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Fomin G, Tabynov K, Islamov R, Turebekov N, Yessimseit D, Yerubaev T. Cytokine response and damages in the lungs of aging Syrian hamsters on a high-fat diet infected with the SARS-CoV-2 virus. Front Immunol 2023; 14:1223086. [PMID: 37520568 PMCID: PMC10375707 DOI: 10.3389/fimmu.2023.1223086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 06/22/2023] [Indexed: 08/01/2023] Open
Abstract
Hypertriglyceridemia, obesity, and aging are among the key risk factors for severe COVID-19 with acute respiratory distress syndrome (ARDS). One of the main prognostic biomarkers of ARDS is the level of cytokines IL-6 and TNF-α in the blood. In our study, we modeled hyperglyceridemia and hypercholesterolemia on 18-month-old Syrian hamsters (Mesocricetus auratus). By 18 months, the animals showed such markers of aging as weight stabilization with a tendency to reduce it, polycystic liver disease, decreased motor activity, and foci of alopecia. The high-fat diet caused an increase in triglycerides and cholesterol, as well as fatty changes in the liver. On the third day after infection with the SARS-CoV-2 virus, animals showed a decrease in weight in the groups with a high-fat diet. In the lungs of males on both diets, there was an increase in the concentration of IFN-α, as well as IL-6 in both males and females, regardless of the type of diet. At the same time, the levels of TNF-α and IFN-γ did not change in infected animals. Morphological studies of the lungs of hamsters with SARS-CoV-2 showed the presence of a pathological process characteristic of ARDS. These included bronchointerstitial pneumonia and diffuse alveolar damages. These observations suggest that in aging hamsters, the immune response to pro-inflammatory cytokines may be delayed to a later period. Hypertriglyceridemia, age, and gender affect the severity of COVID-19. These results will help to understand the pathogenesis of COVID-19 associated with age, gender, and disorders of fat metabolism in humans.
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Affiliation(s)
- Gleb Fomin
- Central Reference Laboratory, Aikimbayev’s National Scientific Center for Especially Dangerous Infections, Almaty, Kazakhstan
- Department of Biodiversity and Bioresources, Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty, Kazakhstan
| | - Kairat Tabynov
- Central Reference Laboratory, Aikimbayev’s National Scientific Center for Especially Dangerous Infections, Almaty, Kazakhstan
- International Center for Vaccinology, Kazakh National Agrarian Research University, Almaty, Kazakhstan
| | - Rinat Islamov
- Central Reference Laboratory, Aikimbayev’s National Scientific Center for Especially Dangerous Infections, Almaty, Kazakhstan
| | - Nurkeldi Turebekov
- Central Reference Laboratory, Aikimbayev’s National Scientific Center for Especially Dangerous Infections, Almaty, Kazakhstan
| | - Duman Yessimseit
- Central Reference Laboratory, Aikimbayev’s National Scientific Center for Especially Dangerous Infections, Almaty, Kazakhstan
| | - Toktasyn Yerubaev
- Central Reference Laboratory, Aikimbayev’s National Scientific Center for Especially Dangerous Infections, Almaty, Kazakhstan
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Hiruma S, Shigiyama F, Kumashiro N. Empagliflozin versus sitagliptin for ameliorating intrahepatic lipid content and tissue-specific insulin sensitivity in patients with early-stage type 2 diabetes with non-alcoholic fatty liver disease: A prospective randomized study. Diabetes Obes Metab 2023; 25:1576-1588. [PMID: 36749298 DOI: 10.1111/dom.15006] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 01/24/2023] [Accepted: 02/02/2023] [Indexed: 02/08/2023]
Abstract
AIM To compare the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 inhibitors on ectopic fat accumulation and tissue-specific insulin sensitivity. MATERIALS AND METHODS This randomized controlled trial enrolled 44 patients with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). They were randomly assigned to receive either empagliflozin 10 mg/day or sitagliptin 100 mg/day for 12 weeks. The primary endpoint was the change in intrahepatic lipid content (IHL) measured using proton magnetic resonance spectroscopy (1 H-MRS). The secondary endpoints included intramuscular and extramuscular lipid content seen in 1 H-MRS, body composition seen through dual-energy X-ray absorptiometry and tissue-specific insulin sensitivity shown through hyperinsulinaemic-euglycaemic clamp using stable isotopic glucose. Liver biopsy samples were pathologically evaluated at baseline. RESULTS At baseline, the mean duration of diabetes, HbA1c level and IHL were 3.7 years, 7.2% and 20.9%, respectively. The median NAFLD activity score was 3.0. IHL was significantly more decreased in the empagliflozin group than that in the sitagliptin group (between-group difference was -5.2% ± 1.1% and -1.9% ± 1.2%, respectively, (95% confidence interval); -3.3 (-6.5, -0.1), P = .044). However, there were no significant between-group differences in the change of insulin sensitivity in the liver, muscle or adipose tissues. Interestingly, hepatic insulin sensitivity was significantly increased only in the empagliflozin group and was significantly negatively associated with the change in IHL. CONCLUSIONS Empagliflozin significantly improves hepatic steatosis compared with sitagliptin, and this may protect against subsequent hepatic insulin resistance. Early administration of SGLT2 inhibitors is preferable for T2D patients with NAFLD.
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Affiliation(s)
- Shigenori Hiruma
- Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan
| | - Fumika Shigiyama
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Ishikawa, Japan
| | - Naoki Kumashiro
- Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, Tokyo, Japan
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Ishikawa, Japan
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3
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Melis M, Tang XH, Trasino SE, Gudas LJ. Retinoids in the Pathogenesis and Treatment of Liver Diseases. Nutrients 2022; 14:1456. [PMID: 35406069 PMCID: PMC9002467 DOI: 10.3390/nu14071456] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 03/24/2022] [Accepted: 03/28/2022] [Indexed: 02/06/2023] Open
Abstract
Vitamin A (VA), all-trans-retinol (ROL), and its analogs are collectively called retinoids. Acting through the retinoic acid receptors RARα, RARβ, and RARγ, all-trans-retinoic acid, an active metabolite of VA, is a potent regulator of numerous biological pathways, including embryonic and somatic cellular differentiation, immune functions, and energy metabolism. The liver is the primary organ for retinoid storage and metabolism in humans. For reasons that remain incompletely understood, a body of evidence shows that reductions in liver retinoids, aberrant retinoid metabolism, and reductions in RAR signaling are implicated in numerous diseases of the liver, including hepatocellular carcinoma, non-alcohol-associated fatty liver diseases, and alcohol-associated liver diseases. Conversely, restoration of retinoid signaling, pharmacological treatments with natural and synthetic retinoids, and newer agonists for specific RARs show promising benefits for treatment of a number of these liver diseases. Here we provide a comprehensive review of the literature demonstrating a role for retinoids in limiting the pathogenesis of these diseases and in the treatment of liver diseases.
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Affiliation(s)
- Marta Melis
- Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA; (M.M.); (X.-H.T.)
| | - Xiao-Han Tang
- Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA; (M.M.); (X.-H.T.)
| | - Steven E. Trasino
- Nutrition Program, Hunter College, City University of New York, New York, NY 10065, USA;
| | - Lorraine J. Gudas
- Department of Pharmacology, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA; (M.M.); (X.-H.T.)
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4
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Nomura S, Sakamoto H, Rauniyar SK, Shimada K, Yamamoto H, Kohsaka S, Ichihara N, Kumamaru H, Miyata H. Analysis of the relationship between the HbA1c screening results and the development and worsening of diabetes among adults aged over 40 years: a 4-year follow-up study of 140,000 people in Japan - the Shizuoka study. BMC Public Health 2021; 21:1880. [PMID: 34663286 PMCID: PMC8524880 DOI: 10.1186/s12889-021-11933-z] [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: 02/15/2021] [Accepted: 09/30/2021] [Indexed: 11/11/2022] Open
Abstract
Background Hemoglobin A1c (HbA1c) levels are routinely measured during health check-ups and are used as an indicator of glycemic control in Japan. However, only a few studies have followed up individuals to assess the risk of diabetes development and worsening based on HbA1c screening results. This study evaluated the relationship between HbA1c screening results and the risk of diabetes development and worsening. Methods Data were collected from the Shizuoka Kokuho Database, a Japanese administrative claims database of insured individuals aged > 40 years. We included individuals available for follow-up from April 2012 to March 2018 who had not received any diabetes treatment before March 2014. HbA1c screening results were categorized into 4 groups based on the HbA1c levels at the 2012 and 2013 health check-ups: group A, those whose HbA1c levels were < 6.5% in 2012 and 2013; group B, those whose HbA1c levels > 6.5% in 2012 but < 6.5% in 2013; group C, those whose HbA1c levels were > 6.5% in 2012 and 2013; and group D, those whose HbA1c levels were < 6.5% in 2012 and > 6.5% in 2013. Logistic regression models were used to analyze diabetes development and worsening, defined as the initiation of diabetes treatment by March 2018 and the use of injection drugs by participants who initiated diabetes treatment by March 2018. Results Overall, 137,852 individuals were analyzed. After adjusting for covariates, compared with group A, group B was more likely to initiate treatment within 4 years (odds ratio: 22.64; 95% confidence interval: 14.66–34.99). In patients who initiated diabetes treatment by March 2018, injection drugs were less likely used by group D than by group A (odds ratio: 0.28; 95% confidence interval: 0.12–0.61). Conclusions Our study suggests that although HbA1c levels measured during health check-ups were correlated with the risk of diabetes development and worsening, HbA1c levels in a single year may not necessarily provide sufficient information to consider these future risks. Supplementary Information The online version contains supplementary material available at 10.1186/s12889-021-11933-z.
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Affiliation(s)
- Shuhei Nomura
- Research Support Center, Shizuoka General Hospital, Shizuoka, Japan. .,Department of Health Policy and Management, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. .,Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. .,Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
| | - Haruka Sakamoto
- Department of Health Policy and Management, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.,Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Santosh Kumar Rauniyar
- Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Koki Shimada
- Research Support Center, Shizuoka General Hospital, Shizuoka, Japan.,Department of Health Policy and Management, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Hiroyuki Yamamoto
- Research Support Center, Shizuoka General Hospital, Shizuoka, Japan.,Department of Health Policy and Management, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.,Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shun Kohsaka
- Research Support Center, Shizuoka General Hospital, Shizuoka, Japan.,Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Department of Cardiology, School of Medicine, Keio University, Tokyo, Japan
| | - Nao Ichihara
- Research Support Center, Shizuoka General Hospital, Shizuoka, Japan.,Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiraku Kumamaru
- Research Support Center, Shizuoka General Hospital, Shizuoka, Japan.,Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Miyata
- Research Support Center, Shizuoka General Hospital, Shizuoka, Japan.,Department of Health Policy and Management, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.,Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.,Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Goday A, Julià H, de Vargas-Machuca A, Pedro-Botet J, Benavente S, Ramon JM, Pera M, Casajoana A, Villatoro M, Fontané L, Bisbe M, Climent E, Castañer O, Flores Le Roux JA, Benaiges D. Bariatric surgery improves metabolic and nonalcoholic fatty liver disease markers in metabolically healthy patients with morbid obesity at 5 years. Surg Obes Relat Dis 2021; 17:2047-2053. [PMID: 34509375 DOI: 10.1016/j.soard.2021.07.021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 07/22/2021] [Accepted: 07/31/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND No studies have evaluated the effect of metabolic and bariatric surgery (MBS) on nonalcoholic fatty liver disease (NAFLD) and cardiometabolic markers in metabolically healthy patients with morbid obesity (MHMO) at midterm. OBJECTIVES To assess the effect of MBS on NAFLD and cardiometabolic markers in MHMO patients and ascertain whether metabolically unhealthy patients with morbid obesity (MUMO) remain metabolically healthy at 5 years after MBS. SETTING University hospital. METHODS A total of 191 patients with a body mass index >40 kg/m2 and at least 5 years of follow-up were retrospectively analyzed. Lost to follow-up were 37.6% (151 of 401 patients). Patients were classified as MHMO if 1 or 0 of the cardiometabolic markers were present using the Wildman criteria. The degree of liver fibrosis was assessed using the NAFLD fibrosis score (NFS). RESULTS Forty-one patients (21.5%) fulfilled the criteria for MHMO. They showed significant improvements in blood pressure (from 135.1 ± 22.1 and 84.2 ± 14.3 mm Hg to 117.7 ± 19.2 and 73.0 ± 10.9 mm Hg), plasma glucose (from 91.0 ± 5.6 mg/dL to 87.2 ± 5.2 mg/dL), homeostatic model assessment for insulin resistance (from 2.2 ± .9 to 1.0 ± .8), triglycerides (from 88.0 [range, 79.5-103.5] mg/dL to 61.0 [range, 2.0-76.5] mg/dL), alanine aminotransferase, gamma-glutamyl transpeptidase NFS (from -1.0 ± 1.0 to -1.9 ± 1.2), and high-density lipoprotein cholesterol (from 56.9 ± 10.5 mg/dL to 77.9 ± 17.4 mg/dL) at 5 years after surgery. A total of 108 MUMO patients (84.4%) who became metabolically healthy after 1 year stayed healthy at 5 years. CONCLUSIONS MBS induced a midterm improvement in cardiometabolic and NAFLD markers in MHMO patients. Seventy-six percent of MUMO patients became metabolically healthy at 5 years after MBS.
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Affiliation(s)
- Alberto Goday
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain; Cardiovascular Risk and Nutrition Research Group (CARIN-ULEC), Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona Biomedical Research Park, Barcelona, Spain; Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain; Centro de Investigaciones Biomédicas en Red de Obesidad y Nutrición, Madrid, Spain
| | - Helena Julià
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain; Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain
| | | | - Juan Pedro-Botet
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain; Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain
| | - Sergi Benavente
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Jose M Ramon
- Unit of Gastrointestinal Surgery, Hospital del Mar, Institut de Recerca Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain
| | - Manuel Pera
- Unit of Gastrointestinal Surgery, Hospital del Mar, Institut de Recerca Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain
| | - Anna Casajoana
- Unit of Gastrointestinal Surgery, Hospital del Mar, Institut de Recerca Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain
| | | | - Laia Fontané
- Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain
| | - Maria Bisbe
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Elisenda Climent
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain; Cardiovascular Risk and Nutrition Research Group (CARIN-ULEC), Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona Biomedical Research Park, Barcelona, Spain; Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain
| | - Olga Castañer
- Cardiovascular Risk and Nutrition Research Group (CARIN-ULEC), Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona Biomedical Research Park, Barcelona, Spain; Centro de Investigaciones Biomédicas en Red de Obesidad y Nutrición, Madrid, Spain
| | - Juana A Flores Le Roux
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain; Cardiovascular Risk and Nutrition Research Group (CARIN-ULEC), Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona Biomedical Research Park, Barcelona, Spain; Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain
| | - David Benaiges
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain; Cardiovascular Risk and Nutrition Research Group (CARIN-ULEC), Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona Biomedical Research Park, Barcelona, Spain; Department of Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain; Consorci Sanitari de l'Alt Penedès i Garraf, Vilafranca del Penedès, Spain.
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Sinha R, Kachru D, Ricchetti RR, Singh-Rambiritch S, Muthukumar KM, Singaravel V, Irudayanathan C, Reddy-Sinha C, Junaid I, Sharma G, Francis-Lyon PA. Leveraging Genomic Associations in Precision Digital Care for Weight Loss: Cohort Study. J Med Internet Res 2021; 23:e25401. [PMID: 33849843 PMCID: PMC8173391 DOI: 10.2196/25401] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 12/18/2020] [Accepted: 04/11/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The COVID-19 pandemic has highlighted the urgency of addressing an epidemic of obesity and associated inflammatory illnesses. Previous studies have demonstrated that interactions between single-nucleotide polymorphisms (SNPs) and lifestyle interventions such as food and exercise may vary metabolic outcomes, contributing to obesity. However, there is a paucity of research relating outcomes from digital therapeutics to the inclusion of genetic data in care interventions. OBJECTIVE This study aims to describe and model the weight loss of participants enrolled in a precision digital weight loss program informed by the machine learning analysis of their data, including genomic data. It was hypothesized that weight loss models would exhibit a better fit when incorporating genomic data versus demographic and engagement variables alone. METHODS A cohort of 393 participants enrolled in Digbi Health's personalized digital care program for 120 days was analyzed retrospectively. The care protocol used participant data to inform precision coaching by mobile app and personal coach. Linear regression models were fit of weight loss (pounds lost and percentage lost) as a function of demographic and behavioral engagement variables. Genomic-enhanced models were built by adding 197 SNPs from participant genomic data as predictors and refitted using Lasso regression on SNPs for variable selection. Success or failure logistic regression models were also fit with and without genomic data. RESULTS Overall, 72.0% (n=283) of the 393 participants in this cohort lost weight, whereas 17.3% (n=68) maintained stable weight. A total of 142 participants lost 5% bodyweight within 120 days. Models described the impact of demographic and clinical factors, behavioral engagement, and genomic risk on weight loss. Incorporating genomic predictors improved the mean squared error of weight loss models (pounds lost and percent) from 70 to 60 and 16 to 13, respectively. The logistic model improved the pseudo R2 value from 0.193 to 0.285. Gender, engagement, and specific SNPs were significantly associated with weight loss. SNPs within genes involved in metabolic pathways processing food and regulating fat storage were associated with weight loss in this cohort: rs17300539_G (insulin resistance and monounsaturated fat metabolism), rs2016520_C (BMI, waist circumference, and cholesterol metabolism), and rs4074995_A (calcium-potassium transport and serum calcium levels). The models described greater average weight loss for participants with more risk alleles. Notably, coaching for dietary modification was personalized to these genetic risks. CONCLUSIONS Including genomic information when modeling outcomes of a digital precision weight loss program greatly enhanced the model accuracy. Interpretable weight loss models indicated the efficacy of coaching informed by participants' genomic risk, accompanied by active engagement of participants in their own success. Although large-scale validation is needed, our study preliminarily supports precision dietary interventions for weight loss using genetic risk, with digitally delivered recommendations alongside health coaching to improve intervention efficacy.
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Affiliation(s)
| | - Dashyanng Kachru
- Digbi Health, Los Altos, CA, United States
- Health Informatics, University of San Francisco, San Francisco, CA, United States
| | | | | | | | | | | | | | | | | | - Patricia Alice Francis-Lyon
- Digbi Health, Los Altos, CA, United States
- Health Informatics, University of San Francisco, San Francisco, CA, United States
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7
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Kohsaka S, Morita N, Okami S, Kidani Y, Yajima T. Current trends in diabetes mellitus database research in Japan. Diabetes Obes Metab 2021; 23 Suppl 2:3-18. [PMID: 33835639 DOI: 10.1111/dom.14325] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 01/14/2021] [Accepted: 01/24/2021] [Indexed: 02/06/2023]
Abstract
With the widespread use of electronic medical records and administrative claims databases, analytic results from so-called real-world data have become increasingly important in healthcare decision-making. Diabetes mellitus is a heterogeneous condition that involves a broad spectrum of patients. Real-world database studies have been recognised as a powerful tool to understand the impact of current practices on clinical courses and outcomes, such as long-term glucose control, development of microvascular or macro-vascular diseases, and mortality. Diabetes is also a major global health issue and poses a significant social and economic burden worldwide. Therefore, it is critical to understand the epidemiology, clinical course, treatment reality, and long-term outcomes of diabetes to determine realistic solutions to a variety of disease-related issues that we are facing. In the present review, we summarise the healthcare system and large-scale databases currently available in Japan, introduce the results from recent database studies involving Japanese patients with diabetes, and discuss future opportunities and challenges for the use of databases in the management of diabetes.
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Affiliation(s)
- Shun Kohsaka
- Department of Cardiology, Keio University School of Medicine, Tokyo, Japan
| | - Naru Morita
- Cardiovascular, Renal, and Metabolism, Medical Affairs, AstraZeneca K.K., Osaka, Japan
| | - Suguru Okami
- Cardiovascular, Renal, and Metabolism, Medical Affairs, AstraZeneca K.K., Osaka, Japan
| | - Yoko Kidani
- Cardiovascular, Renal, and Metabolism, Medical Affairs, AstraZeneca K.K., Osaka, Japan
| | - Toshitaka Yajima
- Cardiovascular, Renal, and Metabolism, Medical Affairs, AstraZeneca K.K., Osaka, Japan
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8
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Cho HW, Chung W, Moon S, Ryu OH, Kim MK, Kang JG. Effect of Sarcopenia and Body Shape on Cardiovascular Disease According to Obesity Phenotypes. Diabetes Metab J 2021; 45:209-218. [PMID: 32662256 PMCID: PMC8024159 DOI: 10.4093/dmj.2019.0223] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 12/06/2019] [Indexed: 12/13/2022] Open
Abstract
Background This study aimed to assess the effects of sarcopenia and A Body Shape Index (ABSI) on cardiovascular disease (CVD) risk according to obesity phenotypes. Methods We used data from the National Health and Nutrition Examination Survey 1999 to 2012. A total of 25,270 adults were included and classified into the following groups: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Sarcopenia was defined as the appendicular skeletal mass index <7 kg/m2 in men and <5.5kg/m2 in women. A multivariate logistic regression analysis was performed to evaluate the odds ratio (OR) of sarcopenia and ABSI for CVD events according to the obesity phenotype. Results The MHNW participants with sarcopenia had higher risk for CVD than those without sarcopenia (OR, 2.69; 95% confidence interval [CI], 1.56 to 4.64). In the analysis with MHNW participants without sarcopenia as a reference, the participants with sarcopenia showed a higher OR for CVD than those without sarcopenia in both MHO (OR in participants without sarcopenia, 3.31; 95% CI, 1.94 to 5.64) (OR in participants with sarcopenia, 8.59; 95% CI, 2.63 to 28.04) and MUO participants (OR in participants without sarcopenia, 5.11; 95% CI, 3.21 to 8.15) (OR in participants with sarcopenia, 8.12; 95% CI, 4.04 to 16.32). Participants within the second and third tertiles of ABSI had higher ORs for CVDs than the counterpart of obesity phenotypes within the first tertile. Conclusion These results suggest that clinical approaches that consider muscle and body shape are required.
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Affiliation(s)
- Hyun-Woong Cho
- Division of Endocrinology and Metabolism, Hallym University College of Medicine, Chuncheon, Korea
| | - Wankyo Chung
- Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, Korea
- Institute of Health and Environment, Seoul National University, Seoul, Korea
| | - Shinje Moon
- Division of Endocrinology and Metabolism, Hallym University College of Medicine, Chuncheon, Korea
| | - Ohk-Hyun Ryu
- Division of Endocrinology and Metabolism, Hallym University College of Medicine, Chuncheon, Korea
| | - Min Kyung Kim
- Division of Endocrinology and Metabolism, Hallym University College of Medicine, Chuncheon, Korea
| | - Jun Goo Kang
- Division of Endocrinology and Metabolism, Hallym University College of Medicine, Chuncheon, Korea
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9
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Lee YS, Hwang LC, Hsu HY, Tsou MT. The Association Between Different Obesity Phenotypes and Liver Fibrosis Scores in Elderly Individuals with Fatty Liver in Taiwan. Diabetes Metab Syndr Obes 2021; 14:1473-1483. [PMID: 33833538 PMCID: PMC8019606 DOI: 10.2147/dmso.s302207] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 03/11/2021] [Indexed: 04/14/2023] Open
Abstract
PURPOSE To examine the association between different phenotypes of obesity or metabolic syndromes and liver fibrosis score in a Taiwanese elderly population with fatty liver. PATIENTS AND METHODS This cross-sectional study included 1817 participants aged ≥65 years with fatty liver diagnosed by sonography. We used ethnicity-specific criteria for body mass index and metabolic syndrome, and to define obesity phenotypes as metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Correlated fibrosis severity was calculated using the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and Fibrosis-4 (FIB-4). Fibrosis severity was divided into two categories according to NFS (no-to-mild fibrosis and advanced fibrosis, defined as NFS ≤ 0.676 and >0.676, respectively) and FIB-4 score (no-to-mild fibrosis and advanced fibrosis, defined as FIB-4 score ≤2.67 and >2.67, respectively). RESULTS Compared with that in the MHNO group, the associated risk (odds ratio [OR], 95% confidence interval [CI]) of advanced fibrosis by NFS was 2.43 (1.50-3.93), 2.35 (1.25-4.41), and 6.11 (3.90-9.59), whereas that of advanced fibrosis by FIB-4 score was 1.34 (0.83-2.18), 2.37 (1.36-4.13), and 1.38 (0.82-2.31) in the MUNO, MHO, and MUO groups, respectively. CONCLUSION Both metabolic syndrome and obesity were positively associated with more advanced fibrosis according to NFS. The detrimental effect of obesity appears to be more than metabolic abnormalities per se in the elderly with more advanced fibrosis severity according to the FIB-4 score.
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Affiliation(s)
- Yu-Shan Lee
- Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Lee-Ching Hwang
- Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
| | - Hsin-Yin Hsu
- Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Meng-Ting Tsou
- Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan
- Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
- Correspondence: Meng-Ting Tsou Department of Family Medicine, Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Road, Taipei City, 10449, Taiwan, R.O.C.Tel +886 2 2543 3535 (Ext. 2131 or 2132)Fax +886 2 2543 3642 Email
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10
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Itabashi F, Hirata T, Kogure M, Narita A, Tsuchiya N, Nakamura T, Nakaya N, Sasaki R, Takanashi N, Sakata K, Tanno K, Sugawara J, Kuriyama S, Tsuji I, Kure S, Hozawa A. Combined associations of liver enzymes and obesity with diabetes mellitus prevalence: The Tohoku Medical Megabank Community-based Cohort Study. J Epidemiol 2020; 32:221-227. [PMID: 33390464 PMCID: PMC8979920 DOI: 10.2188/jea.je20200384] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) are enzymes associated with diabetes mellitus (DM) prevalence. However, limited information is available regarding the association of liver enzymes and DM consistently present in obese and non-obese individuals. We examined whether the combination of ALT and GGT enzymes is associated with the prevalence of DM regardless of obesity in a general Japanese population. METHODS We conducted a cross-sectional study of 62,786 participants aged ≥20 years who lived in Miyagi and Iwate, Japan. We divided all the participants into eight groups according to the ALT level (low: <30 IU/L and high: ≥30 IU/L), GGT level (low: <50 IU/L and high: ≥50 IU/L), and the presence of obesity. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression analysis, adjusting for potential confounders, to determine associations of the combination of ALT and GGT levels and obesity with DM prevalence. RESULTS Overall, 6,008 participants (9.6%) had DM. Compared to non-obese individuals with low ALT and GGT levels, the participants with high ALT and GGT levels had high ORs for DM in both obese (OR 4.06; 95% CI, 3.61-4.56) and non-obese groups (OR 2.19; 95% CI, 1.89-2.52). The obese group had high ORs for DM, even at low ALT and GGT levels. CONCLUSION High ALT and GGT levels are associated with DM prevalence in obese and non-obese participants. This finding suggests that correcting ALT and GGT levels and controlling obesity are important for the prevention of DM.
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Affiliation(s)
- Fumi Itabashi
- Tohoku Medical Megabank Organization, Tohoku University
| | - Takumi Hirata
- Tohoku Medical Megabank Organization, Tohoku University.,Hokkaido University Faculty of Medicine
| | - Mana Kogure
- Tohoku Medical Megabank Organization, Tohoku University
| | - Akira Narita
- Tohoku Medical Megabank Organization, Tohoku University
| | - Naho Tsuchiya
- Tohoku Medical Megabank Organization, Tohoku University
| | | | - Naoki Nakaya
- Tohoku Medical Megabank Organization, Tohoku University.,Saitama Prefectural University
| | - Ryohei Sasaki
- Department of Human Sciences, Center for Liberal Arts and Sciences, Iwate Medical University
| | - Nobuyuki Takanashi
- Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University
| | - Kiyomi Sakata
- Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University
| | - Kozo Tanno
- Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University
| | | | | | - Ichiro Tsuji
- Tohoku Medical Megabank Organization, Tohoku University
| | - Shigeo Kure
- Tohoku Medical Megabank Organization, Tohoku University
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11
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Klitgaard HB, Kilbak JH, Nozawa EA, Seidel AV, Magkos F. Physiological and Lifestyle Traits of Metabolic Dysfunction in the Absence of Obesity. Curr Diab Rep 2020; 20:17. [PMID: 32232577 DOI: 10.1007/s11892-020-01302-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW Individuals with metabolically unhealthy normal weight (MUNW) have an adverse cardiometabolic risk factor profile in the absence of excess body weight, and increased risk for diabetes and heart disease. We critically review some physiological traits and lifestyle characteristics of the MUNW phenotype. RECENT FINDINGS The prevalence of MUNW varies considerably around the world and among ethnicities, partly because of different definitions; on average, this phenotype affects about ~ 30% of normal weight persons globally. Most studies have recruited MUNW subjects who, although within the normal weight range, are significantly "more obese" than their metabolically healthy lean peers (greater body mass index or total body fat); hence one cannot ascertain whether observed differences are true traits of the MUNW phenotype of simply secondary to greater relative adiposity within the normal range. Carefully matched studies have indicated that MUNW can exist in the absence of excess total body fat. These subjects have a preferential accumulation of fat in the upper body (abdominal subcutaneous and visceral adipose tissues) and the liver, but not skeletal muscle; perhaps surprisingly, this predominantly "android" fat distribution does not translate into increased waist circumference. The MUNW phenotype is associated with lower aerobic fitness and muscle mass and strength, but whether this is simply due to inadequate regular physical activity is not entirely clear. Likewise, no consistent associations have been found between any dietary factors and the development of MUNW phenotype, but diet-induced modest weight loss facilitates its resolution. Delineating the mechanisms leading to metabolic dysfunction in the absence of increased body weight and body fat will likely reveal important targets for improving metabolic health and eventually for reducing the burden of cardiometabolic disease, not only in individuals with normal body weight but also in people with obesity.
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Affiliation(s)
- Hanna Bjørk Klitgaard
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
| | - Jesper Hoffmann Kilbak
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
| | - Erica Arhnung Nozawa
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
| | - Ann V Seidel
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
| | - Faidon Magkos
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
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12
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Lee S, Lacy ME, Jankowich M, Correa A, Wu WC. Association between obesity phenotypes of insulin resistance and risk of type 2 diabetes in African Americans: The Jackson Heart Study. J Clin Transl Endocrinol 2020; 19:100210. [PMID: 31871895 PMCID: PMC6909037 DOI: 10.1016/j.jcte.2019.100210] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 11/05/2019] [Accepted: 11/18/2019] [Indexed: 01/14/2023] Open
Abstract
OBJECTIVE To determine whether insulin resistance (IR) measured by homeostasis model of insulin resistance (HOMA-IR) can further stratify diabetes risk in African Americans (AAs) beyond obesity and identify obese, low risk and non-obese, high risk individuals. METHODS Using the Jackson Heart Study cohort, we categorized participants without diabetes into four phenotypes: non-obese/insulin-sensitive, non-obese/IR, obese/insulin-sensitive and obese/IR. Obesity was defined as BMI ≥ 30 or BMI 25-30 plus an increased waist circumference. IR was defined as HOMA-IR ≥ 2. We used modified Poisson regression models to estimate the incident risk-ratios (IRR) of diabetes across these phenotypes adjusting for potential confounders and HbA1c. RESULTS Among 3219 AAs without diabetes, 14.0% were non-obese/insulin-sensitive, 24.6% non-obese/IR, 6.2% obese/insulin-sensitive, and 55.3% obese/IR. The overall crude incidence rate of diabetes was 29.91 cases/1000 person-years. In fully-adjusted models, compared to the non-obese/insulin-sensitive group, the relative risk of diabetes was highest in obese/IR (IRR = 2.35; 95% CI: 1.53, 3.60), followed by non-obese/IR (IRR = 1.59; 95% CI: 1.02, 2.46), and non-significant for the obese/insulin-sensitive (IRR = 1.70; 95% CI: 0.97, 2.99) group. CONCLUSIONS HOMA-IR can further stratify diabetes risk in AA adults beyond obesity, identifying non-obese high-risk and lower-risk obese individuals. However, diabetes risk should still be carefully monitored in obese populations despite insulin sensitivity.
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Affiliation(s)
- Sean Lee
- Providence VA Medical Center, Alpert Medical School & School of Public Health at Brown University, United States
| | - Mary E. Lacy
- Department of Epidemiology and Biostatistics, University of California, San Francisco, United States
- Department of Epidemiology, University of Kentucky, United States
| | - Mathew Jankowich
- Providence VA Medical Center, Alpert Medical School & School of Public Health at Brown University, United States
| | - Adolfo Correa
- Departments of Medicine and Population Health Science, University of Mississippi Medical Center, United States
| | - Wen-Chih Wu
- Providence VA Medical Center, Alpert Medical School & School of Public Health at Brown University, United States
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13
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Kim D, Kim W, Joo SK, Han J, Kim JH, Harrison SA, Younossi ZM, Ahmed A. Association between body size-metabolic phenotype and nonalcoholic steatohepatitis and significant fibrosis. J Gastroenterol 2020; 55:330-341. [PMID: 31535207 DOI: 10.1007/s00535-019-01628-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 09/03/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Body size-metabolic phenotype may help predict whether or not individuals with nonalcoholic fatty liver disease (NAFLD) develop advanced liver disease. We studied the association of body size-metabolic phenotype with nonalcoholic steatohepatitis (NASH) and significant fibrosis. METHODS Our cross-sectional study included 559 subjects (mean age of 53 years; women 51%) with biopsy-proven NAFLD. Clinical, genetic, and histological characteristic features of NAFLD were evaluated. The metabolically unhealthy phenotype was defined by the presence of two or more metabolic components, while body size was categorized based on body mass index: obese (≥ 25 kg/m2) or non-obese (< 25 kg/m2). Body size-metabolic phenotypes were divided into four study groups: (1) non-obese metabolic syndrome (MS)-, (2) non-obese MS+ , (3) obese MS-, and (4) obese MS+. RESULTS Obese MS- and non-obese MS+ groups demonstrated comparable levels of insulin resistance, adipose tissue insulin resistance indexes, and visceral adipose tissue (VAT) areas. The VAT area was significantly higher in the obese MS+ group versus obese MS- group. However, the VAT to subcutaneous adipose tissue (SAT) ratio was highest in the non-obese MS+ group. There was no difference in histology between the non-obese MS+, obese MS-, and obese MS+ groups. Multivariate analyses adjusted for age, sex, smoking status, PNPLA3, TM6SF2, and VAT/SAT areas demonstrated an independent and dose-dependent relationship between the body size-metabolic phenotype and NASH or significant fibrosis. CONCLUSION The non-obese MS+ group displayed similar degree of hepatic histological severity compared to their obese MS- counterparts. Metabolic milieu beyond obesity may play a pathogenic role in non-obese MS+ individuals who develop NASH with significant hepatic fibrosis. CLINICAL TRIAL NUMBER NCT02206841.
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Affiliation(s)
- Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
| | - Won Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, South Korea.
| | - Sae Kyung Joo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, South Korea
| | - Jimin Han
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, South Korea
| | - Jung Ho Kim
- Department of Pathology, Seoul Metropolitan Government Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea
| | | | - Zobair M Younossi
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA
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14
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Wei Y, Wang J, Han X, Yu C, Wang F, Yuan J, Miao X, Yao P, Wei S, Wang Y, Liang Y, Zhang X, Guo H, Zheng D, Tang Y, Yang H, He M. Metabolically healthy obesity increased diabetes incidence in a middle-aged and elderly Chinese population. Diabetes Metab Res Rev 2020; 36:e3202. [PMID: 31291052 DOI: 10.1002/dmrr.3202] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 07/01/2019] [Accepted: 07/06/2019] [Indexed: 12/23/2022]
Abstract
BACKGROUND We examined the association between metabolically healthy obese (MHO) and diabetes incidence in a middle-aged and elderly population and whether the association differed by the presence of nonalcoholic fatty liver disease (NAFLD). METHODS We examined 17 801 participants without diabetes at study entry (7980 males and 9821 females with a mean age of 63.2 years) derived from the Dongfeng-Tongji cohort study (median follow-up: 4.6 years). Participants were divided into six groups based on BMI (normal weight, overweight, or obese) and metabolic health (healthy/unhealthy) defined by the Adult Treatment Panel III criteria. The MHO was defined as BMI greater than 28.0 kg/m2 with 0 or 1 of four metabolic abnormalities (elevated blood pressure, triglyceridaemia, hyperglycaemia, low HDL cholesterol). The hazard ratio (HR) and 95% confidence interval (CI) for incident diabetes were derived from the Cox proportional hazard regression model. RESULTS During 79 843 person-years of follow-up, 1453 individuals developed diabetes. Compared with metabolically healthy normal weight (MH-NW) individuals, the multivariable-adjusted HRs (95% CI) were 1.74 (1.16-2.59) for MHO and 2.15 (1.65-2.81) for metabolically unhealthy obese subjects after adjusting for age, sex, smoking, alcohol drinking, physical activity, fruit and vegetable consumption, family history of diabetes, fasting glucose, waist circumference, and NAFLD. Among those without NAFLD, MHO individuals showed higher incidence of diabetes (multivariate-adjusted HR = 2.71, 95% CI: 1.47-5.00) than MH-NW individuals. CONCLUSIONS The MHO phenotype was associated with increased incidence of diabetes in a middle-aged and elderly population, and the association did not differ by the presence or absence of NAFLD.
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Affiliation(s)
- Yue Wei
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Wang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xu Han
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Caizheng Yu
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fei Wang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Yuan
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoping Miao
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ping Yao
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Sheng Wei
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Youjie Wang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuan Liang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaomin Zhang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huan Guo
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dan Zheng
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuhan Tang
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Handong Yang
- Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, China
| | - Meian He
- Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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15
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Tajik S, Mirzababaei A, Ghaedi E, Kord-Varkaneh H, Mirzaei K. Risk of type 2 diabetes in metabolically healthy people in different categories of body mass index: an updated network meta-analysis of prospective cohort studies. J Cardiovasc Thorac Res 2019; 11:254-263. [PMID: 31824606 PMCID: PMC6891044 DOI: 10.15171/jcvtr.2019.43] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 10/05/2019] [Indexed: 12/20/2022] Open
Abstract
Introduction: Risk of diabetes mellitus type 2 (T2DM) is variable between individuals due to different metabolic phenotypes. In present network meta-analysis, we aimed to evaluate the risk of T2DM related with current definitions of metabolic health in different body mass index (BMI) categories.
Methods: Relevant articles were collected by systematically searching PubMed and Scopus databases up to 20 March 2018 and for analyses we used a random-effects model. Nineteen prospective cohort studies were included in the analyses and metabolically healthy normal weight (MHNW) was considered as the reference group in direct comparison for calculating indirect comparisons in difference type of BMI categories.
Results: Total of 199403 participants and 10388 cases from 19 cohort studies, were included in our network meta-analysis. Metabolically unhealthy obesity (MUHO) group poses highest risk for T2DM development with 10 times higher risk when is compared with MHNW (10.46 95% CI; 8.30, 13.18) and after that Metabolically unhealthy overweight (MUOW) individuals were at highest risk of T2DM with 7 times higher risk comparing with MHNW (7.25, 95% CI; 5.49, 9.57). Metabolically healthy overweight and obese (MHOW/MHO) individuals have (1.77, 95% CI; 1.33, 2.35) and (3.00, 95% CI; 2.33, 3.85) risk ratio for T2DM development in comparison with MHNW respectively.
Conclusion: In conclusion we found that being classified as overweight and obese increased the risk of T2DM in comparison with normal weight. In addition, metabolically unhealthy (MUH) individuals are at higher risk of T2DM in all categories of BMI compared with metabolically healthy individuals.
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Affiliation(s)
- Somayeh Tajik
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Atieh Mirzababaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran.,Student's Scientific Research Center, Tehran, Iran
| | - Ehsan Ghaedi
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamed Kord-Varkaneh
- Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Khadijeh Mirzaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
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Metabolic Features of Individuals with Obesity Referred for Bariatric and Metabolic Surgery: a Cohort Study. Obes Surg 2019; 29:3966-3977. [DOI: 10.1007/s11695-019-04067-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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17
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Obesity and risk of hearing loss: A prospective cohort study. Clin Nutr 2019; 39:870-875. [PMID: 30954364 DOI: 10.1016/j.clnu.2019.03.020] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 01/19/2019] [Accepted: 03/13/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND & AIMS The existing yet limited prospective studies reported conflicting results about obesity and hearing loss. We investigated the prospective association between obesity and hearing loss in a large-scale Japanese working population, as well as the association between metabolic phenotype and hearing loss. METHODS The study included 48,549 employees aged 20-64 years and free of hearing loss at baseline. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression was used to investigate the risk of hearing loss associated with body mass index (BMI) and metabolic phenotype (based on a BMI of ≥25.0/<25.0 kg/m2 and presence/absence of ≥2 components of metabolic syndrome, except waist circumference). Baseline and updated information were obtained from annual health checkups. RESULTS With a median follow-up of 7 years, 1595 and 3625 individuals developed unilateral hearing loss at 1 and 4 kHz, respectively. The adjusted hazard ratios (HR) for hearing loss at 1 kHz were 1.21 (1.08, 1.36) and 1.66 (1.33, 2.08) for those with BMI 25.0-29.9 kg/m2 and BMI ≥30.0 kg/m2, respectively, compared to individuals with BMI <25.0 kg/m2. For hearing loss at 4 kHz, the corresponding HRs were 1.14 (1.05, 1.23) and 1.29 (1.09, 1.52). Compared with metabolically healthy non-obese individuals, the adjusted HRs for hearing loss at 1 kHz were 1.19 (1.03, 1.39), 1.27 (1.01, 1.61), and 1.48 (1.25, 1.76) for unhealthy non-obese, healthy obese, and unhealthy obese individuals, respectively. For hearing loss at 4 kHz, the corresponding HRs were 1.13 (1.04, 1.25), 1.21 (1.04, 1.41), and 1.26 (1.12, 1.41). CONCLUSIONS Overweight and obesity are associated with an increased risk of hearing loss, and metabolically unhealthy obesity may confer additional risk.
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Tanaka N, Kimura T, Fujimori N, Nagaya T, Komatsu M, Tanaka E. Current status, problems, and perspectives of non-alcoholic fatty liver disease research. World J Gastroenterol 2019; 25:163-177. [PMID: 30670907 PMCID: PMC6337019 DOI: 10.3748/wjg.v25.i2.163] [Citation(s) in RCA: 102] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 12/24/2018] [Accepted: 12/27/2018] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and ultimately death. NAFLD is pathologically classified as non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH) based on the existence of ballooned hepatocytes, although the states have been known to transform into each other. Moreover, since the detection of ballooned hepatocytes may be difficult with limited biopsied specimens, its clinical significance needs reconsideration. Repeated liver biopsy to assess histological NAFLD activity for therapeutic response is also impractical, creating the need for body fluid biomarkers and less invasive imaging modalities. Recent longitudinal observational studies have emphasized the importance of advanced fibrosis as a determinant of NAFLD outcome. Thus, identifying predictors of fibrosis progression and developing better screening methods will enable clinicians to isolate high-risk NAFLD patients requiring early intensive intervention. Despite the considerable heterogeneity of NAFLD with regard to underlying disease, patient age, and fibrosis stage, several clinical trials are underway to develop a first-in-class drug. In this review, we summarize the present status and future direction of NAFLD/NASH research towards solving unmet medical needs.
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Affiliation(s)
- Naoki Tanaka
- Department of Metabolic Regulation, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
- International Research Center for Agricultural Food Industry, Shinshu University, Matsumoto 390-8621, Japan
| | - Takefumi Kimura
- Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Naoyuki Fujimori
- Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Tadanobu Nagaya
- Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Michiharu Komatsu
- Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
| | - Eiji Tanaka
- Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
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Chung W, Park JH, Ryu OH, Yu JM, Yoo HJ, Moon S. Association of Z-Score of the Log-Transformed A Body Shape Index with Cardiovascular Disease in People Who Are Obese but Metabolically Healthy: The Korea National Health and Nutrition Examination Survey 2007-2010. J Obes Metab Syndr 2018; 27:158-165. [PMID: 31089558 PMCID: PMC6504195 DOI: 10.7570/jomes.2018.27.3.158] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 04/22/2018] [Accepted: 07/18/2018] [Indexed: 01/20/2023] Open
Abstract
Background We aimed at evaluating the effect of the z-score of the log-transformed A Body Shape Index (LBSIZ) on cardiovascular disease (CVD) outcomes according to obesity phenotype. Methods Data were collected from the Korea National Health and Nutrition Examination Survey conducted from 2007 to 2010. Obesity was defined as a body mass index above 25 kg/m2 and metabolic abnormality was defined as the presence of two or more metabolic risk factors of the Adult Treatment Panel III definition. The participants were classified by obesity and metabolic healthy status: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Each group was further classified into three groups based on the tertile of LBSIZ. A multivariate logistic regression analysis with adjustment for age, sex, smoking status, income, education level, physical activities, alcohol, and energy intake was conducted to evaluate the odds ratio (OR) for CVD events. Results In the multivariate logistic regression model, MHO participants who are within the third tertile of LBSIZ had a significantly higher OR for CVD events, whereas those who are within the first and second tertile of LBSIZ were not at high risk of developing CVDs compared to MHNO participants who are within the first tertile of LBSIZ. In addition, a similar increase in the OR was observed in MUNO or MUO participants. Conclusion LBSIZ had the lowest risk for CVDs in the first tertile of LBSIZ and a linear relationship with all its tertiles in MHO, MUNO, and MUO participants.
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Affiliation(s)
- Wankyo Chung
- Department of Public Health Science, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Jung Hwan Park
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Ohk-Hyun Ryu
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, Korea
| | - Jae Myung Yu
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, Korea
| | - Hyung Joon Yoo
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, Korea.,Department of Internal Medicine, CM Hospital, Seoul, Korea
| | - Shinje Moon
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Hallym University College of Medicine, Seoul, Korea
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20
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Sung KC, Lee MY, Kim YH, Huh JH, Kim JY, Wild SH, Byrne CD. Obesity and incidence of diabetes: Effect of absence of metabolic syndrome, insulin resistance, inflammation and fatty liver. Atherosclerosis 2018; 275:50-57. [PMID: 29860108 DOI: 10.1016/j.atherosclerosis.2018.05.042] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Revised: 04/24/2018] [Accepted: 05/22/2018] [Indexed: 01/14/2023]
Abstract
BACKGROUND AND AIMS Obesity is frequently associated with non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR), inflammation and metabolic syndrome (MetS), all of which increase the risk of type 2 diabetes (T2DM). However, the role of these risk factors in mediating the effect of obesity remains unclear. We investigated the association between obesity and T2DM in the absence and presence of NAFLD, IR, inflammation and MetS components. METHODS 29,836 obese subjects without diabetes were studied in a Korean health screening program. Obesity was defined by the appropriate ethnic-specific body mass index (BMI) threshold ≥25 kg/m2. Hazard ratios (HRs and 95% confidence intervals, CIs) for incident T2DM were estimated for the group with no hypertension, dyslipidemia, impaired fasting glucose, fatty liver, IR, or inflammation (n = 1717), compared to the reference group, with one or more of these factors (n = 19,757). RESULTS Mean (SD) age at baseline was 37 (7) years and 1200 incident cases of diabetes occurred. Crude T2D incidence was 12.6/10,000 person-years in the group without metabolic abnormality and 143/10,000 person-years in the reference group. HR (95% CIs) for incident diabetes was 0.13 (0.06, 0.33) in the group without metabolic abnormality. CONCLUSIONS Obese subjects without components of the metabolic syndrome, IR, fatty liver and inflammation have an approximately 11-fold lower risk of incident type 2 diabetes than obese subjects who have these risk factors. These simple factors could be used to target limited resources in high risk obese subjects in the prevention of diabetes.
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Affiliation(s)
- Ki-Chul Sung
- Division of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Mi Yeon Lee
- Division of Biostatistics, Department of R&D Management, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young-Hwan Kim
- Department of Nuclear Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Ji-Hye Huh
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Jang-Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Sarah H Wild
- Centre for Population Health Sciences, Lothian Place University of Edinburgh, Edinburgh, Scotland, UK
| | - Christopher D Byrne
- Endocrinology and Metabolism Unit, IDS Building, Southampton General Hospital, University of Southampton, MP 887, Southampton, UK; Southampton National Institute for Health Research, Biomedical Research Centre, Southampton General Hospital, Southampton, UK.
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21
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Sung KC, Lee MY, Lee JY, Lee SH, Kim JY, Wild SH, Byrne CD. Resolution of fatty liver and weight loss: Independent associations with changes in serum lipids and apolipoproteins. Atherosclerosis 2018; 272:47-53. [PMID: 29547708 DOI: 10.1016/j.atherosclerosis.2018.03.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 02/24/2018] [Accepted: 03/07/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIMS It is uncertain whether resolution of fatty liver can improve cardiovascular disease risk factors, independently of changes in body mass index (BMI). Our aim was to test whether resolution of fatty liver is associated with improvements in components of the lipid profile, independently of changes in BMI, and to quantify and compare the magnitude of benefit of resolution of liver fat, and decreases in BMI on the lipid profile. METHODS 36,195 subjects with fatty liver were studied. Persistence/resolution of fatty liver was determined by ultrasound at follow up (mean = 4.93 years). Total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoproteins were measured at baseline and follow up. Regression modelling was undertaken to test the independence of associations between change in fatty liver status or change in BMI, with any change in lipid profile concentrations between baseline and follow up. RESULTS Mean (SD) age was 36.3 ± 6.6 and 39.8 ± 8.7 years (men and women, respectively). Resolution of fatty liver occurred in 7,086, and persisted in 29,109 subjects. Mean ± SD weight change was -3.2 ± 4.3 (∼1 kg/m2 decrease in BMI) with resolution of, and +0.5 ± 3.5 kg with persistence of fatty liver, respectively. Both resolution of fatty liver and decrease in BMI were independently associated with improvements in all components of the lipid profile and there was a similar magnitude of benefit associated with resolution of fatty liver, or 1 kg/m2 decrease in BMI. CONCLUSIONS Resolution of fatty liver improves the lipid profile, independently of weight loss.
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Affiliation(s)
- Ki-Chul Sung
- Division of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Mi-Yeon Lee
- Division of Biostatistics, Department of R&D Management, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jong-Young Lee
- Division of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sung-Ho Lee
- Division of Cardiology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jang-Young Kim
- Department of Cardiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Sarah H Wild
- Centre for Population Health Sciences, Lothian Place University of Edinburgh, Edinburgh, Scotland, UK
| | - Christopher D Byrne
- Endocrinology and Metabolism Unit, IDS Building, Southampton General Hospital, University of Southampton, Southampton, UK; Southampton National Institute for Health Research, Biomedical Research Centre, Southampton General Hospital, University of Southampton, Southampton, UK.
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22
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Sam S. Differential effect of subcutaneous abdominal and visceral adipose tissue on cardiometabolic risk. Horm Mol Biol Clin Investig 2018. [PMID: 29522417 DOI: 10.1515/hmbci-2018-0014] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Metabolic and cardiovascular diseases are increasing worldwide due to the rise in the obesity epidemic. The metabolic consequences of obesity vary by distribution of adipose tissue. Visceral and ectopic adipose accumulation are associated with adverse cardiometabolic consequences, while gluteal-femoral adipose accumulation are negatively associated with these adverse complications and subcutaneous abdominal adipose accumulation is more neutral in its associations. Gender, race and ethnic differences in adipose tissue distribution have been described and could account for the observed differences in risk for cardiometabolic disease. The mechanisms behind the differential impact of adipose tissue on cardiometabolic risk have started to be unraveled and include differences in adipocyte biology, inflammatory profile, connection to systemic circulation and most importantly the inability of the subcutaneous adipose tissue to expand in response to positive energy balance.
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Affiliation(s)
- Susan Sam
- University of Chicago Pritzker School of Medicine, Department of Medicine, Section of Endocrinology, 5841 S. Maryland Avenue, Chicago, IL 60637, USA, Phone: +773-702 5641, Fax: +773-702 7686
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23
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Vecchié A, Dallegri F, Carbone F, Bonaventura A, Liberale L, Portincasa P, Frühbeck G, Montecucco F. Obesity phenotypes and their paradoxical association with cardiovascular diseases. Eur J Intern Med 2018; 48:6-17. [PMID: 29100895 DOI: 10.1016/j.ejim.2017.10.020] [Citation(s) in RCA: 223] [Impact Index Per Article: 31.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 10/24/2017] [Accepted: 10/26/2017] [Indexed: 12/15/2022]
Abstract
The pro-inflammatory state of the visceral adipose tissue (VAT) is supposed to accelerate cardiovascular (CV) and metabolic diseases in obese subjects. Some studies have recently reported an improved CV prognosis in certain obese and overweight patients as compared with leaner ones. This phenomenon, known as the "obesity paradox" (OP), has been described in many chronic diseases. This narrative review is based on the material searched for and obtained via PubMed and Web of Science up to May 2017. The search terms we used were: "obesity, paradox, adipose tissue" in combination with "cardiovascular, coronary heart disease, heart failure, arrhythmias". Using the current Body Mass Index (BMI)-based obesity definition, individuals with different clinical and biochemical characteristics are gathered together in the same category. Emerging evidence point to the existence of many "Obesity phenotypes" with different association with CV risk, accordingly to physical and life-style features. In this narrative review, we discussed if obesity phenotypes may be associated with a different CV risk, potentially explaining the OP. As a globally accepted definition of obesity is still lacking, we emphasized the need of a new approach, which should consider the heterogeneity of obesity. Better defining "obesities" and related CV risk is critical to markedly improve the classical BMI-based definition of obesity.
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Affiliation(s)
- Alessandra Vecchié
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - Franco Dallegri
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico per l'Oncologia, 10 Largo Benzi, 16132 Genoa, Italy
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - Aldo Bonaventura
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Centre for Molecular Cardiology, University of Zürich, 12 Wagistrasse, 8952 Schlieren, Switzerland
| | - Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro" Medical School, Bari, Italy
| | - Gema Frühbeck
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Spain; Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico per l'Oncologia, 10 Largo Benzi, 16132 Genoa, Italy; Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 viale Benedetto XV, 16132 Genoa, Italy.
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Tatsukawa Y, Misumi M, Kim YM, Yamada M, Ohishi W, Fujiwara S, Nakanishi S, Yoneda M. Body composition and development of diabetes: a 15-year follow-up study in a Japanese population. Eur J Clin Nutr 2018; 72:374-380. [PMID: 29362458 DOI: 10.1038/s41430-017-0077-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Revised: 12/04/2017] [Accepted: 12/05/2017] [Indexed: 11/09/2022]
Abstract
BACKGROUND/OBJECTIVES Few longitudinal studies have examined the association between diabetes risk and body composition in Asians. The aim of this prospective cohort study was to determine the role of body composition, estimated by whole-body dual-energy X-ray absorptiometry, in the development of diabetes and to examine the impact of body composition on diabetes risk in normal weight (body mass index (BMI) <23 kg/m2) and overweight/obese groups (≥23 kg/m2). SUBJECTS/METHODS We measured the body composition for 1532 diabetes-free subjects (463 men and 1069 women), aged 48-79 years, at the baseline examination period from 1994-96 and followed-up to detect new cases of diabetes over the next 15 years (median 13.4 years). RESULTS After being adjusted for BMI and other potential confounding factors, body fat distribution was associated with diabetes risk. Percentage of trunk fat was positively associated with the development of diabetes (hazards ratio (HR) per 1 SD (95% confidential interval (CI)), 1.58 (1.10-2.28) in men, and 1.34 (0.99-1.83) in women), and percentage of leg fat was negatively associated with the development of diabetes (HR per 1 SD (95% CI), 0.68 (0.50-0.91) in men and 0.68 (0.55-0.85) in women). The estimated HRs of % trunk and leg fat on the development of diabetes differed little between normal weight and overweight/obese subjects. Appendicular lean mass was also negatively associated with diabetes risk only in normal weight men. CONCLUSIONS Opposite associations of trunk fat and leg fat with diabetes risk were observed. Assessment of body composition might help in the evaluation of diabetes risk.
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Affiliation(s)
- Yoshimi Tatsukawa
- Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan.
| | - Munechika Misumi
- Department of Statistics, Radiation Effects Research Foundation, Hiroshima, Japan
| | - Young Min Kim
- Department of Statistics, Radiation Effects Research Foundation, Hiroshima, Japan.,Department of Statistics, Kyungpook National University, Daegu, Korea
| | - Michiko Yamada
- Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan
| | - Waka Ohishi
- Department of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan
| | - Saeko Fujiwara
- Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan
| | - Shuhei Nakanishi
- Division of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan
| | - Masayasu Yoneda
- Department of Molecular and Internal Medicine, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
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25
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Hashimoto Y, Hamaguchi M, Tanaka M, Obora A, Kojima T, Fukui M. Metabolically healthy obesity without fatty liver and risk of incident type 2 diabetes: A meta-analysis of prospective cohort studies. Obes Res Clin Pract 2018; 12:4-15. [PMID: 29307656 DOI: 10.1016/j.orcp.2017.12.003] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 11/24/2017] [Accepted: 12/18/2017] [Indexed: 02/07/2023]
Abstract
OBJECTIVE A meta-analysis indicated that metabolically healthy obesity (MHO) presents a risk of incident type 2 diabetes, but it has not yet been established whether MHO without fatty liver (w/o FL) also presents a risk of incident diabetes. METHODS plus the presence of non or one of the following factors: hypertension, impaired fasting glucose, low high-density lipoprotein cholesterol, and hypertriglyceridemia. Using a random effects model, we calculated the pooled relative risks (RRs) and 95% confidence intervals (CIs) of incident diabetes. RESULTS Our meta-analysis included three studies from the databases plus the NAGALA study, with a total of 134,667 subjects, including 8675 MHO subjects w/o FL and 7218 MHO subjects with fatty liver (wFL). Compared to the metabolically healthy non-overweight subjects w/o FL, the RRs of incident diabetes in the MHO w/o FL and MHO wFL groups were 1.42 (95%CI 1.11-1.77) and 3.28 (95%CI 2.30-4.67). CONCLUSIONS Our meta-analysis results demonstrate that the MHO phenotype, with or without fatty liver, presents a risk of the development of type 2 diabetes. Individuals with MHO who do not have fatty liver should be monitored carefully - similarly to those with fatty liver - for the development of diabetes.
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Affiliation(s)
- Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | | | - Muhei Tanaka
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Akihiro Obora
- Department of Gastroenterology, Murakami Memorial Hospital, Asahi University, Gifu, Japan
| | - Takao Kojima
- Department of Gastroenterology, Murakami Memorial Hospital, Asahi University, Gifu, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
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Coker RH, Wolfe RR. Weight Loss Strategies in the Elderly: A Clinical Conundrum. Obesity (Silver Spring) 2018; 26:22-28. [PMID: 29265771 PMCID: PMC5744894 DOI: 10.1002/oby.21961] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 07/18/2017] [Accepted: 07/19/2017] [Indexed: 12/13/2022]
Abstract
The age-related concomitant loss of skeletal muscle and accumulation of excess adipose tissue have been commonly referred to as sarcopenic obesity. While weight loss may help mitigate the metabolic abnormalities linked to obesity, low fitness levels and muscle atrophy complicate the effectiveness of lifestyle interventions. Because of low levels of compliance, suboptimal economic efficiency, and low functional capacity, there has been no consensus on optimal therapy. This includes the use of high-protein diets that do not ensure muscle preservation during weight loss in this segment of the population. The primary objectives of this review are to discuss the relevance of sarcopenic obesity, examine the feasibility of weight loss in the elderly, and highlight new approaches to the problem.
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Affiliation(s)
- Robert H. Coker
- Institute of Arctic Biology, University of Alaska-Fairbanks, AK, USA
- Essential Blends, LLC, Center for Translational Research in Aging & Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR
- Department of Geriatrics, Center for Translational Research in Aging & Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR
| | - Robert R. Wolfe
- Essential Blends, LLC, Center for Translational Research in Aging & Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR
- Department of Geriatrics, Center for Translational Research in Aging & Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR
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27
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Chung HS, Lee HJ, Hwang SY, Choi JH, Yoo HJ, Seo JA, Kim SG, Kim NH, Choi DS, Baik SH, Choi KM. Relationship of Circulating Fetuin-A Levels with Body Size and Metabolic Phenotypes. Int J Endocrinol 2018; 2018:7918714. [PMID: 30675162 PMCID: PMC6323440 DOI: 10.1155/2018/7918714] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 10/27/2018] [Accepted: 11/13/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Previous studies have suggested the existence of distinct body size subgroups according to metabolic health referred to as metabolically healthy obesity (MHO) and metabolically abnormal but normal weight (MANW) patients. Although nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and metabolic syndrome, the relationship between these phenotypes and fetuin-A, a representative hepatokine, has not been explored. METHODS We examined the association between circulating fetuin-A levels, metabolic health phenotypes, cardiometabolic risk parameters, and subclinical atherosclerosis in 290 subjects who were randomly selected from an ongoing cohort study. RESULTS Fetuin-A concentrations were significantly associated with detrimental anthropometric and laboratory measurements, including increased waist circumference, blood pressure, alanine aminotransferase, fasting plasma glucose, and triglyceride levels. Furthermore, fetuin-A levels were significantly increased in the metabolically abnormal (MA) group compared to the metabolically healthy (MH) group in subjects without obesity (717.1 [632.1, 769.7] vs. 599.5 [502.0, 709.3], P = 0.001) and subjects with obesity (704.1 [595.5-880.9] vs. 612.2 [547.9-802.1], P = 0.016). In addition, brachial-ankle pulse wave velocity (baPWV), which reflects arterial stiffness, was higher in MA individuals compared to MH individuals. Multiple logistic regression analysis revealed that both individuals without obesity (P for trend = 0.017) and with obesity (P for trend = 0.028) in the higher tertiles of fetuin-A had an increased risk of MA than those in the lowest tertile. CONCLUSIONS This study demonstrates that fetuin-A levels are significantly associated with metabolic health phenotypes, such as MHO and MANW, in Korean adults.
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Affiliation(s)
- Hye Soo Chung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Hyun Jung Lee
- Division of Endocrinology and Metabolism, Departments of Internal Medicine, Korea University, Seoul, Republic of Korea
| | - Soon Young Hwang
- Department of Biostatistics, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Ju-Hee Choi
- Division of Endocrinology and Metabolism, Departments of Internal Medicine, Korea University, Seoul, Republic of Korea
| | - Hye Jin Yoo
- Division of Endocrinology and Metabolism, Departments of Internal Medicine, Korea University, Seoul, Republic of Korea
| | - Ji A. Seo
- Division of Endocrinology and Metabolism, Departments of Internal Medicine, Korea University, Seoul, Republic of Korea
| | - Sin Gon Kim
- Division of Endocrinology and Metabolism, Departments of Internal Medicine, Korea University, Seoul, Republic of Korea
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Departments of Internal Medicine, Korea University, Seoul, Republic of Korea
| | - Dong Seop Choi
- Division of Endocrinology and Metabolism, Departments of Internal Medicine, Korea University, Seoul, Republic of Korea
| | - Sei Hyun Baik
- Division of Endocrinology and Metabolism, Departments of Internal Medicine, Korea University, Seoul, Republic of Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Departments of Internal Medicine, Korea University, Seoul, Republic of Korea
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Lin H, Zhang L, Zheng R, Zheng Y. The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: A PRISMA-compliant article. Medicine (Baltimore) 2017; 96:e8838. [PMID: 29381992 PMCID: PMC5708991 DOI: 10.1097/md.0000000000008838] [Citation(s) in RCA: 101] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND We conducted a systematic review and meta-analysis to firstly obtain a reliable estimation of the prevalence of metabolically healthy obese (MHO) individuals in obesity, then assessed the risk of developing metabolic abnormalities (MA) among MHO individuals. At last, we evaluated the effects of traditional lifestyle interventions on metabolic level for MHO subjects. METHODS A systematic review and meta-analysis (PRISMA) guideline were conducted, and original studies were searched up to December 31, 2016. The prevalence of MHO in obesity from each study was pooled using random effects models. The relative risks (RRs) were pooled to determine the risk of developing MA for MHO compared with metabolically healthy normal-weight (MHNW) subjects. For the meta-analysis of intervention studies, the mean difference and standardized mean differences were both estimated for each metabolic parameter within each study, and then pooled using a random-effects model. RESULTS Overall, 40 population-based studies reported the prevalence of MHO in obesity, 12 cohort studies and 7 intervention studies were included in the meta-analysis. About 35.0% obese individuals were metabolically healthy in the obese subjects. There were dramatic differences in the prevalence among different areas. However, 0.49 (95% confidence intervals [CI]: 0.38 to 0.60) of the MHO individuals would develop one or more MA within 10 years. Compared with MHNW subjects, the MHO subjects presented higher risk of incident MA (pooled RR = 1.80, 95%CI: 1.53-2.11). Following intervention, there was certain and significant improvement of metabolic state for metabolically abnormal obesity (MAO) subjects. Only diastolic blood pressure had reduced for MHO individuals after intervention. CONCLUSIONS Almost one-third of the obese individuals are in metabolic health. However, they are still at higher risk of advancing to unhealthy state. Therefore, it is still needed to advise MHO individuals to maintain or adopt a healthy lifestyle, so as to counterbalance the adverse effects of obesity.
