Nonalcoholic fatty liver disease: cause or consequence of insulin resistance?

Mishina, Ekaterina E.; Mayorov, Alexander Y.; Богомолов, П. О.; Matsievich, Maria V.; Кокина, К. Ю.; Bogolyubova, Apollinariya V.

doi:10.14341/dm9372

Cited by 14 publications

(10 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Insulin resistance leading to hyperinsulinemia inhibits lipolysis and simultaneously activates lipogenesis in the liver; as a result, fat accumulates in hepatocytes under the influence of adipohormones [11,18]. More free fatty acids accumulated in liver cells; the more pronounced becomes the insulin resistance of the hepatocytes themselves, thereby stimulating uncontrolled gluconeogenesis and glucose production by the liver.…”

Section: Adverse Eventsmentioning

confidence: 99%

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

Khripun¹,

Воробьев²,

Аллахвердиева³

2020

Diabetes mellitus

View full text Add to dashboard Cite

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.

show abstract

Section: Adverse Eventsmentioning

confidence: 99%

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

Khripun¹,

Воробьев²,

Аллахвердиева³

2020

Diabetes mellitus

View full text Add to dashboard Cite

show abstract

“…Ключевую роль в развитии нарушений углеводного обмена при ХЗП играет инсулинорезистентность (ИР). Механизм ее формирования сложен и является результатом взаимодействия многочисленных метаболических, генетических и внутриклеточных факторов, основными из которых являются: оксидативный стресс, воспаление, стресс эндоплазматического ретикулума, действие церамидов, дисбаланс гепатокинов [7][8][9][10].…”

Section: âçàèìîñâÿçü íàðóøåíèé óãëåâîäíîãî îáìåíà è õçïunclassified

“…Повышенный внутрипеченочный уровень триглицеридов индуцирует изменения в транскрипции гепатокинов и процессинге в эндоплазматическом ретикулуме, что ведет к сниженной секреции одних гепатокинов и повышенной секреции других. Представленные эффекты в сумме ведут к развитию ИР, эктопической аккумуляции жира, воспалению [9,18].…”

Section: âçàèìîñâÿçü íàðóøåíèé óãëåâîäíîãî îáìåíà è õçïunclassified

“…После накопления в печени жирных кислот она становится более восприимчивой к действию последующих «ударов», приводящих к печеночному повреждению и прогрессированию до стадии НАСГ с фиброзом или без него. К этим «ударам» относятся оксидативное повреждение, апоптоз гепатоцитов, активация профиброгенных факторов, дисрегуляция адипокинов и активация звездчатых клеток печени [9].…”

Section: íåàëêîãîëüíàÿ Aeèðîâàÿ áîëåçíü ïå÷åíèunclassified

“…Учитывая значимое сочетание НАЖБП с ИР и другими компонентами метаболического синдрома, данная нозология длительное время рассматривалась как печеночное проявление метаболического синдрома. Однако такое суждение сейчас устарело: НАЖБП можно рассматривать как ранний предиктор и решающий фактор в развитии СД и других клинических проявлений метаболического синдрома [6,9,20], при этом риск развития СД2 варьирует в зависимости от тяжести НАЖБП [29]. Это нашло подтверждение в работе R.V.…”

Section: íåàëêîãîëüíàÿ Aeèðîâàÿ áîëåçíü ïå÷åíèunclassified

See 2 more Smart Citations

Diabetes mellitus and chronic liver diseases. Part 1: general mechanisms of etiology and pathogenesis

Калмыкова

Асхатовна²,

Кононенко

et al. 2019

Terapevticheskii arkhiv

View full text Add to dashboard Cite

In recent years there has been an active discussion about the relationship between diabetes mellitus (DM) and chronic liver diseases (CLD). On the one hand, patients with diabetes have an increased risk of developing CLD. On the other hand, patients with CLD very often identify abnormal glucose metabolism which ultimately leads to impaired glucose tolerance and the development of diabetes. This review outlines potential causal relationships between some CLD and DM. Common mechanisms that provoke metabolic and autoimmune disorders in the development of various nosologies of the CKD group, leading to steatosis, insulin resistance, impaired glucose tolerance and the development of diabetes are described. Certain features of the assessment of carbohydrate metabolism compensation in patients with hepatic dysfunction, anemia and protein metabolism disorders are described.

show abstract

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Nonalcoholic fatty liver disease: cause or consequence of insulin resistance?

Cited by 14 publications

References 30 publications

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

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

Diabetes mellitus and chronic liver diseases. Part 1: general mechanisms of etiology and pathogenesis

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

Contact Info

Product

Resources

About