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Using Genotypes to Individualize Diabetes Treatment

Apr 14, 2010

A panel of diabetes experts is encouraging efforts to increase understanding of the heterogeneity of Type 2 diabetes to achieve individualized treatments and improve treatment responses….

A new consensus report outlines current knowledge of the heterogeneity of Type 2 diabetes as well as areas that need to be further explored, based on phenotypes and genotypes. Experts also provide recommendations to bring health care professionals closer to the goal of individualizing therapy.


“Although Type 2 diabetes is considered to be heterogeneous with regard to its clinical presentation, features and pathogenesis, including pathophysiology and underlying genetic risk factors, patients are generally treated similarly, independent of the underlying differences that might affect therapeutic response. Further insight into the heterogeneity of the Type 2 diabetes patient population might help explain and, ultimately, reduce the high rate of treatment failure,” the experts wrote.

Current knowledge is based on head-to-head comparison studies, crude or deficient baseline phenotyping and genotyping, and inadequate subset analyses, rendering the current models of treatment for Type 2 diabetes nonspecific, according to the report. To date, understanding “has not yet reached a point at which it can guide individualized therapy decisions,” the experts wrote. However, progress is apparent.

“Recent advances in genetics, such as the identification of the responsible genes for several forms of Maturity Onset Diabetes of the Young (MODY), now referred to as monogenic diabetes, have established precedents linking specific drug therapies to defined subtypes of diabetes patients,” Robert J. Smith, MD, of Brown University, Providence, RI, said in a press release. “As more genetic factors related to Type 2 diabetes are identified and as our understanding of the progression of the disease evolves, we can expect to gain precision in identifying the best drug choices for individual patients and to more effectively halt the progression of diabetes.”

An international working group of experts in epidemiology, pathophysiology, genetics, clinical trials and clinical care participated in an April 2009 conference during which they reviewed the current knowledge of phenotypic and genotypic heterogeneity in Type 2 diabetes. The conference was sponsored by The Endocrine Society and American Diabetes Association. Then, a writing group prepared recommendations for individualized treatment of Type 2 diabetes, such as:

  • Extend analysis of existing data and data sources: data and sources that could be potentially valuable in individualizing therapy have been largely underutilized. Pooled analyses or meta-analyses of such data may provide insight into the relative effectiveness of specific interventions in subgroups of patients with Type 2 diabetes.
  • Expand existing or develop new data registries: All new and existing diabetes registries should systematically collect data to address phenotypic and genetic heterogeneity measures, including material for future biomarker and genetic analysis and hypotheses generated by examining existing data.
  • Develop new clinical trials: future randomized studies of diabetes therapies should collect phenotypic information relevant to response to therapy.
  • Develop new technologies: targeting therapy toward more appropriate subgroups of patients will require increasingly accurate and efficient methods to measure markers for diabetes heterogeneity and heterogeneous response to treatment.
  • Expand basic research: basic research is needed to explore numerous fundamental issues that underlie the heterogeneous response to diabetes therapies.

“The recommendations in this consensus statement highlight the need for the research community and industry to each play their part in improving our ability to individualize therapy so that patients can get the most accurate and appropriate treatment,” Robert A. Vigersky, MD, president of The Endocrine Society, said in a press release.

Smith RJ. J Clin Endocrinol Metab. 2010;95:1566-1574.