Research Article Details
| Article ID: | A37330 |
| PMID: | 15950075 |
| Source: | Arch Med Res |
| Title: | Hypomagnesemia, insulin resistance, and non-alcoholic steatohepatitis in obese subjects. |
| Abstract: | BACKGROUND: Epidemiological evidence shows a strong relationship between decreased serum magnesium levels (DSML) and insulin resistance. As nonalcoholic steatohepatitis (NASH) seems to be related to insulin resistance, the aim of this study was to determine the potential relationship between DSML and NASH in obese subjects. METHODS: We compared obese individuals with the diagnosis of diabetes, insulin-resistance, and non-insulin resistance to a control group of non-obese, non-insulin-resistant subjects. Participants were required to have negative viral markers and negligible alcohol intake. Other liver diseases and well-known causes for decreasing of magnesium were exclusion criteria. A liver biopsy was performed in subjects with aspartate aminotransferase (AST) and alanine aminotransferease (ALT) levels > or =40 IU/mL. RESULTS: Of the 60 obese subjects, 20 were non-insulin resistant, 20 were insulin resistant, and 20 were type 2 diabetics. Twenty subjects were in the control group. Eleven (33.3%) diabetics, 14 (42.4%) insulin-resistant subjects, and 8 (24.2%) non-insulin-resistant subjects underwent liver biopsies. Diagnosis of NASH was established in 29 (36.2%) individuals. Subjects with the diagnosis of NASH exhibited lower serum magnesium levels of 1.7 +/- 0.2 mg/dL (0.70 +/- 0.08 mmol/L), and those with fibrosis showed the lowest serum magnesium concentration at 1.5 +/- 0.3 mg/dL (0.62 +/- 0.12 mmol/L). Multiple regression analysis adjusted by age showed that low serum magnesium concentration was independently related to a high HOMA-IR index (OR 7.6, CI 95% 2.1-11.2; p <0.0001) and that a high HOMA-IR index was related to NASH (OR 6.5, CI 95% 1.5-8.8; p <0.01). After adjusting for age and a high HOMA-IR index, hypomagnesemia remained independently related to NASH (OR 1.4, CI 95% 1.1-5.4; p <0.05). CONCLUSIONS: The results of this study demonstrate an independent relationship between DSML and NASH. |
| DOI: | 10.1016/j.arcmed.2005.03.008 |
| 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 |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |