BMI; r = 0.248, P < 0.02) and age (r = 0.212, P < 0.03), after correction for age, sex and BMI. In a multivariable linear regression analysis, 1-hour PG (β = 0.274, P = 0.008) and fasting insulin levels (β = 0.225, P = 0.029) were found to be independent predictors of CAP. After excluding subjects with prediabetes, 1-hour PG was the sole predictor of CAP variation (β = 0.442, P < 0.001). In a logistic regression model, we observed that the group with 1-hour PG ≥ 8.6 mmol/L (155 mg/dL) had a significantly higher risk of steatosis (odds ratio 3.98, 95% confidence interval 1.43-11.13; P = 0.008) than individuals with 1-hour PG < 8.6 mmol/L, after correction for potential confounders. No association was observed between 1-hour PG and LS. CONCLUSION Our data confirm that 1-hour PG ≥ 8.6 mmol/L is associated with higher signs of NAFLD, even among individuals with normal glucose tolerance, categorized as low risk by canonical diagnostic standards. TE is a safe low-impact approach that could be employed for stratifying the risk profile in these patients, with a high level of accuracy.
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Affiliation(s)
- Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
- Research Centre for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elettra Mancuso
- Department of Science of Health, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elisa Mazza
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Gaia Chiara Mannino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Franco Arturi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Elena Succurro
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Maria Perticone
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Tiziana Montalcini
- Research Centre for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
- Department of Clinical and Experimental Medicine, University Magna Greaecia of Catanzaro, Catanzaro, Italy
| | - Arturo Pujia
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
- Research Centre for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy
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Wang M, Zhao Y, He Y, Zhang L, Liu J, Zheng S, Bai Y. The bidirectional relationship between NAFLD and type 2 diabetes: A prospective population-based cohort study. Nutr Metab Cardiovasc Dis 2023; 33:1521-1528. [PMID: 37336719 DOI: 10.1016/j.numecd.2023.05.018] [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: 01/14/2023] [Revised: 05/06/2023] [Accepted: 05/10/2023] [Indexed: 06/21/2023]
Abstract
BACKGROUND AND AIMS To explore the bidirectional relationship between NAFLD and type 2 diabetes and the possible directions of the main effect. METHODS AND RESULTS 30 633 participants from the Jinchang cohort were enrolled. Firstly, cox proportional hazards regression model was used to assess the unidirectional causality between NAFLD and prediabetes and type 2 diabetes. Secondly, cross-lag path analysis model was conducted to estimate the bidirectional relationship between NAFLD and prediabetes and type 2 diabetes, and to determine the direction of the main effects. Finally, potential effect modifications were also considered by age, sex, hyperlipidemia, and overweight/obesity. We found that NAFLD increased the risk of prediabetes and type 2 diabetes with adjusted HR (95%CI) of 1.355(95%CI: 1.255-1.462) and 1.898(95%CI: 1.415-2.545), respectively. Prediabetes and type 2 diabetes also increased the risk of NAFLD, with adjusted HR (95%CI) of 1.245(95%CI: 1.115-1.392) and 1.592(95%CI: 1.373-1.846), respectively. Cross-lag path analysis showed that NAFLD significantly affected the incidence of prediabetes (β = 0.285, P < 0.001), while the effect on type 2 diabetes was not statistically significant. The effect of prediabetes and type 2 diabetes on the risk of NAFLD was weak, and the path coefficients were 0.076 and 0.037, respectively. Stratified analyses showed similar results. CONCLUSION This study provides evidence that there was a bidirectional causal association between NAFLD and type 2 diabetes, and the progression from NAFLD through prediabetes to type 2 diabetes may be the main pathway.
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Affiliation(s)
- Minzhen Wang
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China
| | - Yanan Zhao
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China
| | - Yingqian He
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China
| | - Lulu Zhang
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China
| | - Jing Liu
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China
| | - Shan Zheng
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China.
| | - Yana Bai
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu, China.
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Damtie S, Workineh L, Berhan A, Tiruneh T, Legese B, Getie B, Kiros T, Eyayu T. The magnitude of undiagnosed diabetes mellitus, prediabetes, and associated factors among adults living in Debre Tabor town, northcentral Ethiopia: A community-based cross-sectional study. Heliyon 2023; 9:e17729. [PMID: 37519754 PMCID: PMC10372355 DOI: 10.1016/j.heliyon.2023.e17729] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/21/2023] [Accepted: 06/27/2023] [Indexed: 08/01/2023] Open
Abstract
Background Diabetes mellitus (DM) is a worldwide public health problem. The burden of diabetes has been continuously increasing from day to day, especially in developing countries like Ethiopia. Globally, half of all cases of diabetes mellitus are undiagnosed. Diabetes mellitus can be easily handled if it is detected early. There is limited evidence on the magnitude of undiagnosed diabetics and prediabetes at the community level in Ethiopia, particularly in the study area. Objective To assess the magnitude of undiagnosed diabetes mellitus, prediabetes, and associated factors among adults living in Debre Tabor town. Methods A community-based cross-sectional study was conducted in Debre Tabor town from October to December 2021. A total of 407 participants were selected using a multistage sampling technique. A pretested structural questionnaire was used to collect demographic, behavioral, and clinical data. Anthropometric measurements were taken with standardized and calibrated equipment. A fasting venous blood sample was collected for blood glucose level determination. Logistic regression was used to identify risk factors. A P-value ≤0.05 was considered statistically significant. Result The magnitude of undiagnosed diabetes mellitus and prediabetes was found to be 4.5% (95% CI: 2.9-7.4) and 14.5% (95% CI: 11.1-18.1), respectively. Older age (AOR: 6.50, 95% CI: 1.82-23.21), abnormal body mass index (AOR: 6.84, 95% CI: 1.91-24.54), systolic hypertension (AOR: 8.74, 95% CI: 2.53-30.19), and family history of diabetes mellitus (FHDM) (AOR: 12.45, 95% CI: 3.63-42.65) were significantly associated with undiagnosed diabetes mellitus. Using saturated oil (AOR: 1.97, 95% CI: 1.09-3.55), having a high waist circumference (AOR: 2.16, 95% CI: 1.20-3.87), and being hypertensive (AOR: 2.26, 95% CI: 1.04-4.96) were all significantly associated with Prediabetes. Conclusion Adults in Debre Tabor town have a high prevalence of undiagnosed diabetes and prediabetes. A variety of modifiable risk factors were also identified. As a result, focusing the prevention strategy on such modifiable risk factors may help to minimize the prevalence of undiagnosed diabetes mellitus and prediabetes as well as future disease complications.
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Affiliation(s)
- Shewaneh Damtie
- Corresponding author. Department of Medical Laboratory Science, College of Health Sciences, Debre Tabor University, Ethiopia
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Corbin KD, Pittas AG, Desouza C, Grdinovac KK, Herzig KH, Kashyap SR, Kim SH, Nelson J, Rasouli N, Vickery EM, Knowler WC, Pratley RE. Indices of hepatic steatosis and fibrosis in prediabetes and association with diabetes development in the vitamin D and type 2 diabetes study. J Diabetes Complications 2023; 37:108475. [PMID: 37104979 PMCID: PMC10683797 DOI: 10.1016/j.jdiacomp.2023.108475] [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: 12/12/2022] [Revised: 04/07/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023]
Abstract
AIMS Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity that leads to poor outcomes in people at high risk for development of type 2 diabetes (T2D). Vitamin D is a possible mediator. In the vitamin D and type 2 diabetes study (D2d), we investigated the relationship of baseline indices of NAFLD with incident T2D and whether the effect of vitamin D on diabetes was modified by NAFLD. METHODS Cross-sectional associations of indices of NAFLD with glycemia and vitamin D status were assessed in 3972 individuals screened for the D2d study. In those with prediabetes randomized to vitamin D or placebo (n = 2423), we examined longitudinal associations of NAFLD indices with incident T2D. We used validated non-invasive scores to assess steatosis [(hepatic steatosis index (HSI); NAFLD-liver fat score (NAFLD-LFS)] and advanced fibrosis [fibrosis-4 (FIB-4) index; AST to Platelet Ratio Index (APRI)]. RESULTS Eighty-five percent of screened participants had likely steatosis by HSI and 71 % by NAFLD-LFS; 3 % were likely to have advanced fibrosis by FIB-4 and 1.2 % by APRI. FIB-4 indicated that 20.4 % of individuals require further follow up to assess liver health. Steatosis and fibrosis scores were higher among participants with worse glycemia. The NAFLD-LFS and APRI predicted development of diabetes (hazard ratios [95%CI] 1.35 [1.07, 1.70]; P = 0.012) and 2.36 (1.23, 4.54; P = 0.010), respectively). The effect of vitamin D on diabetes risk was not modified by baseline NAFLD indices. Individuals with likely steatosis had a smaller increase in serum 25-hydroxyvitamin D level in response to vitamin D than those without steatosis. CONCLUSIONS The predicted high prevalence of steatosis, the need for further fibrosis workup, and the relationship between liver health and incident T2D suggest that routine screening with clinically accessible scores may be an important strategy to reduce disease burden.
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Affiliation(s)
- Karen D Corbin
- AdventHealth Translational Research Institute, Orlando, FL, United States of America.
| | | | - Cyrus Desouza
- The University of Nebraska Medical Center and Omaha Veterans Affairs Medical Center, Omaha, NE, United States of America
| | | | - Karl-Heinz Herzig
- Research Unit of Biomedicine and Internal Medicine, Faculty of Medicine, and Medical Research Center, University of Oulu and Oulu University Hospital, 90220 Oulu, Finland; Department of Pediatric Gastroenterology and Metabolic Diseases, Pediatric Institute, Poznan University of Medical Sciences, 60-572 Poznań, Poland
| | | | - Sun H Kim
- Stanford University Medical Center, Stanford, CA, United States of America
| | - Jason Nelson
- Tufts Medical Center, Boston, MA, United States of America
| | - Neda Rasouli
- The University of Colorado School of Medicine, Aurora, CO, United States of America; The Veterans Affairs Eastern Colorado Health Care System, Aurora, CO, United States of America
| | | | - William C Knowler
- National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, United States of America
| | - Richard E Pratley
- AdventHealth Translational Research Institute, Orlando, FL, United States of America.
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Carbinatti T, Régnier M, Parlati L, Benhamed F, Postic C. New insights into the inter-organ crosstalk mediated by ChREBP. Front Endocrinol (Lausanne) 2023; 14:1095440. [PMID: 36923222 PMCID: PMC10008936 DOI: 10.3389/fendo.2023.1095440] [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: 11/11/2022] [Accepted: 01/11/2023] [Indexed: 03/01/2023] Open
Abstract
Carbohydrate response element binding protein (ChREBP) is a glucose responsive transcription factor recognized by its critical role in the transcriptional control of glycolysis and de novo lipogenesis. Substantial advances in the field have revealed novel ChREBP functions. Indeed, due to its actions in different tissues, ChREBP modulates the inter-organ communication through secretion of peptides and lipid factors, ensuring metabolic homeostasis. Dysregulation of these orchestrated interactions is associated with development of metabolic diseases such as type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). Here, we recapitulate the current knowledge about ChREBP-mediated inter-organ crosstalk through secreted factors and its physiological implications. As the liver is considered a crucial endocrine organ, we will focus in this review on the role of ChREBP-regulated hepatokines. Lastly, we will discuss the involvement of ChREBP in the progression of metabolic pathologies, as well as how the impairment of ChREBP-dependent signaling factors contributes to the onset of such diseases.
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9
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Xie Y, Li S, Chen R, He R, Qian L, Zou J, Luo Y, Zhang Y, Ji M, Liu Y. Differences in Insulin Sensitivity, Secretion, and the Metabolic Clearance Rate of Glucose in Newly Diagnosed Type 2 Diabetes Mellitus Patients: The Influences of Body Mass Index and Fatty Liver. Metab Syndr Relat Disord 2022; 20:451-458. [PMID: 36260098 DOI: 10.1089/met.2021.0090] [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] [Indexed: 06/16/2023] Open
Abstract
Background: Obesity and nonalcoholic fatty liver disease are strongly associated with type 2 diabetes mellitus (T2DM), affecting insulin sensitivity and β-cell function. They interact, exacerbating the development of hyperinsulinemia to T2DM. Methods: Through oral glucose tolerance and insulin secretion tests, the relationships between insulin sensitivity and secretion, glucose clearance, body mass index (BMI), and fatty liver were studied in newly diagnosed T2DM patients. The homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-β), insulin sensitivity index (ISI), and metabolic clearance rate (MCR) of glucose were calculated to analyze insulin sensitivity and β-cell function. Results: There were no differences in HOMA-IR, HOMA-β, first-phase insulin secretion (1st PH), second-phase insulin secretion (2nd PH), ISI, or MCR between lean fatty liver and lean nonfatty liver patients. Both overweight/obesity (ow/ob) and patients with fatty liver increased HOMA-IR, and decreased ISI and MCR. In the ow/ob subgroup, patients with fatty liver had severe insulin resistance but greater HOMA-β, 1st PH, and 2nd PH than individuals with nonfatty liver. The difference in MCR between fatty liver and nonfatty liver groups was not significant. Conclusion: BMI and hepatic steatosis are independent determinants of increased insulin resistance and decreased MCR. However, it is steatosis, not BMI, related to the increase in insulin secretion.
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Affiliation(s)
- Yuan Xie
- Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, P.R. China
| | - Shaoqing Li
- Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, P.R. China
| | - Rourou Chen
- Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, P.R. China
| | - Rongbo He
- Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, P.R. China
| | - Li Qian
- Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, P.R. China
| | - Jing Zou
- Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, P.R. China
| | - Yan Luo
- Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, P.R. China
| | - Ying Zhang
- Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, P.R. China
| | - Minjun Ji
- Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Center for global health, Nanjing Medical University, Nanjing, P.R. China
| | - Yu Liu
- Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, P.R. China
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10
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Kolluru K, Giri A, Kumar S, Acharya S, Agrawal S, Wanjari A, Gaidhane SA. Association of Metabolic-Associated Fatty Liver Disease With Various Anthropometric Parameters in Pre-diabetes in Comparison With Diabetes and Control: A Single Tertiary Care Center Study. Cureus 2022; 14:e27130. [PMID: 36004015 PMCID: PMC9392852 DOI: 10.7759/cureus.27130] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 07/21/2022] [Indexed: 11/17/2022] Open
Abstract
Introduction Individuals with pre-diabetes and metabolic-associated fatty liver disease (MAFLD) have an increased risk of developing diabetes mellitus (type-2) when compared with individuals with pre-diabetes without MAFLD. Patients with any of the components of metabolic syndrome should be screened for the risk of MAFLD, as all its components are well correlated with the degree of liver fat content. In this research article, we have highlighted the association of MAFLD with various anthropometric parameters in pre-diabetes as compared to diabetes and normal individual. Methods In this cross-sectional study a total of 356 patients more than 18 years of age who meet the criteria for diabetes and pre-diabetes according to WHO, were enrolled. Anthropometric indices like body mass index (BMI), waist-hip ratio, waist to height ratio, and neck circumference were recorded. Patients underwent ultrasonography of liver and blood investigations like lipid profile, and liver function tests. Results The prevalence of MAFLD observed in this study was 44.1% in diabetics and 22% in pre-diabetics, compared to 9.2% in healthy controls. The ROC analyses showed that MAFLD predict pre-diabetes using the waist-hip ratio was higher in women compared to men (0.750 and 0.693 respectively). In men, the waist-hip ratio was followed by 0.648 for Neck Circumference, 0.646 for BMI, and 0.635 for waist-to-height ratio respectively, whereas the ROC analyses in women showed that other than waist-hip ratio, no other anthropometric index that had consistently higher AUC value. Conclusion Though there was an association between high BMI, waist-hip ratio, waist to height ratio, and neck circumference with MAFLD in pre-diabetes, it was not strongly associated as in the diabetic group.
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11
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Zambon Azevedo V, Silaghi CA, Maurel T, Silaghi H, Ratziu V, Pais R. Impact of Sarcopenia on the Severity of the Liver Damage in Patients With Non-alcoholic Fatty Liver Disease. Front Nutr 2022; 8:774030. [PMID: 35111794 PMCID: PMC8802760 DOI: 10.3389/fnut.2021.774030] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
An extensive body of the literature shows a strong interrelationship between the pathogenic pathways of non-alcoholic fatty liver disease (NAFLD) and sarcopenia through the muscle-liver-adipose tissue axis. NAFLD is one of the leading causes of chronic liver diseases (CLD) affecting more than one-quarter of the general population worldwide. The disease severity spectrum ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and its complications: end-stage chronic liver disease and hepatocellular carcinoma. Sarcopenia, defined as a progressive loss of the skeletal muscle mass, reduces physical performances, is associated with metabolic dysfunction and, possibly, has a causative role in NAFLD pathogenesis. Muscle mass is a key determinant of the whole-body insulin-mediated glucose metabolism and impacts fatty liver oxidation and energy homeostasis. These mechanisms drive the accumulation of ectopic fat both in the liver (steatosis, fatty liver) and in the muscle (myosteatosis). Myosteatosis rather than the muscle mass per se, seems to be closely associated with the severity of the liver injury. Sarcopenic obesity is a recently described entity which associates both sarcopenia and obesity and may trigger worse clinical outcomes including hepatic fibrosis progression and musculoskeletal disabilities. Furthermore, the muscle-liver-adipose tissue axis has a pivotal role in changes of the body composition, resulting in a distinct clinical phenotype that enables the identification of the "sarcopenic NAFLD phenotype." This review aims to bring some light into the complex relationship between sarcopenia and NAFLD and critically discuss the key mechanisms linking NAFLD to sarcopenia, as well as some of the clinical consequences associated with the coexistence of these two entities: the impact of body composition phenotypes on muscle morphology, the concept of sarcopenic obesity, the relationship between sarcopenia and the severity of the liver damage and finally, the future directions and the existing gaps in the knowledge.
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Affiliation(s)
- Vittoria Zambon Azevedo
- Doctoral School Physiology, Physiopathology and Therapeutics 394, Sorbonne Université, Paris, France
- Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
| | - Cristina Alina Silaghi
- Department of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Thomas Maurel
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
| | - Horatiu Silaghi
- Department of Surgery V, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Vlad Ratziu
- Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
- Sorbonne Université, Paris, France
| | - Raluca Pais
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
- Sorbonne Université, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS 938, Paris, France
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12
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Hüttl M, Markova I, Miklankova D, Zapletalova I, Poruba M, Racova Z, Vecera R, Malinska H. The Beneficial Additive Effect of Silymarin in Metformin Therapy of Liver Steatosis in a Pre-Diabetic Model. Pharmaceutics 2021; 14:pharmaceutics14010045. [PMID: 35056941 PMCID: PMC8780287 DOI: 10.3390/pharmaceutics14010045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 12/17/2021] [Accepted: 12/21/2021] [Indexed: 12/30/2022] Open
Abstract
The combination of plant-derived compounds with anti-diabetic agents to manage hepatic steatosis closely associated with diabetes mellitus may be a new therapeutic approach. Silymarin, a complex of bioactive substances extracted from Silybum marianum, evinces an antioxidative, anti-inflammatory, and hepatoprotective activity. In this study, we investigated whether metformin (300 mg/kg/day for four weeks) supplemented with micronized silymarin (600 mg/kg/day) would be effective in mitigating fatty liver disturbances in a pre-diabetic model with dyslipidemia. Compared with metformin monotherapy, the metformin-silymarin combination reduced the content of neutral lipids (TAGs) and lipotoxic intermediates (DAGs). Hepatic gene expression of enzymes and transcription factors involved in lipogenesis (Scd-1, Srebp1, Pparγ, and Nr1h) and fatty acid oxidation (Pparα) were positively affected, with hepatic lipid accumulation reducing as a result. Combination therapy also positively influenced arachidonic acid metabolism, including its metabolites (14,15-EET and 20-HETE), mitigating inflammation and oxidative stress. Changes in the gene expression of cytochrome P450 enzymes, particularly Cyp4A, can improve hepatic lipid metabolism and moderate inflammation. All these effects play a significant role in ameliorating insulin resistance, a principal background of liver steatosis closely linked to T2DM. The additive effect of silymarin in metformin therapy can mitigate fatty liver development in the pre-diabetic state and before the onset of diabetes.
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Affiliation(s)
- Martina Hüttl
- Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic; (I.M.); (D.M.); (H.M.)
- Correspondence: ; Tel.: +420-261-365-369
| | - Irena Markova
- Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic; (I.M.); (D.M.); (H.M.)
| | - Denisa Miklankova
- Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic; (I.M.); (D.M.); (H.M.)
| | - Iveta Zapletalova
- Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech Republic; (I.Z.); (M.P.); (Z.R.); (R.V.)
| | - Martin Poruba
- Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech Republic; (I.Z.); (M.P.); (Z.R.); (R.V.)
| | - Zuzana Racova
- Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech Republic; (I.Z.); (M.P.); (Z.R.); (R.V.)
| | - Rostislav Vecera
- Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech Republic; (I.Z.); (M.P.); (Z.R.); (R.V.)
| | - Hana Malinska
- Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic; (I.M.); (D.M.); (H.M.)
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13
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Gut microbiota in nonalcoholic fatty liver diseases with and without type-2 diabetes mellitus. Eur J Gastroenterol Hepatol 2021; 33:e548-e554. [PMID: 33795579 DOI: 10.1097/meg.0000000000002140] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS The association between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) is not very well described but gut microbiota composition is mentioned as a risk factor. The present study aimed to characterize the differences of dominant gut microbiota phyla among people with NAFLD as compared to T2DM and control groups. PATIENTS AND METHODS The major bacterial phylum of gut microbiota including Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and total bacteria of 15 NAFLD patients with T2DM, 15 NAFLD patients without T2DM, 15 patients with T2DM, and 20 healthy control subjects were assessed by a quantitative PCR (qPCR). RESULTS NAFLD patients with T2DM had significantly higher BMI, triglyceride level, and total cholesterol level were compared with controls (Pv < 0.05). Bacteroidetes and Firmicutes phyla were significantly low in NAFLD patients with T2DM (Firmicutes, 2.55 ± 2.25, Pv 0/0002 and Bacteroidetes, 1.55 ± 2.29, Pv 0/0007), while the content of Proteobacteria and Actinobacteria was high in NAFLD patients with T2DM group and there were no significant differences between phyla with NAFLD patients with T2DM group (Pv > 0.05). Furthermore, Firmicutes copy number was lower in the separate groups of NAFLD and T2DM as compared to the healthy controls (Pv < 0.05). CONCLUSIONS This study performed gut microbiota for the first time among NAFLD and TDM patients separately and together. This investigation indicated that NAFLD patients with T2DM have a different gut composition in comparison to NAFLD, T2DM alone, which could be associated with disease development.
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14
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Wu N, Yuan F, Yue S, Jiang F, Ren D, Liu L, Bi Y, Guo Z, Ji L, Han K, Yang X, Feng M, Su K, Yang F, Wu X, Lu Q, Li X, Wang R, Liu B, Le S, Shi Y, He G. Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation. Cell Biosci 2021; 11:189. [PMID: 34736535 PMCID: PMC8569968 DOI: 10.1186/s13578-021-00701-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 10/25/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a disorder that extends from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is effectively alleviated by lifestyle intervention. Nevertheless, DNA methylation mechanism underling the effect of environmental factors on NAFLD and NASH is still obscure. The aim of this study was to investigate the effect of exercise and diet intervention in NAFLD and NASH via DNA methylation of GAB2. METHODS Methylation of genomic DNA in human NAFLD was quantified using Infinium Methylation EPIC BeadChip assay after exercise (Ex), low carbohydrate diet (LCD) and exercise plus low carbohydrate diet (ELCD) intervention. The output Idat files were processed using ChAMP package. False discovery rate on genome-wide analysis of DNA methylation (q < 0.05), and cytosine-guanine dinucleotides (CpGs) which are located in promoters were used for subsequent analysis (|Δβ|≥ 0.1). K-means clustering was used to cluster differentially methylated genes according to 3D genome information from Human embryonic stem cell. To quantify DNA methylation and mRNA expression of GRB2 associated binding protein 2 (GAB2) in NASH mice after Ex, low fat diet (LFD) and exercise plus low fat diet (ELFD), MassARRAY EpiTYPER and quantitative reverse transcription polymerase chain reaction were used. RESULTS Both LCD and ELCD intervention on human NAFLD can induce same DNA methylation alterations at critical genes in blood, e.g., GAB2, which was also validated in liver and adipose of NASH mice after LFD and ELFD intervention. Moreover, methylation of CpG units (i.e., CpG_10.11.12) inversely correlated with mRNA expression GAB2 in adipose tissue of NASH mice after ELFD intervention. CONCLUSIONS We highlighted the susceptibility of DNA methylation in GAB2 to ELFD intervention, through which exercise and diet can protect against the progression of NAFLD and NASH on the genome level, and demonstrated that the DNA methylation variation in blood could mirror epigenetic signatures in target tissues of important biological function, i.e., liver and adipose tissue. Trial registration International Standard Randomized Controlled Trial Number Register (ISRCTN 42622771).
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Affiliation(s)
- Na Wu
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Fan Yuan
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Siran Yue
- Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fengyan Jiang
- Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Decheng Ren
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Liangjie Liu
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Bi
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Zhenming Guo
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Lei Ji
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Ke Han
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Xiao Yang
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Mofan Feng
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Kai Su
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Fengping Yang
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Xi Wu
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Qing Lu
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Xingwang Li
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China.,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
| | - Ruirui Wang
- Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Baocheng Liu
- Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shenglong Le
- Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Yi Shi
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China. .,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China.
| | - Guang He
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China. .,Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China.
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15
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Si J, Lee G, You HJ, Joo SK, Lee DH, Ku BJ, Park S, Kim W, Ko G. Gut microbiome signatures distinguish type 2 diabetes mellitus from non-alcoholic fatty liver disease. Comput Struct Biotechnol J 2021; 19:5920-5930. [PMID: 34849196 PMCID: PMC8591343 DOI: 10.1016/j.csbj.2021.10.032] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is closely associated with type 2 diabetes mellitus (T2D), and these two metabolic diseases demonstrate bidirectional influences. The identification of microbiome profiles that are specific to liver injury or impaired glucose metabolism may assist understanding of the role of the gut microbiota in the relationship between NAFLD and T2D. Here, we studied a biopsy-proven Asian NAFLD cohort (n = 329; 187 participants with NAFLD, 101 with NAFLD and T2D, and 41 with neither) and identified Enterobacter, Romboutsia, and Clostridium sensu stricto as the principal taxa associated with the severity of NAFLD and T2D, whereas Ruminococcus and Megamonas were specific to NAFLD. In particular, the taxa that were associated with both severe liver pathology and T2D were also significantly associated with markers of diabetes, such as fasting blood glucose and Hb1Ac. Enterotype analysis demonstrated that participants with NAFLD had a significantly higher proportion of Bacteroides and a lower proportion of Ruminococcus than a Korean healthy twin cohort (n = 756). However, T2D could not be clearly distinguished from NAFLD. Analysis of an independent T2D cohort (n = 185) permitted us to validate the T2D-specific bacterial signature identified in the NAFLD cohort. Functional inference analysis revealed that endotoxin biosynthesis pathways were significantly enriched in participants with NAFLD and T2D, compared with those with NAFLD alone. These findings may assist with the development of effective therapeutic approaches for metabolic diseases that are associated with specific bacterial signatures.
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Key Words
- ALT, alanine aminotransferase
- BMI, body mass index
- Biomarker
- Enterotype
- FBS, fasting blood sugar
- FDR, false discovery rate
- FLI, fatty liver index
- Gut microbiome
- HbA1c, glycosylated hemoglobin
- LDL, low-density lipoprotein
- LPS, lipopolysaccharide
- MaAsLin2, microbiome multivariable association with linear models 2
- NAFL, non-alcoholic fatty liver
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- NASH-CRN, non-alcoholic steatohepatitis clinical research network
- Non-alcoholic fatty liver disease (NAFLD)
- PICRUSt2, phylogenetic investigation of communities by reconstruction of unobserved states 2
- T2D, type 2 diabetes mellitus
- Type 2 diabetes mellitus
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Affiliation(s)
- Jiyeon Si
- Medical Science Research Institute, School of Medicine, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
| | - Giljae Lee
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea
| | - Hyun Ju You
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea
- Institute of Health and Environment, Seoul National University, Seoul 08826, Republic of Korea
| | - Sae Kyung Joo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul 07061, Republic of Korea
| | - Dong Hyeon Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul 07061, Republic of Korea
| | - Bon Jeong Ku
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea
| | - Seoyeon Park
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul 07061, Republic of Korea
| | - GwangPyo Ko
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea
- Center for Human and Environmental Microbiome, Institute of Health and Environment, Seoul National University, Seoul 08826, Republic of Korea
- KoBioLabs, Inc., Seoul 08826, Republic of Korea
- Bio-MAX/N-Bio, Seoul National University, Seoul 08826, Republic of Korea
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García-Escobar E, Valdés S, Soriguer F, Vendrell J, Urrutia-Etxebarria IM, Maldonado-Araque C, Ortega E, Ocón P, Montanya E, Menéndez E, Lago-Sampedro A, González-Frutos T, Gomis R, Goday A, García-Serrano S, Galán-García JL, Castell C, Bordiú E, Badía R, Aguilera-Venegas G, Girbés J, Gaztambide S, Delgado E, Chaves FJ, Castaño L, Calle-Pascual A, Rojo-Martínez G, Franch-Nadal J. Fatty liver index as a predictor for type 2 diabetes in subjects with normoglycemia in a nationwide cohort study. Sci Rep 2021; 11:16453. [PMID: 34385479 PMCID: PMC8361016 DOI: 10.1038/s41598-021-95546-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 07/20/2021] [Indexed: 01/21/2023] Open
Abstract
Our aim was to evaluate whether fatty liver index (FLI) is associated with the risk of type 2 diabetes (T2DM) development within the Spanish adult population and according to their prediabetes status; additionally, to examine its incremental predictive value regarding traditional risk factors. A total of 2260 subjects (Prediabetes: 641 subjects, normoglycemia: 1619 subjects) from the Di@bet.es cohort study were studied. Socio-demographic, anthropometric, clinical data and survey on habits were recorded. An oral glucose tolerance test was performed and fasting determinations of glucose, lipids and insulin were made. FLI was calculated and classified into three categories: Low (< 30), intermediate (30–60) and high (> 60). In total, 143 people developed diabetes at follow-up. The presence of a high FLI category was in all cases a significant independent risk factor for the development of diabetes. The inclusion of FLI categories in prediction models based on different conventional T2DM risk factors significantly increase the prediction power of the models when all the population was considered. According to our results, FLI might be considered an early indicator of T2DM development even under normoglycemic condition. The data also suggest that FLI could provide additional information for the prediction of T2DM in models based on conventional risk factors.
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Affiliation(s)
- E García-Escobar
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain. .,Endocrinology and Nutrition Department, Biomedical Research Institute of Malaga (IBIMA), Regional University Hospital of Malaga, Málaga, Spain.
| | - S Valdés
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Endocrinology and Nutrition Department, Biomedical Research Institute of Malaga (IBIMA), Regional University Hospital of Malaga, Málaga, Spain
| | - F Soriguer
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Endocrinology and Nutrition Department, Biomedical Research Institute of Malaga (IBIMA), Regional University Hospital of Malaga, Málaga, Spain
| | - J Vendrell
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Rovira i Virgili University; Department of Endocrinology and Nutrition, Hospital Universitario Joan XXIII, Institut d'Investigacions Sanitaries Pere Virgili, Tarragona, Spain
| | - I M Urrutia-Etxebarria
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Cruces University Hospital, BioCruces Bizkaia, UPV/EHU, Endo-ERN, Barakaldo, Spain.,Spanish Biomedical Research Network in Rare Diseases (CIBERER), Madrid, Spain
| | - C Maldonado-Araque
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Endocrinology and Nutrition Department, Biomedical Research Institute of Malaga (IBIMA), Regional University Hospital of Malaga, Málaga, Spain
| | - E Ortega
- Department of Endocrinology and Nutrition, August Pi i Sunyer Biomedical Research Institute - IDIBAPS, Hospital Clínic of Barcelona, Barcelona, Spain.,Spanish Biomedical Research Network in Physiopathology of Obesity and Nutrition (CIBEROBN), Barcelona, Spain
| | - P Ocón
- General Laboratory, Regional University Hospital of Malaga, Málaga, Spain
| | - E Montanya
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Bellvitge University Hospital, Barcelona, Spain
| | - E Menéndez
- Spanish Biomedical Research Network in Rare Diseases (CIBERER), Madrid, Spain.,Department of Endocrinology and Nutrition, Central University Hospital of Asturias/University of Oviedo, Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Spain
| | - A Lago-Sampedro
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Endocrinology and Nutrition Department, Biomedical Research Institute of Malaga (IBIMA), Regional University Hospital of Malaga, Málaga, Spain
| | - T González-Frutos
- Cruces University Hospital, BioCruces Bizkaia, UPV/EHU, Endo-ERN, Barakaldo, Spain
| | - R Gomis
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Department of Endocrinology and Nutrition, August Pi i Sunyer Biomedical Research Institute - IDIBAPS, Hospital Clínic of Barcelona, Barcelona, Spain
| | - A Goday
- Spanish Biomedical Research Network in Physiopathology of Obesity and Nutrition (CIBEROBN), Barcelona, Spain.,Endocrinology and Nutrition Department, Hospital del Mar/Medicine Departament, Univeristat Autonoma de Barcelona, Barcelona, Spain
| | - S García-Serrano
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Endocrinology and Nutrition Department, Biomedical Research Institute of Malaga (IBIMA), Regional University Hospital of Malaga, Málaga, Spain
| | - J L Galán-García
- Department of Applied Mathematics, Malaga University, Málaga, Spain
| | - C Castell
- Department of Health, Public Health Agency of Catalonia, Barcelona, Spain
| | - E Bordiú
- Department of Endocrinology and Nutrition, San Carlos University Hospital of Madrid, Madrid, Spain
| | - R Badía
- Endocrinology and Nutrition Department, Biomedical Research Institute of Malaga (IBIMA), Regional University Hospital of Malaga, Málaga, Spain
| | | | - J Girbés
- Diabetes Unit, Hospital Arnau de Vilanova, Valencia, Spain
| | - S Gaztambide
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Cruces University Hospital, BioCruces Bizkaia, UPV/EHU, Endo-ERN, Barakaldo, Spain.,Spanish Biomedical Research Network in Rare Diseases (CIBERER), Madrid, Spain
| | - E Delgado
- Spanish Biomedical Research Network in Rare Diseases (CIBERER), Madrid, Spain.,Department of Endocrinology and Nutrition, Central University Hospital of Asturias/University of Oviedo, Health Research Institute of the Principality of Asturias (ISPA), Oviedo, Spain
| | - F J Chaves
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Genomic and Genetic Diagnosis Unit, Research Foundation of Valencia University Clinical Hospital-INCLIVA, Valencia, Spain
| | - L Castaño
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Cruces University Hospital, BioCruces Bizkaia, UPV/EHU, Endo-ERN, Barakaldo, Spain.,Spanish Biomedical Research Network in Rare Diseases (CIBERER), Madrid, Spain
| | - A Calle-Pascual
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,Department of Endocrinology and Nutrition, San Carlos University Hospital of Madrid, Madrid, Spain
| | - G Rojo-Martínez
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain. .,Endocrinology and Nutrition Department, Biomedical Research Institute of Malaga (IBIMA), Regional University Hospital of Malaga, Málaga, Spain.
| | - J Franch-Nadal
- Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain.,EAP Raval Sud, Catalan Institute of Health, GEDAPS Network, Primary Care, Research Support Unit (IDIAP - Jordi Gol Foundation), Barcelona, Spain
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17
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Sonmez A, Dogru T, Ercin CN, Genc H, Celebi G, Gurel H, Tapan S, Cicek AF, Barcin C, Haymana C, Kirik A, Rizzo M. Betatrophin Levels Are Related to the Early Histological Findings in Nonalcoholic Fatty Liver Disease. Metabolites 2021; 11:425. [PMID: 34203342 PMCID: PMC8306475 DOI: 10.3390/metabo11070425] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 06/17/2021] [Accepted: 06/24/2021] [Indexed: 02/06/2023] Open
Abstract
Betatrophin, a liver hormone, regulates glucose and lipid metabolism. We investigated the betatrophin levels in nonalcoholic fatty liver disease (NAFLD) and searched for any relationship with histological severity and metabolic parameters. Fifty males with NAFLD [Nonalcoholic Steatohepatitis (NASH) (n = 32); non-NASH (n = 18)] and 30 healthy controls were included. Plasma betatrophin was measured by ELISA method. Insulin sensitivity was assessed by HOMA-IR index. Histological features were scored by the semi quantitative classification and combined as the NAFLD activity score (NAS). Betatrophin levels in the non-NASH group were significantly higher than the controls. Betatrophin was positively correlated to the age, waist circumference, total cholesterol, triglycerides, LDL cholesterol, glucose, insulin, HOMA-IR index and gamma glutamyl transpeptidase levels, and negatively correlated to the steatosis and NAS. In the stepwise linear regression analysis, the triglyceride (β = 0.457, p < 0.001), glucose (β = 0.281, p = 0.02) and NAS (β = -0.260, p = 0.03) were the independent determinants of betatrophin. Betatrophin levels are higher in the early stages of NAFLD and tend to decrease when the disease progresses. This could be an important preliminary mechanistic finding to explain the increased frequency of glucose intolerance during the course of NAFLD.
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Affiliation(s)
- Alper Sonmez
- Department of Endocrinology and Metabolism, Gulhane School of Medicine, University of Health Sciences, Ankara 06010, Turkey
| | - Teoman Dogru
- Department of Gastroenterology, School of Medicine, Balikesir University, Cagis, Balikesir 10145, Turkey;
| | - Cemal Nuri Ercin
- Department of Gastroenterology, Gulhane School of Medicine, University of Health Sciences, Ankara 06010, Turkey; (C.N.E.); (G.C.)
| | - Halil Genc
- Department of Gastroenterology, Batigoz Hospital, Balcova, Izmir 35330, Turkey;
| | - Gurkan Celebi
- Department of Gastroenterology, Gulhane School of Medicine, University of Health Sciences, Ankara 06010, Turkey; (C.N.E.); (G.C.)
| | - Hasan Gurel
- Department of Gastroenterology, University of Health Sciences, Samsun Training and Research Hospital, Samsun 55090, Turkey;
| | - Serkan Tapan
- Section of Biochemistry, ENA Laboratory, Ankara 06680, Turkey;
| | - Ali Fuat Cicek
- Department of Pathology, Gulhane School of Medicine, University of Health Sciences, Etlik, Ankara 06010, Turkey;
| | - Cem Barcin
- Department of Cardiology, Gulhane School of Medicine, University of Health Sciences, Ankara 06010, Turkey;
| | - Cem Haymana
- Department of Endocrinology and Metabolism, Gulhane Training and Research Hospital, University of Health Sciences, Ankara 06010, Turkey;
| | - Ali Kirik
- Department of Internal Medicine, School of Medicine, Balikesir University, Cagis, Balikesir 10145, Turkey;
| | - Manfredi Rizzo
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of South Carolina, Columbia, SC 29208, USA;
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90133 Palermo, Italy
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18
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Association of hepatic steatosis derived from ultrasound and quantitative MRI with prediabetes in the general population. Sci Rep 2021; 11:13276. [PMID: 34168217 PMCID: PMC8225774 DOI: 10.1038/s41598-021-92681-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 06/11/2021] [Indexed: 12/23/2022] Open
Abstract
The aim of our study was to investigate the association of hepatic steatosis derived from quantitative ultrasound and magnetic resonance imaging (MRI) with prediabetes in a large population-based study conducted in Northeast Germany. Hepatic steatosis was assessed through transabdominal ultrasound and quantitative MRI. For analysis we included 1622 subjects with MRI who participated in an oral glucose tolerance test and reported no known type 2 diabetes mellitus (T2DM). We classified participants as proposed by the American Diabetes Association: isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT), and undiagnosed T2DM. Regression models were adjusted for age, sex body mass index and alcohol consumption. We observed positive associations of hepatic steatosis with glycated hemoglobin, fasting glucose and insulin, 2-h glucose and insulin, as well as homeostasis model assessment-insulin resistance index. Similarly, individuals having hepatic steatosis as defined by MRI had a higher relative risk ratio (RR) to be in the prediabetes groups i-IFG (RR = 1.6; 95% confidence interval (CI) 1.2; 2.2), i-IGT (RR = 3.3, 95% CI 2.0; 5.6) and IFG + IGT (RR = 2.5, 95% CI 1.6; 3.9) or to have undiagnosed T2DM (RR = 4.8, 95% CI 2.6; 9.0). All associations were attenuated when defining hepatic steatosis by ultrasound. Hepatic steatosis is associated with prediabetes and undiagnosed T2DM in the general population. Quantitative liver MRI revealed stronger associations with prediabetes and undiagnosed T2DM compared to ultrasound, which indicates the higher sensitivity and specificity of MRI to determine hepatic steatosis.
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19
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Evaluation of Beneficial and Adverse Effects of a Diet Supplemented with Schisandrae Fructus Seed Ethanol Extract on Lipid and Glucose Metabolism in Normal and Hypercholesterolemic/Hyperglycemic Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:8858962. [PMID: 33688367 PMCID: PMC7920717 DOI: 10.1155/2021/8858962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 12/01/2020] [Accepted: 01/21/2021] [Indexed: 11/17/2022]
Abstract
Schisandrae Fructus (SF), the fruit of Schisandra chinensis (Turcz.) Baillon, has been used for the treatment of liver injury and metabolism-related disorders in China. The objective of this study was to investigate the effects of supplementation with ethanol extract of SF seed (EtSF-S) on serum/hepatic lipid and glucose levels as well as fecal total cholesterol (TC) contents in mice fed a normal diet (ND) or high-fat/fructose diet (HFFD) containing 15% lard oil and 15% fructose. Female ICR mice (18–20 g in body weight) were fed with ND or HFFD for 3 months, and then EtSF-S was added to both chow diets at increasing concentrations of 1, 5, and 10% (w/w). Thirty days later, serum and hepatic lipids, including TC, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucose, were measured. Dietary supplementation with EtSF-S reduced hepatic TC (36 and 18%) and TG levels (38 and 28%) and increased serum HDL/LDL ratio (16 and 26%) in both ND- and HFFD-fed mice, respectively. Moreover, supplementation with EtSF-S elevated serum HDL (31%) in HFFD-fed mice and reduced serum LDL (27%) in ND-fed mice. EtSF-S treatment reduced fat mass (40%) in ND-fed mice and increased fecal TC contents (33%) in HFFD-fed mice. EtSF-S supplementation decreased hepatic glucose contents (29%) in both ND- and HFFD-fed mice. However, diet supplemented with EtSF-S elevated serum TG levels (up to 123%) and hepatic size (28%), but more importantly, suppressed the body weight gain (approximately 130%) in mice fed with HFFD. These findings suggested that dietary supplementation with EtSF-S as natural herbal function food may be a useful strategy for the treatment of patients with fatty liver disease or overweight without a high intake of sugar and fat.
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20
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Caserza L, Casula M, Elia E, Bonaventura A, Liberale L, Bertolotto M, Artom N, Minetti S, Contini P, Verzola D, Pontremoli R, Viazzi F, Viviani GL, Bertolini S, Pende A, Pisciotta L, Montecucco F, Carbone F. Serum osteopontin predicts glycaemic profile improvement in metabolic syndrome: A pilot study. Eur J Clin Invest 2021; 51:e13403. [PMID: 32918277 DOI: 10.1111/eci.13403] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/06/2020] [Accepted: 08/15/2020] [Indexed: 12/27/2022]
Abstract
Prediabetes is often observed in patients with Metabolic Syndrome (MetS) and might be associated with metabolic and inflammatory alterations. Here, we investigated whether the inflammatory molecule osteopontin (OPN) might have a prognostic impact in a cohort of MetS patients (n = 85) with baseline normal glycaemia or impaired fasting glucose (IFG) over one year of recommended pharmacological treatments and Mediterranean diet. Patients were then followed up for 12 months with intermediate evaluation after 6 months. At all time points, anthropometric and clinical data were recorded, alongside with haematological and biochemical profiles, including serum concentrations of OPN. As expected, Mediterranean diet improves glycaemic profile in patients with IFG. Baseline serum OPN failed to be associated with baseline anthropometric or biochemical variables. At baseline, higher levels of OPN were shown in patients with IFG as compared to normal glycaemia. Two distinct subgroups of patients in whom OPN decreased or remained stable/increased at follow-up were identified. When higher serum OPN levels were observed at baseline, greater reduction was observed at 1-year follow-up. Reduction in circulating OPN levels was associated with metabolic improvement in terms of blood pressure, LDL-c, HDL-c, and glycaemia. At both univariate and adjusted logistic regression analyses, serum OPN emerged as an independent predictor of glycaemic profile improvement at 1-year follow-up (adjOR 1.05 [1.00-1.10]; P = .041). In conclusion, pharmacological and dietetic interventions improved glycaemic profile in patients with MetS. In particular, glycaemic improvement was demonstrated in patients who also reduce circulating OPN levels. Higher OPN levels at baseline predict normalization of glycaemic profile.
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Affiliation(s)
- Lara Caserza
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Matteo Casula
- Division of Cardiology, Department of Internal Medicine, Turin, Italy
| | - Edorado Elia
- Division of Cardiology, Department of Internal Medicine, Turin, Italy
| | - Aldo Bonaventura
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.,Department of Internal Medicine, Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA, USA
| | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.,Center for Molecular Cardiology, University of Zürich, Switzerland
| | - Maria Bertolotto
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Nathan Artom
- Department of Internal Medicine, Ospedale S. Paolo di Savona, Savona, Italy
| | - Silvia Minetti
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Paola Contini
- Department of Internal Medicine, University of Genoa, Genoa, Italy.,IRCCS Ospedale Policlinico San Martino Genoa, Genoa, Italy
| | - Daniela Verzola
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Roberto Pontremoli
- Department of Internal Medicine, University of Genoa, Genoa, Italy.,IRCCS Ospedale Policlinico San Martino Genoa, Genoa, Italy
| | - Franesca Viazzi
- Department of Internal Medicine, University of Genoa, Genoa, Italy.,IRCCS Ospedale Policlinico San Martino Genoa, Genoa, Italy
| | | | | | - Aldo Pende
- Department of Internal Medicine, University of Genoa, Genoa, Italy.,IRCCS Ospedale Policlinico San Martino Genoa, Genoa, Italy
| | - Livia Pisciotta
- Department of Internal Medicine, University of Genoa, Genoa, Italy.,IRCCS Ospedale Policlinico San Martino Genoa, Genoa, Italy
| | - Fabrizio Montecucco
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Italy.,Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), First Clinic of Internal Medicine, University of Genoa, Genoa, Italy
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.,IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Italy
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21
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Cha DI, Kang TW, Min JH, Joo I, Sinn DH, Ha SY, Kim K, Lee G, Yi J. Deep learning-based automated quantification of the hepatorenal index for evaluation of fatty liver by ultrasonography. Ultrasonography 2021; 40:565-574. [PMID: 33966363 PMCID: PMC8446496 DOI: 10.14366/usg.20179] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 02/24/2021] [Indexed: 12/19/2022] Open
Abstract
PURPOSE The aim of this study was to develop and validate a fully-automatic quantification of the hepatorenal index (HRI) calculated by a deep convolutional neural network (DCNN) comparable to the interpretations of radiologists experienced in ultrasound (US) imaging. METHODS In this retrospective analysis, DCNN-based organ segmentation with Gaussian mixture modeling for automated quantification of the HRI was developed using abdominal US images from a previous study. For validation, 294 patients who underwent abdominal US examination before living-donor liver transplantation were selected. Interobserver agreement for the measured brightness of the liver and kidney and the calculated HRI were analyzed between two board-certified radiologists and DCNN using intraclass correlation coefficients (ICCs). RESULTS Most patients had normal (n=95) or mild (n=198) fatty liver. The ICCs of hepatic and renal brightness measurements and the calculated HRI between the two radiologists were 0.892 (95% confidence interval [CI], 0.866 to 0.913), 0.898 (95% CI, 0.873 to 0.918), and 0.681 (95% CI, 0.615 to 0.738) for the first session and 0.920 (95% CI, 0.901 to 0.936), 0.874 (95% CI, 0.844 to 0.898), and 0.579 (95% CI, 0.497 to 0.650) for the second session, respectively; the results ranged from moderate to excellent agreement. Using the same task, the ICCs of the hepatic and renal measurements and the calculated HRI between the average values of the two radiologists and DCNN were 0.919 (95% CI, 0.899 to 0.935), 0.916 (95% CI, 0.895 to 0.932), and 0.734 (95% CI, 0.676 to 0.782), respectively, showing high to excellent agreement. CONCLUSION Automated quantification of HRI using DCNN can yield HRI measurements similar to those obtained by experienced radiologists in patients with normal or mild fatty liver.
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Affiliation(s)
- Dong Ik Cha
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae Wook Kang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Hye Min
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang Yun Ha
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyunga Kim
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
| | - Gunwoo Lee
- Medical Imaging R&D Group, Health & Medical Equipment Business, Samsung Electronics Co., Ltd., Seoul, Korea
| | - Jonghyon Yi
- Medical Imaging R&D Group, Health & Medical Equipment Business, Samsung Electronics Co., Ltd., Seoul, Korea
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23
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León-Mimila P, Villamil-Ramírez H, Li XS, Shih DM, Hui ST, Ocampo-Medina E, López-Contreras B, Morán-Ramos S, Olivares-Arevalo M, Grandini-Rosales P, Macías-Kauffer L, González-González I, Hernández-Pando R, Gómez-Pérez F, Campos-Pérez F, Aguilar-Salinas C, Larrieta-Carrasco E, Villarreal-Molina T, Wang Z, Lusis AJ, Hazen SL, Huertas-Vazquez A, Canizales-Quinteros S. Trimethylamine N-oxide levels are associated with NASH in obese subjects with type 2 diabetes. DIABETES & METABOLISM 2020; 47:101183. [PMID: 32791310 DOI: 10.1016/j.diabet.2020.07.010] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 07/08/2020] [Accepted: 07/28/2020] [Indexed: 12/23/2022]
Abstract
AIMS Trimethylamine N-oxide (TMAO), choline and betaine serum levels have been associated with metabolic diseases including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). These associations could be mediated by insulin resistance. However, the relationships among these metabolites, insulin resistance and NAFLD have not been thoroughly investigated. Moreover, it has recently been suggested that TMAO could play a role in NAFLD by altering bile acid metabolism. We examined the association between circulating TMAO, choline and betaine levels and NAFLD in obese subjects. METHODS Serum TMAO, choline, betaine and bile acid levels were measured in 357 Mexican obese patients with different grades of NAFLD as determined by liver histology. Associations of NAFLD with TMAO, choline and betaine levels were tested. Moreover, association of TMAO levels with non-alcoholic steatohepatitis (NASH) was tested separately in patients with and without T2D. RESULTS TMAO and choline levels were significantly associated with NAFLD histologic features and NASH risk. While increased serum TMAO levels were significantly associated with NASH in patients with T2D, in non-T2D subjects this association lost significance after adjusting for sex, BMI and HOMA2-IR. Moreover, circulating secondary bile acids were associated both with increased TMAO levels and NASH. CONCLUSIONS In obese patients, circulating TMAO levels were associated with NASH mainly in the presence of T2D. Functional studies are required to evaluate the role of insulin resistance and T2D in this association, both highly prevalent in NASH patients.
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Affiliation(s)
- P León-Mimila
- Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, USA; Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
| | - H Villamil-Ramírez
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
| | - X S Li
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - D M Shih
- Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, USA
| | - S T Hui
- Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, USA
| | - E Ocampo-Medina
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
| | - B López-Contreras
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
| | - S Morán-Ramos
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico; Cátedras, CONACyT, Mexico City, Mexico
| | - M Olivares-Arevalo
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
| | - P Grandini-Rosales
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
| | - L Macías-Kauffer
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
| | - I González-González
- Clínica Integral de Cirugía para la Obesidad y Enfermedades Metabólicas, Hospital General Dr. Rubén Lénero, Mexico City, Mexico
| | - R Hernández-Pando
- Departamento de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, Mexico
| | - F Gómez-Pérez
- Departamento de Endocrinología, INCMNSZ, Mexico City, Mexico
| | - F Campos-Pérez
- Clínica Integral de Cirugía para la Obesidad y Enfermedades Metabólicas, Hospital General Dr. Rubén Lénero, Mexico City, Mexico
| | - C Aguilar-Salinas
- Departamento de Endocrinología, INCMNSZ, Mexico City, Mexico; Unidad de Investigación en Enfermedades Metabólicas, INCMNSZ, Mexico City, Mexico; Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey, Nuevo Leon 64710, Mexico
| | | | - T Villarreal-Molina
- Laboratorio de Genómica de Enfermedades Cardiovasculares, INMEGEN, Mexico City, Mexico
| | - Z Wang
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - A J Lusis
- Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, USA
| | - S L Hazen
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA
| | - A Huertas-Vazquez
- Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, USA.
| | - S Canizales-Quinteros
- Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico.
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Nasr P, Fredrikson M, Ekstedt M, Kechagias S. The amount of liver fat predicts mortality and development of type 2 diabetes in non-alcoholic fatty liver disease. Liver Int 2020; 40:1069-1078. [PMID: 32087038 DOI: 10.1111/liv.14414] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 02/18/2020] [Accepted: 02/19/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients. METHODS 129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re-evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow-up and were evaluated with conventional histopathological methodology and SPC. RESULTS Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow-up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction in liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease). CONCLUSION Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction in liver fat decreases the risk of developing T2DM.
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Affiliation(s)
- Patrik Nasr
- Department of Gastroenterology and Hepatology, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Mats Fredrikson
- Forum Östergötland, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.,Department of Biomedical and Clinical Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden
| | - Mattias Ekstedt
- Department of Gastroenterology and Hepatology, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Stergios Kechagias
- Department of Gastroenterology and Hepatology, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
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25
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Microbiota, type 2 diabetes and non-alcoholic fatty liver disease: protocol of an observational study. J Transl Med 2019; 17:408. [PMID: 31801616 PMCID: PMC6891972 DOI: 10.1186/s12967-019-02130-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 11/07/2019] [Indexed: 02/07/2023] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the hepatocytes in the absence of alcohol overconsumption, commonly associated with insulin resistance and obesity. Both NAFLD and type 2 diabetes (T2D) are characterized by an altered microbiota composition, however the role of the microbiota in NAFLD and T2D is not well understood. To assess the relationship between alteration in the microbiota and NAFLD while dissecting the role of T2D, we established a nested study on T2D and non-T2D individuals within the Cooperative Health Research In South Tyrol (CHRIS) study, called the CHRIS-NAFLD study. Here, we present the study protocol along with baseline and follow-up characteristics of study participants. Methods Among the first 4979 CHRIS study participants, 227 individuals with T2D were identified and recalled, along with 227 age- and sex-matched non-T2D individuals. Participants underwent ultrasound and transient elastography examination to evaluate the presence of hepatic steatosis and liver stiffness. Additionally, sampling of saliva and faeces, biochemical measurements and clinical interviews were carried out. Results We recruited 173 T2D and 183 non-T2D participants (78% overall response rate). Hepatic steatosis was more common in T2D (63.7%) than non-T2D (36.3%) participants. T2D participants also had higher levels of liver stiffness (median 4.8 kPa, interquartile range (IQR) 3.7, 5.9) than non-T2D participants (median 3.9 kPa, IQR 3.3, 5.1). The non-invasive scoring systems like the NAFLD fibrosis score (NFS) suggests an increased liver fibrosis in T2D (mean − 0.55, standard deviation, SD, 1.30) than non-T2D participants (mean − 1.30, SD, 1.17). Discussion Given the comprehensive biochemical and clinical characterization of study participants, once the bioinformatics classification of the microbiota will be completed, the CHRIS-NAFLD study will become a useful resource to further our understanding of the relationship between microbiota, T2D and NAFLD.
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26
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Prediabetes Is Associated With Increased Liver Stiffness Identified by Noninvasive Liver Fibrosis Assessment. Ultrasound Q 2019; 35:330-338. [PMID: 30724873 DOI: 10.1097/ruq.0000000000000419] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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27
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Fawad A, Nilsson PM, Struck J, Bergmann A, Melander O, Bennet L. The association between plasma proneurotensin and glucose regulation is modified by country of birth. Sci Rep 2019; 9:13640. [PMID: 31541150 PMCID: PMC6754414 DOI: 10.1038/s41598-019-50040-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 09/05/2019] [Indexed: 12/13/2022] Open
Abstract
The prevalence of type 2 diabetes (T2D) has increased dramatically in Middle Eastern populations that represent the largest non-European immigrant group in Sweden today. As proneurotensin predicts T2D, the aim of this study was to investigate differences in proneurotensin levels across populations of Middle Eastern and Caucasian origin and to study its associations with indices of glucose regulation. Participants in the age 30 to 75 years, living in Malmö, Sweden, and born in Iraq or Sweden, were recruited from the census register. Anthropometrics and fasting samples were collected and oral glucose tolerance tests conducted assessing insulin secretion (DIo) as well as insulin sensitivity (ISI). A total of 2155 individuals participated in the study, 1398 were Iraqi-born and 757 were Swedish-born participants. Higher fasting proneurotensin levels were observed in Iraqi- compared to Swedish-born participants (137.5 vs. 119.8 pmol/L; p < 0.001) data adjusted for age, sex and body mass index. In Iraqi participants only, plasma proneurotensin was associated with impaired glucose regulation assessed as ISI, DIo and HbA1c, and significant interactions between country of birth and proneurotensin were observed (Pinteraction ISI = 0.048; Pinteraction DIo = 0.014; PinteractionHbA1c = 0.029). We report higher levels of proneurotensin in the general Middle Eastern population. The finding that Middle Eastern origin modifies the relationship of proneurotensin with indices of glucose regulation suggests that proneurotensin may be a stronger determinant of T2D in Middle Eastern as compared to Caucasian populations. These findings may explain part of the excess T2D risk in the Middle Eastern population but needs to be explored further.
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Affiliation(s)
- A Fawad
- Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - P M Nilsson
- Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - J Struck
- Sphingotec GmbH, Hennigsdorf, Germany
| | - A Bergmann
- Sphingotec GmbH, Hennigsdorf, Germany
- Waltraut Bergmann Foundation, Hohen Neuendorf, Germany
| | - O Melander
- Department of Clinical Sciences, Lund University, Malmö, Sweden
- Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden
- Metabolic Center, Region Skåne, Malmö, Sweden
| | - L Bennet
- Department of Clinical Sciences, Lund University, Malmö, Sweden.
- Center for Primary Health Care Research, Region Skåne, Malmö, Sweden.
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Weinstein G, Zelber-Sagi S, Preis SR, Beiser AS, DeCarli C, Speliotes EK, Satizabal CL, Vasan RS, Seshadri S. Association of Nonalcoholic Fatty Liver Disease With Lower Brain Volume in Healthy Middle-aged Adults in the Framingham Study. JAMA Neurol 2019; 75:97-104. [PMID: 29159396 DOI: 10.1001/jamaneurol.2017.3229] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Importance Nonalcoholic fatty liver disease (NAFLD) is a common condition that is most often asymptomatic. It is associated with metabolic syndrome, incident diabetes, carotid atherosclerosis, and endothelial dysfunction, conditions that in turn are strongly linked with brain damage and cognitive impairment. However, it is not known whether NAFLD is associated with structural brain measures in humans. Objective To assess the association between prevalent NAFLD and brain magnetic resonance imaging (MRI) measures. Design, Setting, and Participants The cross-sectional association between NAFLD and brain MRI measures was assessed from November 6, 2002, to March 16, 2011, in 766 individuals from the Offspring cohort of the Framingham Study. Participants were included if they did not have excessive alcohol intake and were free of stroke and dementia. Data analysis was conducted from December 30, 2015, to June 15, 2016. Exposures Nonalcoholic fatty liver disease was assessed by multidetector computed tomographic scans of the abdomen. Main Outcomes and Measures Linear or logistic regression models were used to evaluate the cross-sectional association between NAFLD and brain MRI measures, adjusting for age, sex, alcohol consumption, visceral adipose tissue, body mass index, menopausal status, systolic blood pressure, hypertension, current smoking, high-density lipoprotein and low-density lipoprotein cholesterol levels, lipid treatment, type 2 diabetes, cardiovascular disease, physical activity, insulin resistance, C-reactive protein levels, and plasma homocysteine values. Brain MRI measures included total cerebral brain volume, hippocampal and white matter hyperintensity volumes, and presence or absence of covert brain infarcts. Results Of the 766 individuals in the study sample (410 women and 356 men; mean [SD] age at the time of brain MRI, 67 [9] years), 137 (17.9%) had NAFLD. Nonalcoholic fatty liver disease was significantly associated with smaller total cerebral brain volume even after adjustment for all the covariates included in the study (β [SE], -0.26 [0.11]; P = .02). Differences in total cerebral brain volume between those with and without NAFLD corresponded to 4.2 years of brain aging in the general sample and to 7.3 years in individuals younger than 60 years of age. No statistically significant associations were observed between NAFLD and hippocampal or white matter hyperintensity volumes or covert brain infarcts. Conclusions and Relevance Nonalcoholic fatty liver disease is associated with a smaller total cerebral brain volume, independent of visceral adipose tissue and cardiometabolic risk factors, pointing to a possible link between hepatic steatosis and brain aging.
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Affiliation(s)
| | - Shira Zelber-Sagi
- School of Public Health, University of Haifa, Haifa, Israel.,Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Sarah R Preis
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.,The Framingham Study, Framingham, Massachusetts
| | - Alexa S Beiser
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.,The Framingham Study, Framingham, Massachusetts.,Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
| | - Charles DeCarli
- Department of Neurology, University of California at Davis, Sacramento
| | - Elizabeth K Speliotes
- Department of Gastroenterology, Massachusetts General Hospital, Boston.,Department of Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts
| | - Claudia L Satizabal
- The Framingham Study, Framingham, Massachusetts.,Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
| | - Ramachandran S Vasan
- The Framingham Study, Framingham, Massachusetts.,Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.,Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts
| | - Sudha Seshadri
- The Framingham Study, Framingham, Massachusetts.,Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
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Rajput R, Ahlawat P. Prevalence and predictors of non-alcoholic fatty liver disease in prediabetes. Diabetes Metab Syndr 2019; 13:2957-2960. [PMID: 31425963 DOI: 10.1016/j.dsx.2019.07.060] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 07/29/2019] [Indexed: 12/31/2022]
Abstract
BACKGROUD AND AIMS Various studies have evaluated the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with diabetes but few studies on prevalence of NAFLD in prediabetes have been performed so far. The present study aimed to evaluate the prevalence and predictors of NAFLD in prediabetics. MATERIAL AND METHODS In this cross-sectional study, 100 diagnosed cases of Prediabetes were compared with 100 normoglycemic people after random selection from OPD for NAFLD by using various biochemical parameters and ultrasonography. RESULTS Among 100 prediabetic cases, IFG was present in 28%, IGT in 26% and both were impaired in 46%. FPG, 2 Hour glucose post OGTT, diastolic blood pressure, weight, BMI, waist circumference, waist hip ratio, waist height ratio was significantly more in prediabetics as compared to controls. On USG, prevalence of NAFLD was more in prediabetics (59%) as compared to controls (26%) with p value =<0.001. Grade 1 fatty liver was present in 37% (n = 37) prediabetics as compare to 22% (n = 22) controls and Grade 2 fatty liver was present in 22% (n = 22) cases as compare to 4% (n = 4) controls with p value < 0.001. SGOT, SGPT, GGT, ALP, UA, TG were significantly higher in prediabetics as compared to controls. GGT and WC are best predictor of NAFLD in pre-diabetes with adjusted odd's ratio of 6.604 and 6.589 respectively. CONCLUSION To conclude with, prevalence of NAFLD is substantially more in prediabetic patients as compared to normoglycemic individuals and elevated WC and GGT were the best predictor of underlying NAFLD among prediabetic individuals.
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Affiliation(s)
- Rajesh Rajput
- Department of Endocrinology & Medicine Unit IV, Pt. B D Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India.
| | - Parul Ahlawat
- Department of Endocrinology & Medicine Unit IV, Pt. B D Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana, India
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30
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Abstract
OBJECTIVES We examined the dose-dependent association of habitual moderate-to-vigorous physical activity (MVPA) with the biochemical markers for nonalcoholic fatty liver disease (NAFLD) and whether this association changes with age and degree of impaired glucose metabolism. We also investigated whether the associations depend on the domain of MVPA. METHODS In this study, using data from the population-based Lifelines cohort (N = 42,661), MVPA was self-reported on the short questionnaire to assess health-enhancing physical activity. NAFLD was defined as a fatty liver index value of >60, based on body mass index, waist circumference, plasma triglycerides, and gamma-glutamyltransferase. Glucose metabolism was defined as normal (NGM), impaired (IGM), and type 2 diabetes mellitus (T2DM). Exclusion criteria were previously diagnosed hepatitis or cirrhosis and excessive alcohol use. All analyses were adjusted for age, sex, and education. RESULTS Higher MVPA was dose dependently associated with a lower risk of having NAFLD: compared with "No MVPA," the odds ratios (ORs) (95% confidence intervals) for MVPA quintiles were 0.78 (0.71-0.86), 0.64 (0.58-0.70), 0.53 (0.48-0.59), 0.51 (0.46-0.56), and 0.45 (0.41-0.50) for the highest level of MVPA. The association between MVPA and NAFLD was stronger for more impaired glucose status (ORNGM = 0.49 (0.42-0.57), ORIGM = 0.46 (0.40-0.54), ORT2DM = 0.42 (0.27-0.66)) and for older age (OR20-40 years = 0.51 (0.42-0.62), OR60-80 years = 0.37 (0.29-0.48)) with the highest level of MVPA, relative to No MVPA. No favorable association was observed for occupational MVPA. With regard to MVPA and fibrosis, associations with fibrosis markers showed contradictory results. CONCLUSIONS Higher MVPA levels are dose dependently associated with a lower NAFLD risk. This association is stronger in people with diabetes and older adults.
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31
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Zsóri G, Illés D, Ivány E, Kosár K, Holzinger G, Tajti M, Pálinkás E, Szabovik G, Nagy A, Palkó A, Czakó L. In New-Onset Diabetes Mellitus, Metformin Reduces Fat Accumulation in the Liver, But Not in the Pancreas or Pericardium. Metab Syndr Relat Disord 2019; 17:289-295. [PMID: 31013454 DOI: 10.1089/met.2018.0086] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background: Nonalcoholic fatty pancreas and liver disease (NAFPD and NAFLD) and pericardial adipose tissue (PAT) are often associated with type 2 diabetes mellitus (T2DM). Our aim was to evaluate the incidence rate of NAFLD and NAFPD, PAT size, and the effect of metformin treatment on NAFLD, NAFPD, and PAT in new-onset T2DM (NODM). Methods: Seventeen patients with NODM and 10 subjects used as a control group were involved in the study. Computed tomography (CT) and laboratory tests were performed before the beginning of metformin therapy and 4 months afterward. PAT and the amount of fat in the pancreas and liver were determined by X-ray attenuation during unenhanced CT examination and compared with the values for the control subjects. Results: Metabolic parameters improved significantly after metformin therapy. NAFLD was diagnosed in 64.7% of the patients with NODM and in 10% of the control subjects. The radiation absorption of the liver was significantly lower in the patients with NODM compared with the control group and significantly higher after metformin therapy compared with the baseline values. Only six patients (35.3%) had NAFLD after metformin therapy. NAFPD was diagnosed in 82.3% of the patients with NODM and in 20% of the control subjects. The radiation absorption of the pancreas was significantly lower in the patients with NODM compared with the control group but did not change significantly after treatment. PAT size was significantly larger in the patients with NODM and did not change significantly after metformin treatment. Conclusions: NAFLD, NAFPD, and increased PAT were detected in the majority of patients with NODM. Metformin therapy decreased the amount of fat in the liver in parallel with an improvement in the metabolic parameters and may, thus, be beneficial for preventing the late consequences of NAFLD.
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Affiliation(s)
- Gábor Zsóri
- 1 First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Dóra Illés
- 1 First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Emese Ivány
- 1 First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Klára Kosár
- 1 First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Gábor Holzinger
- 1 First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Máté Tajti
- 1 First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Eszter Pálinkás
- 1 First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Géza Szabovik
- 2 Department of Radiology, University of Szeged, Szeged, Hungary
| | - András Nagy
- 2 Department of Radiology, University of Szeged, Szeged, Hungary
| | - András Palkó
- 2 Department of Radiology, University of Szeged, Szeged, Hungary
| | - László Czakó
- 1 First Department of Medicine, University of Szeged, Szeged, Hungary
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Braga T, Kraemer-Aguiar LG, Docherty NG, Le Roux CW. Treating prediabetes: why and how should we do it? Minerva Med 2018; 110:52-61. [PMID: 30371047 DOI: 10.23736/s0026-4806.18.05897-4] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Prediabetes is the subclinical impairment in fasting plasma glucose, impaired glucose tolerance or both. The degree of impairment is between euglycemia and the hyperglycemia of type 2 diabetes (T2DM). Prediabetes is not considered benign, because it is a risk factor for T2DM but is also associated with micro and macrovascular complications. Lifestyle interventions including diet and exercise are first-line treatments. Medications can also play a role, as randomized controlled trials of biguanides (metformin) alpha-glucosidase inhibitors (Acarbose), inhibitors of pancreatic lipase (Orlistat), PPAR-gamma agonists (Rosiglitazone, Pioglitazone), meglitinides (Nateglinide) and GLP-1 receptor agonists (Liraglutide) have all shown benefits. Bariatric surgery is another efficacious means of preventing T2DM in patients with prediabetes and obesity. Prediabetes in its various guises is a risk factor for the future development T2DM and diabetic complications. Importantly the prediabetic state is amenable to interventions that prevent/delay transition to overt T2DM. Knowledge gaps exist regarding how best to make prognostication highly sensitive and specific as to which patient will develop T2DM. Moreover, understanding of phenotype specific pathophysiology may add value to funding appropriate interventions for patients with prediabetes. Management of patients with prediabetes should be individualized based on the algorithms that predict phenotype specific risk and allow for the use of phenotype tailored interventions.
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Affiliation(s)
| | - Luiz G Kraemer-Aguiar
- Postgraduate Program in Clinical and Experimental Physiopathology (FISCLINEX), State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | - Neil G Docherty
- Diabetes Complications Research Centre, Conway Institute University College, Dublin, Ireland
| | - Carel W Le Roux
- Diabetes Complications Research Centre, Conway Institute University College, Dublin, Ireland.,Investigative Science, Imperial College, London, UK
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Fiorentino TV, Marini MA, Succurro E, Andreozzi F, Perticone M, Hribal ML, Sciacqua A, Perticone F, Sesti G. One-Hour Postload Hyperglycemia: Implications for Prediction and Prevention of Type 2 Diabetes. J Clin Endocrinol Metab 2018; 103:3131-3143. [PMID: 30020454 DOI: 10.1210/jc.2018-00468] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 07/12/2018] [Indexed: 12/18/2022]
Abstract
CONTEXT Recently, a value of 1-hour postload glucose concentration (1-h-PG) ≥155 mg/dL (8.6 mmol/L) in individuals with normal glucose tolerance (NGT) has been found to be associated with an increased risk for future type 2 diabetes mellitus (T2DM). In this review, we analyze the implication of 1-h-PG determination in prediction of T2DM and cardiovascular disease. DESIGN A literature search was performed using MEDLINE. We included all English studies published up to February 2018 in peer-reviewed journals that examined the relationship between 1-h-PG and diabetes, cardiometabolic alterations, organ damage, and cardiovascular disease. RESULTS Several longitudinal studies have consistently shown that 1-h-PG ≥155 mg/dL can recognize individuals at increased risk for future T2DM among subjects with NGT. Additionally, we describe the pathophysiological abnormalities associated with 1-h-PG ≥155 mg/dL including impaired insulin sensitivity, β-cell dysfunction, and increased glucose intestinal absorption, which are known to be involved in T2DM pathogenesis. Importantly, numerous studies have demonstrated that a value of 1-h-PG ≥155 mg/dL in individuals with NGT is not only linked to an increased risk for future T2DM, but also able to identify those having a worse cardiovascular phenotype and an increased risk of adverse cardiovascular outcomes. CONCLUSIONS Although 1-h-PG determination is not currently recommended by the American Diabetes Association for identifying high-risk individuals, the available evidence indicates that a value of 1-h-PG ≥155 mg/dL may be a useful tool to recognize, among subjects with NGT, those at increased risk of T2DM and cardiovascular disease.
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Affiliation(s)
- Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Viale Europa, Catanzaro, Italy
| | | | - Elena Succurro
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Viale Europa, Catanzaro, Italy
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Viale Europa, Catanzaro, Italy
| | - Maria Perticone
- Department of Experimental and Clinical Medicine, University Magna Græcia of Catanzaro, Viale Europa, Catanzaro, Italy
| | - Marta Letizia Hribal
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Viale Europa, Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Viale Europa, Catanzaro, Italy
| | - Francesco Perticone
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Viale Europa, Catanzaro, Italy
| | - Giorgio Sesti
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Viale Europa, Catanzaro, Italy
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Hohenester S, Christiansen S, Nagel J, Wimmer R, Artmann R, Denk G, Bischoff M, Bischoff G, Rust C. Lifestyle intervention for morbid obesity: effects on liver steatosis, inflammation, and fibrosis. Am J Physiol Gastrointest Liver Physiol 2018; 315:G329-G338. [PMID: 29878845 DOI: 10.1152/ajpgi.00044.2018] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The prevalence of obesity-related nonalcoholic fatty liver disease (NAFLD) is rising. NAFLD may result in nonalcoholic steatohepatitis (NASH), progressing to liver cirrhosis. Weight loss is recommended to treat obesity-related NASH. Lifestyle intervention may improve NASH; however, pertinent trials have so far focused on overweight patients, whereas patients with obesity are at highest risk of developing NAFLD. Furthermore, reports of effects on liver fibrosis are scarce. We evaluated the effect of lifestyle intervention on NAFLD in a real-life cohort of morbidly obese patients. In our observational study, 152 patients underwent lifestyle intervention, with a follow-up of 52 weeks. Noninvasive measures of obesity, metabolic syndrome, liver steatosis, liver damage, and liver fibrosis were analyzed. Treatment response in terms of weight loss was achieved in 85.1% of patients. Dysglycemia and dyslipidemia improved. The proportion of patients with fatty liver dropped from 98.1 to 54.3% ( P < 0.001). Weight loss >10% was associated with better treatment response ( P = 0.0009). Prevalence of abnormal serum transaminases fell from 81.0 to 50.5% ( P < 0.001). The proportion fibrotic patients, as determined by the NAFLD fibrosis score, dropped from 11.8 to 0% ( P < 0.05). Low serum levels of adiponectin correlated with degree of liver damage, i.e., serum liver transaminases ( r = -0,32, P < 0.05). Serum levels of adiponectin improved with intervention. In conclusion, lifestyle intervention effectively targeted obesity and the metabolic syndrome. Liver steatosis, damage and fibrosis were ameliorated in this real-life cohort of morbidly obese patients, mediated in part by changes in the adipokine profile. Patients with weight loss of >10% seemed to benefit most. NEW & NOTEWORTHY We demonstrate new evidence that lifestyle intervention is effective in treating NAFLD in the important group of patients with (morbid) obesity. Although current guidelines on the therapy of NASH recommend weight loss of 5-7%, weight reduction >10% may be favorable in morbid obesity. Serum levels of adipokines correlate with liver damage, which is indicative of their pathogenetic importance in human NASH. Our study adds to the limited body of evidence that NAFLD-associated liver fibrosis may resolve with lifestyle intervention.
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Affiliation(s)
- Simon Hohenester
- Department of Medicine II, University Hospital, LMU Munich, Munich , Germany
| | - Simon Christiansen
- Center for Clinical Nutrition and Preventive Medicine, Hospital Barmherzige Brüder , Munich , Germany
| | - Jutta Nagel
- Department of Medicine II, University Hospital, LMU Munich, Munich , Germany
| | - Ralf Wimmer
- Department of Medicine II, University Hospital, LMU Munich, Munich , Germany
| | - Renate Artmann
- Department of Medicine II, University Hospital, LMU Munich, Munich , Germany
| | - Gerald Denk
- Department of Medicine II, University Hospital, LMU Munich, Munich , Germany
| | - Monika Bischoff
- Center for Clinical Nutrition and Preventive Medicine, Hospital Barmherzige Brüder , Munich , Germany
| | - Gert Bischoff
- Center for Clinical Nutrition and Preventive Medicine, Hospital Barmherzige Brüder , Munich , Germany.,Department of Medicine I, Hospital Barmherzige Brüder , Munich , Germany
| | - Christian Rust
- Center for Clinical Nutrition and Preventive Medicine, Hospital Barmherzige Brüder , Munich , Germany.,Department of Medicine I, Hospital Barmherzige Brüder , Munich , Germany
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Alexander M, Loomis AK, Fairburn-Beech J, van der Lei J, Duarte-Salles T, Prieto-Alhambra D, Ansell D, Pasqua A, Lapi F, Rijnbeek P, Mosseveld M, Avillach P, Egger P, Kendrick S, Waterworth DM, Sattar N, Alazawi W. Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease. BMC Med 2018; 16:130. [PMID: 30099968 PMCID: PMC6088429 DOI: 10.1186/s12916-018-1103-x] [Citation(s) in RCA: 180] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 06/19/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. It affects an estimated 20% of the general population, based on cohort studies of varying size and heterogeneous selection. However, the prevalence and incidence of recorded NAFLD diagnoses in unselected real-world health-care records is unknown. We harmonised health records from four major European territories and assessed age- and sex-specific point prevalence and incidence of NAFLD over the past decade. METHODS Data were extracted from The Health Improvement Network (UK), Health Search Database (Italy), Information System for Research in Primary Care (Spain) and Integrated Primary Care Information (Netherlands). Each database uses a different coding system. Prevalence and incidence estimates were pooled across databases by random-effects meta-analysis after a log-transformation. RESULTS Data were available for 17,669,973 adults, of which 176,114 had a recorded diagnosis of NAFLD. Pooled prevalence trebled from 0.60% in 2007 (95% confidence interval: 0.41-0.79) to 1.85% (0.91-2.79) in 2014. Incidence doubled from 1.32 (0.83-1.82) to 2.35 (1.29-3.40) per 1000 person-years. The FIB-4 non-invasive estimate of liver fibrosis could be calculated in 40.6% of patients, of whom 29.6-35.7% had indeterminate or high-risk scores. CONCLUSIONS In the largest primary-care record study of its kind to date, rates of recorded NAFLD are much lower than expected suggesting under-diagnosis and under-recording. Despite this, we have identified rising incidence and prevalence of the diagnosis. Improved recognition of NAFLD may identify people who will benefit from risk factor modification or emerging therapies to prevent progression to cardiometabolic and hepatic complications.
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Affiliation(s)
| | | | | | | | - Talita Duarte-Salles
- Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina, Barcelona, Spain
| | | | | | - Alessandro Pasqua
- Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy
| | - Francesco Lapi
- Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy
| | - Peter Rijnbeek
- Erasmus Universitair Medisch Centrum, Rotterdam, The Netherlands
| | - Mees Mosseveld
- Erasmus Universitair Medisch Centrum, Rotterdam, The Netherlands
| | | | | | | | | | - Naveed Sattar
- University of Glasgow, BHF Glasgow Cardiovascular Research Centre, Glasgow, UK
| | - William Alazawi
- Barts Liver Centre, Blizard Institute, Queen Mary, University of London, London, UK.
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Hirata A, Sugiyama D, Kuwabara K, Hirata T, Tsutatani H, Funamoto M, Watanabe K, Miyamatsu N, Okamura T. Fatty liver index predicts incident diabetes in a Japanese general population with and without impaired fasting glucose. Hepatol Res 2018; 48:708-716. [PMID: 29341419 DOI: 10.1111/hepr.13065] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 12/27/2017] [Accepted: 01/15/2018] [Indexed: 12/17/2022]
Abstract
AIM Fatty liver is associated with the development of diabetes. However, to our knowledge, no study has examined the relationship between the fatty liver index (FLI), calculated scores of hepatic steatosis, and the development of diabetes among individuals without impaired fasting glucose (IFG). We aimed to examine whether FLI predicts the development of diabetes in individuals with and without IFG in a Japanese general population. METHODS We selected 1498 men and 2941 women who participated in Specific Health Checkups in Japan. We divided all participants into six groups according to tertiles of FLI (low, moderate, and high) and the presence or absence of IFG, by sex. We calculated hazard ratios for incident diabetes for each group using a Cox proportional hazard model, adjusting for potential confounders. RESULTS During a mean follow-up period of 3.0 years, 176 cases of diabetes in men and 320 cases in women were identified. Compared with the low FLI group without IFG, the high FLI group without IFG was significantly associated with incident diabetes in both men (hazard ratio, 1.90; 95% confidence interval, 1.08-3.36) and women (hazard ratio, 1.72; 95% confidence interval, 1.18-2.51). All IFG groups were significantly associated with incident diabetes regardless of FLI levels. CONCLUSIONS Our results showed that FLI is associated with the development of diabetes regardless of sex and the presence or absence of IFG, and that it may be a useful predictor of future risk of incident diabetes even in individuals without IFG.
