Research Article Details
| Article ID: | A22589 |
| PMID: | 24440936 |
| Source: | J Clin Gastroenterol |
| Title: | Nonalcoholic steatohepatitis associated with metabolic syndrome: relationship to insulin resistance and liver histology. |
| Abstract: | BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of metabolic syndrome. We aimed to assess the relationship of metabolic syndrome-associated NASH and insulin resistance (IR), and to define the correlation of chemicometabolic components with different degree of liver histology in NASH subjects. STUDY: Ninety-four subjects with NASH (mean age, 38±14 y; 77% male) were enrolled. IR was calculated using a homeostasis model assessment of insulin resistance (HOMA-IR). Clinical characteristics including IR and accompanying metabolic risk components in NASH subjects were compared with those of 52 diabetics and 21 healthy controls. The relationship between IR and chemicometabolic variables was analyzed according to different clustering of metabolic risk components and the histologic activity. RESULTS: NASH subjects had a stronger association with metabolic syndrome than healthy controls. HOMA-IR was significantly higher in NASH subjects than in healthy controls (4.4±2.5 vs. 1.7±0.6; P<0.001) but not than in diabetics. NASH subjects with metabolic syndrome were more likely to have higher HOMA-IR compared with that of NASH subjects without metabolic syndrome (5.0±2.9 vs. 3.6±1.7; P=0.032). HOMA-IR showed a positive correlation with body mass index (r=0.428, P=0.015) and serum fasting blood sugar (r=0.365, P=0.037). Serum aspartate aminotransferase/alanine aminotransferase ratio (P=0.029) and high-density lipoprotein cholesterol level (P=0.034) were significantly affected according to the degree of fibrotic activity in 41 histology-proven NASH subjects. CONCLUSIONS: NASH subjects showed increased IR with a significant association of metabolic syndrome. The severity of hepatic fibrosis revealed a strong correlation with serum aspartate aminotransferase/alanine aminotransferase ratio and high-density lipoprotein cholesterol level. |
| DOI: | 10.1097/MCG.0000000000000065 |
| 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 | |
|---|---|---|---|---|---|
| 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 |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | 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 |