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Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus.
- Source :
- Journal of Translational Medicine; 7/5/2016, Vol. 14, p1-11, 11p
- Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response to ARBs in patients with diabetes mellitus and micro- or macroalbuminuria.<bold>Methods: </bold>Liquid chromatography-tandem mass spectrometry metabolomics was performed on serum samples. Data from patients with type 2 diabetes and microalbuminuria (n = 49) treated with irbesartan 300 mg/day were used for discovery. LASSO and ridge regression were performed to develop the classifier. Improvement in albuminuria response prediction was assessed by calculating differences in R(2) between a reference model of clinical parameters and a model with clinical parameters and the classifier. The classifier was externally validated in patients with type 1 diabetes and macroalbuminuria (n = 50) treated with losartan 100 mg/day. Molecular process analysis was performed to link metabolites to molecular mechanisms contributing to ARB response.<bold>Results: </bold>In discovery, median change in urinary albumin excretion (UAE) was -42 % [Q1-Q3: -69 to -8]. The classifier, consisting of 21 metabolites, was significantly associated with UAE response to irbesartan (p < 0.001) and improved prediction of UAE response on top of the clinical reference model (R(2) increase from 0.10 to 0.70; p < 0.001). In external validation, median change in UAE was -43 % [Q1-Q35: -63 to -23]. The classifier improved prediction of UAE response to losartan (R(2) increase from 0.20 to 0.59; p < 0.001). Specifically ADMA impacting eNOS activity appears to be a relevant factor in ARB response.<bold>Conclusions: </bold>A serum metabolite classifier was discovered and externally validated to significantly improve prediction of albuminuria response to ARBs in diabetes mellitus. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 14
- Database :
- Complementary Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 116788590
- Full Text :
- https://doi.org/10.1186/s12967-016-0960-3