scholarly journals Leptin, free leptin index, insulin resistance and liver fibrosis in children with non-alcoholic fatty liver disease

2006 ◽  
Vol 155 (5) ◽  
pp. 735-743 ◽  
Author(s):  
Valerio Nobili ◽  
Melania Manco ◽  
Paolo Ciampalini ◽  
Vincenzo Diciommo ◽  
Rita Devito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Glucose Tolerance ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Sensitivity Index ◽  
Causative Role ◽  
Alcoholic Fatty Liver ◽  
Nas Score ◽  
Alcoholic Fatty Liver Disease

Objective: Prevalence of non-alcoholic fatty liver disease (NAFLD) among children is increasing dramatically. It is unclear why some patients develop steatohepatitis (NASH), fibrosis and cirrhosis from steatosis, and others do not. A role for leptin has been claimed. This study aims to evaluate the relationship between leptin, insulin resistance (IR) and NAFLD in children. Design and methods: In 72 biopsy-proven NAFLD children (aged 9–18 years; 51M/21F), fasting leptin and its soluble receptor (sOB-R) were measured; free leptin index (FLI) was calculated as leptin/sOB-R; IR was estimated by homeostasis model assessment (HOMA-IR) and insulin sensitivity index (ISI-comp); glucose tolerance by oral glucose tolerance test (OGTT). Percentage of total body fat (TBF) by dual-energy X-ray absorptiometry (DXA) was available in 65 patients. Results: Prevalence of diabetes, impaired fasting and/or after load glucose tolerance was 11%. HOMA-IR and ISI-comp values were 2.55 ± 1.39 and 4.4 ± 2. NASH was diagnosed in 38 and simple steatosis in 25 children; diagnosis was indeterminate in 29 children. Increased fibrosis, mostly of mild severity, was observed in 41 patients. Median NAFLD activity (NAS) score was 3.42 ± 1.60. According to histology, levels of leptin and FLI increased as steatosis (leptin from 11.9 ± 6.3 in score 1 to 17.4 ± 6.9 in score 2 (P = 0.01) and 22.2 ± 6.8 ng/ml in score 3 (P < 0.001); FLI 2.56 ± 1.40, 3.57 ± 0.34, 4.45 ± 0.64 respectively (P = 0.05)); ballooning (from 13.7 ± 6.7 in score 1 to 17 ± 7.5 in score 2 (P = 0.001) and 22.1 ± 7.1 ng/ml in score 3 (P = 0.01); FLI 2.81 ± 1.50, 3.40 ± 1.65, 4.57 ± 1.67 (P = 0.01 between 0 and 2)); fibrosis (from 14.3 ± 7 to18.3 ± 6.9; P = 0.03; FLI 3.03 ± 1.57 vs 3.92 ± 077; P < 0.05) and NAS score (score 1–2: 12.9 ± 6.9; score 3–4: 17 ± 6.9 (P = 0.01); score 5–7: 22.9 ± 7.5 ng/ml (P = 0.03); FLI 2.70 ± 1.53, 3.12 ± 1.53, 4.58 ± 1.57 P = 0.01 and P = 0.05 between 1–2 vs 3–4 and 3–4 vs 5–7 respectively) worsened. Higher leptin correlated with more severe steatosis, ballooning and NAS score (r0 = 0.6, 0.4 and 0.6 respectively; for all P < 0.001); FLI with ballooning (r0 = 0.4, P < 0.0001), steatosis (r0 = 0.5, P < 0.0001) and NAS score (r0 = 0.5, P < 0.0001). Conclusions: Leptin and liver injury correlated independently of age, BMI and gender in the present study. Nevertheless, any causative role of leptin in NAFLD progression could be established. Thus, studies are needed to define whether the hormone plays a major role in the disease.

scholarly journals Non-Alcoholic Fatty Liver Disease in Obese Youth With Insulin Resistance and Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Serena Scapaticci ◽  
Ebe D’Adamo ◽  
Angelika Mohn ◽  
Francesco Chiarelli ◽  
Cosimo Giannini
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Natural History ◽  
Glucose Tolerance ◽  
Fatty Liver ◽  
Children And Adolescents ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Currently, Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent form of chronic liver disease in children and adolescents worldwide. Simultaneously to the epidemic spreading of childhood obesity, the rate of affected young has dramatically increased in the last decades with an estimated prevalence of NAFLD of 3%–10% in pediatric subjects in the world. The continuous improvement in NAFLD knowledge has significantly defined several risk factors associated to the natural history of this complex liver alteration. Among them, Insulin Resistance (IR) is certainly one of the main features. As well, not surprisingly, abnormal glucose tolerance (prediabetes and diabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. In addition, other factors such as genetic, ethnicity, gender, age, puberty and lifestyle might affect the development and progression of hepatic alterations. However, available data are still lacking to confirm whether IR is a risk factor or a consequence of hepatic steatosis. There is also evidence that NAFLD is the hepatic manifestation of Metabolic Syndrome (MetS). In fact, NAFLD often coexist with central obesity, impaired glucose tolerance, dyslipidemia, and hypertension, which represent the main features of MetS. In this Review, main aspects of the natural history and risk factors of the disease are summarized in children and adolescents. In addition, the most relevant scientific evidence about the association between NAFLD and metabolic dysregulation, focusing on clinical, pathogenetic, and histological implication will be provided with some focuses on the main treatment options.

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.

Non-alcoholic fatty liver disease and its association with insulin resistance in an obese population

2018 ◽  
Author(s):  
Frederique Van de Velde ◽  
Marlies Bekaert ◽  
Anne Hoorens ◽  
Marleen Praet ◽  
Arsene-Helene Batens ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Obese Population ◽  
Alcoholic Fatty Liver Disease

scholarly journals Higher Sodium Intake Assessed by 24 Hour Urinary Sodium Excretion Is Associated with Non-Alcoholic Fatty Liver Disease: The PREVEND Cohort Study

2019 ◽  
Vol 8 (12) ◽  
pp. 2157 ◽  
Author(s):  
Eline H. van den Berg ◽  
Eke G. Gruppen ◽  
Hans Blokzijl ◽  
Stephan J.L. Bakker ◽  
Robin P.F. Dullaart
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Sodium Excretion ◽  
Fatty Liver Disease ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Model Assessment ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

A higher sodium intake is conceivably associated with insulin resistant conditions like obesity, but associations of non-alcoholic fatty liver disease (NAFLD) with a higher sodium intake determined by 24 hours (24 h) urine collections are still unclear. Dietary sodium intake was measured by sodium excretion in two complete consecutive 24 h urine collections in 6132 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. Fatty Liver Index (FLI) ≥60 and Hepatic Steatosis Index (HSI) >36 were used as proxies of suspected NAFLD. 1936 (31.6%) participants had an FLI ≥60, coinciding with the increased prevalence of type 2 diabetes (T2D), metabolic syndrome, hypertension and history of cardiovascular disease. Sodium intake was higher in participants with an FLI ≥60 (163.63 ± 61.81 mmol/24 h vs. 136.76 ± 50.90 mmol/24 h, p < 0.001), with increasing incidence in ascending quartile categories of sodium intake (p < 0.001). Multivariably, an FLI ≥60 was positively associated with a higher sodium intake when taking account for T2D, a positive cardiovascular history, hypertension, alcohol intake, smoking and medication use (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.44–1.64, p < 0.001). Additional adjustment for the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) diminished this association (OR 1.30, 95% CI 1.21–1.41, p < 0.001). HSI >36 showed similar results. Associations remained essentially unaltered after adjustment for body surface area or waist/hip ratio. In conclusion, suspected NAFLD is a feature of higher sodium intake. Insulin resistance-related processes may contribute to the association of NAFLD with sodium intake.

scholarly journals Beneficial effect of omarigliptin on diabetic patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sachiko Hattori ◽  
Kazuomi Nomoto ◽  
Tomohiko Suzuki ◽  
Seishu Hayashi
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Liver Function ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Hepatic Insulin Resistance ◽  
Diabetic Patients ◽  
Alcoholic Fatty Liver ◽  
Dpp4 Inhibitor ◽  
Alcoholic Fatty Liver Disease

Abstract Background Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides, and also a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis. Method We examined whether weekly DPP4 inhibitor omarigliptin (OMG) can improve liver function as well as levels of inflammation and insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). Further, we investigated the effects of OMG in a diabetic patient with biopsy-confirmed nonalcoholic steatohepatitis (NASH). Results In NAFLD patients, OMG significantly decreased levels of aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP), while no significant change was seen in hemoglobin A1c or body mass index. In the NASH patient, liver function improved markedly, and levels of the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and hsCRP. Slight but clear improvements in intrahepatic fat deposition and fibrosis appeared to be seen on diagnostic ultrasonography. Conclusion Weekly administration of the DPP4 inhibitor OMG in ameliorating hepatic insulin resistance may cause beneficial effects in liver with NAFLD/NASH.

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