Research Article Details
| Article ID: | A17418 |
| PMID: | 27794176 |
| Source: | Hepatol Res |
| Title: | High fasting insulin concentrations may be a pivotal predictor for the severity of hepatic fibrosis beyond the glycemic status in non-alcoholic fatty liver disease patients before development of diabetes mellitus. |
| Abstract: | BACKGROUND: Insulin resistance and type 2 diabetes mellitus (T2DM) contribute to the progression of non-alcoholic fatty liver disease (NAFLD). However, the relationship between glucose metabolic factors and the histological severity in NAFLD patients before development of T2DM is not well known. METHODS: In 103 biopsy-proven NAFLD patients (68 men and 35 women) with hemoglobin A1c of <6.5% and fasting blood glucose of <126 mg/dL, we investigated whether glucose metabolic factors influenced the severity of hepatic fibrosis without prior known T2DM. RESULTS: Female gender, age, serum aspartate aminotransferase, the aspartate aminotransferase/alanine aminotransferase ratio, fasting immunoreactive insulin (f-IRI), homeostasis model assessment - insulin resistance, hemoglobin A1c, hyaluronic acid, and type IV collagen 7 s were significantly higher, and 1,5-anhydroglucitol was significantly lower, in the fibrosis stage F3 group than in the F0-2 group. Multiple logistic regression analysis showed that only f-IRI (P = 0.006; odds ratio, 1.15151; 95% confidence interval, 1.04198-1.27254) was significantly indicated as a predictive factor for F3. As determined by both forward and backward stepwise selection analyses to optimize the model, f-IRI (P = 0001; odds ratio, 1.16788) remained an independent predictive factor for F3. To discriminate the F3 group from the F0-2 group, the area under the receiver operating characteristic curves showed that fasting insulin was 0.7219, and the best cut-off value of f-IRI was 13.2 μU/mL in the receiver operating characteristic curve analysis. CONCLUSIONS: High fasting insulin concentrations may be a pivotal glucose metabolic predictor for the severity of hepatic fibrosis beyond the glycemic status in NAFLD patients before development of T2DM. |
| DOI: | 10.1111/hepr.12832 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under 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 |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |