Research Article Details
| Article ID: | A24634 |
| PMID: | 22672330 |
| Source: | Diabet Med |
| Title: | Dorothy Hodgkin Lecture 2012: non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management. |
| Abstract: | Non-alcoholic fatty liver disease is now recognized as the hepatic component of the metabolic syndrome. Non-alcoholic fatty liver disease is a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in non-alcoholic fatty liver disease and may progress to non-alcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. Prevalence estimates for non-alcoholic fatty liver disease range from 17 to 33% in the general populations and it has been estimated that non-alcoholic fatty liver disease exists in up to 70% of people with Type 2 diabetes. Non-alcoholic fatty liver disease increases risk of Type 2 diabetes and cardiovascular disease. In people with Type 2 diabetes, non-alcoholic fatty liver disease is the most frequent cause (∼80%) of fatty liver diagnosed by ultrasound. As non-alcoholic fatty liver disease is strongly associated with insulin resistance, the presence of non-alcoholic fatty liver disease with diabetes often contributes to poor glycaemic control. Consequently, strategies that decrease liver fat and improve whole-body insulin sensitivity may both contribute to prevention of Type 2 diabetes and to better glycaemic control in people who already have developed diabetes. This review summarizes the Dorothy Hodgkin lecture given by the author at the 2012 Diabetes UK annual scientific conference, proposing that fatty acid fluxes through the liver are crucial for the pathogenesis of non-alcoholic fatty liver disease and for increasing insulin resistance. |
| DOI: | 10.1111/j.1464-5491.2012.03732.x |
| 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 |
| S10 | Liver transplantation | -- | -- | -- | 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 |
| 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 |
| 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 |