scholarly journals New opportunities for the correction of non-alcoholic fatty liver disease in men with type 2 diabetes mellitus and hypogonadism

2020 ◽  
Vol 17 (3) ◽  
pp. 241-248
Author(s):  
Irina A. Khripun ◽  
Sergey V. Vorobyev ◽  
Yanina Y. Allahverdieva ◽  
Elizaveta O. Dzantieva ◽  
Maria A. Rasskazova
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Fatty Liver Disease ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Adipose Tissue Dysfunction ◽  
Fat Fraction ◽  
Hypoglycemic Therapy ◽  
Alcoholic Fatty Liver Disease

Background: The common pathogenetic relations of type 2 diabetes mellitus (T2DM), testosterone (T) deficiency and non-alcoholic fatty liver disease (NAFLD) have indicated a new direction in the study of their mutual influence. It was found that NAFLD is more pronounced in men with T2DM and hypogonadism than in eugonadal patients and associated with hyperinsulinemia, insulin resistance, impaired lipid metabolism and adipose tissue dysfunction. However, the effects of testosterone replacement therapy (TRT) on the severity of NAFLD in men with hypogonadism have not been studied.Aims: To study the effect of TRT on the severity of NAFLD in men with T2DM and hypogonadism.MATERIALS AND METHODS: Anthropometric data, biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (GGTP), glucose, immunoreactive insulin, HOMA index, glycosylated hemoglobin, lipidogram), ELISA analysis (total T, LH, sex hormone binding globulin, resistin, adiponectin, leptin), as well as magnetic resonance imaging with determination of the liver fat fraction were examined.Results: The study included 60 men with T2DM and hypogonadism (mean age 54 [49; 57] years), who were randomized into 2 groups: 1 (n=30) - patients who received 1% transdermal T gel (50 mg/day) in addition to standard hypoglycemictherapy; 2 (n=30) - patients who received standard hypoglycemic therapy. The follow-up period was 6 months. T therapy was associated with a decrease in liver enzyme levels: AST by 31%, ALT by 21%, and GGTP by 15.9% (p<0.05) and the hepatic fat fraction by 1.7 times, which reflect the regress of liver inflammation, and, consequently, a decrease in the severity of NAFLD. Moreover, TRT has improved the function of adipose tissue - reduced the concentration of leptin by 1.4 times and resistin by 1.5 times, which was accompanied by an increase in adiponectin level by 1.3 times (p<0.01). The use of TRT was associated with decrease in the severity of visceral obesity, hyperinsulinemia by 1.5 times, an insulin resistance index HOMA by 2.2 times, fasting glycaemia and HbA1c levels, despite constant hypoglycemic therapy. Statistically significant decrease in the levels of total cholesterol and triglycerides was observed in men receiving TRT. Thus, a decrease in adipose tissue dysfunction and insulin resistance in men receiving TRT can be considered as a pathogenetic mechanism responsible for improving liver function and reducing the severity of NAFLD.Conclusions: TRT in men with T2DM and hypogonadism is accompanied by regress of inflammatory activity in liver and intensity of hepatocytes steatosis, reflected by decrease in liver enzymes levels and liver fat fraction.

scholarly journals Role of ceramide-to-dihydroceramide ratios for insulin resistance and non-alcoholic fatty liver disease in humans

2020 ◽  
Vol 8 (2) ◽  
pp. e001860
Author(s):  
Maria Apostolopoulou ◽  
Ruth Gordillo ◽  
Sofiya Gancheva ◽  
Klaus Strassburger ◽  
Christian Herder ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Fatty Liver Disease ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Alcoholic Fatty Liver ◽  
Visceral Adipose ◽  
Alcoholic Fatty Liver Disease

