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      Liraglutide Decreases Liver Fat Content and Serum Fibroblast Growth Factor 21 Levels in Newly Diagnosed Overweight Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

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          Abstract

          Purposes

          In this study, we aimed to verify plasma fibroblast growth factor 21 (FGF21) elevation in newly diagnosed overweight patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) and to evaluate the effectiveness of liraglutide on reducing liver fat content and serum (FGF21) levels in those patients.

          Methods

          A 12-week, single-center, prospective study was conducted. Twenty newly diagnosed overweight patients with T2DM and NAFLD were recruited. Twenty healthy age, sex, and body mass index (BMI) matched subjects were enrolled as the control group. Enzyme-linked immunosorbent assay was used to measure serum FGF21 levels. Liver fat content was determined using the 3.0 T whole-body MRI scanner.

          Results

          Those newly diagnosed overweight patients with T2DM and NAFLD had a BMI of 27.6 ± 0.5 kg/m 2. They had higher levels of FGF21 (159.6 ± 35.7 vs. 124.1 ± 42.9 pg/ml, P < 0.001) and increased liver fat content (19.3 ± 9.4 vs. 4.5 ± 0.6%, P < 0.001) compared to the controls. Liraglutide treatment for 12 weeks induced a significant 4.9 kg weight loss (95% confidence interval (CI): -6.1, -3.7, P < 0.001), which was equivalent to a relative reduction of 6.8% (95% CI: 5.3%, 8.3%, P < 0.001). FGF21 levels decreased after the 12-week liraglutide treatment (159.6 ± 35.7 vs. 124.2 ± 27.8 pg/ml, P = 0.006). There was a positive correlation between relative changes of liver fat content and relative change of FGF21 ( r = 0.645, P = 0.002). FGF21 levels significantly decreased in patients who had a significant decrease in liver fat content (≥29%) (95% CI: -262.8, -55.1, P = 0.006); however, there was no significant change in the patients without a significant decrease in liver fat content (<29%) (95% CI: -60.0, 54.1, P = 0.899).

          Conclusions

          Liraglutide treatment reduced both liver fat content and FGF21 levels in newly diagnosed overweight patients with T2DM and NAFLD. FGF21 may be a potential biomarker for evaluating the effects of liraglutide treatment on hepatic fat and glucose metabolism.

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          Most cited references38

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          Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.

          Zobair Younossi, Aaron Koenig, Dinan Abdelatif … (2016)
          Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of hepatocellular carcinoma (HCC), cirrhosis, overall mortality, and liver-related mortality were determined. NASH required histological diagnosis. All studies were reviewed by three independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication, and study population. We used random-effects models to provide point estimates (95% confidence interval [CI]) of prevalence, incidence, mortality and incidence rate ratios, and metaregression with subgroup analysis to account for heterogeneity. Of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (95% CI: 22.10-28.65) with highest prevalence in the Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38-61.20), type 2 diabetes (22.51%; 95% CI: 17.92-27.89), hyperlipidemia (69.16%; 95% CI: 49.91-83.46%), hypertension (39.34%; 95% CI: 33.15-45.88), and metabolic syndrome (42.54%; 95% CI: 30.06-56.05). Fibrosis progression proportion, and mean annual rate of progression in NASH were 40.76% (95% CI: 34.69-47.13) and 0.09 (95% CI: 0.06-0.12). HCC incidence among NAFLD patients was 0.44 per 1,000 person-years (range, 0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77 per 1,000 (range, 0.33-1.77) and 11.77 per 1,000 person-years (range, 7.10-19.53) and 15.44 per 1,000 (range, 11.72-20.34) and 25.56 per 1,000 person-years (range, 6.29-103.80). Incidence risk ratios for liver-specific and overall mortality for NAFLD were 1.94 (range, 1.28-2.92) and 1.05 (range, 0.70-1.56).
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            Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies.

            (2004)
            A WHO expert consultation addressed the debate about interpretation of recommended body-mass index (BMI) cut-off points for determining overweight and obesity in Asian populations, and considered whether population-specific cut-off points for BMI are necessary. They reviewed scientific evidence that suggests that Asian populations have different associations between BMI, percentage of body fat, and health risks than do European populations. The consultation concluded that the proportion of Asian people with a high risk of type 2 diabetes and cardiovascular disease is substantial at BMIs lower than the existing WHO cut-off point for overweight (> or =25 kg/m2). However, available data do not necessarily indicate a clear BMI cut-off point for all Asians for overweight or obesity. The cut-off point for observed risk varies from 22 kg/m2 to 25 kg/m2 in different Asian populations; for high risk it varies from 26 kg/m2 to 31 kg/m2. No attempt was made, therefore, to redefine cut-off points for each population separately. The consultation also agreed that the WHO BMI cut-off points should be retained as international classifications. The consultation identified further potential public health action points (23.0, 27.5, 32.5, and 37.5 kg/m2) along the continuum of BMI, and proposed methods by which countries could make decisions about the definitions of increased risk for their population.
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              Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study.

              Matthew Armstrong, Piers Gaunt, Guruprasad P Aithal … (2016)
              Glucagon-like peptide-1 (GLP-1) analogues reduce hepatic steatosis, concentrations of liver enzymes, and insulin resistance in murine models of fatty liver disease. These analogues are licensed for type 2 diabetes, but their efficacy in patients with non-alcoholic steatohepatitis is unknown. We assessed the safety and efficacy of the long-acting GLP-1 analogue, liraglutide, in patients with non-alcoholic steatohepatitis.
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                Author and article information

                Contributors
                Tao Jiang:
                ORCID: https://orcid.org/0000-0001-9229-4330
                Jia Liu:
                ORCID: https://orcid.org/0000-0002-6957-3814
                Guang Wang:
                ORCID: https://orcid.org/0000-0001-9321-5200
                Journal
                Journal ID (nlm-ta): J Diabetes Res
                Journal ID (iso-abbrev): J Diabetes Res
                Journal ID (publisher-id): JDR
                Title: Journal of Diabetes Research
                Publisher: Hindawi
                ISSN (Print): 2314-6745
                ISSN (Electronic): 2314-6753
                Publication date Collection: 2021
                Publication date (Electronic): 8 October 2021
                Volume: 2021
                Electronic Location Identifier: 3715026
                Affiliations
                1Department of Radiology, Beijing Chao Yang Hospital, Capital Medical University, No. 8, Gong ti South Road, Chao Yang District, Beijing 100020, China
                2Department of Endocrinology, Beijing Chao Yang Hospital, Capital Medical University, No. 8, Gong ti South Road, Chao Yang District, Beijing 100020, China
                Author notes

                Academic Editor: Claudia Cardoso

                Author information
                https://orcid.org/0000-0002-7320-2354
                https://orcid.org/0000-0001-9229-4330
                https://orcid.org/0000-0002-6957-3814
                https://orcid.org/0000-0001-9321-5200
                Article
                DOI: 10.1155/2021/3715026
                PMC ID: 8519721
                PubMed ID: 34660809
                SO-VID: fb8aeced-ac8b-436c-a68c-6565c8d527be
                Copyright © Copyright © 2021 Xinyue Li et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 7 June 2021
                Date revision received : 14 September 2021
                Date accepted : 20 September 2021
                Funding
                Funded by: Beijing Talents foundation
                Award ID: 2018-12
                Funded by: Beijing Municipal Education Commission
                Award ID: KZ201810025038
                Funded by: National Natural Science Foundation of China
                Award ID: 81770792
                Categories
                Subject: Research Article

                Data availability:

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