Noemi Malandrino1, Robert J Smith. 1. Division of Endocrinology, Department of Medicine, Alpert Medical School of Brown University, Providence, RI, USA.
Abstract
BACKGROUND: Multiple genes that are associated with the risk of developing diabetes or the risk of diabetes complications have been identified by candidate gene analysis and genomewide scanning. These molecular markers, together with clinical data and findings from proteomics, metabolomics, pharmacogenetics, and other methods, lead to a consideration of the extent to which personalized approaches can be applied to the treatment of diabetes mellitus. CONTENT: Known genes that cause monogenic subtypes of diabetes are reviewed, and several examples are discussed in which the genotype of an individual with diabetes can direct considerations of preferred choices for glycemic therapy. The extent of characterization of polygenic determinants of type 1 and type 2 diabetes is summarized, and the potential for using this information in personalized management of glycemia and complications in diabetes is discussed. The application and current limitations of proteomic and metabolomic methods in elucidating diabetes heterogeneity is reviewed. SUMMARY: There is established heterogeneity in the determinants of diabetes and the risk of diabetes complications. Understanding the basis of this heterogeneity provides an opportunity for personalizing prevention and treatment strategies according to individual patient clinical and molecular characteristics. There is evidence-based support for benefits from a personalized approach to diabetes care in patients with certain monogenic forms of diabetes. It is anticipated that strategies for individualized treatment decisions in the more common forms of diabetes will emerge with expanding knowledge of polygenic factors and other molecular determinants of disease.
BACKGROUND: Multiple genes that are associated with the risk of developing diabetes or the risk of diabetes complications have been identified by candidate gene analysis and genomewide scanning. These molecular markers, together with clinical data and findings from proteomics, metabolomics, pharmacogenetics, and other methods, lead to a consideration of the extent to which personalized approaches can be applied to the treatment of diabetes mellitus. CONTENT: Known genes that cause monogenic subtypes of diabetes are reviewed, and several examples are discussed in which the genotype of an individual with diabetes can direct considerations of preferred choices for glycemic therapy. The extent of characterization of polygenic determinants of type 1 and type 2 diabetes is summarized, and the potential for using this information in personalized management of glycemia and complications in diabetes is discussed. The application and current limitations of proteomic and metabolomic methods in elucidating diabetes heterogeneity is reviewed. SUMMARY: There is established heterogeneity in the determinants of diabetes and the risk of diabetes complications. Understanding the basis of this heterogeneity provides an opportunity for personalizing prevention and treatment strategies according to individual patient clinical and molecular characteristics. There is evidence-based support for benefits from a personalized approach to diabetes care in patients with certain monogenic forms of diabetes. It is anticipated that strategies for individualized treatment decisions in the more common forms of diabetes will emerge with expanding knowledge of polygenic factors and other molecular determinants of disease.
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