Research Article Details
| Article ID: | A26044 |
| PMID: | 21168460 |
| Source: | J Hepatol |
| Title: | Early interplay of intra-hepatic iron and insulin resistance in children with non-alcoholic fatty liver disease. |
| Abstract: | BACKGROUND & AIMS: The liver is a crucial organ at the crossroads of iron and glucose metabolism. The aim of the study was to assess intra-hepatic iron in young patients with non-alcoholic fatty liver disease (NAFLD) and its association with insulin resistance and severity of liver damage. METHODS: Intrahepatic iron content was assessed (Pearl's stain grade) in 66 patients (41 males, age 3.3-17.6years) with biopsy-proven NAFLD. Mutations of the Hereditary Hemochromatosis (HFE) gene were determined by sequence allele-specific polymerase chain reaction. Insulin resistance was estimated by means of the Oral Glucose Tolerance Test and the Insulin Sensitivity Index (ISI); the Insulino-Genic Index was also calculated. Tumor necrosis factor-alpha and interleukin-6 were measured. RESULTS: Low-mild intra-hepatic iron deposition was observed in one out of five children (n=15, 22%), and it was not associated with HFE mutations, carried by 17 patients (26%). Among carriers of HFE mutations, four had siderosis. No abnormalities were observed in systemic indices of iron balance. Serum ferritin was within normal adult ranges in all patients (33.6±7.6ng/ml), but it was correlated with ISI (r(o)=-0.361; p=0.003). No significant difference was observed in insulin sensitivity, iron balance, inflammatory milieu, and liver histology between patients with and without hepatic siderosis. CONCLUSIONS: In young obese individuals with NAFLD, despite normal peripheral iron parameters, mild intra-hepatic iron deposition is a frequent finding, but it is not associated with insulin resistance or severity of liver damage. Longitudinal studies are required to define the long-term relevance of these findings. |
| DOI: | 10.1016/j.jhep.2010.12.007 |
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | 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 |