scholarly journals The value of the triglyceride-glucose index in the diagnosis of insulin resistance in early forms of non-alcoholic fatty liver disease

2021 ◽  
pp. 43-48
Author(s):  
A. A. Shipovskaya ◽  
N. A. Larina ◽  
I. V. Kurbatova ◽  
O. P. Dudanova
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Cytokeratin 18 ◽  
Alcoholic Fatty Liver ◽  
Triglyceride Glucose Index ◽  
Tnf Α ◽  
Alcoholic Fatty Liver Disease

The goal. To determine the value of the triglyceride glucose index (TGI) for the diagnosis of insulin resistance (IR) in early forms of non-alcoholic fatty liver disease (NAFLD).Materials and methods. 99 patients with NAFLD were examined: 38 (38.4%) with liver steatosis (LS) and 61 (61.6%) with steatohepatitis (SH). TGI was determined by the formula — In [fasting TG (mg / dl) × fasting glucose (mg / dl) / 2], patients with LS and SH were divided into quartiles (Q1-Q4) by increasing TGI levels with an assessment of liver tests, insulin levels (“Insulin TEST System”, Monobind Inc., USA), HOMA-IR, fragments of cytokeratin-18 (FCK-18) ("TPS ELISA, Biotech”, Sweden) and TNF-α (“Human TNFα Platinum” ELISA, eBioscience, Austria).Results. In patients with LS with a TGI increase from Q1 to Q4, HOMA-IR increased from 1.12 ± 0.48 to 6.02 ± 3.15 (p <0.05), a direct relationship was found between these indicators — r = 0.52 (p = 0.03). TGI also correlated with waist circumference — r = 0.81 (p = 0.01), cholesterol — r = 0.51 (p = 0.002), alkaline phosphatase — r = 0.41 (p = 0.02). In patients with SH, from Q1 to Q4, HOMA-IR increased from 3.15 ± 1.8 to 6.2 ± 3.04 (p <0.05), but there was no significant correlation between HOMA-IR and TGI. The levels of FCK-18 increased from Q1 to Q4-139.82 ± 72.45 to 359.75 ± 189.03 U / L (p <0.05) and TNF-α — from 6.38 ± 1.25 pg / ml up to 7.75 ± 1.09 pg / ml (p <0.05). There was a connection between TGI and the level of a marker of hepatocyte apoptosis — FCK-18 — r = 0.43 (p = 0.004).Conclusion. In liver steatosis, TGI has demonstrated its diagnostic role as a surrogate marker of insulin resistance, correlating with HOMA-IR. In steatohepatitis, TGI reflected the degree of hepatocytic apoptosis, correlating with fragments of cytokeratin-18.

scholarly journals Supplementation with a Specific Combination of Metabolic Cofactors Ameliorates Non-Alcoholic Fatty Liver Disease and, Hepatic Fibrosis, and Insulin Resistance in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3532
Author(s):  
Sergio Quesada-Vázquez ◽  
Marina Colom-Pellicer ◽  
Èlia Navarro-Masip ◽  
Gerard Aragonès ◽  
Josep M. Del Bas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Fibrosis ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Alcoholic Fatty Liver ◽  
Specific Combination ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have emerged as the leading causes of chronic liver disease in the world. Obesity, insulin resistance, and dyslipidemia are multifactorial risk factors strongly associated with NAFLD/NASH. Here, a specific combination of metabolic cofactors (a multi-ingredient; MI) containing precursors of glutathione (GSH) and nicotinamide adenine dinucleotide (NAD+) (betaine, N-acetyl-cysteine, L-carnitine and nicotinamide riboside) was evaluated as effective treatment for the NAFLD/NASH pathophysiology. Six-week-old male mice were randomly divided into control diet animals and animals exposed to a high fat and high fructose/sucrose diet to induce NAFLD. After 16 weeks, diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (HFHFr group) or with a combination of metabolic cofactors (MI group) for 4 additional weeks, and blood and liver were obtained from all animals for biochemical, histological, and molecular analysis. The MI treatment reduced liver steatosis, decreasing liver weight and hepatic lipid content, and liver injury, as evidenced by a pronounced decrease in serum levels of liver transaminases. Moreover, animals supplemented with the MI cocktail showed a reduction in the gene expression of some proinflammatory cytokines when compared with their HFHFr counterparts. In addition, MI supplementation was effective in decreasing hepatic fibrosis and improving insulin sensitivity, as observed by histological analysis, as well as a reduction in fibrotic gene expression (Col1α1) and improved Akt activation, respectively. Taken together, supplementation with this specific combination of metabolic cofactors ameliorates several features of NAFLD, highlighting this treatment as a potential efficient therapy against this disease in humans.

scholarly journals The efficacy of saxagliptin in T2DM patients with non-alcoholic fatty liver disease: preliminary data

2019 ◽  
Vol 65 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Juan-Juan Li ◽  
Ping Zhang ◽  
Bing Fan ◽  
Xiu-Li Guo ◽  
Zhe-Shu Zheng
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Quantitative Detection ◽  
Alcoholic Fatty Liver ◽  
Group A ◽  
Group B ◽  
Alcoholic Fatty Liver Disease

SUMMARY OBJECTIVE To investigate the clinical efficacy and the possible mechanisms of saxagliptin in the treatment of type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD). METHODS A total of 95 T2DM and NAFLD patients were randomly divided into group A (saxagliptin group), group B (glimepiride group), and group C (glimepiride combined with polyene phosphatidylcholine group). RESULTS After intervention treatment for 24 w, body mass index (BMI), waist-to-hip ratio (WHR), glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and quantitative detection of liver steatosis of study subjects were observed, the action of liver steatosis in subjects of groups A and C were significantly different from those of group B; however, there were no differences between groups A and C. The FINS, HOMA-IR, and IL-6 of subjects in group A was lower than those in groups B and C; however, there were no significant differences between the latter two groups. CONCLUSION For T2DM combined with NAFLD patients, the saxagliptin treatment could not only effectively control blood glucose but also attenuate insulin resistance and inflammatory injury of the liver to improve fatty liver further.

scholarly journals CYTOKERATIN-18 AS A MARKER OF NON-ALCOHOLIC FATTY LIVER DISEASE IN OBESE ADOLESCENTS

2020 ◽  
Vol 5 ◽  
pp. 28-34
Author(s):  
Margaryta Khomenko
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Gamma Glutamyl Transpeptidase ◽  
Cytokeratin 18 ◽  
Alcoholic Fatty Liver ◽  
Gamma Glutamyl ◽  
Glutamyl Transpeptidase ◽  
Alcoholic Fatty Liver Disease

In parallel with the obesity epidemic in the world, the prevalence of non-alcoholic fatty liver disease among children and adolescents is growing. Current data suggest that insulin resistance is one of the main factors in the pathogenesis of non-alcoholic fatty liver disease, and the content of fragments of caspase-cleaved cytokeratin-18 in the blood serum may be one of the informative indicators of non-alcoholic fatty liver disease progression. The aim. To determine mechanisms of formation and progression of non-alcoholic fatty liver disease in obese children and adolescents by evaluating the level of cytokeratin-18. Materials and methods. The study involved 46 adolescents with obesity and non-alcoholic fatty liver disease aged 12–17 years: 19 boys (41.3 %) and 27 girls (58.7 %). Clinical (weight, height, waist and hip circumference), laboratory (glucose, immunoreactive insulin, lipid metabolism, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, cytokeratin-18) parameters were studied and instrumental examination (abdominal ultrasound) was performed. To assess insulin resistance the triglyceride-glucose index was calculated. Results. Depending on the presence of insulin resistance patients were divided into two groups: 21 (45.7 %) of adolescents with insulin resistance and 25 (54.3 %) of adolescents without insulin resistance. Blood tests in patients with insulin resistance revealed significantly higher levels of total cholesterol, triglycerides, very low-density lipoprotein cholesterol, fasting immunoreactive insulin, cytokeratin-18 and gamma-glutamyl transpeptidase. All adolescents were divided into 2 groups depending on the level of cytokeratin-18: patients with cytokeratin-18 >233 mIU/ml and <233 mIU/ml (15 (32.6 %) and 31 (67.4 %) respectively). It was found that there were significantly more patients with insulin resistance in the group with the level of cytokeratin-18 >233 mIU/ml. Conclusion. In obese adolescents with non-alcoholic fatty liver disease insulin resistance is associated with more pronounced disorders of lipid and carbohydrate metabolism and higher levels of markers that characterize the state of the liver such as cytokeratin-18 and gamma-glutamyl transpeptidase. Adolescents with obesity and non-alcoholic fatty liver disease with a threshold level of cytokeratin-18, which indicates the transformation of steatosis into steatohepatitis, two times more often have present insulin resistance.

scholarly journals Fixed combination of ramipril and indapamide in patients with hypertension and non-alcoholic fatty liver disease: focus on the large arteries

2021 ◽  
Vol 27 (3) ◽  
pp. 365-375
Author(s):  
M. E. Statsenko ◽  
A. M. Streltsova ◽  
M. V. Derevyanchenko
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Fixed Combination ◽  
Alcoholic Fatty Liver ◽  
Large Arteries ◽  
Low Intensity ◽  
Tnf Α ◽  
Alcoholic Fatty Liver Disease

Objective. To assess the effect of antihypertensive therapy with ramipril and indapamide on the elasticity of the vascular wall of the large arteries in relation to insulin resistance and chronic low-intensity inflammation in patients with hypertension (HTN) and non-alcoholic fatty liver disease (NAFLD). Design and methods. An open prospective controlled study was conducted: 30 patients with HTN stage I–II in combination with NAFLD (Fatty Liver Index (FLI) > 60) at the age of 45–65 years were included. Washout period was scheduled 5–7 days before the baseline examination, followed by the prescription of one of the fixed combinations of ramipril (2,5/5 mg/day) and indapamide (0,625/1,25 mg), depending on the required dosage (Konsilar-D 24 VERTEX AO, Russia) and were given recommendations on lifestyle changes and weight loss. A clinical examination was carried out, indicators of daily blood pressure (BP) monitoring and central aortic pressure (CAP), pulse wave velocity (PWV), lipid and carbohydrate metabolism, chronic low-intensity inflammation and the severity of insulin resistance before and after treatment were analyzed. Results. After 24-week therapy with a fixed combination of ramipril and indapamide at an average dosage of 4,04 ± 1,24 and 1,01 ± 0,31 mg, respectively, 100% of patients with HTN and NAFLD achieved target BP levels. According to 24-hour BP monitoring data, a significant decrease in systolic BP (SBP) and diastolic BP (DBP) was observed, both in the daytime (Δ12 mm Hg, р = 0,0001; Δ5,5 mm Hg, р = 0,0019, respectively), and at night (Δ13,5 mm Hg, р = 0,0006; Δ5,5 mm Hg, р = 0,0054, respectively). In addition, there was a significant decrease in CAP in the daytime (SBPao p = 0,0011, DBPao p = 0,0022) and night hours (SBPao p = 0,0015, DBPao p = 0,00124), and a statistically significant decrease in augmentation index (day p = 0,0460, night p = 0,0182). When evaluating clinical data and bioimpedance measurements, a decrease in waist circumference (p = 0,0000), hip circumference (p = 0,0001), the proportion of subcutaneous (p = 0,0134) and visceral (p = 0,0019) fat was found, which may indicate a decrease in the severity of visceral obesity. Also, during treatment, there is a decrease in the severity of insulin resistance (and the concentration of tumor necrosis factor alpha (TNF-α) (p < 0,0001) and CRP (p = 0,0002) in blood plasma. Finally, fixed combination of ramipril and indapamide led to a significant decrease in vascular stiffness (p = 0,0166) and a decrease in the proportion of patients with PWV paradoxical test (p = 0,0320). Correlation analysis showed that increased stiffness of the large arteries in patients with HTN and NAFLD is closely related to insulin resistance and lipid metabolism. At the same time, after 24-week therapy by a fixed combination of ramipril and indapamide, a decrease in the vascular stiffness in patients with HTN and NAFLD significantly correlated with the TNF-α concentration. Conclusions. A 24-week therapy by the fixed combination of ramipril and indapamide iin patients with HTN and NAFLD is associated with the persistent decrease in BP and CAP, both during the day and at night. There was a decrease in the vascular rigidity in muscular arteries. The treatment and recommendations for changing the lifestyle are associated with the decrease in the severity of abdominal obesity and insulin resistance, as well as the decrease in the severity of low-intensity systemic inflammation in patients with HTN and NAFLD, and a significant correlation was established between a decrease in TNF-α and an increase in the vascular elasticity of muscle and elastic type arteries.

scholarly journals Non-Alcoholic Fatty Liver Disease, Bile Acids and Intestinal Microbiota

2018 ◽  
Vol 28 (4) ◽  
pp. 84-90
Author(s):  
R. V. Maslennikov ◽  
Yu. V. Evsyutina
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Bile Acids ◽  
Intestinal Microbiota ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Aim.  The aim of the review is to present current data on the relationship between non-alcoholic fatty liver disease (NAFLD) with the metabolic disorders of bile acids (BA) and changes in the composition of the intestinal microbiota.Background.  NAFLD is accompanied by a change in the intestinal microbiotic composition: the proportion of taxa deconjugating BAs increases, while the proportion of taxa converting primary BAs to secondary ones decreases. The number of bacteria forming lipopolysaccharide (LPS) also increases. LPS, entering the liver with the portal vein blood, promotes the development of its inflammation and insulin resistance. The disturbance of bile acid metabolism through the effect on the FXR and TGR5 receptors also leads to insulin resistance and liver steatosis. FXR probiotics and agonists are promising drugs for the NAFLD treatment.Conclusion.  In the course of NAFLD, a change in the composition of the intestinal microbiota is observed, which contributes to the development of inflammation in the liver and disrupts the metabolism of bile acids, leading to insulin resistance. 

scholarly journals Resveratrol Improves Liver Steatosis and Insulin Resistance in Non-alcoholic Fatty Liver Disease in Association With the Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Fan Du ◽  
Rongfeng Huang ◽  
Dan Lin ◽  
Yuying Wang ◽  
Xiaohuang Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Therapeutic Effects ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Resveratrol (RSV) is a potential alternative therapy for non-alcoholic fatty liver disease (NAFLD) that has been evaluated in many clinical trials, but the mechanisms of RSV action have not been fully elucidated. Recent studies suggested that the gut microbiota is an important RSV target; therefore, we speculated that the gut microbiota might mediate the beneficial effects of RSV in NAFLD. To verify this hypothesis, we established a high-fat diet (HFD)-induced NAFLD mouse model, which was subjected to RSV gavage to evaluate the therapeutic effects. We observed that RSV reduced liver steatosis and insulin resistance in NAFLD. RSV significantly changed the diversity and composition of the gut microbiota according to 16S rRNA sequencing. Gut microbiota gene function prediction showed that the enrichment of pathways related to lipid and glucose metabolism decreased after RSV treatment. Furthermore, correlation analysis indicated that the improvements in NAFLD metabolic indicators were closely related to the altered gut microbiota. We further fermented RSV with the gut microbiota in vitro to verify that RSV directly affected the gut microbiota. Our data suggested that the gut microbiota might be an important target through which RSV exerts its anti-NAFLD effect.

Non-Alcoholic Fatty Liver Disease in Overweight Children and its Relationship with Retinol Serum Levels

2008 ◽  
Vol 78 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Suano de Souza ◽  
Silverio Amancio ◽  
Saccardo Sarni ◽  
Sacchi Pitta ◽  
Fernandes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Profile ◽  
Fatty Liver Disease ◽  
Thiobarbituric Acid ◽  
Serum Levels ◽  
Control Group ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Objectives: To evaluate the frequency of non-alcoholic fatty liver disease, the retinol serum levels, lipid profile, and insulin resistance in overweight/obese children. To relate these biochemical variables with the risk of this disease in the population studied. Methods: The study was cross-sectional and prospective, with 46 overweight/obese school children (28 female, 18 male; mean age 8.6 years). The control group consisted of 45 children, paired by age and gender. Hepatic steatosis, evaluated by ultrasound, was classified as normal, mild, moderate, or severe. Also evaluated were serum retinol levels; thiobarbituric acid reactive substances; lipid profile; and fasting glucose and serum insulin levels, used for the calculation of the Homeostasis Model Assessment. Results: Hepatic ultrasound alterations were found in 56.5% and 48,9% of the overweight/obese and control group children, respectively. Presence of obesity was associated with high levels of triglycerides (OR = 4.6; P = 0.002). In the studied children, the risk of steatosis was related to a trend to a higher percentage of retinol inadequacy (OR = 2.8; p = 0.051); there was no association with thiobarbituric acid reactive substances, lipid profile, or insulin resistance. Conclusions: The high frequency of non-alcoholic fatty liver disease in both groups, evaluated by hepatic ultrasound, in low-socioeconomic level children, independent of nutritional condition and without significant association with insulin resistance, emphasizes that especially in developing countries, other risk factors such as micronutrient deficiencies (e.g. vitamin A) are involved.

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