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Affiliation(s)
| | - Liqun Zhang
- Department of Intensive Care Unit, Zhejiang Putuo Hospital, Zhoushan
| | - Ruizhi Zheng
- Department of Epidemiology and Statistic, Zhejiang University, Hangzhou, Zhejiang
| | - Yishan Zheng
- Department of Intensive Care Unit, The Second Hospital of Nanjing. Teaching Hospital of Medical School of Nanjing University, Nanjing, Jiangsu, China
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Abstract
Ligand-activated nuclear receptors, including peroxisome proliferator-activated receptor alpha (PPARα), pregnane X receptor, and constitutive androstane receptor, were first identified as key regulators of the responses against chemical toxicants. However, numerous studies using mouse disease models and human samples have revealed critical roles for these receptors and others, such as PPARβ/δ, PPARγ, farnesoid X receptor (FXR), and liver X receptor (LXR), in maintaining nutrient/energy homeostasis in part through modulation of the gut-liver-adipose axis. Recently, disorders associated with disrupted nutrient/energy homeostasis, e.g., obesity, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD), are increasing worldwide. Notably, in NAFLD, a progressive subtype exists, designated as non-alcoholic steatohepatitis (NASH) that is characterized by typical histological features resembling alcoholic steatohepatitis (ASH), and NASH/ASH are recognized as major causes of hepatitis virus-unrelated liver cirrhosis and hepatocellular carcinoma. Since hepatic steatosis is basically caused by an imbalance between fat/energy influx and utilization, abnormal signaling of these nuclear receptors contribute to the pathogenesis of fatty liver disease. Standard therapeutic interventions have not been fully established for fatty liver disease, but some new agents that activate or inhibit nuclear receptor signaling have shown promise as possible therapeutic targets. In this review, we summarize recent findings on the roles of nuclear receptors in fatty liver disease and discuss future perspectives to develop promising pharmacological strategies targeting nuclear receptors for NAFLD/NASH.
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Affiliation(s)
- Naoki Tanaka
- Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, Japan.
| | - Toshifumi Aoyama
- Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, Japan
| | - Shioko Kimura
- Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Frank J Gonzalez
- Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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Hashimoto Y, Hamaguchi M, Fukuda T, Obora A, Kojima T, Fukui M. Weight gain since age of 20 as risk of metabolic syndrome even in non-overweight individuals. Endocrine 2017; 58:253-261. [PMID: 28965186 DOI: 10.1007/s12020-017-1411-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 08/28/2017] [Indexed: 01/07/2023]
Abstract
PURPOSE Metabolic syndrome (MetS), regardless of the presence of obesity, is known as a risk of diabetes and cardiovascular disease. Weight gain after age 20 reported to be associated with these diseases. Impact of the difference between the body mass index (BMI) at examination and BMI at age 20 (ΔBMIexa-20y) on MetS, especially in non-overweight individuals, remains to be elucidated. METHODS We analyzed the data of 24,363 individuals (14,301 men and 10,062 women) in this cross-sectional study. The diagnosis of MetS was diagnosed when three or more of the following criteria were present: hypertension, hyperglycemia, hypertriglyceridemia, low HDL-cholesterol level, and abdominal obesity. Logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, alcohol, smoking, exercise, and BMI at examination. RESULTS Compared to the lowest ΔBMIexa-20y tertile (ΔBMIexa-20y < 1.2 kg/m2 in men and ≤0 kg/m2 in women), the highest tertile (ΔBMIexa-20y ≥ 3.2 kg/m2 in men and ≥2.0 kg/m2 in women) was associated with the risk of the presence of MetS (multivariate OR = 1.80, 95%CI 1.53-2.11, p < 0.001 in men and OR = 3.27, 95%CI 2.22-4.96, p < 0.001 in women). This result was also applicable in non-overweight individuals (multivariate OR = 2.06, 95%CI 1.46-2.92, p < 0.001 in men and OR = 2.49, 95%CI 1.40-4.64, p < 0.001 in women). CONCLUSIONS Our analyses showed that ΔBMIexa-20y is associated with the risk of the presence of MetS, even in non-overweight individuals. It is thus important to check weight changes from early adulthood, even in non-overweight individuals.
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Affiliation(s)
- Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | | | - Takuya Fukuda
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Akihiro Obora
- Department of Gastroenterology, Murakami Memorial Hospital, Asahi University, Gifu, Japan
| | - Takao Kojima
- Department of Gastroenterology, Murakami Memorial Hospital, Asahi University, Gifu, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
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Hashimoto Y, Hamaguchi M, Fukuda T, Ohbora A, Kojima T, Fukui M. Fatty liver as a risk factor for progression from metabolically healthy to metabolically abnormal in non-overweight individuals. Endocrine 2017; 57:89-97. [PMID: 28508194 DOI: 10.1007/s12020-017-1313-6] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 04/26/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE Recent studies identified that metabolically abnormal non-obese phenotype is a risk factor for cardiovascular diseases. However, little is known about risk factor for progression from metabolically healthy non-overweight to metabolically abnormal phenotype. We hypothesized that fatty liver had a clinical impact on progression from metabolically healthy non-overweight to metabolically abnormal phenotype. METHODS In this retrospective cohort study, 14,093 Japanese (7557 men and 6736 women), who received the health-checkup program from 2004 to 2012, were enrolled. Overweight and obesity were defined as body mass index 23.0-25.0 and ≥25.0 kg/m2. Four metabolic factors (impaired fasting glucose, hypertension, hypertriglyceridemia and low high density lipoprotein-cholesterol concentration) were used for definition of metabolically healthy (less than two factors) or metabolically abnormal (two or more). We divided the participants into three groups: metabolically healthy non-overweight (9755 individuals, men/women = 4290/5465), metabolically healthy overweight (2547 individuals, 1800/747) and metabolically healthy obesity (1791 individuals, 1267/524). Fatty liver was diagnosed by ultrasonography. RESULTS Over the median follow-up period of 5.3 years, 873 metabolically healthy non-overweight, 512 metabolically healthy overweight and 536 metabolically healthy obesity individuals progressed to metabolically abnormal. The adjusted hazard risks of fatty liver on progression were 1.49 (95% confidence interval 1.20-1.83, p = 0.005) in metabolically healthy non-overweight, 1.37 (1.12-1.66, p = 0.002) in metabolically healthy overweight and 1.38 (1.15-1.66, p < 0.001) in metabolically healthy obesity, after adjusting for age, sex, alcohol, smoking, exercise, impaired fasting glucose, hypertension, hypertriglyceridemia, low high density lipoprotein-cholesterol concentration, and abdominal obesity. CONCLUSIONS Fatty liver is an independent risk factor for progression from metabolically healthy status to metabolically abnormal phenotype, even in non-overweight individuals.
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Affiliation(s)
- Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Masahide Hamaguchi
- Department of Diabetology, Kameoka Municipal Hospital, 1-1 Noda, Shinochoshino, Kameoka-city, Kyoto, 621-8585, Japan.
| | - Takuya Fukuda
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
| | - Akihiro Ohbora
- Department of Gastroenterology, Murakami Memorial Hospital, Asahi University, Gifu, Japan
| | - Takao Kojima
- Department of Gastroenterology, Murakami Memorial Hospital, Asahi University, Gifu, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
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Influence of the definition of "metabolically healthy obesity" on the progression of coronary artery calcification. PLoS One 2017; 12:e0178741. [PMID: 28575097 PMCID: PMC5456095 DOI: 10.1371/journal.pone.0178741] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 05/18/2017] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVES Debates whether metabolically healthy obesity (MHO) increases the cardiovascular risk might be due to the metabolic instability of MHO or the absence of a perfect definition of MHO. Therefore, we aimed to investigate the influence of the MHO phenotype on the coronary artery calcium score (CACS) progression according to definition of MHO. METHODS We analyzed a retrospective cohort with a CACS of 0 at baseline and available serial CACS measurements taken ≥ 12 months apart (n = 1,218). Obesity was defined as BMI ≥ 25 kg/m2, and MHO was defined as obesity accompanied by ≤ 1 (MHO class I) or 0 (MHO class II) components of metabolic syndrome (MetS). RESULTS During a median follow-up of 45 months, 32.2% of MHO class I and 10.2% of MHO class II subjects developed MetS. Compared to non-obese/metabolically healthy subjects (reference group), hazard ratios (HR) for development of MetS were 2.174 (95% confidence interval [CI]: 1.513-3.124) and 1.166 (95% CI: 0.434-3.129) for MHO class I and II subjects, respectively. The MHO class I subjects showed a significantly increased risk of CACS progression as compared to the reference group (HR: 1.653; 95% CI: 1.144-2.390), whereas MHO class II subjects did not (HR: 1.195; 95% CI: 0.514-2.778). Among subjects with MHO class I, no significant CACS progression was observed in the subjects who maintained metabolic health during follow-up (HR: 1.448; 95% CI: 0.921-2.278). CONCLUSIONS The risks of metabolic deterioration and CACS progression were significant in subjects with MHO class I, but not in those with MHO class II.
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Peters HPF, Schrauwen P, Verhoef P, Byrne CD, Mela DJ, Pfeiffer AFH, Risérus U, Rosendaal FR, Schrauwen-Hinderling V. Liver fat: a relevant target for dietary intervention? Summary of a Unilever workshop. J Nutr Sci 2017; 6:e15. [PMID: 28630692 PMCID: PMC5468740 DOI: 10.1017/jns.2017.13] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Accepted: 03/09/2017] [Indexed: 12/20/2022] Open
Abstract
Currently it is estimated that about 1 billion people globally have non-alcoholic fatty liver disease (NAFLD), a condition in which liver fat exceeds 5 % of liver weight in the absence of significant alcohol intake. Due to the central role of the liver in metabolism, the prevalence of NAFLD is increasing in parallel with the prevalence of obesity, insulin resistance and other risk factors of metabolic diseases. However, the contribution of liver fat to the risk of type 2 diabetes mellitus and CVD, relative to other ectopic fat depots and to other risk markers, is unclear. Various studies have suggested that the accumulation of liver fat can be reduced or prevented via dietary changes. However, the amount of liver fat reduction that would be physiologically relevant, and the timeframes and dose-effect relationships for achieving this through different diet-based approaches, are unclear. Also, it is still uncertain whether the changes in liver fat per se or the associated metabolic changes are relevant. Furthermore, the methods available to measure liver fat, or even individual fatty acids, differ in sensitivity and reliability. The present report summarises key messages of presentations from different experts and related discussions from a workshop intended to capture current views and research gaps relating to the points above.
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Affiliation(s)
- Harry P. F. Peters
- Unilever R&D Vlaardingen, Olivier van Noortlaan 120, Vlaardingen, The Netherlands
| | - Patrick Schrauwen
- Department of Human Biology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Petra Verhoef
- Unilever R&D Vlaardingen, Olivier van Noortlaan 120, Vlaardingen, The Netherlands
| | - Christopher D. Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton & Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton, UK
| | - David J. Mela
- Unilever R&D Vlaardingen, Olivier van Noortlaan 120, Vlaardingen, The Netherlands
| | - Andreas F. H. Pfeiffer
- Department of Endocrinology, Diabetes and Nutrition, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin
- Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam and German Center for Diabetes Research, DZD, Neuherberg, Germany
| | - Ulf Risérus
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism Unit, Uppsala University, Sweden
| | - Frits R. Rosendaal
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Vera Schrauwen-Hinderling
- Department of Human Biology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
- Department of Radiology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
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Kang YM, Jung CH, Cho YK, Lee SE, Lee MJ, Hwang JY, Kim EH, Park JY, Lee WJ, Kim HK. Fatty liver disease determines the progression of coronary artery calcification in a metabolically healthy obese population. PLoS One 2017; 12:e0175762. [PMID: 28419118 PMCID: PMC5395191 DOI: 10.1371/journal.pone.0175762] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2016] [Accepted: 03/30/2017] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVES Metabolically healthy obese (MHO) phenotype describes an obese state with a favorable metabolic profile. However, the prognosis of this subpopulation remains controversial. We aimed to examine whether MHO phenotype is associated with progression of atherosclerotic activity, reflected as the changes in coronary artery calcification (CAC) over time. If so, we sought to determine the role of fatty liver disease (FLD), the hallmark of hepatic steatosis, in this progression. METHODS We enrolled 1,240 asymptomatic subjects who underwent repeated CAC score measurement during routine health examinations. CAC score progression was defined as either incident CAC in a population free of CAC at baseline, or an increase by ≥2.5 units between the baseline and final square root of CAC scores in participants with detectable CAC at baseline. Subjects were stratified by body mass index (cut-off, 25.0 kg/m2) and metabolic health state using Adult Treatment Panel-III criteria. FLD was assessed via ultrasonography. RESULTS Over 2.9 years of follow-up, 25.2% of total subjects exhibited CAC score progression. The MHO phenotype was not significantly associated with CAC score progression (multivariate adjusted-odds ratio [OR], 1.45; 95% confidence interval [CI], 0.93-2.25), as compared to the metabolically healthy non-obese (MHNO) phenotype. However, subgroup analysis indicated that the MHO/FLD phenotype was significantly associated with CAC score progression (multivariate adjusted-OR, 2.37; 95% CI, 1.34-4.16), as compared to the MHNO/no FLD phenotype, whereas the MHO/no FLD phenotype was not (multivariate adjusted OR, 1.25; 95% CI, 0.71-2.24). CONCLUSIONS Obese individuals with FLD have an increased risk of atherosclerosis progression, despite their healthy metabolic profile. Preventive interventions targeting cardiometabolic risk factors should be considered in such individuals, regardless of the weight status.
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Affiliation(s)
- Yu Mi Kang
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chang Hee Jung
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- * E-mail: (CHJ); (HKK)
| | - Yun Kyung Cho
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung Eun Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min Jung Lee
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jenie Yoonoo Hwang
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Eun Hee Kim
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Joong-Yeol Park
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Woo Je Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hong-Kyu Kim
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- * E-mail: (CHJ); (HKK)
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Heianza Y, Qi L. Gene-Diet Interaction and Precision Nutrition in Obesity. Int J Mol Sci 2017; 18:ijms18040787. [PMID: 28387720 PMCID: PMC5412371 DOI: 10.3390/ijms18040787] [Citation(s) in RCA: 121] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Revised: 03/30/2017] [Accepted: 04/03/2017] [Indexed: 02/06/2023] Open
Abstract
The rapid rise of obesity during the past decades has coincided with a profound shift of our living environment, including unhealthy dietary patterns, a sedentary lifestyle, and physical inactivity. Genetic predisposition to obesity may have interacted with such an obesogenic environment in determining the obesity epidemic. Growing studies have found that changes in adiposity and metabolic response to low-calorie weight loss diets might be modified by genetic variants related to obesity, metabolic status and preference to nutrients. This review summarized data from recent studies of gene-diet interactions, and discussed integration of research of metabolomics and gut microbiome, as well as potential application of the findings in precision nutrition.
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Affiliation(s)
- Yoriko Heianza
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
| | - Lu Qi
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
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Duration and degree of weight change and risk of incident diabetes: Japan Epidemiology Collaboration on Occupational Health Study. Prev Med 2017; 96:118-123. [PMID: 28040517 DOI: 10.1016/j.ypmed.2016.12.046] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Revised: 12/21/2016] [Accepted: 12/23/2016] [Indexed: 01/25/2023]
Abstract
We prospectively examined diabetes risk in association with a summary measure of degree and duration of weight change. The study participants were 51,777 employees from multiple companies in Japan, who were aged 30-59years, free of diabetes at baseline, and followed up for 7years (2008-2015). Exposure was cumulative body mass index (BMI)-years, which was defined as the area of BMI units above or below baseline BMI during follow-up, and was treated as a time-dependent variable in the Cox proportional hazards regression models. During the 263,539 person-years of follow-up, 3465 participants developed diabetes. The adjusted hazard ratio (HR) of diabetes for a 1-unit increase in cumulative BMI-years was 1.11 (95% confidence interval (CI): 1.09, 1.12). The association was more pronounced among overweight (HR=1.11; 95% CI: 1.08, 1.14) and obese (HR=1.12; 95% CI: 1.08, 1.15) adults compared with normal- and under-weight (HR=1.07; 95% CI: 1.03, 1.11) adults (P for interaction of cumulative BMI-years X baseline BMI-group=0.002). The association of higher cumulative BMI-years with incident diabetes did not substantially differ by metabolic phenotype. The present results emphasize the importance of avoiding additional weight gain over an extended period of time for the prevention of type 2 diabetes, especially among overweight and obese adults, irrespective of metabolic health status.
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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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Phillips CM. Metabolically healthy obesity across the life course: epidemiology, determinants, and implications. Ann N Y Acad Sci 2016; 1391:85-100. [PMID: 27723940 DOI: 10.1111/nyas.13230] [Citation(s) in RCA: 126] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 08/09/2016] [Accepted: 08/18/2016] [Indexed: 12/24/2022]
Abstract
In recent years, different subphenotypes of obesity have been described, including metabolically healthy obesity (MHO), in which a proportion of obese individuals, despite excess body fat, remain free of metabolic abnormalities and increased cardiometabolic risk. In the absence of a universally accepted set of criteria to classify MHO, the reported prevalence estimates vary widely. Our understanding of the determinants and stability of MHO over time and the associated cardiometabolic and mortality risks is improving, but many questions remain. For example, whether MHO is truly benign is debatable, and whether risk stratification of obese individuals on the basis of their metabolic health status may offer new opportunities for more personalized approaches in diagnosis, intervention, and treatment of diabetes remains speculative. Furthermore, as most of the research to date has focused on MHO in adults, little is known about childhood MHO. In this review, we focus on the epidemiology, determinants, stability, and health implications of MHO across the life course.
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Affiliation(s)
- Catherine M Phillips
- HRB Centre for Diet and Health Research, Department of Epidemiology and Public Health, University College Cork, Cork, Ireland; and HRB Centre for Diet and Health Research, School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin, Ireland
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Chang Y, Jung HS, Yun KE, Cho J, Ahn J, Chung EC, Shin H, Ryu S. Metabolically healthy obesity is associated with an increased risk of diabetes independently of nonalcoholic fatty liver disease. Obesity (Silver Spring) 2016; 24:1996-2003. [PMID: 27474900 DOI: 10.1002/oby.21580] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Revised: 05/15/2016] [Accepted: 05/17/2016] [Indexed: 12/19/2022]
Abstract
OBJECTIVE This study examined whether the metabolically healthy obesity (MHO) phenotype was associated with an increased risk of diabetes in a large cohort of metabolically healthy individuals and whether that association differed by presence of nonalcoholic fatty liver disease (NAFLD). METHODS The cohort consisted of 74,509 Korean adults who were metabolically healthy at baseline, defined as not having any metabolic syndrome component except large waist circumference and having homeostasis model assessment of insulin resistance <2.5. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or any other identifiable cause. RESULTS Over 304,852.6 person-years of follow-up, 472 participants developed diabetes (incidence density, 1.5 per 1,000 person-years). The multivariable-adjusted hazard ratios (95% confidence intervals) for incident diabetes in subjects with overweight and obesity compared with subjects with normal weight were 1.29 (1.00-2.16) and 1.57 (1.14-2.16), respectively, for subjects without NAFLD and 1.90 (0.95-3.80) and 2.57 (1.32-5.02), respectively, for those with NAFLD (P for interaction =0.57). CONCLUSIONS In this metabolically healthy population, individuals with overweight and obesity exhibited an increased incidence of diabetes, regardless of the presence of NAFLD. This finding suggests that the obese phenotype per se, independent of the presence of NAFLD, can increase the development of diabetes.
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Affiliation(s)
- Yoosoo Chang
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea
| | - Hyun-Suk Jung
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyung Eun Yun
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Juhee Cho
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea
- Department of Medicine and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Jiin Ahn
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Eun Chul Chung
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hocheol Shin
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Seungho Ryu
- Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea
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Abstract
Obesity is a top public health priority but interventions to reverse the condition have had limited success. About one-in-three obese adults are free of metabolic risk factor clustering and are considered 'healthy', and much attention has focused on the implications of this state for obesity management. Areas covered: We searched for individual studies, systematic reviews, and meta-analyses which examined correlates and outcomes of metabolically healthy obesity. We discuss the key roles of fat distribution and physical activity in determining healthy vs. unhealthy obesity and report a greatly increased risk of incident type 2 diabetes associated with healthy obesity vs. healthy normal weight, among other outcomes. We argue that despite inconsistencies in the definition, patterns across studies clearly show that healthy obesity is a state of intermediate disease risk. Expert commentary: Given the current state of population-level evidence, we conclude that obesity and metabolic dysfunction are inseparable and that healthy obesity is best viewed only as a state of relative health but not of absolute health. We recommend that weight loss through energy restriction be a stand-alone target in addition to increased physical activity for minimising risk of future disease.
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Affiliation(s)
- J A Bell
- a Department of Epidemiology & Public Health , University College London , London , UK
- b School of Sport, Exercise & Health Sciences, Loughborough University , Loughborough , UK
| | - M Hamer
- b School of Sport, Exercise & Health Sciences, Loughborough University , Loughborough , UK
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Natural Course of Metabolically Healthy Overweight/Obese Subjects and the Impact of Weight Change. Nutrients 2016; 8:nu8070430. [PMID: 27428997 PMCID: PMC4963906 DOI: 10.3390/nu8070430] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 07/08/2016] [Accepted: 07/11/2016] [Indexed: 02/03/2023] Open
Abstract
Few studies have described the characteristics of metabolically healthy individuals with excess fat in the Chinese population. This study aimed to prospectively investigate the natural course of metabolically healthy overweight/obese (MH-OW/OB) adults, and to assess the impact of weight change on developing metabolic abnormalities. During 2009–2010, 525 subjects without any metabolic abnormalities or other obesity-related diseases were evaluated and reevaluated after 5 years. The subjects were categorized into two groups of overweight/obese and normal weight based on the criteria of BMI by 24.0 at baseline. At follow-up, the MH-OW/OB subjects had a significantly increased risk of developing metabolically abnormalities compared with metabolically healthy normal-weight (MH-NW) individuals (risk ratio: 1.35, 95% confidence interval: 1.17–1.49, p value < 0.001). In the groups of weight gain and weight maintenance, the MH-OW/OB subjects was associated with a larger increase in fasting glucose, triglycerides, systolic blood pressure, diastolic blood pressure and decrease in high-density lipoprotein cholesterol comparing with MH-NW subjects. In the weight loss group, no significant difference of changes of metabolic parameters was observed between MH-OW/OB and MH-NW adults. This study verifies that MH-OW/OB are different from MH-NW subjects. Weight management is needed for all individuals since weight change has a significant effect on metabolic health without considering the impact of weight change according to weight status.
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Jung CH, Kang YM, Jang JE, Hwang JY, Kim EH, Park JY, Kim HK, Lee WJ. Fatty liver index is a risk determinant of incident type 2 diabetes in a metabolically healthy population with obesity. Obesity (Silver Spring) 2016; 24:1373-9. [PMID: 27112320 DOI: 10.1002/oby.21483] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Revised: 01/19/2016] [Accepted: 01/20/2016] [Indexed: 02/06/2023]
Abstract
OBJECTIVE This study investigated the effect of fatty liver disease (FLD) on the risk of incident type 2 diabetes in a population with metabolically healthy obesity (MHO). METHODS The study population comprised 34,258 Koreans without type 2 diabetes. Participants were stratified by BMI (cutoff value, 25.0 kg/m(2) ) and metabolic health state (using Wildman criteria). FLD was defined by the fatty liver index (FLI), a predictive algorithm to detect FLD. Subjects were classified into low and high FLI groups based on tertile. RESULTS At baseline, there were significant differences in FLI between four study groups. During a median follow-up of 36.5 months, 1.7% individuals developed type 2 diabetes. The risk of incident type 2 diabetes varied for the MHO group according to the level of FLI. The risk of type 2 diabetes in the MHO with low FLI was not significantly elevated compared with the metabolically healthy individuals without obesity (MHNO) with low FLI (multivariate-adjusted HR, 1.19 [95% CI 0.66-2.14]). However, the MHO with high FLI had an elevated risk of incident type 2 diabetes (multivariate-adjusted HR, 1.99 [95% CI 1.36-2.92]). CONCLUSIONS MHO subjects have a substantially higher risk of incident type 2 diabetes than MHNO subjects. The presence of FLD assessed by FLI partially explains this increased risk.
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Affiliation(s)
- Chang Hee Jung
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yu Mi Kang
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jung Eun Jang
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jenie Yoonoo Hwang
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Eun Hee Kim
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Joong-Yeol Park
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hong-Kyu Kim
- Department of Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Woo Je Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Obesity or obesities? Controversies on the association between body mass index and premature mortality. Eat Weight Disord 2016; 21:165-74. [PMID: 27043948 DOI: 10.1007/s40519-016-0278-4] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Obesity is still defined on the basis of body mass index (BMI) and BMI in itself is generally accepted as a strong predictor of overall early mortality. However, an inverse association between BMI and mortality has been reported in patients with many disease states and in several clinical settings: hemodialysis, cardiovascular diseases, hypertension, stroke, diabetes, chronic obstructive pulmonary disease, surgery, etc. This unexpected phenomenon is usually called obesity-survival paradox (OP). The contiguous concepts of metabolically healthy obesity (MHO, a phenotype having BMI ≥ 30 but not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance, HOMA, <2.5) and metabolically obese normal weight (MONW, normal-weight individuals displaying obesity-related phenotypic characteristics) have received a great deal of attention in recent years. The interactions that link MHO, MONW and OP with body composition, fat distribution, aging and cardiorespiratory fitness are other crucial areas of research. The article is an introductory narrative overview of the origin and current use of the concepts of MHO, MONW and OP. These phenomena are very controversial and appear as a consequence of the frail current diagnostic definition of obesity based only on BMI. A new commonly established characterization and classification of obesities based on a number of variables is needed urgently.
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Sone H. [The 43rd Scientific Meeting: Perspectives of Internal Medicine; Genetic predisposition and related life-style underlying metabolic disorders; 2. Genetic and Environmental Susceptibility; 3) Epidemiology and large-scale clinical data analysis in metabolic diseases]. NIHON NAIKA GAKKAI ZASSHI. THE JOURNAL OF THE JAPANESE SOCIETY OF INTERNAL MEDICINE 2016; 105:383-390. [PMID: 27319179 DOI: 10.2169/naika.105.383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
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Højland Ipsen D, Tveden-Nyborg P, Lykkesfeldt J. Normal weight dyslipidemia: Is it all about the liver? Obesity (Silver Spring) 2016; 24:556-67. [PMID: 26868960 DOI: 10.1002/oby.21443] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Revised: 09/02/2015] [Accepted: 11/30/2015] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The liver coordinates lipid metabolism and may play a vital role in the development of dyslipidemia, even in the absence of obesity. Normal weight dyslipidemia (NWD) and patients with nonalcoholic fatty liver disease (NAFLD) who do not have obesity constitute a unique subset of individuals characterized by dyslipidemia and metabolic deterioration. This review examined the available literature on the role of the liver in dyslipidemia and the metabolic characteristics of patients with NAFLD who do not have obesity. METHODS PubMed was searched using the following keywords: nonobese, dyslipidemia, NAFLD, NWD, liver, and metabolically obese/unhealthy normal weight. Additionally, article bibliographies were screened, and relevant citations were retrieved. Studies were excluded if they had not measured relevant biomarkers of dyslipidemia. RESULTS NWD and NAFLD without obesity share a similar abnormal metabolic profile. When compared with patients with NAFLD who have obesity, the metabolic abnormalities of NAFLD without obesity are similar or less severe. Furthermore, hepatic lesions develop independent of obesity, and the extent of dyslipidemia seems comparable. CONCLUSIONS NAFLD may impair hepatic lipid handling, causing faulty lipid homeostasis, and serves as a likely starting point for initiation and propagation of dyslipidemia along with associated comorbidities in patients without obesity.
