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Mladenova IL, Tan EF, Ng JY, Sharma P. Non-alcoholic fatty liver disease (NAFLD) and its association to cardiovascular disease: A comprehensive meta-analysis. JRSM Cardiovasc Dis 2025; 14:20480040251325929. [PMID: 40123646 PMCID: PMC11930486 DOI: 10.1177/20480040251325929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 11/13/2024] [Accepted: 11/18/2024] [Indexed: 03/25/2025] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) affects up to nearly a third of the Western population and has been inconsistently associated with cardiovascular diseases (CVDs). Therefore, we conducted a comprehensive meta-analysis to quantify the correlation of NAFLD with all major vascular diseases, acute coronary syndrome (ACS), subclinical atherosclerosis and endothelial dysfunction. Methods We searched PubMed and Embase for studies looking at the relationship between NAFLD and cardiovascular diseases published through September 2023. The parameters we used to assess cardiovascular diseases include acute coronary syndrome, brachial flow-mediated dilatation (FMD), serum asymmetric dimethylarginine (ADMA), carotid intima-media thickness (CIMT), and carotid stenosis (>50%). Data from these studies were then collected and meta-analysis was performed using the random effects model. RevMan v5.4 was used for statistical analysis. Results We interrogated a total of 114 publications which met our inclusion criteria. NAFLD patients showed statistically significant reduction in FMD% [MD: -4.83 (95% CI: -5.84 to 3.81, p < .00001)] and increased serum ADMA [MD: 0.08 (95% CI: 0.05-0.11, p < .00001)]. Mean CIMT was also increased in NAFLD patients [MD 0.13 (95% CI: 0.12-0.14, p < .00001)]. NAFLD showed a higher prevalence of pathological CIMT [MD: 0.11 (95% CI: 0.10-0.12, p < .00001)] and increased carotid plaques [OR: 2.08 (95% CI: 1.52-2.86, p < .00001)]. Furthermore, we demonstrated statistically significant increase in cardiovascular diseases among NAFLD patients compared to controls [OR: 1.92 (95% CI: 1.53-2.41, p < .00001)]. Conclusion NAFLD is a strong predictor for endothelial dysfunction, subclinical atherosclerosis and cardiovascular disease. Further studies are required to determine whether incidental findings of fatty liver on abdominal ultrasonography should prompt the need for detailed assessment of other CVD risk factors.
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Affiliation(s)
| | - Eu Fon Tan
- Queen Mary University of London, London, UK
| | | | - Pankaj Sharma
- Institute of Cardiovascular Research, Royal Holloway University, Egham, Greater London, UK
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Kumar R, Narayan R. Carotid Intima-Media Thickness in Indian Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and a Meta-Analysis. Cureus 2024; 16:e68439. [PMID: 39360047 PMCID: PMC11445799 DOI: 10.7759/cureus.68439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/02/2024] [Indexed: 10/04/2024] Open
Abstract
There is a significant association of non-alcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD). Most CVDs begin with atherosclerosis in the arteries, which can be reliably measured as the carotid intima-media thickness (CIMT) by ultrasound. Given that ethnic and regional differences have an impact on NAFLD, we aimed to evaluate the association of NAFLD patients from India with subclinical atherosclerosis, measured as CIMT. A thorough literature search was performed on four electronic databases using combinations of several keywords. The relevant data were pooled in a random or fixed-effect model, based on heterogeneity, to calculate the pooled standardised mean difference (SMD), or odds ratio (OR) with 95% confidence interval (CI). The final analysis included a total of 15 studies with 1196 NAFLD and 1482 control subjects. NAFLD patients had a 21.3% higher mean CIMT than the controls. The pooled SMD was 1.001 (95% CI: 0.627-1.375, p < 0.001). Three studies that balanced cardiometabolic risk factors found a similar association (p = 0.037). Furthermore, NAFLD was significantly associated with the presence of high (>0.8 mm) CIMT (pooled OR = 5.4, 95% CI: 2.0-14 .9) and carotid plaques (pooled OR = 10.24, 95% CI: 5.74-18.26). The mean CIMT was also higher in diabetic NAFLD than in the diabetic control (pooled SMD = 1.07, 95% CI = 0.818-1.324, p < 0.001). There is a significant positive association between the marker of subclinical atherosclerosis and NAFLD in India. This might give more light on screening and follow-up plans for such patients.
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Affiliation(s)
- Ramesh Kumar
- Gastroenterology, All India Institute of Medical Sciences, Patna, IND
| | - Ruchika Narayan
- Radiodiagnosis, All India Institute of Medical Sciences, Patna, IND
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Dehghani Firouzabadi M, Poopak A, Sheikhy A, Dehghani Firouzabadi F, Moosaie F, Rabizadeh S, Momtazmanesh S, Nakhjavani M, Esteghamati A. Nonalcoholic Fatty Liver Disease as a Potential Risk Factor for Cardiovascular Disease in Patients with Type 2 Diabetes: A Prospective Cohort Study. Int J Endocrinol 2024; 2024:5328965. [PMID: 38962375 PMCID: PMC11221952 DOI: 10.1155/2024/5328965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 06/11/2024] [Accepted: 06/15/2024] [Indexed: 07/05/2024] Open
Abstract
Methods and Results In this prospective cohort study, 1197 patients with type 2 diabetes (T2D) were divided into two groups (360 patients with NAFLD and 847 without NAFLD) and were followed for a median of 5 years for the incidence of CVD. Cox regression analysis was used to assess the association between NAFLD, liver enzyme level, aspartate aminotransferase to platelet ratio index (APRI), and the incidence risk of CVD and its subgroups (i.e., myocardial infarction, chronic heart disease, coronary artery bypass grafting, and percutaneous coronary intervention). There was a significant positive association between CVD incidence and NAFLD (HR = 1.488, 95% CI = 1.041-2.124, p value = 0.029). Although patients with NAFLD had higher levels of ALT and AST levels (p value = <0.001), there was no significant association between liver enzymes and the incidence risk of CVD when adjusted for different variables. Furthermore, NAFLD was associated with NAFLD APRI Q (2), APRI Q (3), and APRIQ (4) (1.365 (1.046-1.781), 1.623 (1.234-2.135), and 3.373 (2.509-4.536)), respectively. Conclusion NAFLD increased the incidence risk of CVD in T2D. However, there was no association between liver enzymes (ALT, AST, ALK-P, and GGT) and a higher incidence risk of CVD in T2D when adjusted for confounding variables.
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Affiliation(s)
- Mohammad Dehghani Firouzabadi
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Amirhossein Poopak
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Ali Sheikhy
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
- Department of Radiology and Imaging SciencesClinical CenterNational Institutes of Health, Bethesda, USA
| | - Fatemeh Dehghani Firouzabadi
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
- Department of Radiology and Imaging SciencesClinical CenterNational Institutes of Health, Bethesda, USA
| | - Fatemeh Moosaie
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Soghra Rabizadeh
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Sara Momtazmanesh
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Manouchehr Nakhjavani
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
| | - Alireza Esteghamati
- Endocrinology and Metabolism Research Center (EMRC)Vali-Asr HospitalTehran University of Medical Sciences, Tehran, Iran
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Abosheaishaa H, Nassar M, Abdelhalim O, Bahbah AA, Abbas S, Morsi SM, Ghallab M, Alagha Z, Omran A, Elfert K, Bandaru P, Forlemu AN, Reddy M. Relation between non-alcoholic fatty liver disease and carotid artery intimal media thickness as a surrogate for atherosclerosis: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2024; 36:592-607. [PMID: 38489662 DOI: 10.1097/meg.0000000000002721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/17/2024]
Abstract
BACKGROUND AND OBJECTIVE Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis without heavy alcohol consumption or other chronic conditions, encompasses a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis leading to cirrhosis. This analysis aimed to investigate the correlation between NAFLD and carotid intimal media thickness (C-IMT), a non-invasive surrogate for atherosclerosis. METHODOLOGY Database searches, including PubMed, EMBASE and Cochrane Library, yielded studies up to April 2023. Included were studies exploring the NAFLD-C-IMT relationship in populations aged >18 years. Exclusions comprised non-English papers, those involving animals or pediatric populations and studies lacking control groups. RESULTS No statistical significance was noted between mild and moderate NAFLD compared to the control group regarding C-IMT [95% confidence intervals (CI): -0.03, 0.12] and (95% CI: -0.03, 0.21), respectively. There was a statistically significant difference only in the Severe NAFLD group ( P value 0.03). NAFLD with and without metabolic syndrome showed statistically significant differences compared to control regarding C-IMT (95% CI: 0.04, 0.12) and (95% CI: 0.01, 0.07), respectively. Fifty-nine studies were mentioned without classification of NAFLD severity and revealed a high statistically significant difference between NAFLD and controls regarding C-IMT with (95% CI: 0.09, 0.12, P < 0.00001). Stratified analysis according to sex was done in two studies and revealed statistical differences between NAFLD and control regarding C-IMT in both groups. CONCLUSION This meta-analysis underscores a significant association between NAFLD and increased C-IMT, emphasizing the importance of assessing C-IMT in NAFLD patients to identify cardiovascular risk and tailor therapeutic interventions for improved patient outcomes.
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Affiliation(s)
- Hazem Abosheaishaa
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health + Hospitals Queens, New York
| | - Mahmoud Nassar
- University at Buffalo School of Medicine and Biomedical Sciences, New York, USA
| | - Omar Abdelhalim
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health + Hospitals Queens, New York
| | | | - Sharif Abbas
- Koc University School of Medicine, Istanbul, Turkey
| | - Samah M Morsi
- John's Hopkins School of Medicine, Department of Radiology, Duke University, Department of Radiology
| | - Muhammad Ghallab
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health + Hospitals Queens, New York
| | - Zakaria Alagha
- Marshall University, Joan Edward School of Medicine, West Virginia, New York, USA
| | - Ahmed Omran
- Trinitas Regional Medical Center|RWJBH, Lindon
| | | | - Praneeth Bandaru
- Gastroenterology and Hepatology, The Brooklyn Hospital Center, Brooklyn, New York, USA
| | | | - Madhavi Reddy
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health + Hospitals Queens, New York
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Khoshbaten M, Maleki SH, Hadad S, Baral A, Rocha AV, Poudel L, Abdshah A. Association of nonalcoholic fatty liver disease and carotid media-intima thickness: A systematic review and a meta-analysis. Health Sci Rep 2023; 6:e1554. [PMID: 37701352 PMCID: PMC10493365 DOI: 10.1002/hsr2.1554] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 07/04/2023] [Accepted: 08/29/2023] [Indexed: 09/14/2023] Open
Abstract
Introduction The relationship between cardiovascular disorders and nonalcoholic fatty liver disease (NAFLD) has been extensively studied. To better pool this data and make a more definite conclusion, we performed a meta-analysis to evaluate the association between NAFLD and the thickness of media and intima of carotid artery (CIMT) and cardiovascular disorders. Methods We searched PubMed, Ovid, Scopus, ProQuest, Web of Science, and the Cochrane Library, and analyzed the pooled data using R studio and the "metafor" package. Results The final analysis included a total of 59 studies with 16,179 cases and 26,120 control individuals. NAFLD was shown to be associated with an increase of 0.1231 mm (20.6%) in carotid artery intima-media thickness (CIMT) (p = 0.002, 95% confidence interval [CI]: 0.0462-0.2000) in individuals with NAFLD. The prevalence of atherosclerotic plaques in the carotid arteries and the occurrence of NAFLD are significantly correlated, according to a meta-analysis based on 17 distinct studies (p = 0.001, 1.28-1.43, 95% CI, odds ratio = 1.356). Conclusion Patients with increased CIMT are considerably more likely to have NAFLD. Large prospective investigations are required to corroborate these findings and their prognostic significance, along with the effectiveness of the available interventions.
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Affiliation(s)
- Manouchehr Khoshbaten
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | - Sepideh H. Maleki
- Department of PathologyImam Reza Hospital, Tabriz University of Medical SciencesTabrizIran
| | - Sara Hadad
- Liver and Gastrointestinal Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | - Amrit Baral
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
| | - Ana V. Rocha
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
| | | | - Alireza Abdshah
- Department of Public Health SciencesMiller School of Medicine, University of MiamiMiamiFloridaUSA
- School of MedicineTehran University of Medical SciencesTehranIran
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Béland-Bonenfant S, Petit JM, Vergès B. NAFLD et NASH au cours du diabète : données épidémiologiques, cliniques et pronostiques. MÉDECINE DES MALADIES MÉTABOLIQUES 2023; 17:248-252. [DOI: 10.1016/j.mmm.2023.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Yamane R, Yoshioka K, Hayashi K, Shimizu Y, Ito Y, Matsushita K, Yoshizaki M, Kajikawa G, Mizutani T, Watarai A, Tachi K, Goto H. Prevalence of nonalcoholic fatty liver disease and its association with age in patients with type 2 diabetes mellitus. World J Hepatol 2022; 14:1226-1234. [PMID: 35978658 PMCID: PMC9258257 DOI: 10.4254/wjh.v14.i6.1226] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 03/24/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a risk factor for nonalcoholic fatty liver disease (NAFLD). AIM To determine the prevalence and clinical correlates of NAFLD in a large cohort of patients with T2DM. METHODS Four hundred thirty-seven participants with T2DM who consulted at Meijo Hospital from April 2019 to September 2020 and underwent computed tomography (CT) were assessed. The mean age was 74 ± 13 years, and 269 were men. Hepatic attenuation minus splenic attenuation (CTL-S) less than 1 Hounsfield unit was considered fatty liver. NAFLD was defined as fatty liver in the absence of significant alcohol consumption and hepatitis virus infection. A multiple logistic regression was used to assess the independent factors associated with NAFLD. RESULTS NAFLD was identified in 25.2% of the participants. Young age (odds ratio [OR] = -0.945; 95% confidence interval [CI]: 0.922-0.969), higher hemoglobin levels (OR = 1.501, 95%CI: 1.278-1.764), lower high-density lipoprotein (HDL) cholesterol levels (OR = 0.971, 95%CI: 0.953-0.989), and the absence of dialysis (OR = 0.109, 95%CI: 0.014-0.856) were independent predictors of NAFLD. CONCLUSION NAFLD was detected with CT in 25.2% of the participants. NAFLD was associated with younger age, higher hemoglobin levels, lower HDL cholesterol levels, and an absence of dialysis.
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Affiliation(s)
- Ryosuke Yamane
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
| | - Kentaro Yoshioka
- Center for Liver Diseases, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan.
| | - Kazuhiko Hayashi
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
| | - Yuko Shimizu
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
| | - Yuki Ito
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
| | - Komei Matsushita
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
| | - Michiyo Yoshizaki
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
| | - Go Kajikawa
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
| | - Taro Mizutani
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
| | - Atsuko Watarai
- Department of Diabetes and Endocrinology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
| | - Kosuke Tachi
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
| | - Hidemi Goto
- Department of Gastroenterology and Hepatology, Federation of National Public Service Personnel Mutual Aid Associations Meijo Hospital, Nagoya 460-0001, Aichi, Japan
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Sonaglioni A, Cerini F, Nicolosi GL, Lombardo M, Rumi MG, Viganò M. Left ventricular strain predicts subclinical atherosclerosis in nonadvanced nonalcoholic fatty liver disease patients. Eur J Gastroenterol Hepatol 2022; 34:707-716. [PMID: 35412487 DOI: 10.1097/meg.0000000000002375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The association between nonalcoholic fatty liver disease (NAFLD) and carotid atherosclerosis is still controversial. The present study was designed to assess the relationship between left ventricular systolic mechanics, noninvasively assessed by two-dimensional (2D) speckle-tracking echocardiography (STE) and common carotid artery (CCA) intima-media thickness (IMT), in patients with nonadvanced NAFLD. METHODS All consecutive NAFLD patients diagnosed with liver stiffness measurement (LSM) <12.5 kPa on transient elastography between September 2021 and December 2021 were prospectively enrolled. All participants underwent blood tests, transient elastography, 2D transthoracic echocardiography (TTE) implemented with 2D-STE analysis of left ventricular (LV) global longitudinal strain (GLS) and finally carotid ultrasonography. Main independent predictors of subclinical atherosclerosis, defined as CCA-IMT >0. 9 mm, were evaluated. RESULTS A total of 92 NAFLD patients (54.0 ± 11.1 years, 50% males) were prospectively analyzed. Mean LSM was 6.2 ± 2.4 kPa. FibroScan results revealed that 76.1% of patients had F0-F1, 5.4% F2 and 18.5% F3 liver fibrosis. Despite normal biventricular systolic function on 2D-TTE, LV-GLS was reduced (less negative than -20%) in 64.1% of patients. However, 62.0% of NAFLD patients were found with CCA-IMT >0. 9 mm. Age [odds ratio (OR),1.19; 95% confidence interval (CI), 1.05-1.36], hypertension (OR, 3.73; 95% CI, 1.53-9.11), LSM (OR, 4.83; 95% CI, 2.43-9.59), LV-GLS (OR, 0.49; 95% CI, 0.36-0.68) and statin therapy (OR, 0.10; 95% CI, 0.02-0.60) were independently associated with subclinical atherosclerosis. Age ≥51 years, LSM ≥5.5 kPa and LV-GLS less negative than -20% were the best cutoff values for predicting subclinical atherosclerosis. CONCLUSIONS Subclinical myocardial dysfunction and subclinical atherosclerosis are simultaneously present in patients with nonadvanced NAFLD.
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Affiliation(s)
| | - Federica Cerini
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, University of Milan, Milan
| | | | | | - Maria Grazia Rumi
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, University of Milan, Milan
| | - Mauro Viganò
- Division of Hepatology, Ospedale San Giuseppe MultiMedica IRCCS, University of Milan, Milan
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Wong MYZ, Yap JJL, Sultana R, Cheah M, Goh GBB, Yeo KK. Association between non-alcoholic fatty liver disease and subclinical atherosclerosis in Western and Asian cohorts: an updated meta-analysis. Open Heart 2021; 8:openhrt-2021-001850. [PMID: 34933963 PMCID: PMC8693165 DOI: 10.1136/openhrt-2021-001850] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/25/2021] [Indexed: 11/16/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is a well-established risk factor for cardiovascular disease, with ethnic and regional differences noted. With the recent surge of research within this field, we re-examine the evidence associating NAFLD with subclinical atherosclerosis, and investigate potential regional differences. Methods This is a systematic review and meta-analysis. PubMed and EMBASE were systematically searched for publications from January 1967 to July 2020 using standardised criteria. Original, observational studies investigating the association between NAFLD and either carotid intima-media thickness (CIMT) and/or coronary artery calcification (CAC) were included. Key outcomes included differences in mean CIMT, the presence of increased CIMT, the presence of CAC and the development/progression of CAC. Pooled ORs and pooled standard differences in means were calculated using random-effects models. Between-study heterogeneity was quantified using the Q statistic and I². Subgroup analyses stratified by region of study (Asian vs Western) were also conducted. Results 64 studies involving a total of 172 385 participants (67 404 with NAFLD) were included. 44 studies assessed the effect of NAFLD on CIMT, with the presence of NAFLD associated with increased CIMT (OR 2.00, 95% CI 1.56 to 2.56). 22 studies assessed the effects of NAFLD on CAC score, with the presence of NAFLD associated with the presence of any coronary calcification (OR 1.21, 95% CI 1.12 to 1.32), and the development/progression of CAC (OR 1.26, 95% CI 1.04 to 1.52). When stratified by region, these associations remained consistent across both Asian and Western populations (p>0.05). The majority (n=39) of studies were classified as ‘high quality’, with the remaining 25 of ‘moderate quality’. Conclusions There is a significant positive association between various measures of subclinical atherosclerosis and NAFLD, seen across both Western and Asian populations. These results re-emphasise the importance of early risk evaluation and prophylactic intervention measures to preclude progression to clinical cardiovascular disease in patients with NAFLD.
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Affiliation(s)
| | - Jonathan Jiunn Liang Yap
- Department of Cardiology, National Heart Center Singapore, Singapore.,Duke-NUS Medical School, Singapore
| | | | - Mark Cheah
- Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
| | - George Boon Bee Goh
- Duke-NUS Medical School, Singapore.,Department of Gastroenterology & Hepatology, Singapore General Hospital, Singapore
| | - Khung Keong Yeo
- Department of Cardiology, National Heart Center Singapore, Singapore .,Duke-NUS Medical School, Singapore
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10
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Cai X, Rospleszcz S, Mensel B, Schminke U, Kühn JP, Aghdassi AA, Storz C, Lorbeer R, Schlett CL, Rathmann W, Roden M, Hohenester S, Bülow R, Bamberg F, Peters A, Thorand B, Völzke H, Nano J. Association between hepatic fat and subclinical vascular disease burden in the general population. BMJ Open Gastroenterol 2021; 8:bmjgast-2021-000709. [PMID: 34593525 PMCID: PMC8487174 DOI: 10.1136/bmjgast-2021-000709] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 07/27/2021] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE It is still controversial if increased hepatic fat independently contributes to cardiovascular risk. We aimed to assess the association between hepatic fat quantified by MRI and various subclinical vascular disease parameters. DESIGN We included two cross-sectional investigations embedded in two independent population-based studies (Study of Health in Pomerania (SHIP): n=1341; Cooperative Health Research in the Region of Augsburg (KORA): n=386). The participants underwent a whole-body MRI examination. Hepatic fat content was quantified by proton-density fat fraction (PDFF). Aortic diameters in both studies and carotid plaque-related parameters in KORA were measured with MRI. In SHIP, carotid intima-media thickness (cIMT) and plaque were assessed by ultrasound. We used (ordered) logistic or linear regression to assess associations between hepatic fat and subclinical vascular disease. RESULTS The prevalence of fatty liver disease (FLD) (PDFF >5.6%) was 35% in SHIP and 43% in KORA. In SHIP, hepatic fat was positively associated with ascending (β, 95% CI 0.06 (0.04 to 0.08)), descending (0.05 (0.04 to 0.07)) and infrarenal (0.02 (0.01 to 0.03)) aortic diameters, as well as with higher odds of plaque presence (OR, 95% CI 1.22 (1.05 to 1.42)) and greater cIMT (β, 95% CI 0.01 (0.004 to 0.02)) in the age-adjusted and sex-adjusted model. However, further adjustment for additional cardiometabolic risk factors, particularly body mass index, attenuated these associations. In KORA, no significant associations were found. CONCLUSIONS The relation between hepatic fat and subclinical vascular disease was not independent of overall adiposity. Given the close relation of FLD with cardiometabolic risk factors, people with FLD should still be prioritised for cardiovascular disease screening.
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Affiliation(s)
- Xinting Cai
- Institute of Epidemiology, Helmholtz Center Munich German Research Center for Environmental Health, Neuherberg, Germany.,Institute for Medical Information Processing, Biometry, and Epidemiology-IBE, Pettenkofer School of Public Health, Ludwig-Maximilians-Universitat Munchen, Munich, Germany
| | - Susanne Rospleszcz
- Institute of Epidemiology, Helmholtz Center Munich German Research Center for Environmental Health, Neuherberg, Germany.,Department of Epidemiology, Institute for Medical Information Processing, Biometry and Epidemiology-IBE, Ludwig-Maximilians-Universitat Munchen, Munich, Germany.,German Center for Cardiovascular Disease Research (DZHK), partner site Munich Heart Alliance, Munich, Germany
| | - Birger Mensel
- Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany
| | - Ulf Schminke
- Department of Neurology, University Medicine Greifswald, Greifswald, Germany
| | - Jens-Peter Kühn
- Institute and Policlinic for Diagnostic and Interventional Radiology, University Hospital Carl-Gustav-Carus, Dresden University of Technology, Dresden, Germany
| | | | - Corinna Storz
- Department of Neuroradiology, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany
| | - Roberto Lorbeer
- Department of Radiology, University Hospital, LMU Munich, Munich, Bayern, Germany
| | - Christopher L Schlett
- Department of Diagnostic and Interventional Radiology, Medical Center-University of Freiburg, Freiburg, Germany
| | - Wolfgang Rathmann
- Institute for Biometrics and Epidemiology, German Diabetes Center Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,Partner site Düsseldorf, German Center for Diabetes Research, Neuherberg, Germany
| | - Michael Roden
- Partner site Düsseldorf, German Center for Diabetes Research, Neuherberg, Germany.,Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.,Institute for Clinical Diabetology, German Diabetes Center, German Diabetes Center Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Simon Hohenester
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Robin Bülow
- Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany
| | - Fabian Bamberg
- Department of Diagnostic and Interventional Radiology, Medical Center-University of Freiburg, Freiburg, Germany
| | - Annette Peters
- Institute of Epidemiology, Helmholtz Center Munich German Research Center for Environmental Health, Neuherberg, Germany.,German Center for Cardiovascular Disease Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.,Institute for Medical Information Processing, Biometry, and Epidemiology-IBE, Ludwig Maximilians University Munich, Munich, Germany.,Partner site Munich-Neuherberg, German Center for Diabetes Research, Neuherberg, Germany
| | - Barbara Thorand
- Institute of Epidemiology, Helmholtz Center Munich German Research Center for Environmental Health, Neuherberg, Germany.,Partner site Munich-Neuherberg, German Center for Diabetes Research, Neuherberg, Germany
| | - Henry Völzke
- Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, University Medicine Greifswald, Greifswald, Germany.,Partner site Greifswald, German Center for Cardiovascular Disease Research, Greifswald, Germany
| | - Jana Nano
- Institute of Epidemiology, Helmholtz Center Munich German Research Center for Environmental Health, Neuherberg, Germany .,Partner site Munich-Neuherberg, German Center for Diabetes Research, Neuherberg, Germany
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11
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Alhinai A, Patel K, Fonseca VA, Sebastiani G. Non-invasive diagnosis of nonalcoholic fatty liver disease in patients with type 2 diabetes. J Diabetes Complications 2021; 35:107978. [PMID: 34183247 DOI: 10.1016/j.jdiacomp.2021.107978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 05/19/2021] [Accepted: 06/12/2021] [Indexed: 02/07/2023]
Abstract
Liver disease has emerged as a significant cause of death in people with type 2 diabetes (T2D). Due to a common underlying pathogenic mechanism, namely insulin resistance, T2D represents the main risk factor for nonalcoholic fatty liver disease (NAFLD), characterized by a buildup of fat in the liver. Globally, NAFLD is the most common liver disease, affecting a quarter of the general adult population. The development of nonalcoholic steatohepatitis (NASH) signifies an increased risk of liver fibrosis progression that can result in cirrhosis, hepatocellular carcinoma (HCC), and death. Liver fibrosis progression and development of cirrhosis is mostly asymptomatic until complications from decompensated end-stage liver disease arise. Traditionally, liver biopsy is used to diagnose NASH and stage fibrosis, however, it is invasive and costly. Non-invasive diagnostic alternatives include serum biomarkers and imaging techniques. Early identification of advanced liver fibrosis is pivotal to prompt initiation of targeted surveillance, including screening for HCC, as well as providing options for current and investigational therapeutic interventions to reduce fibrosis progression. This review gives an update on non-invasive diagnostic tools for NAFLD and liver fibrosis in the specific context of T2D, providing clinicians a pragmatic diagnostic approach to this frequent comorbidity in diabetes medicine.
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Affiliation(s)
- Alshaima Alhinai
- Division of Experimental Medicine, McGill University, Montreal, QC, Canada
| | - Keyur Patel
- Division of Gastroenterology and Hepatology, University Health Network Toronto, Toronto General Hospital, Toronto, ON, Canada
| | - Vivian A Fonseca
- Department of Medicine, Division of Endocrinology and Metabolism, School of Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA
| | - Giada Sebastiani
- Division of Experimental Medicine, McGill University, Montreal, QC, Canada; Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada.
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12
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Mertens J, Van Gaal LF, Francque SM, De Block C. NAFLD in type 1 diabetes: overrated or underappreciated? Ther Adv Endocrinol Metab 2021; 12:20420188211055557. [PMID: 34840719 PMCID: PMC8613893 DOI: 10.1177/20420188211055557] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 10/04/2021] [Indexed: 12/18/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries, affecting 25-30% of the general population and up to 65% in those with obesity and/or type 2 diabetes. Accumulation of visceral adipose tissue and insulin resistance (IR) contributes to NAFLD. NAFLD is not an innocent entity as it not only may cause nonalcoholic steatohepatitis and cirrhosis but also contribute to cardiovascular morbidity and mortality. More and more people with type 1 diabetes (T1D) are becoming overweight and present with features of IR, but the prevalence and impact of NAFLD in this population are still unclear. The utility of noninvasive screening tools for NAFLD in T1D is being explored. Recent data indicate that based upon ultrasonographic criteria NAFLD is present in 27% (ranging between 19% and 31%) of adults with T1D. Magnetic resonance imaging data indicate a prevalence rate of 8.6% (ranging between 2.1% and 18.6%). There are, however, multiple factors affecting these data, ranging from study design and referral bias to discrepancies in between diagnostic modalities. Individuals with T1D have a 7-fold higher risk of cardiovascular disease (CVD) and cardiovascular mortality is the most prominent cause of death in T1D. Patients with T1D and NALFD are also more prone to develop CVD, but the independent contribution of NAFLD to cardiovascular events has to be determined in this population. Furthermore, limited data in T1D also point towards a 2 to 3 times higher risk for microvascular complications in those with NAFLD. In this article, we will discuss epidemiological and diagnostic challenges of NAFLD in T1D, explore the link between IR and NAFLD and chronic complications, and examine the independent contribution of NAFLD to the presence of macro-, and microvascular complications.
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Affiliation(s)
- Jonathan Mertens
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics and Member of the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Edegem, Belgium
| | - Luc F. Van Gaal
- Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics and Member of the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | - Sven M. Francque
- Department of Gastroenterology & Hepatology, Antwerp University Hospital, Drie Eikenstraat 655, 2650 Edegem, Belgium
- Laboratory of Experimental Medicine and Pediatrics and Member of the Infla-Med Centre of Excellence, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
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13
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Ismaiel A, Dumitraşcu DL. Cardiovascular Risk in Fatty Liver Disease: The Liver-Heart Axis-Literature Review. Front Med (Lausanne) 2019; 6:202. [PMID: 31616668 PMCID: PMC6763690 DOI: 10.3389/fmed.2019.00202] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 08/27/2019] [Indexed: 12/14/2022] Open
Abstract
According to the World Health Organization, cardiovascular disease (CVD) remains the leading cause of death worldwide, accounting for approximately 18 million deaths per year. Nevertheless, the worldwide prevalence of metabolic diseases, such as type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease (NAFLD), also known to be common risk factors for CVD, have dramatically increased over the last decades. Chronic alcohol consumption is a major cause of chronic liver diseases (CLD) as well as being a major health care cost expenditure accounting for the spending of tremendous amounts of money annually. NAFLD has become one of the major diseases plaguing the world while standing as the most common cause of liver disease in the Western countries by representing about 75% of all CLD. Currently, the most common cause of death in NAFLD remains to be CVD. Several mechanisms have been suggested to be responsible for associating FLD with CVD through several mechanisms including low-grade systemic inflammation, oxidative stress, adipokines, endoplasmic reticulum stress, lipotoxicity and microbiota dysbiosis which may also be influenced by other factors such as genetic and epigenetic variations. Despite of all this evidence, the exact mechanisms of how FLD can causally contribute to CVD are not fully elucidated and much remains unknown. Moreover, the current literature supports the increasing evidence associating FLD with several cardiovascular (CV) adverse events including coronary artery disease, increased subclinical atherosclerosis risk, structural alterations mainly left ventricular hypertrophy, increased epicardial fat thickness, valvular calcifications including aortic valve sclerosis and mitral annular calcification and functional cardiac modifications mainly diastolic dysfunction in addition to cardiac arrhythmias such as atrial fibrillation and ventricular arrythmias and conduction defects including atrioventricular blocks and bundle branch blocks. Patients with FLD should be evaluated and managed accordingly in order to prevent further complications. Possible management methods include non-pharmacological strategies including life style modifications, pharmacological therapies as well as surgical management. This review aims to summarize the current state of knowledge regarding the pathophysiological mechanisms linking FLD with an increased CV risk, in addition to associated CV adverse events and current management modalities.
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Affiliation(s)
- Abdulrahman Ismaiel
- Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- 2nd Department of Internal Medicine, Cluj-Napoca, Romania
| | - Dan L. Dumitraşcu
- Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- 2nd Department of Internal Medicine, Cluj-Napoca, Romania
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14
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Han J, Wang Y, Yuan Z, Liu L, Zhao M, Guan Q, Zhang H, Li Q, Xu J, Gao L, Zhao J, Zhang X. Nonalcoholic fatty liver disease represents a greater metabolic burden in patients with atherosclerosis: A cross-sectional study. Medicine (Baltimore) 2019; 98:e14896. [PMID: 30882706 PMCID: PMC6426626 DOI: 10.1097/md.0000000000014896] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [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
How nonalcoholic fatty liver disease (NAFLD) is linked to atherosclerosis is still disputed. This study aimed to explore the association between NAFLD and atherosclerosis among adults in Shandong province, China.A total of 6849 individuals were enrolled in the final analyses for a community-based study. The relationship between NAFLD and atherosclerosis was evaluated after adjusting for common confounding factors.Hypertension, diabetes, and higher serum low-density lipoprotein cholesterol (LDL-c) level were positively correlated with NAFLD. An odds ratio (OR) (95% confidence interval [CI]) of 1.325 (range 1.157-1.518) for hypertension, 2.153 (range 1.814-2.555) for diabetes, and 1.161 (range 1.071-1.259) for LDL-c was noticed. These factors also were positively correlated with atherosclerosis, with an OR (95% CI) of 1.501 (range 1.286-1.751) for hypertension, 1.716 (range 1.414-2.084) for diabetes, and 1.344 (range 1.231-1.466) for LDL-c. The prevalence of metabolic syndrome was higher in the atherosclerosis+NAFLD group (81.8%) when compared with the NAFLD-only (30.3%), atherosclerosis-only (32.2%), and control (20.3%) groups (P <.01).NAFLD and atherosclerosis have common metabolic characteristics, such as hypertension, diabetes, and higher serum LDL-c level. Patients with NAFLD in combination with atherosclerosis were found to have a more severe metabolic burden and greater chances of having hypertension, diabetes, dyslipidemia, and higher metabolic syndrome scores than those in the other groups.
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Affiliation(s)
- Jie Han
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan
- Department of Endocrinology and Metabolism, Hiser Medical Center of Qingdao, Qingdao
| | - Yong Wang
- Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University
| | - Zhongshang Yuan
- Department of Epidemiology and Biostatistics, School of Public Health, Shandong University
| | - Lu Liu
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan
- Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Jinan, Shandong, China
| | - Meng Zhao
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan
- Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Jinan, Shandong, China
| | - Qingbo Guan
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan
- Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Jinan, Shandong, China
| | - Haiqing Zhang
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan
- Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Jinan, Shandong, China
| | - Qiu Li
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan
- Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Jinan, Shandong, China
| | - Jin Xu
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan
- Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Jinan, Shandong, China
| | - Ling Gao
- Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Jinan, Shandong, China
| | - Jiajun Zhao
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan
- Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Jinan, Shandong, China
| | - Xu Zhang
- Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan
- Institute of Endocrinology and Metabolic Diseases, Shandong Academy of Clinical Medicine, Jinan, Shandong, China
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15
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Bril F, McPhaul MJ, Caulfield MP, Castille JM, Poynard T, Soldevila-Pico C, Clark VC, Firpi-Morell RJ, Lai J, Cusi K. Performance of the SteatoTest, ActiTest, NashTest and FibroTest in a multiethnic cohort of patients with type 2 diabetes mellitus. J Investig Med 2019; 67:303-311. [PMID: 30309884 PMCID: PMC6581087 DOI: 10.1136/jim-2018-000864] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/15/2018] [Indexed: 02/05/2023]
Abstract
Fibromax is a diagnostic tool composed of the combination of 4 non-invasive biomarker panels for the diagnosis of steatosis (SteatoTest), necrosis and inflammation (ActiTest and NashTest-2) and fibrosis (FibroTest). The purpose of this study was to assess the performance of these biomarker panels in patients with type 2 diabetes mellitus (T2DM). All patients underwent routine labs, a 75 g oral glucose tolerance test, a liver proton magnetic resonance spectroscopy (1H-MRS) to measure intrahepatic triglyceride content, and a percutaneous liver biopsy to establish the diagnosis of non-alcoholic steatohepatitis (NASH) and to grade and stage the disease in those patients with non-alcoholic fatty liver disease (NAFLD) by 1H-MRS. For determination of the scores, plasma samples were blindly provided to establish the SteatoTest, ActiTest, NashTest-2 and FibroTest scores. A total of 220 patients with T2DM were included in this study. When the ability of the SteatoTest to identify patients with T2DM with NAFLD by 1H-MRS was assessed, the overall performance expressed as the area under the receiver operating characteristic curve was 0.73 (95% CI 0.65 to 0.81). The performance of the ActiTest and NashTest-2 to diagnose definite NASH among patients with T2DM was 0.70 (95% CI 0.63 to 0.77) and 0.69 (95% CI 0.62 to 0.76), respectively. Regarding the FibroTest score, its performance to identify patients with moderate or advanced fibrosis was 0.67 (95% CI 0.58 to 0.76) and 0.72 (95% CI 0.61 to 0.83), respectively. Non-invasive panels for the diagnosis of steatosis, NASH and/or fibrosis, which were developed and validated in non-diabetic cohorts, underperformed when applied to a large cohort of patients with T2DM. Results from non-diabetic populations should not be extrapolated to patients with T2DM.
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Affiliation(s)
- Fernando Bril
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA
- Malcom Randall Veterans Administration Medical Center, Quest Diagnostics Nichols Institute, Gainesville, Florida, USA
| | - Michael J McPhaul
- Quest Diagnostics Nichols Institute, San Juan Capistrano, California, USA
| | | | | | | | - Consuelo Soldevila-Pico
- Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
| | - Virginia C Clark
- Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
| | - Roberto J Firpi-Morell
- Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, Florida, USA
| | - Jinping Lai
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USA
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA
- Malcom Randall Veterans Administration Medical Center, Quest Diagnostics Nichols Institute, Gainesville, Florida, USA
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16
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Gummesson A, Strömberg U, Schmidt C, Kullberg J, Angerås O, Lindgren S, Hjelmgren O, Torén K, Rosengren A, Fagerberg B, Brandberg J, Bergström G. Non-alcoholic fatty liver disease is a strong predictor of coronary artery calcification in metabolically healthy subjects: A cross-sectional, population-based study in middle-aged subjects. PLoS One 2018; 13:e0202666. [PMID: 30133541 PMCID: PMC6105021 DOI: 10.1371/journal.pone.0202666] [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] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Accepted: 08/07/2018] [Indexed: 12/11/2022] Open
Abstract
Objectives This study aims to estimate the relationship between non-alcoholic fatty liver disease (NAFLD) and measures of atherosclerotic cardiovascular disease (ASCVD), and to determine to what extent such relationships are modified by metabolic risk factors. Methods The study was conducted in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort (n = 1015, age 50–64 years, 51.2% women). NAFLD was defined as computed tomography liver attenuation ≤40 Hounsfield Units, excluding other causes of liver fat. Coronary artery calcification score (CACS) was assessed using the Agatston method. Carotid plaques and intima media thickness (IMT) were measured by ultrasound. Metabolic status was based on assessments of glucose homeostasis, serum lipids, blood pressure and inflammation. A propensity score model was used to balance NAFLD and non NAFLD groups with regards to potential confounders and associations between NAFLD status and ASCVD variables in relation to metabolic status were examined by logistic and generalized linear regression models. Results NAFLD was present in 106 (10.4%) of the subjects and strongly associated with obesity-related traits. NAFLD was significantly associated with CACS after adjustment for confounders and metabolic risk factors (OR 1.77, 95% CI 1.07–2.94), but not with carotid plaques and IMT. The strongest association between NAFLD and CACS was observed in subjects with few metabolic risk factors (n = 612 [60% of all] subjects with 0–1 out of 7 predefined metabolic risk factors; OR 5.94, 95% CI 2.13–16.6). Conclusions NAFLD was independently associated with coronary artery calcification but not with measures of carotid atherosclerosis in this cohort. The association between NAFLD and CACS was most prominent in the metabolically healthy subjects.
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Affiliation(s)
- Anders Gummesson
- Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- * E-mail:
| | - Ulf Strömberg
- Health Metrics Unit, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Caroline Schmidt
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Joel Kullberg
- Department of Surgical Sciences, Section of Radiology, Uppsala University, Uppsala, Sweden
- Antaros Medical, Mölndal, Sweden
| | - Oskar Angerås
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Stefan Lindgren
- Gastroenterology Division, Department of Clinical Sciences, Lund University, University Hospital Skåne, Malmö, Sweden
| | - Ola Hjelmgren
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Kjell Torén
- Section of Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Annika Rosengren
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Björn Fagerberg
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - John Brandberg
- Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Göran Bergström
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden
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17
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Zheng J, Zhou Y, Zhang K, Qi Y, An S, Wang S, Zhao X, Tang YD. Association between nonalcoholic fatty liver disease and subclinical atherosclerosis: a cross-sectional study on population over 40 years old. BMC Cardiovasc Disord 2018; 18:147. [PMID: 30012085 PMCID: PMC6048911 DOI: 10.1186/s12872-018-0877-2] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) refers to fatty infiltration of liver in the absence of excessive alcohol abuse. However, the problem that whether NAFLD is correlated with subclinical atherosclerosis assessed by carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) remains a source of controversy. This can be attributed to the differences in diagnosis methods, population ethnicity, sampling size and bias. This study aimed to further investigate the association of NAFLD with subclinical atherosclerosis. METHODS A cross-sectional study was carried out in the current study on population aged over 40 years derived from Kailuan community-based prospective study among Chinese adults from June 2010 to June 2011. NAFLD was evaluated through ultrasonography and histories of alcohol consumption. Clinical parameters and medical histories of patients were collected in the manner of interview performed by trained investigators using the standardized questionnaires. The biochemical parameters were analyzed at the central laboratory. CIMT and ba-PWV of each patient were measured. Multivariate logistic regression was used to analyze the associations of NAFLD with subclinical atherosclerosis assessed by CIMT or ba-PWV. RESULTS A total of 4112 participants aged over 40 years were enrolled from Kailuan cohort, including 2229 men and 1883 women. The overall prevalence of NAFLD was 38.2% in the total population. Statistically significant differences were found in CIMT (P < 0.0001) and ba-PWV (P = 0.0007) according to the presence of NAFLD. It is notably that the multivariate logistic regression revealed NAFLD was independently associated with elevated CIMT after adjusting the conventional cardiovascular and metabolic risk factors (OR = 1.663, 95% CI = 1.391-1.989, P < 0.0001). In addition, NAFLD was also found to be positively associated with elevated ba-PWV after adjusting age, gender, BMI, current smoking and regular exercising (OR = 1.319, 95% CI = 1.072-1.624, P = 0.0089). CONCLUSIONS Our findings suggest that NAFLD is remarkably correlated with subclinical atherosclerosis, which should be strongly advised to engage in the preventive strategies for cardiovascular diseases (CVDs).
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Affiliation(s)
- Jilin Zheng
- Department of Internal Medicine, Coronary Heart Disease Center State, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Beijing, 100037, China
| | - Yong Zhou
- Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Kuo Zhang
- Department of Internal Medicine, Coronary Heart Disease Center State, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Beijing, 100037, China
| | - Yu Qi
- Department of Internal Medicine, Coronary Heart Disease Center State, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Beijing, 100037, China
| | - Shimin An
- Department of Internal Medicine, Coronary Heart Disease Center State, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Beijing, 100037, China
| | - Siyuan Wang
- Department of Internal Medicine, Coronary Heart Disease Center State, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Beijing, 100037, China
| | - Xingquan Zhao
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
| | - Yi-Da Tang
- Department of Internal Medicine, Coronary Heart Disease Center State, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Beijing, 100037, China.
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18
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Radaelli MG, Martucci F, Perra S, Accornero S, Castoldi G, Lattuada G, Manzoni G, Perseghin G. NAFLD/NASH in patients with type 2 diabetes and related treatment options. J Endocrinol Invest 2018; 41:509-521. [PMID: 29189999 DOI: 10.1007/s40618-017-0799-3] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Accepted: 11/17/2017] [Indexed: 02/06/2023]
Abstract
Type 2 diabetes may reduce life expectancy and patients' quality of life due to its micro- and macro-vascular complications and to the higher risk of several types of cancer. An emerging important factor is represented by the hepatic involvement; it is recognized that excessive hepatic fat accumulation represents a typical feature of diabetic patients and that it also plays an important pathogenic role. It is now evident that non-alcoholic fatty liver disease (NAFLD), generally perceived as a benign condition, may have on the contrary an important deleterious impact for diabetic patients increasing the risk to develop cardiovascular complications but also serious hepatic diseases, in particular non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Lifestyle intervention, bariatric surgery and several drug therapies have now accumulated evidence of efficacy in treating NASH. On the other hand, their durability and safety in the long-term is yet to be proven and their use may be sometimes associated with side effects or higher risk of adverse events limiting the regular administration or contraindicating it. Professional health care providers, building awareness about the importance of these hepatic complications, should put more efforts in primary prevention using a behavioral therapy needing a multidisciplinary approach, in secondary prevention applying on a regular basis in the clinical setting available predictive algorithms to identify the patients at higher cardiovascular and hepatologic risk, and in tertiary prevention treating, when not contraindicated, the diabetic patients preferentially with drugs with proven benefit on NAFLD/NASH.
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Affiliation(s)
- M G Radaelli
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - F Martucci
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - S Perra
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - S Accornero
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - G Castoldi
- Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano Bicocca, Milan, MI, Italy
| | - G Lattuada
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - G Manzoni
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy
| | - G Perseghin
- Dipartimento di Medicina e Riabilitazione, Policlinico di Monza, Via Amati 111, 20900, Monza, MB, Italy.
- Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano Bicocca, Milan, MI, Italy.
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Zhou Y, Zhou X, Wu S, Fan D, Van Poucke S, Chen Y, Fu S, Zheng M. Nonalcoholic fatty liver disease contributes to subclinical atherosclerosis: A systematic review and meta-analysis. Hepatol Commun 2018; 2:376-392. [PMID: 29619417 PMCID: PMC5880194 DOI: 10.1002/hep4.1155] [Citation(s) in RCA: 97] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 01/09/2018] [Accepted: 01/11/2018] [Indexed: 12/21/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease. In our meta-analysis, we aimed to assess the correlation of NAFLD and four surrogate markers of subclinical atherosclerosis. PubMed, Embase, and the Cochrane Library were searched up until April 2017. Original studies investigating the association between NAFLD and subclinical atherosclerosis were included. The outcome data were extracted and pooled for the effect estimate by using a random-effects model. We used the Newcastle-Ottawa Quality Assessment Scale to assess the quality of the included studies. Of the 434 initially retrieved studies, 26 studies involving a total of 85,395 participants (including 29,493 patients with NAFLD) were included in this meta-analysis. The Newcastle-Ottawa Quality Assessment Scale scores suggested the included studies were of high quality. The pooled effects estimate showed that subjects with NAFLD exhibited a significant independent association with subclinical atherosclerosis compared to the non-NAFLD group (odds ratio, 1.60; 95% confidence interval, 1.45-1.78). Subgroup analysis suggested that the presence of NAFLD yielded a remarkable higher risk of increased carotid artery intima-media thickness/plaques, arterial stiffness, coronary artery calcification, and endothelial dysfunction with odds ratios (95% confidence interval) of 1.74 (1.47-2.06), 1.56 (1.24-1.96), 1.40 (1.22-1.60), and 3.73 (0.99-14.09), respectively. Conclusion: Our meta-analysis revealed a close link between NAFLD and subclinical atherosclerosis in light of four different indices. Patients with NAFLD might benefit from screening and surveillance of early atherosclerosis, which would facilitate the prediction of potential cardiovascular disease burden, risk stratification, and appropriate intervention in the long term. (Hepatology Communications 2018;2:376-392).
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Affiliation(s)
- Yao‐Yao Zhou
- Department of CardiologyJinhua Municipal HospitalJinhuaChina
| | - Xiao‐Dong Zhou
- Department of Cardiovascular Medicine, Heart CenterFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Sheng‐Jie Wu
- Department of Cardiovascular Medicine, Heart CenterFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Dan‐Hong Fan
- Department of Cardiovascular Medicine, Heart CenterFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Sven Van Poucke
- Department of Anesthesiology, Intensive Care, Emergency Medicine and Pain TherapyZiekenhuis Oost‐LimburgGenkBelgium
| | - Yong‐Ping Chen
- Department of Hepatology, NAFLD Research CenterFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Institute of HepatologyWenzhou Medical UniversityWenzhouChina
| | - Shen‐Wen Fu
- Department of CardiologyJinhua Municipal HospitalJinhuaChina
| | - Ming‐Hua Zheng
- Department of Hepatology, NAFLD Research CenterFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
- Institute of HepatologyWenzhou Medical UniversityWenzhouChina
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20
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Severity of nonalcoholic fatty liver disease is associated with subclinical cerebro-cardiovascular atherosclerosis risk in Korean men. PLoS One 2018; 13:e0193191. [PMID: 29565984 PMCID: PMC5863945 DOI: 10.1371/journal.pone.0193191] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Accepted: 02/06/2018] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND No studies have reported the relationship between nonalcoholic fatty liver disease (NAFLD) and concurrent cerebral artery and coronary artery atherosclerosis simultaneously. We aimed at determining whether NAFLD, as assessed by ultrasound, is associated with subclinical cerebro-cardio vascular atherosclerosis (CCVA) by multidetector-row computed tomography (MDCT), and high resolution-magnetic resonance angiography (HR-MRA). This cross-sectional study included men in the general Korean population aged 20-70 years. RESULTS A total of 1,652 men participated in the study (normal, n = 835; mild-to-moderate NAFLD, n = 512; severe NAFLD, n = 305). The risk of subclinical CCVA was positively associated with age (odds ratio [OR] 1.068; 1.054-1.081, p < 0.001), body mass index (OR 1.120; 1.08 0-1.162, p < 0.001), hepatic enzyme levels (OR 1.012; 1.001-1.023, p = 0.027; OR 1.006; 1.001-1.012, p = 0.036), fasting glucose (OR 1.021; 1.015-1.027, p < 0.001), triglycerides (OR 1.002; 1.000-1.003, p = 0.016), hypertension (OR 2.836; 2.268-3.546, p < 0.001), and diabetes (OR 2.911; 2.137-3.964, p < 0.001). Also, high-density lipoprotein cholesterol was inversely associated with subclinical CCVA (OR 0.974; 0.965-0.982, p < 0.001). Compared with normal controls, the OR for subclinical CCVA after full adjustment was 1.46 in the mild-to-moderate NAFLD group (95% confidence interval [CI]: 1.10 to 1.93) and 2.04 in the severe NAFLD group (95% CI: 1.44 to 2.89). CONCLUSIONS Our data show that NAFLD is common among Korean men, and NAFLD severity on ultrasonography is associated with subclinical CCVA, as assessed by MDCT, and HR-MRA.
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21
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Serra-Planas E, Aguilera E, Castro L, Rodríguez R, Salinas I, Lucas A, Joaquín C, Puig R, Mauricio D, Puig-Domingo M. Low prevalence of non-alcoholic fatty liver disease in patients with type 1 diabetes is associated with decreased subclinical cardiovascular disease. J Diabetes 2017; 9:1065-1072. [PMID: 28220621 DOI: 10.1111/1753-0407.12539] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 01/10/2017] [Accepted: 02/16/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has been proposed as an independent cardiovascular risk factor. The present study evaluated the prevalence of NAFLD in a cohort of type 1 diabetic (T1D) patients and its potential relationship with subclinical cardiovascular disease (CVD). METHODS One hundred T1D patients (mean [±SD] age 39.4 ± 7.8 years, disease duration 21.7 ± 8.6 years) were included in the present cross-sectional study. All subjects underwent abdominal ultrasonography for detection of NAFLD, carotid ultrasonography to measure the carotid intima-media thickness (CIMT) and atheroma plaques, and cardiac tomography for evaluation of the coronary artery calcium score (CACS). RESULTS Of the study cohort, 12% had NAFLD and 23% had a CACS >0. The T1D subjects with NAFLD had a greater CIMT than those without NAFLD (0.65 ± 0.17 vs 0.55 ± 0.14 mm; P = 0.029), but there were no significant differences between the two groups with regard to CACS, glycemic control, or the presence of carotid plaques. Patients with high liver enzyme concentrations (>20 U/L) had a higher CIMT (0.60 ± 0.16 vs 0.54 ± 0.13; P = 0.04) and there was a higher proportion of altered CACS (17 [73.9%] vs 6 [26.1%]; P = 0.001) and detection of carotid plaques (10 [76.9%] vs 3 [23.1%]; P = 0.014) in this group. CONCLUSIONS A low prevalence of NAFLD was found in the T1D cohort that was associated globally with a low proportion of abnormal CVD imaging markers, although these imaging parameters were worse in subjects in whom NAFLD was detected.
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Affiliation(s)
- Enric Serra-Planas
- Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Eva Aguilera
- Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
- Department of Endocrinology and Nutrition, CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Badalona, Spain
| | - Laura Castro
- Service of Radiology, Institute of Research and Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Raúl Rodríguez
- Service of Radiology, Institute of Research and Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Isabel Salinas
- Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Anna Lucas
- Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
- Department of Endocrinology and Nutrition, CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Badalona, Spain
| | - Clara Joaquín
- Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Rocio Puig
- Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Dídac Mauricio
- Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
- Department of Endocrinology and Nutrition, CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Badalona, Spain
| | - Manel Puig-Domingo
- Department of Endocrinology and Nutrition, Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
- Department of Endocrinology and Nutrition, CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Health Sciences Research Institute and University Hospital Germans Trias i Pujol, Badalona, Spain
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22
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Evaluation of endothelial dysfunction in patients with nonalcoholic fatty liver disease: Association of selenoprotein P with carotid intima-media thickness and endothelium-dependent vasodilation. Clin Res Hepatol Gastroenterol 2017; 41:516-524. [PMID: 28760353 DOI: 10.1016/j.clinre.2017.01.005] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Revised: 01/02/2017] [Accepted: 01/13/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND In patients with NAFLD, there is an increased risk of cardiovascular disease (CVD). Selenoprotein P (SelP), a hepatokine, is associated with insulin resistance (IR) and serum SelP was found to be elevated in patients with NAFLD. AIM This study aimed to determine the risk of CVD in NAFLD patients and the association of serum SelP levels with this NAFLD related CVD risk. METHODS Ninety-three patients with NAFLD and 37 healthy controls were included in the study. Complete blood count, C-reactive protein (CRP), fasting glucose, serum lipid levels, and SelP levels were tested from fasting blood samples. Moreover, body mass index (BMI), HOMA-IR, carotid intima-media thickness (cIMT) and flow-mediated dilatation (FMD) were measured. RESULTS In patients with NAFLD, the FMD ratio was significantly lower than in controls (P=0.027). cIMT measurements were similar in both groups (P=0.996). Serum SelP levels were significantly higher than controls (P<0.001). SelP levels were significantly correlated with BMI, fasting glucose, LDL-cholesterol and HOMA-IR (r=0.395, P<0.001; r=0.322, P=0.002; r=0.353, P<0.001; r=0.521, P<0.001, respectively). Also, SelP levels were significantly lower and correlated with FMD (r=-0.674, P<0.001). SelP, ESR and CRP were significantly higher (P<0.05) and FMD ratios were significantly lower (P<0.05) in patients with nonalcoholic steatohepatitis (NASH) when compared to patients with simple steatosis. CONCLUSION These results suggest that in young NAFLD patients without additional comorbidities, there is an increased risk of CVD. FMD may be a better predictor for assessment of CVD risk when compared with cIMT. We assume that there could also be an important role of SelP in the pathogenesis of NASH.
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23
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Bacha F, Tomsa A, Bartz SK, Barlow SE, Chu ZD, Krishnamurthy R, Krishnamurthy R, Smith EO. Nonalcoholic Fatty Liver Disease in Hispanic Youth With Dysglycemia: Risk for Subclinical Atherosclerosis? J Endocr Soc 2017; 1:1029-1040. [PMID: 29264555 PMCID: PMC5686639 DOI: 10.1210/js.2017-00257] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 06/22/2017] [Indexed: 12/20/2022] Open
Abstract
Context: Obese Hispanic adolescents (OHAs) with dysglycemia have increased cardiovascular disease risk burden. Objective: To investigate if nonalcoholic fatty liver disease (NAFLD) confers added risk for endothelial dysfunction in these youth. Design: Cross-sectional study. Setting: Academic institution. Participants: Thirty-six OHAs (15.3 ± 0.4 years), 20 with prediabetes and 16 with type 2 diabetes, with and without NAFLD. Intervention: Evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) by peripheral arterial tonometry; muscle, hepatic, and adipose tissue insulin sensitivity (IS; hyperinsulinemic-euglycemic clamp 80 mu/m2/min, with [6,6 2H2]glucose and [2H5] glycerol); body composition; and abdominal and hepatic fat by magnetic resonance imaging/spectroscopy. Outcome Measures: RHI and AIx. Hypothesis: OHAs with dysglycemia and NAFLD have worse RHI and AIx vs those without NAFLD. Results: The NAFLD (n = 23) and non-NAFLD (n = 13) groups were of similar age, sex, glycemic status, body mass index, % body fat and abdominal fat. The NAFLD group had higher hepatic fat (P < 0.001) lower skeletal muscle IS (P = 0.01), hepatic IS (P = 0.01), and adipose tissue IS (P = 0.04). The NAFLD vs non-NAFLD group had lower RHI (1.4 ± 0.05 vs 1.7 ± 0.09, P = 0.002), greater AIx (–6.0 ± 1.6 vs –12.0 ± 2.1, P = 0.03). Hepatic fat was inversely related to RHI (r = –0.49, P = 0.002) and positively related to AIx (r = 0.45, P = 0.006). Hepatic IS (r = –0.42, P = 0.01) and adipose IS (r = –.54, P = 0.001) correlated with arterial stiffness (AIx). Conclusion: In OHAs with dysglycemia, NAFLD is associated with worse endothelial function. RHI and AIx were related to hepatic fat content. Vascular stiffness was related to hepatic and adipose tissue insulin resistance.
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Affiliation(s)
- Fida Bacha
- United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030.,Division of Pediatric Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030
| | - Anca Tomsa
- United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030.,Division of Pediatric Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030
| | - Sara K Bartz
- United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030.,Division of Pediatric Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030
| | - Sarah E Barlow
- Division of Gastroenterology, Hepatology, and Nutrition, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030
| | - Zili David Chu
- Division of Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030
| | - Ramkumar Krishnamurthy
- Division of Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030
| | - Rajesh Krishnamurthy
- Division of Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030
| | - E O'Brian Smith
- United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030
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24
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Lee HJ, Lee CH, Kim S, Hwang SY, Hong HC, Choi HY, Chung HS, Yoo HJ, Seo JA, Kim SG, Kim NH, Baik SH, Choi DS, Choi KM. Association between vascular inflammation and non-alcoholic fatty liver disease: Analysis by 18F-fluorodeoxyglucose positron emission tomography. Metabolism 2017; 67:72-79. [PMID: 28081780 DOI: 10.1016/j.metabol.2016.11.004] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 10/26/2016] [Accepted: 11/02/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease as well as metabolic syndrome. FDG-PET is a novel imaging technique that detects vascular inflammation, which may reflect rupture-prone vulnerable atherosclerotic plaques. METHODS Vascular inflammation was measured as the maximum target-to-background ratio (maxTBR), along with various cardiometabolic risk factors in 51 subjects with NAFLD, and compared with 100 age- and gender-matched subjects without NAFLD. The liver attenuation index (LAI), which was measured using computed tomography, was used as a parameter for the diagnosis of NAFLD. RESULTS After adjusting for age and sex, both maxTBR and LAI values were associated with several cardiometabolic risk parameters. Furthermore, there was a significant inter-relationship between LAI and maxTBR values (r=-0.227, P=0.005). Individuals with NAFLD had higher maxTBR values than those without NAFLD (P=0.026), although their carotid intima-media thickness (CIMT) values did not differ. The proportion of subjects with NAFLD showed a step-wise increment following the tertiles of maxTBR values (P for trend=0.015). In multiple logistic regression analysis, maxTBR tertiles were independently associated with NAFLD after adjusting for age, gender, systolic blood pressure, triglycerides, HDL-cholesterol, glucose, BUN, creatinine and homeostasis model assessment of insulin resistance (HOMA-IR) (P=0.030). However, their relationship was attenuated after further adjustment for waist circumference or high sensitive C-reactive protein. CONCLUSION Patients with NAFLD have an increased risk for vascular inflammation as measured via FDG-PET/CT even without difference in CIMT. (Clinical trials No. NCT01958411, http://www.clinicaltrials.gov/).
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Affiliation(s)
- Hyun Jung Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Chang Hee Lee
- Division of Radiology, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Sungeun Kim
- Department of Nuclear Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Soon Young Hwang
- Department of Biostatistics, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Ho Cheol Hong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Hae Yoon Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Hye Soo Chung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Hye Jin Yoo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Sin Gon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Nan Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Sei Hyun Baik
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Dong Seop Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
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The relation between nonalcoholic fatty liver disease and carotid intima-media thickness in Egyptian patients. EGYPTIAN LIVER JOURNAL 2017. [DOI: 10.1097/01.elx.0000524700.07725.37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Guo K, Zhang L, Lu J, Yu H, Wu M, Bao Y, Chen H, Jia W. Non-alcoholic fatty liver disease is associated with late but not early atherosclerotic lesions in Chinese inpatients with type 2 diabetes. J Diabetes Complications 2017; 31:80-85. [PMID: 27742552 DOI: 10.1016/j.jdiacomp.2016.09.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 09/16/2016] [Accepted: 09/21/2016] [Indexed: 12/26/2022]
Abstract
AIMS To investigate the association between non-alcoholic fatty liver disease (NAFLD) and carotid and lower limb atherosclerotic lesions in a large group of hospitalized-based type 2 diabetic population and to assess the prevalence and characteristics of NAFLD in Chinese subjects with type 2 diabetes (T2DM). METHODS A total of 8571 patients (4804 men) with T2DM were included in this cross-sectional study. The main outcome measures were detection of NAFLD, carotid intima-media thickness (C-IMT), carotid and lower limb atherosclerotic plaque formation, and classical risk factors. RESULTS The prevalence of carotid (56.5% vs. 44.5%; p<0.001) and lower limb plaque (56.2% vs. 48.7%; p<0.001), and carotid (11.2% vs. 6.8%; p<0.001) and lower limb stenosis (15.1% vs. 10.3%; p<0.001) was markedly higher in the diabetic patients with NAFLD than in those without, after controlling for age. However, there was no significant difference in C-IMT between diabetic patients with and without NAFLD (0.82±0.30mm vs. 0.85±0.39mm) after controlling for age. Fully adjusted multiple linear regression and logistic regression analyses revealed that NAFLD was significantly associated with increased prevalence of carotid and lower limb atherosclerotic plaque but not with C-IMT. NAFLD, age, sex, longer duration of diabetes and the presence of hypertension were independently associated with carotid and lower limb atherosclerotic plaque (p<0.05). CONCLUSION NAFLD was not associated with elevated C-IMT but was associated with carotid and lower limb atherosclerotic plaque independent of conventional cardiovascular disease risk factors and metabolic syndrome in Chinese inpatients with T2DM.
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Affiliation(s)
- Kaifeng Guo
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Lei Zhang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Junxi Lu
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Haoyong Yu
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Mian Wu
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Yuqian Bao
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Haibing Chen
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
| | - Weiping Jia
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
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Bril F, Cusi K. Nonalcoholic Fatty Liver Disease: The New Complication of Type 2 Diabetes Mellitus. Endocrinol Metab Clin North Am 2016; 45:765-781. [PMID: 27823604 DOI: 10.1016/j.ecl.2016.06.005] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasingly common in patients with type 2 diabetes mellitus (T2DM), with an estimated prevalence of 60% to 80%. The relationship of NAFLD and T2DM is complex, with each condition negatively affecting the other. Although NAFLD is associated with more metabolic and cardiovascular complications and worse hyperglycemia, T2DM accelerates the progression of liver disease in NAFLD. Despite the high prevalence and serious clinical implications, NAFLD is usually overlooked in clinical practice. This article focuses on understanding the relationship between NAFLD and T2DM, to provide better care for these complex patients.
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Affiliation(s)
- Fernando Bril
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine, 1600 South West Archer Road - Room H2, Gainesville, FL 32610, USA
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine, 1600 South West Archer Road - Room H2, Gainesville, FL 32610, USA; Division of Endocrinology, Diabetes, and Metabolism, Malcom Randall Veterans Affairs Medical Center, 1601 South West Archer Road, Gainesville, FL 32608, USA.
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Tarantino G, Finelli C, Gioa S, Citro V, La Sala N, Gentile M. Serum levels of Lp(a) are related to waist circumference in NAFLD patients with low prevalence of co-morbidities. Scand J Clin Lab Invest 2016; 76:544-552. [PMID: 27433943 DOI: 10.1080/00365513.2016.1207249] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 06/26/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Novel evidence suggests a relationship between circulating Lp(a) levels and the presence of cardiovascular events independently from the cardio-metabolic profile. METHODS AND RESULTS The purpose of this study was to investigate serum Lp(a) concentrations in relation to carotid intima-media thickness (IMT), anthropometric measures, lipid profile, assessment of insulin resistance, and other parameters conventionally used to predict CVD risk, in obese patients suffering from hepatic steatosis (HS), the well-known nonalcoholic fatty liver disease (NAFLD). Evidencing the key-points of this research, firstly, serum Lp(a) concentrations were not associated with carotid IMT in this selected population or, consequently, with early atherosclerosis, at least as evaluated by IMT. Secondly, carotid IMT was not predicted by HS severity, as evaluated by ultrasound. Finally, in the adjusted model, Lp(a) was positively predicted by waist circumference (WC) (β = 0.25, t = 2.3, p = 0.02) and negatively by central adiposity, assessed as visceral adipose tissue at US (β = -0.33, t = -3.0, p = 0.003). CONCLUSION Serum Lp(a) values may not play a direct role in increasing IMT, albeit associated with WC.
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Affiliation(s)
- Giovanni Tarantino
- a Department of Clinical Medicine and Surgery , Federico II University Medical School of Naples , Italy
- b Centro Ricerche Oncologiche Di Mercogliano , Istituto Nazionale per Lo Studio E La Cura Dei Tumori "Fondazione Giovanni Pascale", IRCCS , Italy
| | - Carmine Finelli
- c Center of Obesity and Eating Disorders , Stella Maris Mediterraneum Foundation , C/Da S. Lucia , Chiaromonte , Potenza , Italy
| | - Saverio Gioa
- c Center of Obesity and Eating Disorders , Stella Maris Mediterraneum Foundation , C/Da S. Lucia , Chiaromonte , Potenza , Italy
| | - Vincenzo Citro
- d Department of Internal Medicine , Umberto I Hospital , Nocera Inferiore , Salerno , Italy
| | - Nicolina La Sala
- c Center of Obesity and Eating Disorders , Stella Maris Mediterraneum Foundation , C/Da S. Lucia , Chiaromonte , Potenza , Italy
| | - Marco Gentile
- a Department of Clinical Medicine and Surgery , Federico II University Medical School of Naples , Italy
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Wu S, Wu F, Ding Y, Hou J, Bi J, Zhang Z. Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: A systematic review and meta-analysis. Sci Rep 2016; 6:33386. [PMID: 27633274 PMCID: PMC5026028 DOI: 10.1038/srep33386] [Citation(s) in RCA: 224] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 08/24/2016] [Indexed: 12/14/2022] Open
Abstract
Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to cardiovascular disease (CVD). The aim of this study is to assess whether and to what extent the excess risk of CVD is conferred by NAFLD in a meta-analysis. We systematically searched PubMed, EmBase, Web of Science, and Cochrane Library for reports published between 1965 and July 3, 2015. Studies that reported data on association between NAFLD and adverse cardiovascular events or mortality were included. Thirty-four studies (164,494 participants, 21 cross-sectional studies, and 13 cohort studies) were included. NAFLD was not associated with overall mortality (HR = 1.14, 95% CI: 0.99–1.32) and CVD mortality (HR = 1.10, 95% CI: 0.86–1.41). However, NAFLD was associated with an increased risk of prevalent (OR = 1.81, 95% CI: 1.23–2.66) and incident (HR = 1.37, 95% CI: 1.10–1.72) CVD. For some specific CVDs, NAFLD was associated with an increased risk of prevalent (OR = 1.87, 95% CI: 1.47–2.37) and incident (HR = 2.31, 95% CI: 1.46–3.65) coronary artery disease (CAD), prevalent (OR = 1.24, 95% CI: 1.14–1.36) and incident (HR = 1.16, 95% CI: 1.06–1.27) hypertension, and prevalent (OR = 1.32, 95% CI: 1.07–1.62) atherosclerosis. In conclusion, the presence of NAFLD is associated with an increased risk of major adverse cardiovascular events, although it is not related to mortality from all causes or CVD.
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Affiliation(s)
- Shunquan Wu
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China
| | - Fuquan Wu
- Department of General Surgery, 309th Hospital of PLA, Beijing, China
| | - Yingying Ding
- Department of Medical Microbiology and Parasitology, Second Military Medical University, Shanghai, China
| | - Jun Hou
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China
| | - Jingfeng Bi
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China
| | - Zheng Zhang
- Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China
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Abstract
Non-alcoholic fatty liver disease (NAFLD) increases risk of mortality from liver and cardiovascular disease (CVD) and is the major cause of hepatocellular carcinoma (HCC), which may develop without cirrhosis. NAFLD predicts type 2 diabetes, even independently of obesity. Globally, the prevalence of NAFLD averages 25% and is as common as the metabolic syndrome. The majority of patients with type 2 diabetes have NAFLD. The challenge for the diabetologist is to identify patients at risk of advanced liver disease and HCC. At a minimum, liver function tests (LFTs), despite being neither specific nor sensitive, should be performed in all patients with the metabolic syndrome or type 2 diabetes. Increases in LFTs, for which the updated reference values are lower (serum ALT ≈30 U/l in men and ≈20 U/l in women) than those hitherto used in many laboratories, should prompt assessment of fibrosis biomarkers and referral of individuals at risk to a NAFLD/hepatology clinic. Preferably, evaluation of NAFLD should be based on measurement of steatosis biomarkers or ultrasound if easily available. A large number of individuals carry the patatin-like phospholipase domain containing 3 (PNPLA3) I148M variant (30-50%) or the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant (11-15%). These variants increase the risk of advanced liver disease and HCC but not of diabetes or CVD. Genotyping of selected patients for these variants is recommended. Many patients have 'double trouble', i.e. carry both a genetic risk factor and have the metabolic syndrome. Excess use of alcohol could be a cause of 'triple trouble', but such patients would be classified as having alcoholic fatty liver disease. This review summarises a presentation given at the symposium 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1 , and by John Jones, DOI: 10.1007/s00125-016-3940-5 ) and a commentary by the Session Chair, Michael Roden (DOI: 10.1007/s00125-016-3911-x ).
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Affiliation(s)
- Hannele Yki-Järvinen
- Department of Medicine, University of Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland.
- Minerva Foundation Institute for Medical Research, Helsinki, Finland.
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Nonalcoholic Fatty Liver Disease is Associated with Increased Carotid Intima-Media Thickness in Type 1 Diabetic Patients. Sci Rep 2016; 6:26805. [PMID: 27226159 PMCID: PMC4880892 DOI: 10.1038/srep26805] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 05/09/2016] [Indexed: 01/04/2023] Open
Abstract
A growing body of evidence suggests that NAFLD is associated with an increased risk of incident CVD events both in patients without diabetes and in those with type 2 diabetes (T2DM). However, no published data are available regarding the association between NAFLD and C-IMT in T1DM. A total of 722 patients (371 men) with T1DM were included in this cross-sectional study. The main outcome measures were detection of NAFLD, C-IMT and classical risk factors. The mean age of the subjects was 46.2 years, and 51.1% were male. The prevalence of NAFLD was 15.9%. NAFLD patients had a markedly greater C-IMT (0.81 ± 0.25 vs. 0.69 ± 0.18 mm; p < 0.001) and frequency of carotid plaque (28.9% vs. 16.9%; p < 0.05) than those without fatty liver. Moreover, the differences in C-IMT remained after adjusting for potential confounders. A stepwise linear regression analysis revealed that age (standardized β, 0.326; p < 0.001), NAFLD (standardized β, 0.151, p < 0.001), and hsCRP (standardized β, 0.115, p = 0.008) were independently associated with C-IMT in all subjects. Our data show NAFLD is associated with elevated C-IMT in T1DM independent of conventional cardiovascular disease risk factors.
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Petit JM, Masson D, Guiu B, Rollot F, Duvillard L, Bouillet B, Brindisi MC, Buffier P, Hillon P, Cercueil JP, Verges B. GCKR polymorphism influences liver fat content in patients with type 2 diabetes. Acta Diabetol 2016; 53:237-42. [PMID: 25976242 DOI: 10.1007/s00592-015-0766-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Accepted: 04/22/2015] [Indexed: 01/01/2023]
Abstract
AIMS It has recently been shown that an allele in the glucokinase regulatory protein (GCKR) gene was associated with increased liver fat content in obese children. In this study, we set out to determine whether GCKR rs1260326 polymorphism was associated with liver fat content in patients with type 2 diabetes. METHODS Three hundred and eight patients with type 2 diabetes were included in this study. Liver fat content was evaluated using 1H-MR spectroscopy. RESULTS In our population, carriers of the rs1260326 minor T allele had a higher liver fat content than did carriers of the C allele homozygote (12.4 ± 9.6 vs. 10.3 ± 9.1 %, p = 0.03). The number of patients with steatosis was significantly higher in minor T allele carriers than in C allele homozygote carriers (70.7 vs. 55.4 %; p = 0.008). In multivariate analysis, the predictive variables for steatosis were BMI [odds ratio (OR) 1.08; 95 % confidence interval (CI) 1.03-1.13; p = 0.002], statin therapy (yes) [OR 0.54; 95 % CI 0.31-0.94; p = 0.03], metformin therapy (yes) [OR 2.67; 95 % CI 1.50-4.75; p < 0.001], and rs1260326 GCKR polymorphism (TT+CT) [OR 1.99; 95 % CI 1.14-3.47; p = 0.01]. CONCLUSIONS This study shows that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fat content was related to GCKR rs1260326 polymorphism independent of BMI, triglyceride levels, and age.
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Affiliation(s)
- Jean-Michel Petit
- Centre de Recherche INSERM Unité 866, Université de Bourgogne, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France.
- Services de diabétologie et endocrinologie, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France.
| | - David Masson
- Centre de Recherche INSERM Unité 866, Université de Bourgogne, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
| | - Boris Guiu
- Centre de Recherche INSERM Unité 866, Université de Bourgogne, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
- de radiologie, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
| | - Fabien Rollot
- Centre de Recherche INSERM Unité 866, Université de Bourgogne, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
| | - Laurence Duvillard
- Centre de Recherche INSERM Unité 866, Université de Bourgogne, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
| | - Benjamin Bouillet
- Centre de Recherche INSERM Unité 866, Université de Bourgogne, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
- Services de diabétologie et endocrinologie, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
| | - Marie-Claude Brindisi
- Centre de Recherche INSERM Unité 866, Université de Bourgogne, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
- Services de diabétologie et endocrinologie, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
| | - Perrine Buffier
- Services de diabétologie et endocrinologie, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
| | - Patrick Hillon
- Centre de Recherche INSERM Unité 866, Université de Bourgogne, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
- d'hépatologie, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
| | | | - Bruno Verges
- Centre de Recherche INSERM Unité 866, Université de Bourgogne, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
- Services de diabétologie et endocrinologie, CHU du Bocage, BP 77908, 21079, Dijon Cedex, France
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Hong HC, Hwang SY, Ryu JY, Yoo HJ, Seo JA, Kim SG, Kim NH, Baik SH, Choi DS, Choi KM. The synergistic impact of nonalcoholic fatty liver disease and metabolic syndrome on subclinical atherosclerosis. Clin Endocrinol (Oxf) 2016; 84:203-209. [PMID: 26342196 DOI: 10.1111/cen.12940] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 07/14/2015] [Accepted: 09/02/2015] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is a well-known contributor for the development of cardiovascular disease (CVD). We examined the influence of NAFLD and metabolic syndrome (MetS) on markers of subclinical atherosclerosis, including carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI), after adjusting for cardiometabolic risk factors. DESIGN A cross-sectional study. PATIENTS AND MEASUREMENTS The association between NAFLD, MetS and markers of subclinical atherosclerosis was assessed in 955 participants without CVD using multiple logistic regression analysis after adjusting for multiple cardiometabolic risk variables. RESULTS After adjusting for age and sex, CIMT and baPWV were found to be significantly correlated with multiple cardiometabolic risk variables, whereas ABI was only associated with obesity parameters. The prevalence of NAFLD differed significantly according to the presence of subclinical atherosclerosis as defined by both CIMT and baPWV (P = 0·004 and P = 0·007, respectively). After adjusting for potential confounding factors, NAFLD or MetS was not associated with subclinical atherosclerosis as defined by CIMT and baPWV. However, individuals with both NAFLD and MetS had a significantly higher risk of subclinical atherosclerosis as defined by CIMT (OR = 2·06, 95% CI = 1·13-3·74) or baPWV (OR = 2·64, 95% CI = 1·46-4·76) compared to normal subjects, even after adjusting for potential confounders. CONCLUSIONS The results show that NAFLD and MetS have a synergistic impact on the subclinical atherosclerosis, which suggests that individuals with both NAFLD and MetS should be strongly advised to engage in CVD prevention strategies.
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Affiliation(s)
- Ho Cheol Hong
- The Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Soon Young Hwang
- Department of Biostatistics, College of Medicine, Korea University, Seoul, Korea
| | - Ja Young Ryu
- The Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Hye Jin Yoo
- The Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Ji-A Seo
- The Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Sin Gon Kim
- The Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Nan Hee Kim
- The Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Sei Hyun Baik
- The Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Dong Seop Choi
- The Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Kyung Mook Choi
- The Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
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Loffroy R, Terriat B, Jooste V, Robin I, Brindisi MC, Hillon P, Vergès B, Cercueil JP, Petit JM. Liver fat content is negatively associated with atherosclerotic carotid plaque in type 2 diabetic patients. Quant Imaging Med Surg 2016; 5:792-8. [PMID: 26807360 DOI: 10.3978/j.issn.2223-4292.2015.12.03] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is independently associated with atherosclerosis in nondiabetic individuals. In type 2 diabetic patients, the link between fatty liver and atherosclerosis is less clear. Here, we assessed whether liver fat content evaluated using (1)H-magnetic resonance spectroscopy ((1)H-MRS) was independently associated with prevalent carotid plaque as a marker of atherosclerosis in type 2 diabetic patients. METHODS One hundred and forty-four prospectively enrolled patients with type 2 diabetes underwent liver fat content measurement using (1)H-MRS and carotid plaque assessment using ultrasound. Multiple logistic regressions were used to identify factors associated with carotid plaque. RESULTS Mean ± SD liver fat content was 9.86±8.12%. Carotid plaque prevalence was 52.1% (75/144). Patients without plaque were younger (P=0.006) and had a smaller visceral fat area (P=0.015), lower reported prevalence of previous cardiovascular events or current statin therapy (P=0.002), and higher liver fat content than those with plaque (P=0.009). By multivariable logistic regression, increased liver fat content independently predicted the absence of carotid plaque [odds ratios (ORs), 0.94; 95% confidence intervals (CIs), 0.89-0.99; P=0.017]. CONCLUSIONS Liver fat content measured by (1)H-MRS is higher in type 2 diabetic patients without carotid plaque compared to those with plaque. This study suggests that increased liver fat content could be associated with a relative protection against carotid atherosclerosis in patients with type 2 diabetes mellitus.
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Affiliation(s)
- Romaric Loffroy
- 1 Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 2 LE2I, UMR CNRS 6306, University of Burgundy, Dijon, France ; 3 Department of Angiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 4 Inserm U866, University of Burgundy, Dijon, France ; 5 Department of Endocrinology, Diabetes and Nutrition, 6 Department of Hepatology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France
| | - Béatrice Terriat
- 1 Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 2 LE2I, UMR CNRS 6306, University of Burgundy, Dijon, France ; 3 Department of Angiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 4 Inserm U866, University of Burgundy, Dijon, France ; 5 Department of Endocrinology, Diabetes and Nutrition, 6 Department of Hepatology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France
| | - Valérie Jooste
- 1 Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 2 LE2I, UMR CNRS 6306, University of Burgundy, Dijon, France ; 3 Department of Angiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 4 Inserm U866, University of Burgundy, Dijon, France ; 5 Department of Endocrinology, Diabetes and Nutrition, 6 Department of Hepatology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France
| | - Isabelle Robin
- 1 Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 2 LE2I, UMR CNRS 6306, University of Burgundy, Dijon, France ; 3 Department of Angiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 4 Inserm U866, University of Burgundy, Dijon, France ; 5 Department of Endocrinology, Diabetes and Nutrition, 6 Department of Hepatology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France
| | - Marie-Claude Brindisi
- 1 Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 2 LE2I, UMR CNRS 6306, University of Burgundy, Dijon, France ; 3 Department of Angiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 4 Inserm U866, University of Burgundy, Dijon, France ; 5 Department of Endocrinology, Diabetes and Nutrition, 6 Department of Hepatology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France
| | - Patrick Hillon
- 1 Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 2 LE2I, UMR CNRS 6306, University of Burgundy, Dijon, France ; 3 Department of Angiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 4 Inserm U866, University of Burgundy, Dijon, France ; 5 Department of Endocrinology, Diabetes and Nutrition, 6 Department of Hepatology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France
| | - Bruno Vergès
- 1 Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 2 LE2I, UMR CNRS 6306, University of Burgundy, Dijon, France ; 3 Department of Angiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 4 Inserm U866, University of Burgundy, Dijon, France ; 5 Department of Endocrinology, Diabetes and Nutrition, 6 Department of Hepatology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France
| | - Jean-Pierre Cercueil
- 1 Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 2 LE2I, UMR CNRS 6306, University of Burgundy, Dijon, France ; 3 Department of Angiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 4 Inserm U866, University of Burgundy, Dijon, France ; 5 Department of Endocrinology, Diabetes and Nutrition, 6 Department of Hepatology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France
| | - Jean-Michel Petit
- 1 Department of Vascular and Interventional Radiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 2 LE2I, UMR CNRS 6306, University of Burgundy, Dijon, France ; 3 Department of Angiology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France ; 4 Inserm U866, University of Burgundy, Dijon, France ; 5 Department of Endocrinology, Diabetes and Nutrition, 6 Department of Hepatology, François-Mitterrand Teaching Hospital, University of Burgundy, Dijon, France
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Doycheva I, Cui J, Nguyen P, Costa EA, Hooker J, Hofflich H, Bettencourt R, Brouha S, Sirlin CB, Loomba R. Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE. Aliment Pharmacol Ther 2016; 43:83-95. [PMID: 26369383 PMCID: PMC4673036 DOI: 10.1111/apt.13405] [Citation(s) in RCA: 152] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 07/29/2015] [Accepted: 08/26/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Current guidelines do not recommend screening for non-alcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis. AIM To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness. METHODS We performed a cross-sectional analysis of a prospective study that included 100 (53% men) consecutively enrolled diabetics who did not have any other aetiology of liver disease. All patients underwent a standardised research visit, laboratory tests, MRI-PDFF, and MRE. RESULTS Mean (±s.d.) age and body mass index (BMI) was 59.7 (±11.2) years and 30.8 (±6.5) kg/m(2) , respectively. The prevalence of NAFLD (defined as MRI-PDFF ≥5%) and advanced fibrosis (defined as MRE ≥3.6 kPa) was 65% and 7.1%, respectively. One patient with advanced fibrosis had definite hepatocellular carcinoma. When compared to those without NAFLD, patients with NAFLD were younger (P = 0.028) and had higher mean BMI (P = 0.0008), waist circumference (P < 0.0001) and prevalence of metabolic syndrome (84.6% vs. 40.0%, P < 0.0001). Only 26% of those with NAFLD had elevated alanine aminotransferase. CONCLUSIONS This proof-of-concept study demonstrates that T2DM has significant rates of both NAFLD and advanced fibrosis. Concomitant screening for NAFLD and advanced fibrosis by using MRI-proton density fat fraction and magnetic resonance elastography in T2DM is feasible and may be considered after validation in a larger cohort.
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Affiliation(s)
- Iliana Doycheva
- NAFLD Translational Research Unit, University of California, San Diego, La Jolla, CA
| | - Jeffrey Cui
- NAFLD Translational Research Unit, University of California, San Diego, La Jolla, CA
| | - Phirum Nguyen
- NAFLD Translational Research Unit, University of California, San Diego, La Jolla, CA,Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA
| | - Eduardo A. Costa
- Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla, CA
| | - Jonathan Hooker
- Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla, CA
| | - Heather Hofflich
- Division of General Internal Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA
| | - Ricki Bettencourt
- Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
| | - Sharon Brouha
- Department of Radiology, University of California, San Diego, La Jolla, CA
| | - Claude B. Sirlin
- Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla, CA
| | - Rohit Loomba
- NAFLD Translational Research Unit, University of California, San Diego, La Jolla, CA,Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA,Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA
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Petit JM, Pedro L, Guiu B, Duvillard L, Bouillet B, Jooste V, Habchi M, Crevisy E, Fourmont C, Buffier P, Hillon P, Cercueil JP, Verges B. Type 1 diabetes is not associated with an increased prevalence of hepatic steatosis. Diabet Med 2015; 32:1648-51. [PMID: 25981893 DOI: 10.1111/dme.12805] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/13/2015] [Indexed: 02/06/2023]
Abstract
AIM Non-alcoholic fatty liver disease (NAFLD) is commonly associated with Type 2 diabetes. Recently, it has been suggested that NAFLD is also frequently associated with Type 1 diabetes and diabetic complications. In this study, we set out to determine whether Type 1 diabetes was associated with liver fat content measured using magnetic resonance imaging. METHODS One hundred and twenty-eight patients with Type 1 diabetes, 264 patients with Type 2 diabetes and 67 participants without diabetes were included in this study. Hepatic steatosis was defined as a liver fat content > 5.5%. RESULTS People with Type 1 diabetes and controls were similar for age and BMI. Liver fat content was significantly higher in patients with Type 2 diabetes than in patients with Type 1 diabetes and controls. In the control group, nine people (13.4%) had steatosis compared with six (4.7%) patients with Type 1 diabetes (P = 0.04). Among patients with Type 2 diabetes group, 166 (62.8%) had steatosis. In multivariate analysis that included patients with Type 1 diabetes and participants without diabetes, steatosis was associated only with BMI, whereas age, sex, statin therapy and Type 1 diabetes were not. In patients with Type 1 diabetes, there was no correlation between liver fat content and estimated glomerular filtration rate or carotid intima media thickness. CONCLUSIONS Our data showed that Type 1 diabetes was not associated with an increased prevalence of steatosis. Moreover, our study provided no specific arguments concerning a link between liver fat content and diabetic complications in patients with Type 1 diabetes.
