Research Article Details
| Article ID: | A27977 |
| PMID: | 16817817 |
| Source: | Clin Endocrinol (Oxf) |
| Title: | Effects of HRT on liver enzyme levels in women with type 2 diabetes: a randomized placebo-controlled trial. |
| Abstract: | BACKGROUND: Increasingly strong links are being recognized between diabetes, insulin resistance and liver fat accumulation [e.g. nonalcoholic fatty liver disease (NAFLD)]. Recent data indicating that hormone replacement therapy (HRT) may lessen diabetes risk is intriguing but explanatory mechanisms are unclear. OBJECTIVE: Post hoc investigation of the possibility that HRT may favourably influence liver enzyme levels commonly elevated in patients with diabetes. We examined liver function test data from a 6-month trial of a low-dose continuous combined HRT (1 mg 17beta oestradiol and 0.5 mg norethisterone acetate). DESIGN: Double-blind, randomized placebo-controlled. PATIENTS: Fifty women with type 2 diabetes. MEASUREMENTS: Liver enzyme levels (AST, ALT, gamma-glutamylytransferase [GGT], and alkaline phosphatase [ALP]). RESULTS: Forty-five women completed the study with 19/22 in the active group demonstrating compliance as measured by sex hormone changes. Relative to placebo recipients (n = 23), women randomized and compliant to HRT demonstrated significant reductions in ALT [-14 (-23 to -6) U/l, P = 0.002], AST [-9.2 (-14 to -5) U/l, P < 0.001] and ALP [-60.8 (-80 to -42) U/l, P < 0.001]. Circulating concentrations in GGT were also significantly reduced (P = 0.035). All changes were significant using an intention-to-treat analysis. CONCLUSION: HRT containing low-dose oestradiol and norethisterone reduces serum concentrations of liver function enzymes, potentially due to a lowering of liver fat accumulation. Better understanding of mechanisms by which this HRT improves liver function tests could help the design of new therapies to treat individuals with NAFLD. |
| DOI: | 10.1111/j.1365-2265.2006.02543.x |
| 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 | |
|---|---|---|---|---|---|
| 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 | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| 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 |
| D476 | Estradiol | Chemical drug | DB00783 | -- | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |