Research Article Details
| Article ID: | A52267 |
| PMID: | 29477938 |
| Source: | Curr Opin Genet Dev |
| Title: | Genetic syndromes of severe insulin resistance. |
| Abstract: | Insulin resistance underpins the link between obesity and most of its associated metabolic disorders including type 2 diabetes, fatty liver disease, dyslipidaemia and cardiovascular disease. Despite its importance and extensive scientific endeavour, its precise molecular pathogenesis remains unclear. Monogenic syndromes of extreme insulin resistance, whilst rare in themselves, can provide unique insights into the pathogenesis of human insulin resistance. Severe insulin resistance syndromes are broadly classified into three categories: lipodystrophies, primary insulin signalling defects or complex syndromes including severe insulin resistance. Genetically confirmed classification has facilitated the identification of robust diagnostic biochemical features accelerating accurate clinical diagnosis. Interestingly the biochemical features of lipodystrophies are far more closely aligned to what is seen in prevalent forms of insulin resistance than those of primary insulin signalling defects, suggesting that lipodystrophy could be a relevant model for common disease. This assertion is supported by genome-wide association data indicating that SNPs associated with fasting hyperinsulinemia and metabolic dyslipidaemia, are strongly associated with a subtle reduction in hip fat, suggesting that subtle forms of lipodystrophy are likely to be a significant contributor to prevalent insulin resistance. |
| DOI: | 10.1016/j.gde.2018.02.002 |
| 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 |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| 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 |
| I06 | 811 | Lipodystrophy | A connective tissue disease that is characterized by marked reduction, absence, and/or the redistribution of adipose tissue. https://www.ncbi.nlm.nih.gov/pubmed/25690482, https://www.ncbi.nlm.nih.gov/pubmed/25833179 | disease of anatomical entity/ musculoskeletal system disease/ connective tissue disease | 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 | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under 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 |