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Affiliation(s)
- J-M Petit
- Centre de Recherche INSERM Unité 866
- Services de diabétologie et endocrinologie
| | - L Pedro
- Services de diabétologie et endocrinologie
| | - B Guiu
- Centre de Recherche INSERM Unité 866
- Services de radiologie, Université de Bourgogne, Dijon, France
| | | | - B Bouillet
- Centre de Recherche INSERM Unité 866
- Services de diabétologie et endocrinologie
| | - V Jooste
- Centre de Recherche INSERM Unité 866
| | - M Habchi
- Services de diabétologie et endocrinologie
| | - E Crevisy
- Services de diabétologie et endocrinologie
| | - C Fourmont
- Services de diabétologie et endocrinologie
| | - P Buffier
- Services de diabétologie et endocrinologie
| | - P Hillon
- Centre de Recherche INSERM Unité 866
| | - J-P Cercueil
- Centre de Recherche INSERM Unité 866
- Services de radiologie, Université de Bourgogne, Dijon, France
| | - B Verges
- Centre de Recherche INSERM Unité 866
- Services de diabétologie et endocrinologie
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Clinical and biochemical determinants of the extent of liver steatosis in type 2 diabetes mellitus. Eur J Gastroenterol Hepatol 2015; 27:1386-91. [PMID: 26398456 DOI: 10.1097/meg.0000000000000462] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVE Nonalcoholic fatty liver disease is very frequent in both type 2 diabetes mellitus (T2DM) and the metabolic syndrome (MS), which share clinical and metabolic characteristics. Whether and to which extent these characteristics can predict the degree of liver steatosis are not entirely clear. PATIENTS AND METHODS We determined liver fat (divided into four classes) by standard sonographic images, and clinical and biochemical variables, in 60 consecutive patients with T2DM and with features of the MS. We examined both simple and multiple correlations between the degree of liver steatosis and the variables measured. RESULTS Increased liver fat (defined as >5% of liver mass) was detected in 88% of the participants. Using simple regression analysis, the class of steatosis correlated positively with BMI, waist, number of factors of the MS, sex (female>male), diastolic blood pressure, insulin resistance, metabolic control, inflammation, C-reactive protein, fibrinogen, and leptin, whereas it correlated negatively with high-density lipoprotein-cholesterol. Using multiple regression analysis, only metabolic control, insulin resistance and/or plasma insulin, and waist, remained correlated significantly with the degree of steatosis. Using an ordered probit statistical model, metabolic control, waist, and insulin concentration predicted the steatosis class in 58% of the cases (≤97% with allowance for one class in either excess or deficit). CONCLUSION In patients with T2DM, the extent of liver steatosis is correlated with variables associated with metabolic control and features of the MS. The combination of metabolic control, visceral obesity, and insulin resistance may reasonably predict the degree of liver steatosis in T2DM.
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Madan SA, John F, Pyrsopoulos N, Pitchumoni CS. Nonalcoholic fatty liver disease and carotid artery atherosclerosis in children and adults: a meta-analysis. Eur J Gastroenterol Hepatol 2015; 27:1237-1248. [PMID: 26193052 DOI: 10.1097/meg.0000000000000429] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Observational studies suggest that nonalcoholic fatty liver disease (NAFLD) is associated with increased carotid intimal medial thickness (C-IMT) and carotid plaques in both children and adults. We carried out a meta-analysis to evaluate the relationship between NAFLD and carotid atherosclerosis measured as C-IMT and carotid plaque prevalence. Medline (Ovid), PubMed, Web of Science, and CINAHL databases were searched from 1946 to September 2014, complemented with a manual review of references of the published articles for studies that compared C-IMT or carotid plaque prevalence in adults and children. Results were pooled using both fixed and random effects models. Of the studies identified, 20 were suitable for testing the effect of NAFLD on C-IMT in adults, 13 for testing the effect of NAFLD on carotid plaque prevalence in adults, and five for testing the effect of NAFLD on C-IMT in the pediatric population. The pooled data from 20 studies (19,274 adult participants: NAFLD=8652, controls=10,622) showed significantly increased C-IMT in patients with NAFLD, compared with controls without NAFLD, according to both fixed [standardized mean difference (SMD)=0.251, 95% confidence interval (CI): 0.220-0.282, P<0.001] and random effects models (SMD=0.944, 95% CI: 0.728-1.160, P<0.001). NAFLD was also found to be associated with a higher carotid artery plaque prevalence when compared with controls, according to both fixed (OR=1.273, 95% CI=1.162-1.394, P<0.001) and random effects models (OR=1.769, 95% CI: 1.213-2.581, P=0.003), on pooling of 13 studies (14,445 adult participants: NAFLD=5399 and controls=9046). Analysis of pooled data from five studies in the pediatric population (1121 pediatric participants: NAFLD=312 and controls=809) also found NAFLD to be associated with significantly increased C-IMT according to fixed (SMD=0.995, 95% CI: 0.840-1.150, P<0.001) and random effects models (1.083, 95% CI: 0.457-1.709, P=0.001). NAFLD is associated with increased C-IMT in both children and adults, and with increased carotid plaque prevalence in adults. Individuals identified with carotid disease should be evaluated for NAFLD and vice versa.
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Affiliation(s)
- Shivank A Madan
- aDepartment of Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, New York City, New York bDepartment of Medicine, Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School/Saint Peters University Hospital, New Brunswick cDepartment of Medicine, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School/University Hospital, Newark, New Jersey, USA
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Portillo-Sanchez P, Bril F, Maximos M, Lomonaco R, Biernacki D, Orsak B, Subbarayan S, Webb A, Hecht J, Cusi K. High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. J Clin Endocrinol Metab 2015; 100:2231-8. [PMID: 25885947 PMCID: PMC6287506 DOI: 10.1210/jc.2015-1966] [Citation(s) in RCA: 386] [Impact Index Per Article: 38.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
CONTEXT AND OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) and its more severe form with steatohepatitis (NASH) are common in patients with type 2 diabetes mellitus (T2DM). However, they are usually believed to largely affect those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD by the gold standard, liver magnetic resonance spectroscopy ((1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. PARTICIPANTS AND METHODS We recruited 103 patients with T2DM and normal plasma aminotransferases (age, 60 ± 8 y; body mass index [BMI], 33 ± 5 kg/m(2); glycated hemoglobin [A1c], 7.6 ± 1.3%). We measured the following: 1) liver triglyceride content by (1)H-MRS; 2) systemic insulin sensitivity (homeostasis model assessment-insulin resistance); and 3) adipose tissue insulin resistance, both fasting (as the adipose tissue insulin resistance index: fasting plasma free fatty acids [FFA] × insulin) and during an oral glucose tolerance test (as the suppression of FFA). RESULTS The prevalence of NAFLD and NASH were much higher than expected (50% and 56% of NAFLD patients, respectively). The prevalence of NAFLD was higher in obese compared with nonobese patients as well as with increasing BMI (P = .001 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (P = .01). Compared with nonobese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle) and, particularly, adipose tissue (fasting/postprandial) insulin resistance (all P < .01). CONCLUSIONS The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of NASH. Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH.
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Affiliation(s)
- Paola Portillo-Sanchez
- Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., R.L., S.S., K.C.), University of Florida, Gainesville, Florida 32610; Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., D.B., S.S., K.C.), Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida 32608; Division of Diabetes (B.O., J.H., K.C.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Diabetes (B.O., J.H., K.C.), and Division of Hepatology (A.W.), Audie L. Murphy VAMC, San Antonio, Texas 78229
| | - Fernando Bril
- Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., R.L., S.S., K.C.), University of Florida, Gainesville, Florida 32610; Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., D.B., S.S., K.C.), Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida 32608; Division of Diabetes (B.O., J.H., K.C.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Diabetes (B.O., J.H., K.C.), and Division of Hepatology (A.W.), Audie L. Murphy VAMC, San Antonio, Texas 78229
| | - Maryann Maximos
- Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., R.L., S.S., K.C.), University of Florida, Gainesville, Florida 32610; Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., D.B., S.S., K.C.), Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida 32608; Division of Diabetes (B.O., J.H., K.C.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Diabetes (B.O., J.H., K.C.), and Division of Hepatology (A.W.), Audie L. Murphy VAMC, San Antonio, Texas 78229
| | - Romina Lomonaco
- Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., R.L., S.S., K.C.), University of Florida, Gainesville, Florida 32610; Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., D.B., S.S., K.C.), Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida 32608; Division of Diabetes (B.O., J.H., K.C.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Diabetes (B.O., J.H., K.C.), and Division of Hepatology (A.W.), Audie L. Murphy VAMC, San Antonio, Texas 78229
| | - Diane Biernacki
- Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., R.L., S.S., K.C.), University of Florida, Gainesville, Florida 32610; Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., D.B., S.S., K.C.), Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida 32608; Division of Diabetes (B.O., J.H., K.C.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Diabetes (B.O., J.H., K.C.), and Division of Hepatology (A.W.), Audie L. Murphy VAMC, San Antonio, Texas 78229
| | - Beverly Orsak
- Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., R.L., S.S., K.C.), University of Florida, Gainesville, Florida 32610; Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., D.B., S.S., K.C.), Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida 32608; Division of Diabetes (B.O., J.H., K.C.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Diabetes (B.O., J.H., K.C.), and Division of Hepatology (A.W.), Audie L. Murphy VAMC, San Antonio, Texas 78229
| | - Sreevidya Subbarayan
- Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., R.L., S.S., K.C.), University of Florida, Gainesville, Florida 32610; Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., D.B., S.S., K.C.), Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida 32608; Division of Diabetes (B.O., J.H., K.C.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Diabetes (B.O., J.H., K.C.), and Division of Hepatology (A.W.), Audie L. Murphy VAMC, San Antonio, Texas 78229
| | - Amy Webb
- Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., R.L., S.S., K.C.), University of Florida, Gainesville, Florida 32610; Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., D.B., S.S., K.C.), Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida 32608; Division of Diabetes (B.O., J.H., K.C.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Diabetes (B.O., J.H., K.C.), and Division of Hepatology (A.W.), Audie L. Murphy VAMC, San Antonio, Texas 78229
| | - Joan Hecht
- Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., R.L., S.S., K.C.), University of Florida, Gainesville, Florida 32610; Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., D.B., S.S., K.C.), Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida 32608; Division of Diabetes (B.O., J.H., K.C.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Diabetes (B.O., J.H., K.C.), and Division of Hepatology (A.W.), Audie L. Murphy VAMC, San Antonio, Texas 78229
| | - Kenneth Cusi
- Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., R.L., S.S., K.C.), University of Florida, Gainesville, Florida 32610; Division of Endocrinology, Diabetes and Metabolism (P.P.S., F.B., M.M., D.B., S.S., K.C.), Malcom Randall Veterans Administration Medical Center (VAMC), Gainesville, Florida 32608; Division of Diabetes (B.O., J.H., K.C.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and Division of Diabetes (B.O., J.H., K.C.), and Division of Hepatology (A.W.), Audie L. Murphy VAMC, San Antonio, Texas 78229
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Kwak MS, Yim JY, Kim D, Park MJ, Lim SH, Yang JI, Chung GE, Kim YS, Yang SY, Kim MN, Lee CH, Yoon JH, Lee HS. Nonalcoholic fatty liver disease is associated with coronary artery calcium score in diabetes patients with higher HbA1c. Diabetol Metab Syndr 2015; 7:28. [PMID: 25844093 PMCID: PMC4384364 DOI: 10.1186/s13098-015-0025-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 03/18/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND In patients with diabetes, studies investigating the association between nonalcoholic fatty liver disease (NAFLD) and coronary artery calcium score (CACS) have shown conflicting results. The aim of this study was to evaluate the association between NAFLD and CACS in diabetic patients. METHODS This is the cohort study performed in Seoul National University Hospital Gangnam Healthcare Center. NAFLD was defined as cases with the typical ultrasonographic findings without excessive alcohol consumption, medications causing hepatic steatosis or other chronic liver diseases. CACS was evaluated using the Agatston method. Diabetes was defined as cases with fasting serum glucose ≥ 126 mg/dl, glycated hemoglobin (HbA1c) ≥ 6.5%, or those taking anti-diabetic medications. Multivariate linear regression analyses were performed with use of the interaction term of NAFLD × glycemic level and other confounders of CACS such as age, sex, hypertension, body mass index, waist circumference, HDL cholesterol and triglyceride. RESULTS A total of 213 participants with diabetes were included in the study. As 77 subjects (36.2%) had CACS 0, causing left sided skewness, CACS was analyzed after log transformation to Ln (CACS + 1). A statistically significant interaction was observed between NAFLD and HbA1c ≥ 7% (P for interaction = 0.014). While NAFLD was not associated with CACS in the group with HbA1c < 7% (P = 0.229), it was significantly associated in the group with HbA1c ≥ 7% (P = 0.010) after adjusting for covariates in multivariate analyses. CONCLUSIONS This study demonstrated an effect modification of glycemic level on the association between NAFLD and CACS. NAFLD was independently associated with CACS only in diabetes patients with higher HbA1c, after adjustment for confounders.
