Effect of metformin administration and weight loss on plasma ceramide C16:0, C18:0, C24:1 concentrations in patients with non-alcoholic fatty liver disease associated with insulin resistance and type 2 diabetes

Ectodysplasin A (EDA) was recently identified as a liver-secreted protein that is increased in the liver and plasma of obese mice and causes skeletal muscle insulin resistance. We assessed if liver and plasma EDA is associated with worsening non-alcoholic fatty liver disease (NAFLD) in obese patients and evaluated plasma EDA as a biomarker for NAFLD. Using a cross-sectional study in a public hospital, patients with a body mass index >30 kg/m2 (n=152) underwent liver biopsy for histopathology assessment and fasting liver EDA mRNA. Fasting plasma EDA levels were also assessed. Non-alcoholic fatty liver (NAFL) was defined as >5% hepatic steatosis and nonalcoholic steatohepatitis (NASH) as NAFLD activity score ≥3. Patients were divided into three groups: No NAFLD (n=45); NAFL (n=65); and NASH (n=42). Liver EDA mRNA was increased in patients with NASH compared with No NAFLD (P=0.05), but not NAFL. Plasma EDA levels were increased in NAFL and NASH compared with No NAFLD (P=0.03). Plasma EDA was related to worsening steatosis (P=0.02) and fibrosis (P=0.04), but not inflammation or hepatocellular ballooning. ROC analysis indicates that plasma EDA is not a reliable biomarker for NAFL or NASH. Plasma EDA was not increased in patients with type 2 diabetes and did not correlate with insulin resistance. Together, we show that plasma EDA is increased in NAFL and NASH, is related to worsening steatosis and fibrosis but is not a reliable biomarker for NASH. Circulating EDA is not associated with insulin resistance in human obesity.Clinical Trial Registrationhttps://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12615000875505, identifier ACTRN12615000875505.

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Hepatic-Metabolite-Based Intermittent Fasting Enables a Sustained Reduction in Insulin Resistance in Type 2 Diabetes and Metabolic Syndrome

Hormone and Metabolic Research ◽

10.1055/a-1510-8896 ◽

2021 ◽

Author(s):

Markus Rohner ◽

Robert Heiz ◽

Simon Feldhaus ◽

Stefan R. Bornstein

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Intermittent Fasting ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

AbstractInsulin resistance is the hallmark of Type 2 Diabetes and is still an unmet medical need. Insulin resistance lies at the crossroads of non-alcoholic fatty liver disease, obesity, weight loss and exercise resistance, heart disease, stroke, depression, and brain health. Insulin resistance is purely nutrition related, with a typical molecular disease food intake pattern. The insulin resistant state is accessible by TyG as the appropriate surrogate marker, which is found to lead the personalized molecular hepatic nutrition system for highly efficient insulin resistance remission. Treating insulin resistance with a molecular nutrition-centered approach shifts the treatment paradigm of Type 2 Diabetes from management to cure. This allows remission within five months, with a high efficiency rate of 85%. With molecular intermittent fasting a very efficient treatment for prediabetes and metabolic syndrome is possible, improving the non-alcoholic fatty liver disease (NAFL) state and enabling the body to lose weight in a sustainable manner.

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Patient Management in Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

Russian Journal of Gastroenterology Hepatology Coloproctology ◽

10.22416/1382-4376-2021-31-2-14-26 ◽

2021 ◽

Vol 31 (2) ◽

pp. 14-26

Author(s):

A. E. Bagriy ◽

A. D. Zubov ◽

M. V. Khomenko ◽

E. S. Mikhailichenko ◽

E. A. Pylaeva ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Weight Loss ◽

Type 2 Diabetes Mellitus ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Aim. A current overview of non-pharmacological and drug-based approaches to non-alcoholic fatty liver disease (NAFLD) combined with type 2 diabetes mellitus (T2D).Key points. NAFLD is associated with an increased cardiovascular risk (due to association with “metabolic syndrome”) and the risks of liver cirrhosis and hepatocellular carcinoma. Macro- and microvascular complications in T2D comorbidity entail a higher overall mortality. A conjunction of lifestyle change and rational medication strategies to reach the target levels of glycosylated haemoglobin, low-density lipoprotein cholesterol, systolic and diastolic blood pressure is key in management of such patients. A body weight loss by 5–7 % or more (through caloric restriction or a bariatric surgery) promotes a marked reduction in liver fat and even reversal of steatohepatitis. Metered exercise exerts this effect even at insignificant weight loss. Minimising alcohol consumption and smoking is critical. A hepatotropic drug therapy is most essential in moderate fibrotic NAFLD. It includes antidiabetic agents (metformin, thiazolidinediones, glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter-2 inhibitors), bile acid preparations (e.g., 24-nor-ursodeoxycholic acid), farnesoid X receptor agonists (obeticholic acid, tropifexor), statins, acetylsalicylic acid. Combinations are superior to individual-drug schemes.Conclusion. The management of combined NAFLD-T2D requires a close inter-specialty involvement from hepatology, gastroenterology, endocrinology and cardiology. This interdisciplinary problem can be tackled through persuasive lifestyle recommendations and choosing rational medication strategies with a proved hepatoprotective efficacy.

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