Research Article Details
| Article ID: | A22550 |
| PMID: | 24471572 |
| Source: | J Clin Endocrinol Metab |
| Title: | Nonalcoholic fatty liver disease, liver fibrosis, and cardiometabolic risk factors in adolescence: a cross-sectional study of 1874 general population adolescents. |
| Abstract: | CONTEXT: The impact of adolescent nonalcoholic fatty liver disease (NAFLD) on health, independent of fat mass, is unclear. OBJECTIVE: The objective of the study was to determine the independent (of total body fat) association of ultrasound scan (USS)-determined NAFLD with liver fibrosis, insulin resistance, and dyslipidemia among healthy adolescents. DESIGN: This was a cross-sectional analysis in participants from a UK birth cohort. PARTICIPANTS: One thousand eight hundred seventy-four (1059 female) individuals of a mean age of 17.9 years participated in the study. MAIN OUTCOMES: USS assessed liver stiffness (shear velocity, an indicator of fibrosis) and volume, fasting glucose, insulin, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine amino transferase, aspartate amino transferase, γ-glutamyltransferase, and haptoglobin. RESULTS: The prevalence of NAFLD was 2.5% [95% confidence interval (CI) 1.8-3.3] and was the same in females and males. Dual-energy X-ray absorptiometry determined total body fat mass was strongly associated with USS NAFLD: odds ratio 3.15 (95% CI 2.44-4.07) per 1 SD (∼10 kg) fat mass. Those with NAFLD had larger liver volumes and greater shear velocity. They also had higher fasting glucose, insulin, triglycerides, low-density lipoprotein cholesterol, alanine amino transferase, aspartate amino transferase, γ-glutamyltransferase, and haptoglobin and lower high-density lipoprotein cholesterol. Most associations were independent of total body fat. For example, after adjustment for fat mass and other confounders, hepatic shear velocity [mean difference 22.8% (95% CI 15.6-30.5)], triglyceride levels [23.6% (95% CI 6.0-44.2)], and insulin [39.4% (95% CI 10.7-75.5)] were greater in those with NAFLD compared with those without NAFLD. CONCLUSION: In healthy European adolescents, 2.5% have USS-defined NAFLD. Even after accounting for total body fat, those with NAFLD have more adverse levels of liver fibrosis and cardiometabolic risk factors. |
| DOI: | 10.1210/jc.2013-3612 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |