scholarly journals Beneficial effect of omarigliptin on diabetic patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis

2020 ◽  
Author(s):  
Sachiko Hattori ◽  
Kazuhiro Nomoto ◽  
Tomohiko Suzuki ◽  
Seishu Hayashi
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Liver Function ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Hepatic Insulin Resistance ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background: Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides and also a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis. Method: We examined whether weekly DPP4 inhibitor omarigliptin (OMG) improves liver function as well as levels of inflammation and insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). Furthermore, we tried OMG in a diabetic patient with biopsy-confirmed nonalcoholic steatohepatitis (NASH). Results: In NAFLD patients, OMG significantly decreased levels of aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (gGTP), homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP), while no significant change was seen in hemoglobin A1c (HbA1c) or body mass index (BMI). In a NASH patient, liver function had improved markedly, and the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and hsCRP. Improvements in intrahepatic fat deposition and fibrosis appeared to be seen on ultrasonography.Conclusion: The effects of OMG in ameliorating hepatic insulin resistance may lead to decreasing intrahepatic fat accumulation and improving intrahepatic adipose inflammation in NAFLD/NASH.Trial registration: UMIN Clinical Registry (UMIN000029288). Registered 22 September, 2017, https://upload.umin.ac.jp/UMIN000029288

scholarly journals Beneficial effect of omarigliptin on diabetic patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sachiko Hattori ◽  
Kazuomi Nomoto ◽  
Tomohiko Suzuki ◽  
Seishu Hayashi
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Liver Function ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Hepatic Insulin Resistance ◽  
Diabetic Patients ◽  
Alcoholic Fatty Liver ◽  
Dpp4 Inhibitor ◽  
Alcoholic Fatty Liver Disease

Abstract Background Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides, and also a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis. Method We examined whether weekly DPP4 inhibitor omarigliptin (OMG) can improve liver function as well as levels of inflammation and insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). Further, we investigated the effects of OMG in a diabetic patient with biopsy-confirmed nonalcoholic steatohepatitis (NASH). Results In NAFLD patients, OMG significantly decreased levels of aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP), while no significant change was seen in hemoglobin A1c or body mass index. In the NASH patient, liver function improved markedly, and levels of the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and hsCRP. Slight but clear improvements in intrahepatic fat deposition and fibrosis appeared to be seen on diagnostic ultrasonography. Conclusion Weekly administration of the DPP4 inhibitor OMG in ameliorating hepatic insulin resistance may cause beneficial effects in liver with NAFLD/NASH.

scholarly journals Higher Sodium Intake Assessed by 24 Hour Urinary Sodium Excretion Is Associated with Non-Alcoholic Fatty Liver Disease: The PREVEND Cohort Study

2019 ◽  
Vol 8 (12) ◽  
pp. 2157 ◽  
Author(s):  
Eline H. van den Berg ◽  
Eke G. Gruppen ◽  
Hans Blokzijl ◽  
Stephan J.L. Bakker ◽  
Robin P.F. Dullaart
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Sodium Excretion ◽  
Fatty Liver Disease ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Model Assessment ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

A higher sodium intake is conceivably associated with insulin resistant conditions like obesity, but associations of non-alcoholic fatty liver disease (NAFLD) with a higher sodium intake determined by 24 hours (24 h) urine collections are still unclear. Dietary sodium intake was measured by sodium excretion in two complete consecutive 24 h urine collections in 6132 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. Fatty Liver Index (FLI) ≥60 and Hepatic Steatosis Index (HSI) >36 were used as proxies of suspected NAFLD. 1936 (31.6%) participants had an FLI ≥60, coinciding with the increased prevalence of type 2 diabetes (T2D), metabolic syndrome, hypertension and history of cardiovascular disease. Sodium intake was higher in participants with an FLI ≥60 (163.63 ± 61.81 mmol/24 h vs. 136.76 ± 50.90 mmol/24 h, p < 0.001), with increasing incidence in ascending quartile categories of sodium intake (p < 0.001). Multivariably, an FLI ≥60 was positively associated with a higher sodium intake when taking account for T2D, a positive cardiovascular history, hypertension, alcohol intake, smoking and medication use (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.44–1.64, p < 0.001). Additional adjustment for the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) diminished this association (OR 1.30, 95% CI 1.21–1.41, p < 0.001). HSI >36 showed similar results. Associations remained essentially unaltered after adjustment for body surface area or waist/hip ratio. In conclusion, suspected NAFLD is a feature of higher sodium intake. Insulin resistance-related processes may contribute to the association of NAFLD with sodium intake.

scholarly journals Evaluation of potential gene expression as early markers of insulin resistance and non-alcoholic fatty liver disease in the Indonesian population

2018 ◽  
Vol 23 (2) ◽  
pp. 84
Author(s):  
Eunice Limantara ◽  
Felicia Kartawidjajaputra ◽  
Antonius Suwanto
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Model Assessment ◽  
Gene Expressions ◽  
Alcoholic Fatty Liver ◽  
Early Markers ◽  
Alcoholic Fatty Liver Disease

Early detection of insulin resistance (IR) or non-alcoholic fatty liver disease (NAFLD) is crucial to preventing future risks of developing chronic diseases. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Liver Fat Score (LFS), and Fatty Liver Index (FLI) are generally employed to measure severity stages of IR and NAFLD. The study of gene expressions could explain the molecular mechanisms that occur early on in IR and NAFLD; thus providing potential early markers for both diseases. This study was conducted to evaluate the gene expressions that could potentially be early markers of IR and NAFLD. All participants (n = 21) had normal blood glucose and were categorized as without hepatosteatosis (n = 10), at higher risk of hepatosteatosis (n = 6), and hepatosteatosis (n = 5). Gene expression analysis was performed using the 2-∆∆CT relative quantification method. There were significant differences in galnt2 (p < 0.002) and sirt1 (p < 0.010) expression between the first and the third tertiles of HOMA-IR; and in ptpn1 (p < 0.012) expression between the first and the second tertiles of LFS. In conclusion, the expressions of galnt2 and sirt1 could be used as early markers of IR, while the expression of ptpn1 could be employed as an early marker of NAFLD.

scholarly journals Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms

Diabetologia ◽  
2005 ◽  
Vol 48 (4) ◽  
pp. 634-642 ◽  
Author(s):  
E. Bugianesi ◽  
A. Gastaldelli ◽  
E. Vanni ◽  
R. Gambino ◽  
M. Cassader ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Diabetic Patients ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Insulin Resistance and Non-Alcoholic Fatty Liver Disease in Premenopausal Women with Metabolic Syndrome

2021 ◽  
Vol 53 (02) ◽  
pp. 100-104
Author(s):  
Amr Ali El-Sehrawy ◽  
Omnia State ◽  
Rasha Rizk Elzehery ◽  
Ahmed Salem Mohamed
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Premenopausal Women ◽  
Model Assessment ◽  
Fasting Insulin ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractIt is suggested that estrogen protects premenopausal women against non-alcoholic fatty liver disease. From another perspective, the relation between metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) is bidirectional. Role of insulin resistance (IR) in NAFLD continues to be a matter of debate. The present study aimed to assess the relation between IR and NAFLD in premenopausal women with MetS. The study included 51 premenopausal women with MetS. In addition, there were 40 age-matched healthy controls. All participants were subjected to careful history taking and thorough clinical examination. Performed laboratory investigations included fasting blood glucose, fasting insulin, lipid profile, and liver functions. Calculation of IR was achieved by the Homeostasis Model Assessment (HOMA-IR). NAFLD was graded into three grades according to findings of abdominal ultrasound. Patients had significantly higher BMI, SBP, DBP, FBG, fasting insulin, HOMA-IR, total cholesterol, triglycerides, and LDL levels when compared with controls. They also had significantly lower HDL levels in comparison to controls. Moreover, they have more advanced grades of NAFLD in contrast to controls. Comparison between patients with various grades of NAFLD regarding the clinical data revealed significant increase of fasting insulin and HOMA-IR levels with advancing NAFLD grade. Using multivariate regression analysis, HOMA-IR was an independent predictor of advanced NAFLD grade. In conclusion, the present study documented a combined inter-relation between MetS, IR, and NAFLD in premenopausal women with MetS. IR is correlated with NAFLD grade.

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