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Affiliation(s)
- Min-Sun Kwak
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Jeong Yoon Yim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Donghee Kim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Min Jung Park
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Seon Hee Lim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Jong In Yang
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Goh Eun Chung
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Young Sun Kim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Sun Young Yang
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Mi Na Kim
- />Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39FL., Gangnam Finance Center 737, Yeoksam-Dong, Seoul, 135-984 Gangnam-Gu Korea
| | - Chang-Hoon Lee
- />Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- />Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo-Suk Lee
- />Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Idilman IS, Akata D, Hazirolan T, Doganay Erdogan B, Aytemir K, Karcaaltincaba M. Nonalcoholic fatty liver disease is associated with significant coronary artery disease in type 2 diabetic patients: a computed tomography angiography study 2：. J Diabetes 2015; 7:279-86. [PMID: 24893617 DOI: 10.1111/1753-0407.12172] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 05/01/2014] [Accepted: 05/01/2014] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND To investigate whether nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery disease (CAD) in type 2 diabetic patients, who underwent coronary computed tomography angiography (CTA). METHODS Between June 2007 and May 2010, a total of 273 type 2 diabetic patients without known liver disease underwent coronary CTA for chest pain were enrolled. Axial, multiplanar, and Maximum intensity projection (MIP) images were used for determining the cardiovascular disease. Liver fat content was measured from unenhanced CT images obtained for calcium scoring. Moderate and severe NAFLD was defined when mean liver attenuation value is ≤40 Hounsfield Unit (HU). RESULTS Among 273 patients, 76% of the patients (n = 207) had CAD; 48% of them had significant CAD (≥50 stenosis) by coronary CTA. Patients with CAD were older and male gender was predominant. Mean liver attenuation value calculated with CT was 50 ± 12 HU. Mean liver attenuation value was lower in patients with metabolic syndrome compared to patients without metabolic syndrome (P < 0.001). Moderate and severe NAFLD was observed in 22% of the patients (n = 59) with a mean attenuation value of 30 HU. After adjustment of age, gender, obesity, hypertension, smoking status and serum low-density lipoprotein (LDL) levels as coronary risk factors, NAFLD was associated with significant CAD (P = 0.04). CONCLUSIONS In conclusion, the results of the present study indicate that NAFLD is associated with significant CAD in type 2 diabetic patients. Assessment of liver attenuation by CT represents noninvasive evaluation for detection of asymptomatic individuals with NAFLD during coronary CT angiography.
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Affiliation(s)
- Ilkay S Idilman
- Division of Noninvasive Cardiovascular Imaging, Hacettepe University School of Medicine, Ankara, Turkey; Liver Imaging Team, Department of Radiology, Hacettepe University School of Medicine, Ankara, Turkey
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Fargion S, Porzio M, Fracanzani AL. Nonalcoholic fatty liver disease and vascular disease: State-of-the-art. World J Gastroenterol 2014; 20:13306-13324. [PMID: 25309067 PMCID: PMC4188888 DOI: 10.3748/wjg.v20.i37.13306] [Citation(s) in RCA: 165] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Revised: 05/02/2014] [Accepted: 07/30/2014] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.
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Bhatt SP, Guleria R. Sleep apnea and fatty liver disease: The growing link and management issues. World J Respirol 2014; 4:11-18. [DOI: 10.5320/wjr.v4.i2.11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 12/27/2013] [Accepted: 03/17/2014] [Indexed: 02/06/2023] Open
Abstract
Obstructive sleep apnea (OSA) is associated with metabolic, cardiovascular and neuropsychological disorders, with substantial morbidity and economic costs. OSA has been estimated to affect 4%-11% of the population, depending on age. Obesity is a significant risk factor for OSA. Non alcoholic fatty liver disease (NAFLD) has emerged as an integral component of the metabolic syndrome, with insulin resistance as the central pathogenic feature. Estimates based on imaging and autopsy studies suggest that about 20%-30% of adults in the United States and other Western countries have NAFLD. Evidence now suggests that NAFLD is independently correlated to insulin resistance regardless of adiposity. Some authors have suggested that OSA may be another contributor to NAFLD development. In complex diseases, several or many different genes interact with environmental factors in determining disease presence or its phenotype. Individual genes only have a small effect on disease risk and can therefore be very difficult to identify. The genetic and hormonal determinants of OSA and NAFLD have received little attention. A wide variety of intermediate phenotypes and genes are involved in OSA and NAFLD which makes this syndrome genetically complex. Various adipokines, the most important of which are leptin, adiponectin, tumor necrosis factor-alpha, resistin and interleukin-6, have a key role in NAFLD and OSA. Some studies have suggested that oxidative stress may also contribute to the development of NAFLD and OSA. Lifestyle intervention, insulin sensitizer drugs and bariatric surgery aim to improve metabolic syndrome, OSA and NAFLD but need further investigation.
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Munteanu MA, Mircea PA. From NAFLD to Cardiovascular Disease. Is it (Still) the Metabolic Syndrome? ACTA ACUST UNITED AC 2014; 87:80-6. [PMID: 26528002 PMCID: PMC4620846 DOI: 10.15386/cjmed-277] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2014] [Accepted: 06/04/2014] [Indexed: 12/28/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in developed countries. The incidence of NAFLD in the general population is 30–38% deppending on the geographical area and the diagnostic method used. NAFLD is considered to be the liver manifestation of the metabolic syndrome. A better understanding of the natural evolution would have practical consequences related mainly to the need of early and aggressive diagnosis, active monitoring and therapeutic solutions. Cardiovascular disease appears to be the main cause of death in these patients. The mechanisms linking NAFLD with cardiovascular disease are not fully understood yet, but attention was focused primarily on insulin resistance. The visceral adipose tissue, the epicardial adipose tissue, the systemic inflammatory response syndrome, the lipid profile, the procoagulants factors, the oxidative stress, and type 2 diabetes mellitus, they all might play a role in the link between NAFLD and cardiovascular disease. Currently, there isn’t any medication specifically recommended for the treatment of NAFLD. Although the mechanisms underlying the association between NAFLD and cardiovascular disease are not fully known, attention must be paid to this association, given that these patients are more likely to die due to heart disease rather than liver disease.
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Affiliation(s)
- Mihai Alexandru Munteanu
- Department of Internal Medicine, 1 Medical Clinic - Internal Medicine, Cardiology and Gastroenterology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Petru Adrian Mircea
- Department of Internal Medicine, 1 Medical Clinic - Internal Medicine, Cardiology and Gastroenterology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Kim SK, Choi YJ, Huh BW, Park SW, Lee EJ, Cho YW, Huh KB. Nonalcoholic Fatty liver disease is associated with increased carotid intima-media thickness only in type 2 diabetic subjects with insulin resistance. J Clin Endocrinol Metab 2014; 99:1879-84. [PMID: 24512497 DOI: 10.1210/jc.2013-4133] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
CONTEXT The association between nonalcoholic fatty liver disease (NAFLD) and subclinical atherosclerosis in type 2 diabetes is controversial. OBJECTIVE The objective of the study was to investigate the participation of insulin resistance in the association of NAFLD and the carotid atherosclerotic burden in a large cohort of patients with type 2 diabetes. DESIGN, SETTING, AND PATIENTS This was an observational study performed in 4437 consecutively enrolled patients with type 2 diabetes. MAIN OUTCOMES MEASURES Hepatic steatosis and mean carotid intima-media thickness (C-IMT) were measured using ultrasonography. Insulin resistance was assessed using the short insulin tolerance test. RESULTS The prevalence of NAFLD was 72.7% in the whole study population. Among subjects with NAFLD, 23.2% were not insulin resistant. There were significant differences in C-IMT and the frequency of carotid atherosclerosis between groups classified by insulin resistance within the same NAFLD strata. C-IMT was highest in subjects with both NAFLD and insulin resistance [0.844 ± 0.004 (mean ± SE) mm vs 0.786 ± 0.008, 0.821 ± 0.007, and 0.807 ± 0.006 mm, P for trend <.001, respectively, in insulin sensitive subjects without NAFLD, insulin resistant subjects without NAFLD, and insulin sensitive subjects with NAFLD]. These differences remained after adjusting for potential confounders. However, C-IMT in subjects having only NAFLD or insulin resistance was not higher than that in those with neither NAFLD nor insulin resistance. CONCLUSIONS NAFLD is very common in subjects with type 2 diabetes, but NAFLD not accompanied by insulin resistance is not associated with a carotid atherosclerotic burden. However, having both NAFLD and insulin resistance seemed to be an independent predictor of increased C-IMT.
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Affiliation(s)
- Soo-Kyung Kim
- Department of Internal Medicine (S.-K.K., S.W.P., Y.-W.C.), CHA Bundang Medical Center, CHA University, Seongnam 463-712, Korea; Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute (Y.J.C., B.W.H., K.B.H.), Seoul 121-806, Korea; and Department of Internal Medicine (E.J.L.), Yonsei University College of Medicine, Seoul 120-749, Korea
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Kim NH, Park J, Kim SH, Kim YH, Kim DH, Cho GY, Baik I, Lim HE, Kim EJ, Na JO, Lee JB, Lee SK, Shin C. Non-alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population. Heart 2014; 100:938-43. [PMID: 24721975 DOI: 10.1136/heartjnl-2013-305099] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE The effect of non-alcoholic fatty liver disease (NAFLD) on cardiovascular system remains controversial. We investigated the independent contribution of NAFLD to cardiovascular structure and function in the general population. METHODS A total of 1886 participants without known cardiovascular disease were enrolled from the Korean Genome Epidemiology Study. The participants were divided into four groups, based on the presence of NAFLD, metabolic syndrome (MetS), neither or both. NAFLD was diagnosed by CT. Changes in cardiovascular structure and function were assessed by tissue Doppler imaging (TDI) echocardiography, carotid ultrasound and brachial-ankle pulse wave velocity (baPWV). RESULTS In multivariate analyses, subjects with both NAFLD and MetS had a higher E/Ea ratio and baPWV, as well as a lower TDI Ea velocity (all p<0.001) than those with neither NAFLD nor MetS. Subjects with either NAFLD or MetS also showed significant differences in TDI Ea velocity and baPWV (all p<0.05). However, no significant differences of carotid intima-media thickness (CIMT) values were seen among the four groups. Multivariate linear regression revealed that both NAFLD and MetS were independent predictors of TDI Ea velocity and baPWV (all p<0.001). Both MetS and NAFLD were not a determinant of CIMT. CONCLUSIONS NAFLD was associated with early alterations of cardiovascular system, independent of established cardiovascular risk factors and MetS.
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Affiliation(s)
- Nan Hee Kim
- Division of Endocrinology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Juri Park
- Division of Endocrinology, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea
| | - Seong Hwan Kim
- Division of Cardiology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Yong Hyun Kim
- Division of Cardiology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Dong Hyuk Kim
- Division of Cardiology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Goo-Yeong Cho
- Division of Cardiology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Inkyung Baik
- Department of Foods and Nutrition, College of Natural Sciences, Kookmin University, Seoul, Korea
| | - Hong Euy Lim
- Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Eung Ju Kim
- Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Jin Oh Na
- Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Jung Bok Lee
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul, Korea
| | - Seung Ku Lee
- Institute of Human Genomic Study, Korea University Ansan Hospital, Ansan, Korea
| | - Chol Shin
- Institute of Human Genomic Study, Korea University Ansan Hospital, Ansan, Korea
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Trivedi I, Rinella ME. NAFLD and Cardiovascular Disease: Can the Real Association Be Determined? ACTA ACUST UNITED AC 2014. [DOI: 10.1007/s11901-014-0231-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Dogru T, Sertoglu E, Celebi G, Gurel H, Ercin CN. Endothelial dysfunction and carotid atherosclerosis in non-alcoholic fatty liver disease. Ups J Med Sci 2014; 119:58-9. [PMID: 24328674 PMCID: PMC3916721 DOI: 10.3109/03009734.2013.852276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Affiliation(s)
- Teoman Dogru
- Gulhane School of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - Erdim Sertoglu
- Ankara Mevki Military Hospital, Anittepe Dispensary, Biochemistry Laboratory, Ankara, Turkey
| | - Gurkan Celebi
- Gulhane School of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - Hasan Gurel
- Gulhane School of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - Cemal Nuri Ercin
- Gulhane School of Medicine, Department of Gastroenterology, Ankara, Turkey
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Dogru T, Genc H, Ercin CN. Carotid atherosclerosis or nonalcoholic fatty liver disease: Which comes first? Atherosclerosis 2013; 231:187-8. [DOI: 10.1016/j.atherosclerosis.2013.09.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 09/18/2013] [Accepted: 09/19/2013] [Indexed: 02/07/2023]
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Dunn MA, Behari J, Rogal SS, O'Connell MR, Furlan A, Aghayev A, Gumus S, Saul MI, Bae KT. Hepatic steatosis in diabetic patients does not predict adverse liver-related or cardiovascular outcomes. Liver Int 2013; 33:1575-82. [PMID: 23944954 DOI: 10.1111/liv.12285] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Accepted: 07/24/2013] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Steatosis is a defining feature of nonalcoholic fatty liver disease (NAFLD). However, evidence that severity of steatosis can predict adverse outcomes in NAFLD or nonalcoholic steatohepatitis (NASH) is lacking. The aim of this study was to determine whether steatosis assessed by computed tomography (CT) imaging predicts adverse outcomes in diabetic patients at risk for NAFLD/NASH. METHODS We studied deaths, liver-related and cardiovascular adverse outcomes in a 5-year retrospective observational cohort of 2343 type 2 diabetic patients in a large care network who had noncontrast CT imaging for clinical indications. We measured steatosis by subtraction of spleen from liver attenuation, a method that showed low sensitivity (0.417) and high specificity (0.882) compared with histopathological scoring. We evaluated outcomes prediction using multivariate Cox proportional hazards modelling of steatosis both as a categorical (≥ 30%) and continuous variable. RESULTS Steatosis ≥ 30% was present in 233 (9.9%) of the cohort at baseline. Over 5 years, there were 372 total deaths, 18 liver-related and 99 cardiovascular deaths, 48 liver transplants, 51 occurrences of hepatic encephalopathy, 41 hepatocellular carcinomas, 653 myocardial infarctions, 66 strokes, 180 occurrences of angina, 735 occurrences of arrhythmia and 772 occurrences of congestive heart failure. Steatosis had no predictive value for any adverse outcome. Patients with steatosis averaged 8 years younger than those without it. Age had a strong covariate influence on occurrence of total deaths, cardiovascular deaths, myocardial infarctions, arrhythmias and congestive heart failure. CONCLUSION Although steatosis on imaging is often the abnormality that triggers diagnosis and assessment of NAFLD/NASH, it lacks predictive value for adverse clinical outcomes.
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Affiliation(s)
- Michael A Dunn
- Center for Liver Diseases, Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA
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