Research Article Details
| Article ID: | A11867 |
| PMID: | 30703836 |
| Source: | Dtsch Med Wochenschr |
| Title: | [The Diabetic Heart and Heart Failure - Update on Mechanisms and Therapy]. |
| Abstract: | Type 2 Diabetes mellitus (T2 D) is an independent risk factor for cardiovascular diseases and non-ischemic heart failure, an underestimated complication of T2 D. Diastolic dysfunction is an early sign of diabetes-related heart failure preceding its progression to systolic damage. The etiology of heart failure in these patients has recently been partially unveiled. Along with other mechanisms, hyperinsulinemia and hyperlipidemia cause increased myocardial lipid accumulation and oxidation, which leads to lipotoxicity, oxidative stress, inflammatory response and eventually impaired mitochondrial efficiency, fibrosis, apoptosis and contractile dysfunction. These myocardial alterations resemble the cellular mechanisms underlying the development of non-alcoholic fatty liver disease (NAFLD), a frequent comorbidity of T2 D and another risk factor for cardiovascular diseases and heart failure. Control of risk factors, lifestyle intervention and antihyperglycemic treatment are the recommended treatment for patients with T2 D and heart failure. While thiazolidindiones and some dipeptidyl peptidase 4 (DPP4) inhibitors may be detrimental for patients with heart failure, recent studies provided evidence for safe use of glucagon-like peptide 1 (GLP1) receptor agonists and for possible beneficial effects of sodium glucose co-transporter 2 (SGLT2) inhibitors on mortality and hospitalization of T2 D patients with heart failure. Treatment of NAFLD could also be beneficial for the cardiovascular outcome of patients with T2D-related heart failure. This article provides a brief summary of the current research on underlying mechanisms, clinical features and recently recommended therapeutic approaches for T2D-related heart failure. |
| DOI: | 10.1055/a-0646-7871 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 |
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D155 | Glucagon | Biological drug | DB00040 | GCGR agonist | Antidiabetic drug | Under clinical trials | Details |