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Affiliation(s)
- Aya Hirata
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan
| | - Daisuke Sugiyama
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan
| | - Kazuyo Kuwabara
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan
| | - Takumi Hirata
- Center for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan
| | | | | | | | - Naomi Miyamatsu
- Department of Clinical Nursing, Shiga University of Medical Science, Shiga, Japan
| | - Tomonori Okamura
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan
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Franch-Nadal J, Caballeria L, Mata-Cases M, Mauricio D, Giraldez-García C, Mancera J, Goday A, Mundet-Tudurí X, Regidor E. Fatty liver index is a predictor of incident diabetes in patients with prediabetes: The PREDAPS study. PLoS One 2018; 13:e0198327. [PMID: 29856820 PMCID: PMC5983533 DOI: 10.1371/journal.pone.0198327] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 05/17/2018] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES We evaluated the ability of the Fatty Liver Index (FLI), a surrogate marker of hepatic steatosis, to predict the development of type 2 diabetes (T2D) at 3 years follow-up in a Spanish cohort with prediabetes from a prospective observational study in primary care (PREDAPS). METHODS FLI was calculated at baseline for 1,142 adult subjects with prediabetes attending primary care centers, and classified into three categories: FLI <30 (no steatosis), FLI 30-60 (intermediate) and FLI ≥60 (hepatic steatosis). We estimated the incidence rate of T2D in each FLI category at 3 years of follow-up. The association between FLI and incident T2D was calculated using Cox regression models adjusted for age, sex, educational level, family history of diabetes, lifestyles, hypertension, lipid profile and transaminases. RESULTS The proportion of subjects with prediabetes and hepatic steatosis (FLI ≥60) at baseline was 55.7%. The incidence rate of T2D at 3 years follow-up was 1.3, 2.9 and 6.0 per 100 person-years for FLI<30, FLI 30->60 and FLI ≥60, respectively. The most significant variables increasing the risk of developing T2D were metabolic syndrome (hazard ratio [HR] = 3.02; 95% confidence interval [CI] = 2.14-4.26) and FLI ≥60 (HR = 4.52; 95%CI = 2.10-9.72). Moreover, FLI ≥60 was independently associated with T2D incidence: the HR was 4.97 (95% CI: 2.28-10.80) in the base regression model adjusted by sex, age and educational level, and 3.21 (95%CI: 1.45-7.09) in the fully adjusted model. CONCLUSIONS FLI may be considered an easy and valuable early indicator of high risk of incident T2D in patients with prediabetes attended in primary care, which could allow the adoption of effective measures needed to prevent and reduce the progression of the disease.
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Affiliation(s)
- Josep Franch-Nadal
- redGDPS Foundation, Madrid, Spain
- Unitat de Suport a la Recerca Barcelona Ciutat, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
- Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), Madrid, Spain
- Department of Medicine, University of Barcelona, Barcelona, Spain
| | - Llorenç Caballeria
- Department of Medicine, University of Barcelona, Barcelona, Spain
- Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD), Madrid, Spain
- Unitat de Suport a la Recerca Barcelonès Nord, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
| | - Manel Mata-Cases
- redGDPS Foundation, Madrid, Spain
- Unitat de Suport a la Recerca Barcelona Ciutat, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
- Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), Madrid, Spain
| | - Didac Mauricio
- redGDPS Foundation, Madrid, Spain
- Unitat de Suport a la Recerca Barcelona Ciutat, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
- Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), Madrid, Spain
- Department of Endocrinology and Nutrition, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain
| | - Carolina Giraldez-García
- redGDPS Foundation, Madrid, Spain
- Preventive Medicine Service, University Hospital Infanta Elena, Madrid, Spain
- Preventive Medicine, Public Health and History of Science Department, Complutense University of Madrid, Madrid, Spain
| | - José Mancera
- redGDPS Foundation, Madrid, Spain
- Health Center Ciudad Jardín, Málaga, Spain
| | - Albert Goday
- redGDPS Foundation, Madrid, Spain
- Endocrinology Service, Hospital del Mar, Barcelona, Spain
| | - Xavier Mundet-Tudurí
- redGDPS Foundation, Madrid, Spain
- Unitat de Suport a la Recerca Barcelona Ciutat, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain
- Autonomous University of Barcelona, Bellaterra, Spain
| | - Enrique Regidor
- redGDPS Foundation, Madrid, Spain
- Preventive Medicine, Public Health and History of Science Department, Complutense University of Madrid, Madrid, Spain
- Epidemiology and Public Health Networking Biomedical Research Centre (CIBERESP), Madrid, Spain
- Health Research Institute, Hospital Clínico San Carlos (IdISSC), Madrid, Spain
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Mondal SA, Dutta D, Kumar M, Singh P, Basu M, Selvan C, Mukhopadhyay S. Neck Circumference to Height Ratio is a Reliable Predictor of Liver Stiffness and Nonalcoholic Fatty Liver Disease in Prediabetes. Indian J Endocrinol Metab 2018; 22:347-354. [PMID: 30090726 PMCID: PMC6063186 DOI: 10.4103/ijem.ijem_31_18] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) and dysglycemia are public health challenges. There is urgent need for anthropometric surrogates for NAFLD screening. This study evaluated role of neck circumference (NC) and neck-height ratio (NHtR) as predictors of liver stiffness measure (LSM) in individuals with prediabetes (IPD). METHODS In a cross-sectional study, 188 IPD from 1130 screened individuals underwent anthropometry, ultrasonography, Fibroscan® for LSM, dyslipidemia, insulin resistance (IR), and fetuin-A assessment. RESULTS Hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), metabolic syndrome (MetS), NAFLD, and significant liver stiffness (SLS) (LSM >8.5kPa) were observed in 53.7%, 31.4%, 71.3%, 73.9%, 24.5%, and 11.2% prediabetes individuals, respectively. Prediabetes with NAFLD had significantly higher body mass index (BMI), NC, NHtR, glycated hemoglobin, triglycerides, fatty liver index (FLI), and LSM. Prediabetes in highest NHtR quartile had significantly higher BMI, hypertension, MetS, fasting glucose, glycated hemoglobin, homeostatic model assessment-IR, NAFLD, LSM, SLS, and lower HDL-C. Stepwise forward linear regression revealed that NHtR, FLI, and LDL-C were best predictors of LSM, at baseline (Model-1), after adjusting for age and sex (Model-2), and adjusting model-2 plus systolic and diastolic blood pressure (Model-3). NHtR and NC (in females) and NHtR and BMI (in males) had largest area under the curves for predicting LSM, NAFLD, and MetS. NHtR ≥21.54 cm/m (sensitivity: 90%; specificity: 52.5%; females) and ≥21.62 cm/m (sensitivity: 80%; specificity: 49.4%; males) was best predictor of SLS. INTERPRETATION AND CONCLUSION NHtR is a reliable tool for community screening of NAFLD and liver stiffness in prediabetes.
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Affiliation(s)
- Samim Ali Mondal
- Department of Biochemistry, Institute of Postgraduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India
| | - Deep Dutta
- Department of Endocrinology, Venkateshwar Hospitals, New Delhi, India
| | - Manoj Kumar
- Department of Endocrinology, Institute of Postgraduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India
| | - Pankaj Singh
- Department of Gastroenterology, School of Digestive and Liver Disease, Institute of Postgraduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India
| | - Madhurima Basu
- Department of Biochemistry, Institute of Postgraduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India
| | - Chitra Selvan
- Department of Endocrinology, MS Ramaiah Medical College, Bengaluru, Karnataka, India
| | - Satinath Mukhopadhyay
- Department of Endocrinology, Institute of Postgraduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India
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Abstract
Hepatic steatosis is an underlying feature of nonalcoholic fatty liver disease (NAFLD), which is the most common form of liver disease and is present in up to ∼70% of individuals who are overweight. NAFLD is also associated with hypertriglyceridaemia and low levels of HDL, glucose intolerance, insulin resistance and type 2 diabetes mellitus. Hepatic steatosis is a strong predictor of the development of insulin resistance and often precedes the onset of other known mediators of insulin resistance. This sequence of events suggests that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle. Hepatokines are proteins that are secreted by hepatocytes, and many hepatokines have been linked to the induction of metabolic dysfunction, including fetuin A, fetuin B, retinol-binding protein 4 (RBP4) and selenoprotein P. In this Review, we describe the factors that influence the development of hepatic steatosis, provide evidence of strong links between hepatic steatosis and insulin resistance in non-hepatic tissues, and discuss recent advances in our understanding of how steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication.
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Affiliation(s)
- Ruth C R Meex
- Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program and the Department of Physiology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
- Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
| | - Matthew J Watt
- Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program and the Department of Physiology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
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Zelber-Sagi S, Salomone F, Kolodkin-Gal I, Erez N, Buch A, Yeshua H, Webb M, Halpern Z, Shibolet O. Protective role of soluble receptor for advanced glycation end-products in patients with non-alcoholic fatty liver disease. Dig Liver Dis 2017; 49:523-529. [PMID: 28179090 DOI: 10.1016/j.dld.2017.01.148] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 01/10/2017] [Accepted: 01/10/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Soluble receptor for advanced glycation end-products (sRAGE) exerts protective metabolic effects. AIMS To identify if sRAGE plays a protective role in NAFLD. METHODS sRAGE (n=55) and Nε-(Carboxymethyl) lysine (CML) (n=36) serum levels were measured in NAFLD patients. Liver steatosis and fibrosis were non-invasively quantified by the hepatorenal index and the NAFLD fibrosis score (NFS). RESULTS sRAGE levels were lower in NAFLD patients compared to controls (1207±439 vs. 1596±562ng/l, P<0.001) and were lower among subjects with moderate-severe steatosis compared with mild (1043±287 vs. 1378±506, P=0.005). Higher sRAGE was associated with lower steatosis with adjustment for age, gender, BMI and fasting insulin (OR=0.998, 0.996-0.999 95%CI, P=0.018). CML was not correlated with liver steatosis (r=0.07, P=0.683), but was positively correlated with AST (r=0.34, P=0.04), GGT (r=0.38, P=0.023) and HbA1C (r=0.37, P=0.027). sRAGE tended to be higher in subjects with NFS<-1.455 compared with NFS>-1.455 (1287±450 n=36 vs. 1051±364 n=13, P=0.08). While sRAGE was positively correlated with vegetables consumption (r=0.268, P=0.05), CML levels were not associated with sRAGE or dietary intake. sRAGE increased following a 3 month-lifestyle intervention (1194±446 vs. 1367±440 n=31, P<0.001) and change in sRAGE levels was negatively correlated with change in ALT levels (r=-0.37, P=0.041). CONCLUSION sRAGE plays a protective role in NAFLD and it is influenced by lifestyle.
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Affiliation(s)
- Shira Zelber-Sagi
- Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel; School of Public Health, University of Haifa, Haifa, Israel
| | - Federico Salomone
- Division of Gastroenterology, Acireale Hospital, Azienda Sanitaria Provinciale di Catania, Catania, Italy.
| | - Ilana Kolodkin-Gal
- Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
| | - Noam Erez
- Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Assaf Buch
- Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Hanny Yeshua
- Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Muriel Webb
- Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Zamir Halpern
- Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Oren Shibolet
- Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel; The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Liu M, Wang J, Zeng J, Cao X, He Y. Association of NAFLD With Diabetes and the Impact of BMI Changes: A 5-Year Cohort Study Based on 18,507 Elderly. J Clin Endocrinol Metab 2017; 102:1309-1316. [PMID: 28324002 DOI: 10.1210/jc.2016-3440] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 01/09/2017] [Indexed: 02/08/2023]
Abstract
CONTEXT Previous studies about the relationship between nonalcoholic fatty liver disease (NAFLD) and diabetes are limited by inconsistent conclusions, mainly being cross-sectional and having a small sample size, no elderly people, or a lack of prediabetes. OBJECTIVE This study sought to examine the relationship between NAFLD and diabetes and prediabetes in a large cohort based on Chinese male elderly. DESIGN This was a retrospective cohort study that was followed up for ∼5 years. SETTING This study was conducted in Beijing, China. PARTICIPANTS Chinese male elderly (n = 18,507). Participants with diabetes/prediabetes at baseline were excluded. MAIN OUTCOME MEASURES Ultrasound was used for diagnosis of NAFLD. RESULTS Mean age of the 18,507 participants was 71.38 ± 14.15 years. The prevalence of NAFLD was 18.77% (3474/18,503), and participants with NAFLD had higher body mass index (BMI), blood pressure levels, blood lipid levels, and also higher alanine aminotransferase levels (P < 0.001). The total 5-year incidence was 2.448% for diabetes and 10.628% for prediabetes. Participants with NAFLD at baseline had a higher incidence of both diabetes and prediabetes. The adjusted relative risks (RRs) were 1.672 [95% confidence interval (CI), 1.361 to 2.052] and 1.336 (95% CI, 1.205 to 1.481). The RRs were closely related to BMI changes. The adjusted RRs for diabetes according to three BMI change groups (<-1.00 kg/m2, -1.00 to 1.00 kg/m2, >1.00 kg/m2) were 1.599 (95% CI, 1.054 to 2.426), 1.640 (95% CI, 1.241 to 2.167), and 1.918 (95% CI, 1.239 to 2.969), respectively. Similar results were obtained when prediabetes was used as the dependent variable. CONCLUSIONS There was a strong and independent association between NAFLD and both diabetes and prediabetes among Chinese male elderly, and this relationship was closely related to BMI changes.
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Affiliation(s)
- Miao Liu
- Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics and
| | - Jianhua Wang
- Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics and
| | - Jing Zeng
- Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics and
| | - Xiutang Cao
- Department of Health and Economics, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Yao He
- Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics and
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Tokita Y, Maejima Y, Shimomura K, Takenoshita S, Ishiyama N, Akuzawa M, Shimomura Y, Nakajima K. Non-alcoholic Fatty Liver Disease Is a Risk Factor for Type 2 Diabetes in Middle-aged Japanese Men and Women. Intern Med 2017; 56:763-771. [PMID: 28381741 PMCID: PMC5457918 DOI: 10.2169/internalmedicine.56.7115] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Objective Emerging studies have focused on the association between non-alcoholic fatty liver disease (NAFLD) and the risk of type 2 diabetes mellitus (T2DM). We aimed to investigate whether NAFLD diagnosed by ultrasonography could predict the risk of future T2DM in a Japanese middle-aged health check population. Methods We conducted a 10-year observational study in a health checkup population of middle-aged Japanese men and women at Hidaka Hospital from 2004 to 2013. We excluded cases with an alcohol intake exceeding 20 g/day and those with impaired glucose tolerance. The remaining 1,544 men and 864 women were classified into fatty liver and non-fatty liver groups based on the findings of abdominal ultrasonography. Both groups were followed for the development of diabetes. A multiple regression analysis was performed for each variable to predict the risk of future diabetes. Results The median age of the participants was 46.0 years at the entry, and the follow-up period was 10 years. The incidence of diabetes in the fatty liver group was 12.5% (29/232) in men and 26.3% (10/38) in women, whereas the incidence of diabetes in the non-fatty liver group was 2.5% (34/1,312) in men and 1.8% (15/826) in women. The relative risk of diabetes associated with fatty liver was 4.8 [95% confidence interval (CI) 3.0-7.8, p<0.0001] in men and 14.5 (95% CI 7.0-30.1, p<0.0001) in women. Conclusion NAFLD was a significant predictor for future diabetes in a Japanese middle-aged health check population, especially in women.
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Affiliation(s)
- Yoshiharu Tokita
- Diabetes and Metabolic Disease Research Center, Hidaka Hospital, Japan
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Dorcely B, Katz K, Jagannathan R, Chiang SS, Oluwadare B, Goldberg IJ, Bergman M. Novel biomarkers for prediabetes, diabetes, and associated complications. Diabetes Metab Syndr Obes 2017; 10:345-361. [PMID: 28860833 PMCID: PMC5565252 DOI: 10.2147/dmso.s100074] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recognizing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders.
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Affiliation(s)
- Brenda Dorcely
- New York University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY
| | - Karin Katz
- New York University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY
| | - Ram Jagannathan
- Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Stephanie S Chiang
- New York University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY
| | - Babajide Oluwadare
- New York University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY
| | - Ira J Goldberg
- New York University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY
| | - Michael Bergman
- New York University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY
- Correspondence: Michael Bergman, New York University School of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, 550 1st Avenue, Suite 5E, New York, NY 10016, USA, Tel +1 212 481 1350, Fax +1 212 481 1355, Email
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Transient remission of nonalcoholic fatty liver disease decreases the risk of incident type 2 diabetes mellitus in Japanese men. Eur J Gastroenterol Hepatol 2016; 28:1443-1449. [PMID: 27603300 DOI: 10.1097/meg.0000000000000736] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION It is unclear how the transient remission of nonalcoholic fatty liver disease (NAFLD) affects incident type 2 diabetes mellitus (T2DM). Here, we sought to determine the effect of the transient remission of NAFLD on incident T2DM in Japanese men. MATERIALS AND METHODS We used a population-based health check-up program. The primary outcome was set as incident T2DM. We divided the participants who showed NAFLD at the time of enrollment into three groups according to their clinical course of NAFLD: the Regression group, in which the participants showed a regression of NAFLD and no relapse during the follow-up period; the Transient Remission group, in which participants achieved a transient remission of NAFLD, but had a relapse of NAFLD; and the Persistent group, in which participants showed NAFLD throughout the follow-up. The Never group of participants who did not show NAFLD throughout the follow-up served as a reference. RESULTS The incidence rates of T2DM in the Never group, the Regression group, the Transient Remission group, and the Persistent group were 4.7% (62/1306), 9.2% (14/153), 18.0% (25/139), and 35.1% (120/342), respectively. In a multivariate Cox regression analysis with covariates, the adjusted hazard ratios for incident T2DM compared with the Never group were as follows: Regression group: 1.08 [95% confidence interval (CI) 0.53-2.04, P=0.81], Transient Remission group: 2.12 (95% CI 1.22-3.57, P<0.01), and Persistent group: 3.44 (95% CI 2.29-5.21, P<0.001). The adjusted hazard ratio of the Transient Remission group was significantly lower than that of the Persistent group (P<0.05). CONCLUSION Transient remission of NAFLD significantly decreased the risk of developing T2DM.
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Jorge-Galarza E, Medina-Urrutia A, Posadas-Sánchez R, Posadas-Romero C, Cardoso-Saldaña G, Vargas-Alarcón G, Caracas-Portilla N, González-Salazar C, Torres-Tamayo M, Juárez-Rojas JG. Adipose tissue dysfunction increases fatty liver association with pre diabetes and newly diagnosed type 2 diabetes mellitus. Diabetol Metab Syndr 2016; 8:73. [PMID: 27843495 PMCID: PMC5105292 DOI: 10.1186/s13098-016-0189-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 11/05/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To evaluate the role of adipose tissue function on the association of fatty liver (FL) with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes mellitus (nT2D). METHODS In 1264 subjects, computed tomography was used to evaluate FL and elevated visceral adipose tissue (VAT). Fasting plasma glucose, <5.6, 5.6-6.9 and ≥7 mmol/l, were used to defined normoglycemic (NG), IFG or nT2D, respectively. Elevated free fatty acids, low serum adiponectin levels and adipose tissue insulin resistance (Adipo-IR), were used as markers of adipose tissue dysfunction. RESULTS Compared to NG subjects, those with IFG or nT2D had higher prevalence of FL and elevated VAT. FL was found to be independently associated with IFG and nT2D. Adipo-IR increased the association between FL and IFG [OR: 2.46 (95% I.C.: 1.73-3.49) to 5.42 (3.11-9.41)], whereas low adiponectin levels had a higher effect on the FL and nT2D association [OR: 4.26 (2.18-8.34) to 8.53 (2.96-24.55)]. CONCLUSION Fatty liver was independently associated with IFG and nT2D. Our results indicate for the first time, that adipose tissue dysfunction increases these associations.
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Affiliation(s)
- Esteban Jorge-Galarza
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Aida Medina-Urrutia
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Rosalinda Posadas-Sánchez
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Carlos Posadas-Romero
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Guillermo Cardoso-Saldaña
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Gilberto Vargas-Alarcón
- Molecular Biology Department, National Institute of Cardiology “Ignacio Chávez”, Mexico, Mexico
| | - Nacú Caracas-Portilla
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Carmen González-Salazar
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Margarita Torres-Tamayo
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
| | - Juan Gabriel Juárez-Rojas
- Endocrinology Department, National Institute of Cardiology “Ignacio Chávez”, Juan Badiano No. 1, Col Sección XVI, Tlalpan, 14080 Mexico, Mexico
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El Sohafy SM, Metwally AM, Omar AA, Amer ME, Radwan MM, Abdel-Kader MS, El Toumy SA, ElSohly MA. Cornigerin, a new sesqui-lignan from the hepatoprotective fractions of Cynara cornigera L. Fitoterapia 2016; 115:101-105. [PMID: 27693744 DOI: 10.1016/j.fitote.2016.09.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Revised: 09/21/2016] [Accepted: 09/26/2016] [Indexed: 01/23/2023]
Abstract
The ethanol extract of Cynara cornigera L. was fractionated and the fractions were subjected to hepatoprotective assays using Wistar albino rats at a dose of 500 and 250mg/kg. The liver injury was induced in rats using carbon tetrachloride. Biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin were estimated as reflections of the liver condition, with silymarin as a positive control. Phytochemical investigation and chromatographic separation of the hepatoprotective fractions led to the isolation of a new sesqui-lignan namely cornigerin (1), along with eight known compounds: apigenin (2), luteolin (3), β-sitosterol glycoside (4), apigenin 7-O-β-D-glucopyranoside (5), luteolin-7-O-β-D-glucopyranoside (6), apigenin-7-O-rutinoside (7), cynarin 1,5-di-O-caffeoylquinic acid (8), and apigenin-7-O-β-D-glucuronide (9). This is the first report for the isolation of 8 and 9 from this plant.
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Affiliation(s)
- Samah M El Sohafy
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21215, Egypt.
| | - Aly M Metwally
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21215, Egypt
| | - Abdalla A Omar
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21215, Egypt
| | - Masouda E Amer
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21215, Egypt
| | - Mohamed M Radwan
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21215, Egypt; National Center for Natural Products Research School of Pharmacy, University of Mississippi, University, MS 38677, USA
| | - Maged S Abdel-Kader
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21215, Egypt; Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin AbdulAziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia
| | - Sayed A El Toumy
- Chemistry of Tannins Department, National Research Center, Dokki, 12622 Cairo, Egypt
| | - Mahmoud A ElSohly
- National Center for Natural Products Research School of Pharmacy, University of Mississippi, University, MS 38677, USA; Department of Pharmaceutics and Drug delivery, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
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Stefan N, Fritsche A, Schick F, Häring HU. Phenotypes of prediabetes and stratification of cardiometabolic risk. Lancet Diabetes Endocrinol 2016; 4:789-798. [PMID: 27185609 DOI: 10.1016/s2213-8587(16)00082-6] [Citation(s) in RCA: 147] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Revised: 02/17/2016] [Accepted: 02/26/2016] [Indexed: 02/07/2023]
Abstract
Prediabetes is associated with increased risks of type 2 diabetes, cardiovascular disease, dementia, and cancer, and its prevalence is increasing worldwide. Lifestyle and pharmacological interventions in people with prediabetes can prevent the development of diabetes and possibly cardiovascular disease. However, prediabetes is a highly heterogeneous metabolic state, both with respect to its pathogenesis and prediction of disease. Improved understanding of these features and precise phenotyping of prediabetes could help to improve stratification of disease risk. In this Personal View, we focus on the extreme metabolic phenotypes of metabolically healthy obesity and metabolically unhealthy normal weight, insulin secretion failure, insulin resistance, visceral obesity, and non-alcoholic fatty liver disease. We present new analyses aimed at improving characterisation of phenotypes in lean, overweight, and obese people with prediabetes. We discuss evidence from lifestyle intervention studies to explore whether these phenotypes can also be used for individualised prediction and prevention of cardiometabolic diseases.
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Affiliation(s)
- Norbert Stefan
- Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany.
| | - Andreas Fritsche
- Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Fritz Schick
- Section of Experimental Radiology, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany
| | - Hans-Ulrich Häring
- Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Centre for Diabetes Research (DZD), Tübingen, Germany
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Nishi T, Babazono A, Maeda T, Imatoh T, Une H. Effects of Eating Fast and Eating Before Bedtime on the Development of Nonalcoholic Fatty Liver Disease. Popul Health Manag 2016; 19:279-83. [DOI: 10.1089/pop.2015.0088] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Affiliation(s)
- Takumi Nishi
- Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Fukuoka Institute of Health and Environment Sciences, Fukuoka, Japan
| | - Akira Babazono
- Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshiki Maeda
- Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takuya Imatoh
- Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan
| | - Hiroshi Une
- Medical Research Center, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
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Hazlehurst JM, Woods C, Marjot T, Cobbold JF, Tomlinson JW. Non-alcoholic fatty liver disease and diabetes. Metabolism 2016; 65:1096-108. [PMID: 26856933 PMCID: PMC4943559 DOI: 10.1016/j.metabol.2016.01.001] [Citation(s) in RCA: 371] [Impact Index Per Article: 41.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 01/04/2016] [Accepted: 01/05/2016] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) are common conditions that regularly co-exist and can act synergistically to drive adverse outcomes. The presence of both NAFLD and T2DM increases the likelihood of the development of complications of diabetes (including both macro- and micro- vascular complications) as well as augmenting the risk of more severe NAFLD, including cirrhosis, hepatocellular carcinoma and death. The mainstay of NAFLD management is currently to reduce modifiable metabolic risk. Achieving good glycaemic control and optimising weight loss are pivotal to restricting disease progression. Once cirrhosis has developed, it is necessary to screen for complications and minimise the risk of hepatic decompensation. Therapeutic disease modifying options for patients with NAFLD are currently limited. When diabetes and NAFLD co-exist, there are published data that can help inform the clinician as to the most appropriate oral hypoglycaemic agent or injectable therapy that may improve NAFLD, however most of these data are drawn from observations in retrospective series and there is a paucity of well-designed randomised double blind placebo controlled studies with gold-standard end-points. Furthermore, given the heterogeneity of inclusion criteria and primary outcomes, as well as duration of follow-up, it is difficult to draw robust conclusions that are applicable across the entire spectrum of NAFLD and diabetes. In this review, we have summarised and critically evaluated the available data, with the aim of helping to inform the reader as to the most pertinent issues when managing patients with co-existent NAFLD and T2DM.
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Affiliation(s)
- Jonathan M Hazlehurst
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK, OX3 7LE
| | - Conor Woods
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK, OX3 7LE
| | - Thomas Marjot
- Department of Gastroenterology, Oxford University Hospitals NHS Trust, Oxford, UK, OX3 9DU
| | - Jeremy F Cobbold
- Department of Gastroenterology, Oxford University Hospitals NHS Trust, Oxford, UK, OX3 9DU
| | - Jeremy W Tomlinson
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK, OX3 7LE.
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Abstract
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of liver disease from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is commonly associated with features of the metabolic/insulin resistance syndrome ('Metabolic/Obese NAFLD') and may therefore predict type 2 diabetes (T2DM). For this review, we searched for prospective studies examining whether NAFLD predicts T2DM, and if so, whether this occurs independently of factors such as age and obesity. These studies included NAFLD diagnosed by ultrasonography (n = 6) or liver enzymes (n = 14). All ultrasonography studies found NAFLD to predict the risk of T2DM independently of age, and in 4 out of 6 studies NAFLD was also a predictor independently of BMI. NAFLD was a predictor of T2DM in all 14 studies where NAFLD was diagnosed by liver enzymes. In 12 of these studies, ALT or AST or GGT were significant predictors of T2DM risk, independently of age and BMI. NAFLD, however, is heterogeneous and may also be caused by common genetic variants. The I148M variant in PNPLA3 and the E167K variant in TM6SF2 are both associated with increased liver fat content, but not features of the metabolic/insulin resistance syndrome. These genetic forms of NAFLD predict NASH and cirrhosis but not T2DM. Taken together these data imply that 'Metabolic/Obese NAFLD' predicts T2DM independently of age and obesity and support the role of hepatic insulin resistance in the pathogenesis of this disease.
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Affiliation(s)
- S Lallukka
- Department of Medicine, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
| | - H Yki-Järvinen
- Department of Medicine, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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