Failure of islet β-cell compensation for insulin resistance causes type 2 diabetes: What causes non-alcoholic fatty liver disease and non-alcoholic steatohepatitis?

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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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

GASTROENTEROLOGY ◽

10.22141/2308-2097.54.2.2020.206227 ◽

2020 ◽

Vol 54 (2) ◽

pp. 96-100

Author(s):

L.L. Pavlovskyi

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Weight Loss ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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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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PNPLA3 rs738409 polymorphism in Patients with Type 2 Diabetes and Concomitant Liver Pathology in Yakutia

International Journal of Biomedicine ◽

10.21103/article10(4)_oa21 ◽

2020 ◽

Vol 10 (4) ◽

pp. 438-441

Author(s):

Khariton Kurtanov ◽

Nadezhda Pavlova ◽

Aleksandra Diakonova ◽

Lyubovy Sydykova ◽

Sardana Markova ◽

...

Keyword(s):

Type 2 Diabetes ◽

Liver Disease ◽

Fatty Liver ◽

Healthy Volunteers ◽

Fatty Liver Disease ◽

Liver Diseases ◽

Alcoholic Fatty Liver ◽

Alcoholic Steatohepatitis ◽

Alcoholic Fatty Liver Disease

Background: The pathogenetic mechanisms of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) are closely related. Currently, multiple studies have demonstrated a link between the PNPLA3 148M variant and the development and progression of NAFLD, including liver fibrosis. The aim of our research was to study the distribution of alleles and genotypes of the PNPLA3 rs738409 SNP in Russians and Yakuts living in Yakutia, as well as to search for associations of the PNPLA3 rs738409 SNP in patients with T2D and non-alcoholic fatty liver disease / non-alcoholic steatohepatitis. Methods and Results: The study included 179 patients (28 Russians and 151 Yakuts) with T2D and concomitant liver diseases of non-infectious origin. The comparison group consisted of 147 healthy volunteers of Russian ethnicity and 246 healthy volunteers of Yakut ethnicity. The PNPLA3 738409 SNP was analyzed by PCR-RFLP reaction. The results found a significant difference between the frequencies of the PNPLA3 rs738409 genotypes and alleles in Russians and Yakuts, both among healthy volunteers and in T2D patients with liver diseases. The frequency of the G allele occurrence in the group of healthy Yakuts was significantly higher (OR- 3.313; 95% CI: 2.444-4.499; P<0.001) than in the group of healthy Russians. No significant differences were found for the PNPLA3 rs738409 genotype and allele frequencies among a healthy sample and a sample of T2D patients with non-alcoholic fatty liver disease / non-alcoholic steatohepatitis, both in the Russian and Yakut populations.

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