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SGLT2 Inhibitor Treatment Outcome in Nonalcoholic Fatty Liver Disease Complicated with Diabetes Mellitus: The Long-term Effects on Clinical Features and Liver Histopathology.

ABSTRACT: Objective The aim of this study was to determine the long-term effects of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) in nonalcoholic fatty liver disease (NAFLD) patients with type 2 diabetes mellitus (T2DM) on the clinical features and liver histopathology. Methods In this retrospective study, the long-term histological impacts of SGLT2i in NAFLD patients with T2DM were investigated. Patients Seven patients with NAFLD and T2DM were treated for the long term with 100 mg/day canagliflozin, an SGLT2i, and liver biopsies were obtained at the 3 points of pretreatment, 24 weeks, and ?1 year (third liver biopsy) after the start of treatment. Six of seven patients were evaluated with third liver biopsy at the point of three or more years. The primary outcome was liver histopathological changes (defined as a decrease in the NAFLD activity score of one point or more without worsening of the fibrosis stage, compared to pretreatment). Results All 7 patients showed worsening of body mass index and waist circumference at the third liver biopsy compared to 24 weeks. However, the scores of steatosis, lobular inflammation, ballooning, and fibrosis stage improved at the third liver biopsy in 57%, 43%, 14%, and 29% of the patients, respectively, compared to pretreatment. One of the seven patients showed histopathological worsening at the third liver biopsy compared to pretreatment, but the improvement was maintained in the other six patients. Conclusion The long-term treatment of NAFLD complicated by T2DM using an SGLT2i is associated with long-term improvement in liver histopathology despite the worsening of clinical features.

SUBMITTER: Akuta N

PROVIDER: S-EPMC7492114 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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SGLT2 Inhibitor Treatment Outcome in Nonalcoholic Fatty Liver Disease Complicated with Diabetes Mellitus: The Long-term Effects on Clinical Features and Liver Histopathology.

Akuta Norio N Kawamura Yusuke Y Fujiyama Shunichiro S Sezaki Hitomi H Hosaka Tetsuya T Kobayashi Masahiro M Kobayashi Mariko M Saitoh Satoshi S Suzuki Fumitaka F Suzuki Yoshiyuki Y Arase Yasuji Y Ikeda Kenji K Kumada Hiromitsu H

Internal medicine (Tokyo, Japan) 20200523 16

Objective The aim of this study was to determine the long-term effects of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) in nonalcoholic fatty liver disease (NAFLD) patients with type 2 diabetes mellitus (T2DM) on the clinical features and liver histopathology. Methods In this retrospective study, the long-term histological impacts of SGLT2i in NAFLD patients with T2DM were investigated. Patients Seven patients with NAFLD and T2DM were treated for the long term with 100 mg/day canagliflozin ...[more]

PMID: 32448832

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Project description:Metformin and liraglutide are used in the treatment of type 2 diabetes mellitus (T2DM) complicated with nonalcoholic fatty liver disease (NAFLD). Although these drugs can alter the intestinal microbiome, clinical data are required to explore their mechanisms of action. Using 16S sequencing technology, we analyzed and compared the intestinal bacterial community structure and function between patients before and after treatment (12 weeks) with the two drugs (metformin or liraglutide, n = 15) and healthy controls (n = 15). Moreover, combined with 19 clinical indices, the potential therapeutic mechanisms of the two drugs were compared. The studied clinical indices included those associated with islet β-cell function (FPG, FINS, HbA1c, and HOMA-IR), inflammation (TNF-α, IL-6, and APN), lipid metabolism (TC, TG, and LDL-C), and liver function (ALT, AST, and GGT); the values of all indices changed significantly after treatment (p < 0.01). In addition, the effect of the two drugs on the intestinal bacterial community varied. Liraglutide treatment significantly increased the diversity and richness of the intestinal bacterial community (p < 0.05); it significantly increased the relative abundances of Bacteroidetes, Proteobacteria, and Bacilli, whereas metformin treatment significantly increased the relative abundance of Fusobacteria and Actinobacteria (p < 0.05). Metformin treatment increased the complexity and stability of the intestinal bacterial network. However, liraglutide treatment had a weaker effect on the intestinal bacterial network, and the network after treatment was similar to that in healthy controls. Correlation matrix analysis between dominant genera and clinical indicators showed that the correlation between the bacterial community and islet β-cell function was stronger after liraglutide treatment, whereas the correlation between the bacterial community and inflammation-related factors was stronger after metformin treatment. Functional prediction showed that liraglutide could significantly affect the abundance of functional genes related to T2DM and NAFLD (p < 0.05), but the effect of metformin was not significant. This study is the first to report the changes in the intestinal bacterial community in patients treated with metformin or liraglutide and the differences between the mechanisms of action of metformin and liraglutide. Metformin or liraglutide has a therapeutic value in T2DM complicated with NAFLD, with liraglutide having a weaker effect on the intestinal bacterial community but a better therapeutic efficacy.

Project description:BACKGROUND:Previous study reported that patients who suffered coronary heart disease (CHD) complicated with non-alcoholic fatty liver disease (NAFLD) had worse cardiac function and clinical outcomes than patients with CHD only. Notably, the mechanism is still unclear. This study aimed to investigate the changes and roles of intestinal bacterial microbiota in CHD-NAFLD patients. METHODS AND RESULTS:People were recruited and divided into three groups, including CHD patients (without NAFLD), CHD-NAFLD patients and healthy controls (HCs). Each group contained 24 people. Fecal samples and clinical information were carefully collected. The Illumina sequencing of 16S rRNA was applied to profile the overall structure of the fecal bacterial microbiota and the characteristics of the bacterial microbiota based on the Operational Taxonomic Units. In clinical information, the CHD-NAFLD patients showed an increase in BMI, uric acid and triglyceride. There was a significant reduction in the abundance of Parabacteroides and Collinsella in overall CHD patients (including CHD-NAFLD and CHD patients). The intestinal bacterial microbiota in CHD-NAFLD patients showed an increase in the abundance of Copococcus and Veillonella, and a reduction in the abundance of Parabacteroides, Bacteroides fragilis, Ruminococcus gnavus, Bacteroides dorei, and Bifidobacterium longum subsp infantis. Among them, the abundance of Ruminococcus gnavus and Bacteroides dorei was significantly lower than that in CHD patients. Additionally, BMI positively correlated with the abundance of Copococcus and negatively correlated with the abundance of Bifidobacterium longum subsp infantis. The abundance of Veillonella positively correlated with AST. The abundance of Bacteroides dorei negatively correlated with ALT and AST. It indicates that the abundance of intestinal microbiota was related to the changes in clinical indexes. CONCLUSIONS:Changes of intestinal bacterial microbiota in CHD-NAFLD patients may be important factors affecting the degree of metabolic disorder, which may be one of the important reasons for the worse clinical outcome and disease progression in CHD-NAFLD patients than in CHD patients.

Dataset Information

SGLT2 Inhibitor Treatment Outcome in Nonalcoholic Fatty Liver Disease Complicated with Diabetes Mellitus: The Long-term Effects on Clinical Features and Liver Histopathology.

Publications

SGLT2 Inhibitor Treatment Outcome in Nonalcoholic Fatty Liver Disease Complicated with Diabetes Mellitus: The Long-term Effects on Clinical Features and Liver Histopathology.

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