Research Article Details
| Article ID: | A20846 |
| PMID: | 25690560 |
| Source: | Eur J Clin Invest |
| Title: | Low-normal thyroid function and the pathogenesis of common cardio-metabolic disorders. |
| Abstract: | BACKGROUND: Subclinical hypothyroidism may adversely affect the development of cardiovascular disease (CVD). Less is known about the role of low-normal thyroid function, that is higher thyroid-stimulating hormone and/or lower free thyroxine levels within the euthyroid reference range, in the development of cardio-metabolic disorders. This review is focused on the relationship of low-normal thyroid function with CVD, plasma lipids and lipoprotein function, as well as with metabolic syndrome (MetS), chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This narrative review, which includes results from previously published systematic reviews and meta-analyses, is based on clinical and basic research papers, obtained via MEDLINE and PubMed up to November 2014. RESULTS: Low-normal thyroid function could adversely affect the development of (subclinical) atherosclerotic manifestations. It is likely that low-normal thyroid function relates to modest increases in plasma total cholesterol, LDL cholesterol and triglycerides, and may convey pro-atherogenic changes in lipoprotein metabolism and in HDL function. Most available data support the concept that low-normal thyroid function is associated with MetS, insulin resistance and CKD, but not with high blood pressure. Inconsistent effects of low-normal thyroid function on NAFLD have been reported so far. CONCLUSIONS: Observational studies suggest that low-normal thyroid function may be implicated in the pathogenesis of CVD. Low-normal thyroid function could also play a role in the development of MetS, insulin resistance and CKD, but the relationship with NAFLD is uncertain. The extent to which low-normal thyroid function prospectively predicts cardio-metabolic disorders has been insufficiently established so far. |
| DOI: | 10.1111/eci.12423 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I04 | 1459 | Hypothyroidism | A thyroid gland disease which involves an underproduction of thyroid hormone. https://medlineplus.gov/hypothyroidism.html | disease of anatomical entity/ endocrine system disease/ thyroid gland disease | 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 |
| 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 |
| D203 | Levothyroxine | Chemical drug | DB00451 | THRA agonist; THRB agonist | Anti-fibrosis | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |