Research Article Details
| Article ID: | A03040 |
| PMID: | 34155798 |
| Source: | Liver Int |
| Title: | Non-alcoholic fatty liver disease in type 2 diabetes - A specific entity? |
| Abstract: | Individuals with obesity or type 2 diabetes (T2D) have an increased risk of developing non-alcoholic fatty liver disease (NAFLD). In insulin-resistant states, altered adipose tissue function may be the initial abnormality underlying NAFLD. Hepatic lipid oversupply interferes with insulin signalling and mitochondrial function. In obese individuals, adaptation of hepatic mitochondrial respiration fails with the progression of NAFLD and can activate pro-inflammatory pathways. T2D as well as type 1 diabetes are associated with altered hepatic mitochondrial function. Screening for NAFLD remains challenging especially in those with diabetes because liver enzymes are often in the normal range and the performance of NAFLD scores is limited. Patients with T2D and severe insulin-resistant diabetes (SIRD) have the highest prevalence of NAFLD at diagnosis and the greatest risk of progression. In this subgroup, the single-nucleotide-polymorphism (SNP) rs738409(G) of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene is associated with high liver fat content and adipose tissue insulin resistance. This frequent SNP is also known to be associated with lean NAFLD so that genetic testing for this and other SNPs could improve future screening strategies to identify high-risk individuals. Although lifestyle modifications are effective, this approach is limited owing to difficulties with compliance and several classes of drugs are being tested to treat NAFLD. Antihyperglycaemic drugs such as glucagon-like peptide 1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i) and pioglitazone are promising and halt the progression of NAFLD. In conclusion, although NAFLD in diabetes may not be a separate entity, there are specific features to its pathogenesis and clinical management. |
| DOI: | 10.1111/liv.14846 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| 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 | |
|---|---|---|---|---|---|---|---|
| T02 | Sodium/glucose cotransporter 2 | SLC5A2 | inhibitor | Transporter | P31639 | SC5A2_HUMAN | Details |
| T21 | Diacylglycerol O-acyltransferase 2 | DGAT2 | inhibitor | Enzyme | Q96PD7 | DGAT2_HUMAN | Details |
| T06 | Glucagon-like peptide 1 receptor | GLP1R | agonist | GPCR | P43220 | GLP1R_HUMAN | 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in 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 |
| D155 | Glucagon | Biological drug | DB00040 | GCGR agonist | Antidiabetic drug | Under clinical trials | Details |