Research Article Details
| Article ID: | A14739 |
| PMID: | 29264555 |
| Source: | J Endocr Soc |
| Title: | Nonalcoholic Fatty Liver Disease in Hispanic Youth With Dysglycemia: Risk for Subclinical Atherosclerosis? |
| Abstract: | Context: Obese Hispanic adolescents (OHAs) with dysglycemia have increased cardiovascular disease risk burden. Objective: To investigate if nonalcoholic fatty liver disease (NAFLD) confers added risk for endothelial dysfunction in these youth. Design: Cross-sectional study. Setting: Academic institution. Participants: Thirty-six OHAs (15.3 ± 0.4 years), 20 with prediabetes and 16 with type 2 diabetes, with and without NAFLD. Intervention: Evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) by peripheral arterial tonometry; muscle, hepatic, and adipose tissue insulin sensitivity (IS; hyperinsulinemic-euglycemic clamp 80 mu/m2/min, with [6,6 2H2]glucose and [2H5] glycerol); body composition; and abdominal and hepatic fat by magnetic resonance imaging/spectroscopy. Outcome Measures: RHI and AIx. Hypothesis: OHAs with dysglycemia and NAFLD have worse RHI and AIx vs those without NAFLD. Results: The NAFLD (n = 23) and non-NAFLD (n = 13) groups were of similar age, sex, glycemic status, body mass index, % body fat and abdominal fat. The NAFLD group had higher hepatic fat (P < 0.001) lower skeletal muscle IS (P = 0.01), hepatic IS (P = 0.01), and adipose tissue IS (P = 0.04). The NAFLD vs non-NAFLD group had lower RHI (1.4 ± 0.05 vs 1.7 ± 0.09, P = 0.002), greater AIx (-6.0 ± 1.6 vs -12.0 ± 2.1, P = 0.03). Hepatic fat was inversely related to RHI (r = -0.49, P = 0.002) and positively related to AIx (r = 0.45, P = 0.006). Hepatic IS (r = -0.42, P = 0.01) and adipose IS (r = -.54, P = 0.001) correlated with arterial stiffness (AIx). Conclusion: In OHAs with dysglycemia, NAFLD is associated with worse endothelial function. RHI and AIx were related to hepatic fat content. Vascular stiffness was related to hepatic and adipose tissue insulin resistance. |
| DOI: | 10.1210/js.2017-00257 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| 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 |
| I07 | 1936 | Arteriosclerosis | Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 | disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| 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 |