IntroductionSphingolipid accumulation has been linked to obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). A recent study showed that depletion of dihydroceramide desaturase-1 (DES-1) in adipose and/or liver tissue decreases ceramide-to-dihydroceramide ratios (ceramide/dihydroceramide) in several tissues and improves the metabolic profile in mice. We tested the hypothesis that ceramide/dihydroceramide would also be elevated and relate positively to liver fat content and insulin resistance in humans.Research design and methodsThus, we assessed total and specific ceramide/dihydroceramide in various biosamples of 7 lean and 21 obese volunteers without or with different NAFLD stages, who were eligible for abdominal or bariatric surgery, respectively. Biosamples were obtained from serum, liver, rectus abdominis muscle as well as subcutaneous abdominal and visceral adipose tissue during surgery.ResultsSurprisingly, certain serum and liver ceramide/dihydroceramide ratios were reduced in both obesity and non-alcoholic steatohepatitis (NASH) and related inversely to liver fat content. Specifically, hepatic ceramide/dihydroceramide (species 16:0) related negatively to hepatic mitochondrial capacity and lipid peroxidation. In visceral adipose tissue, ceramide/dihydroceramide (species 16:0) associated positively with markers of inflammation.ConclusionThese results failed to confirm the relationships of ceramide/dihydroceramide in humans with different degree of insulin resistance. However, the low hepatic ceramide/dihydroceramide favor a role for dihydroceramide accumulation in NASH, while a specific ceramide/dihydroceramide ratio in visceral adipose tissue suggests a role of ceramides in obesity-associated low-grade inflammation.

scholarly journals Testosterone deficiency and non-alcoholic fatty liver disease in men with type 2 diabetes mellitus

2020 ◽  
Vol 22 (6) ◽  
pp. 542-549 ◽  
Author(s):  
Irina A. Khripun ◽  
Sergey V. Vorobyev ◽  
Yanina Allahverdieva
Keyword(s):  
Diabetes Mellitus ◽  
Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Type 2 Dm ◽  
Carbohydrate And Lipid Metabolism ◽  
Fat Fraction ◽  
Alcoholic Fatty Liver Disease

BACKGROUND: Current studies investigated diseases associated with testosterone (T) deficiency; however, data on the combination of non-alcoholic fatty liver disease (NAFLD) with hypogonadism and diabetes mellitus (DM) in men are extremely limited. AIMS: To evaluate the effects of hypogonadism on the formation and progression of NAFLD in men with type 2 DM. METHODS: The study included 90 men with type 2 DM [age 54 (4957) years]. Patients underwent clinical examinations, biochemical analysis (alanine aminotransferase (ALT), aspartate aminotransferase, gamma-glutamyl transpeptidase (GGTP), fasting glucose, immunoreactive insulin, HOMA index, HbA1c, lipid profile), immune enzyme analysis (luteinising hormone, total T, sex hormone binding globulin, resistin, adiponectin, leptin) and magnetic resonance imaging with liver fat fraction determination were performed. Patients were divided into two groups: 132 eugonadal patients and 258 men with newly diagnosed hypogonadism. RESULTS: Increased insulin resistance, hyperinsulinemia, hypertriglyceridemia were observed in men with hypogonadism compared to eugonadal patients. Along with biochemical signs of impaired liver function, such as an increase in liver enzyme concentrations of ALT by 24.5% (p = 0.02), GGTP by 60.5% (p = 0.001), de Rytis coefficient by 60.4% (p = 0.047), of men in the 2nd group, the liver fat fraction also increased, which together indicates NAFLD progression. The proton density of the liver fat fraction according to MRI was 4.12 [2.255.30] % in the 1st group and 10.30 [7.78; 14.44] % in the 2nd group (p=0.001). This was accompanied by an increase in fat production of resistin by 2 times and leptin by 12 times (p 0.001) in patients of group 2 compared to 1. CONCLUSIONS: The combination of type 2 DM with hypogonadism in men leads not only to deterioration of carbohydrate and lipid metabolism but also to disturbance of liver function: increased ALT, GGTP concentrations and liver fat. Increased secretion of leptin and resistin in the adipose tissue is assumed to be a pathogenetically associated with the development of carbohydrate and lipid metabolism disorders, NAFLD and T deficiency.

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