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Affiliation(s)
- David Højland Ipsen
- Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Pernille Tveden-Nyborg
- Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens Lykkesfeldt
- Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Janghorbani M, Soltanian N, Sirous M, Amini M, Iraj B. Risk of diabetes in combined metabolic abnormalities and body mass index categories. Diabetes Metab Syndr 2016; 10:S71-S78. [PMID: 26610402 DOI: 10.1016/j.dsx.2015.09.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 09/27/2015] [Indexed: 01/22/2023]
Abstract
AIM The present study was designed to estimate the progression rates from combination of normal weight, overweight, obesity, and number of metabolic abnormalities (MA) to type 2 diabetes (T2D) in a non-diabetic high risk population in Isfahan, Iran. METHODS A total of 1869 non-diabetic first-degree relatives (FDR) of patients with T2D 30-70 years old were examined and followed for a mean (SD) of 7.3 (2.2) years for T2D incidence. At baseline and through follow-up, participants underwent a standard 75-g 2-h oral glucose tolerance test. RESULTS The metabolically healthy overweight and obese at baseline were associated with incidence of T2D, independently of age and gender. Any one MA increased the risk of developing T2D among normal weight, overweight and obese individuals. Those with normal weight and ≥3 MA were over 20 times (odds ratios (OR) 20.21; 95% confidence intervals (CI) 2.4, 170.4) and those with overweight and ≥3 MA 22.5 times (OR 22.5; 95% CI 3.0, 167.0) and obese with ≥3 MA were 25.4 times (OR 25.4; 95% CI 3.4, 187) more likely to develop T2D than those with normal weight and without MA. Compared with participants without MA, obese individuals with concomitant MA were not significantly more likely to progress to T2D. CONCLUSION Our data provide further evidence that normal weight, overweight and obese individuals with MA had a higher risk of incident T2D than normal weight individuals without MA.
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Affiliation(s)
- Mohsen Janghorbani
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Norredin Soltanian
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehri Sirous
- Departement of Radiology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Masoud Amini
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Bijan Iraj
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Rey-López JP, de Rezende LF, de Sá TH, Stamatakis E. Is the metabolically healthy obesity phenotype an irrelevant artifact for public health? Am J Epidemiol 2015; 182:737-41. [PMID: 26363513 DOI: 10.1093/aje/kwv177] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 04/08/2015] [Indexed: 01/29/2023] Open
Abstract
Some obese persons do not develop (at least in the short term) the metabolic complications of obesity that are thought to be causally linked to cardiovascular events or premature mortality. This phenomenon has been termed "metabolically healthy obesity" (MHO), and it has received much attention recently, to the extent that some authors argue that "new metrics" must be developed to estimate the risk associated with obesity beyond body mass index. In this commentary, we argue that the MHO phenotype is not benign and as such has very limited relevance as a public health target. More efforts must be allocated to reducing the distal and actual causal agents that lead to weight gain, instead of the current disproportionate scientific interest in the biological processes that explain the heterogeneity of obesity.
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Lotta LA, Abbasi A, Sharp SJ, Sahlqvist AS, Waterworth D, Brosnan JM, Scott RA, Langenberg C, Wareham NJ. Definitions of Metabolic Health and Risk of Future Type 2 Diabetes in BMI Categories: A Systematic Review and Network Meta-analysis. Diabetes Care 2015; 38:2177-87. [PMID: 26494809 PMCID: PMC4826609 DOI: 10.2337/dc15-1218] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Various definitions of metabolic health have been proposed to explain differences in the risk of type 2 diabetes within BMI categories. The goal of this study was to assess their predictive relevance. RESEARCH DESIGN AND METHODS We performed systematic searches of MEDLINE records for prospective cohort studies of type 2 diabetes risk in categories of BMI and metabolic health. In a two-stage meta-analysis, relative risks (RRs) specific to each BMI category were derived by network meta-analysis and the resulting RRs of each study were pooled using random-effects models. Hierarchical summary receiver operating characteristic curves were used to assess predictive performance. RESULTS In a meta-analysis of 140,845 participants and 5,963 incident cases of type 2 diabetes from 14 cohort studies, classification as metabolically unhealthy was associated with higher RR of diabetes in all BMI categories (lean RR compared with healthy individuals 4.0 [95% CI 3.0-5.1], overweight 3.4 [2.8-4.3], and obese 2.5 [2.1-3.0]). Metabolically healthy obese individuals had a high absolute risk of type 2 diabetes (10-year cumulative incidence 3.1% [95% CI 2.6-3.5]). Current binary definitions of metabolic health had high specificity (pooled estimate 0.88 [95% CI 0.84-0.91]) but low sensitivity (0.40 [0.31-0.49]) in lean individuals and satisfactory sensitivity (0.81 [0.76-0.86]) but low specificity (0.42 [0.35-0.49]) in obese individuals. However, positive (<3.3 in all BMI categories) and negative (>0.4) likelihood ratios were consistent with insignificant to small improvements in prediction. CONCLUSIONS Although individuals classified as metabolically unhealthy have a higher RR of type 2 diabetes compared with individuals classified as healthy in all BMI categories, current binary definitions of metabolic health have limited relevance to the prediction of future type 2 diabetes.
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Affiliation(s)
- Luca A Lotta
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, U.K
| | - Ali Abbasi
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, U.K. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Stephen J Sharp
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, U.K
| | | | | | - Julia M Brosnan
- Cardiovascular and Metabolic Diseases Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA
| | - Robert A Scott
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, U.K
| | - Claudia Langenberg
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, U.K
| | - Nicholas J Wareham
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, U.K.
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Ming J, Xu S, Gao B, Liu G, Ji Y, Yang F, Jia Y, Fang Y, Ji Q. Non-alcoholic fatty liver disease predicts type 2 diabetes mellitus, but not prediabetes, in Xi'an, China: a five-year cohort study. Liver Int 2015; 35:2401-7. [PMID: 25879672 DOI: 10.1111/liv.12851] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 04/11/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Emerging studies have focused the association between non-alcoholic fatty liver disease (NAFLD) and the risk of type 2 diabetes mellitus (T2DM) but the results were inconsistent. In addition, few studies have put focus on the association between NAFLD and the risk of prediabetes. We aimed to investigate whether NAFLD diagnosed by ultrasonography could predict the risk of future T2DM and prediabetes in Chinese population. METHODS The population-based cohort study held in Xi'an, Northwestern China, was based on China National Diabetes and Metabolic Disorders Survey. During a follow-up of 5 years, 508 healthy subjects were included as study sample. NAFLD was determined by abdominal ultrasonography. T2DM and prediabetes were diagnosed based on oral glucose tolerance test. RESULTS Of 508 subjects, 97 (19.1%) were diagnosed as NAFLD and 411 (80.9%) were as non-NAFLD; 20 (3.9%) developed diabetes and 85 (16.7%) developed prediabetes during follow-up. The incidence of diabetes and prediabetes in the NAFLD group was 20.6 and 51.6 per 1000 person-years, respectively, whereas that in non-NAFLD group was 4.9 and 29.2 per 1000 person-years respectively. Cox proportional hazard regression showed that the multivariable-adjusted relative risk (RR) of T2DM and prediabetes in the NAFLD group was 4.462 [95% confidence interval (CI): 1.855-10.734, P < 0.001] and 1.642 (95% CI: 0.965-2.793, P = 0.067), respectively, compared with non-NAFLD group. CONCLUSIONS Non-alcoholic fatty liver disease was a significant predictor for future diabetes, but not for prediabetes, in Xi'an, China. More cohort studies are needed to confirm our findings.
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Affiliation(s)
- Jie Ming
- Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Shaoyong Xu
- Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Bin Gao
- Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Guocai Liu
- Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.,Department of Infectious Diseases, 273 Hospital of PLA, Kuele, China
| | - Yufei Ji
- Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Fan Yang
- Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yunan Jia
- Department of Internal Medicine, Avic Xi'an Aero-engine (Group) Hospital, Xi'an, China
| | - Yujie Fang
- Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Qiuhe Ji
- Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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Rondanelli M, Klersy C, Perna S, Faliva MA, Montorfano G, Roderi P, Colombo I, Corsetto PA, Fioravanti M, Solerte SB, Rizzo AM. Effects of two-months balanced diet in metabolically healthy obesity: lipid correlations with gender and BMI-related differences. Lipids Health Dis 2015; 14:139. [PMID: 26511930 PMCID: PMC4625883 DOI: 10.1186/s12944-015-0131-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 10/09/2015] [Indexed: 12/17/2022] Open
Abstract
Background Nowadays no researches has been performed on fatty acid profile (FA) and desaturase activity in metabolically healthy obesity (MHO). The aim of this study was to assessed gender and BMI-related difference in FA, estimated desaturase activities and the efficacy on metabolic changes produced by 2-months well-balance diet in MHO subjects. Methods In 103 MHO subjects (30/73 M/F; age:42.2 ± 9.5) FA, estimated desaturase activity, body composition (by DXA), Body Mass Index (BMI), lipid profile, adipokines (leptin, adiponectin, grelin, glucagon-like peptide-1), insulin resistence (by Homestasis metabolic assessment), C-reactive proteine, Atherogenic index of plasma (AIP) and Body Shape Index (ABSI) have been assessed. Gender and BMI related difference have been evaluated and the efficacy produced by 2-months well-balance diet has been considered. Results At baseline, obese subjects, compared to overweight, show a significantly higher oleic (p <0.050), monounsaturated fatty acids (p <0.040), C18:0 delta-9 desaturase activity (D9D) (p <0.040) and lower linoleic acid (p <0.020), polyunsaturated fatty acids (p <0.020) and n-6 LCPUFA (p <0.010). Concerning gender-related difference, women show a significantly higher arachidonic acid (p <0.001), polyunsaturated fatty acids (p <0.001), n-6 LCPUFA (p <0.002), and lower monounsaturated fatty acids (p <0.001), D6D activity (p <0.030), C18:0 D9D (0.000) and C16:0 D9D (p <0.030). The 2-months diet was associated with a significantly increase in arachidonic acid (p = 0.007), eicosapentaenoic acid (p = 0.030), docosahexaenoic acid (p <0.001), long chain omega 3 polyunsaturated fatty acids (n-3 LCPUFA) (p <0.001), delta-5 desaturase activity (D5D) (p = 0.002), glucagon like peptide-1 (p <0.001) and a significant decrease in palmitoleic acid (p = <0.030), n-6/n-3 LCPUFA (p <0.001), insulin resistance (p = 0.006), leptin (p = 0.006), adiponectin (p <0.001), grelin (p = 0.030), CRP (p = 0.004), BMI (p <0.001) and android fat mass (p <0.001). Conclusions The balanced diet intervention was effective in improving metabolic indices.
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Affiliation(s)
- Mariangela Rondanelli
- Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition andDietetics, Azienda di Servizi alla Persona di Pavia, University of Pavia, Pavia, Italy
| | - Chaterine Klersy
- Service of Biometry & Clinical Epidemiology, Fondazione IRCCS "Policlinico San Matteo", Pavia, Italy
| | - Simone Perna
- Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition andDietetics, Azienda di Servizi alla Persona di Pavia, University of Pavia, Pavia, Italy.
| | - Milena Anna Faliva
- Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition andDietetics, Azienda di Servizi alla Persona di Pavia, University of Pavia, Pavia, Italy
| | - Gigliola Montorfano
- Department of Pharmacological and Biomolecular Sciences, Laboratory of Membrane Biochemistry and Applied Nutrition, Università degli Studi di Milano, Milan, Italy
| | - Paola Roderi
- Department of Pharmacological and Biomolecular Sciences, Laboratory of Membrane Biochemistry and Applied Nutrition, Università degli Studi di Milano, Milan, Italy
| | - Irma Colombo
- Department of Pharmacological and Biomolecular Sciences, Laboratory of Membrane Biochemistry and Applied Nutrition, Università degli Studi di Milano, Milan, Italy
| | - Paola Antonia Corsetto
- Department of Pharmacological and Biomolecular Sciences, Laboratory of Membrane Biochemistry and Applied Nutrition, Università degli Studi di Milano, Milan, Italy
| | - Marisa Fioravanti
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Azienda di Servizi alla Persona di Pavia, University of Pavia, Pavia, Italy
| | - Sebastiano Bruno Solerte
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Azienda di Servizi alla Persona di Pavia, University of Pavia, Pavia, Italy
| | - Angela Maria Rizzo
- Department of Pharmacological and Biomolecular Sciences, Laboratory of Membrane Biochemistry and Applied Nutrition, Università degli Studi di Milano, Milan, Italy
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