Individualizing therapies in type 2 diabetes mellitus based on patient characteristics: what we know and what we need to know.

Abstract

Type 2 diabetes is heterogeneous in its clinical features, pathogenesis, and predisposing or causal genetic factors. This report examines what is known and what needs to be learned about the potential to individualize glycemic therapies in type 2 diabetes, based on phenotypes and genotypes. A 29-member international working group with expertise in diabetes epidemiology, physiology, genetics, clinical trials, and clinical care participated in formal presentations and discussions at a conference on April 16-17, 2009. A writing group subsequently prepared this summary and recommendations. The conference was coendorsed by The Endocrine Society and the American Diabetes Association and was supported by an unrestricted educational grant from Novo Nordisk. Participants reviewed and discussed published literature, plus their own unpublished data. The summary and recommendations were supported unanimously by the writing group as representing the majority or unanimous opinions of the working group. Recent advances in genetics, such as the identification of Kir6.2 mutations and the responsible genes for several forms of maturity onset diabetes of the young (MODY), have established precedents linking specifically effective therapies to defined diabetes subtypes. The recent increase in identified polygenic factors related to type 2 diabetes and our understanding of the pathogenesis of diabetes provide potential opportunities to individualize therapy. To further this process, we recommend expanded analysis of existing data sources and the development of new basic and clinical research studies, including a greater focus on identifying type 2 diabetes subtypes, their response to different therapies, and quantitation of cost-effectiveness.