Research Article Details
| Article ID: | A12424 |
| PMID: | 30459251 |
| Source: | Diabetes |
| Title: | Targeting Metabolism, Insulin Resistance, and Diabetes to Treat Nonalcoholic Steatohepatitis. |
| Abstract: | Obesity, insulin resistance, and diabetes are strongly linked to the accumulation of excessive lipids in the liver parenchyma, a condition known as nonalcoholic fatty liver disease (NAFLD). Given its association with obesity and related metabolic diseases, it is not surprising that the prevalence of NAFLD has dramatically increased in the past few decades. NAFLD has become the most common liver disease in many areas of the world. The term, NAFLD, encompasses a spectrum of disorders that ranges from simple steatosis to steatosis with inflammatory lesions (nonalcoholic steatohepatitis [NASH]). Although simple steatosis might be relatively benign, epidemiologic studies have linked NASH to greatly increased risk of developing cirrhosis and hepatocellular carcinoma. Yet despite this, there are no approved treatments for the disease, and it remains a significant unmet medical need. This Perspective will review some of the relevant literature on the topic and examine approved and experimental NASH therapeutic concepts that target intermediary metabolism, insulin resistance, and diabetes to treat this emerging public health problem. |
| DOI: | 10.2337/dbi18-0024 |
| 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 |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |