Treatments in Endocrinology

, Volume 3, Issue 4, pp 257–267 | Cite as

Genetic Basis of Type 2 Diabetes Mellitus Implications for Therapy

  • Johanna K. WolfordEmail author
  • Barbora Vozarova de Courten
Review Article


Type 2 diabetes mellitus represents a multifactorial, heterogeneous group of disorders, which result from defects in insulin secretion, insulin action, or both. The prevalence of type 2 diabetes has increased dramatically worldwide over the past several decades, a trend that has been heavily influenced by the relatively recent changes in diet and physical activity levels. There is also strong evidence supporting a genetic component to type 2 diabetes susceptibility and several genes underlying monogenic forms of diabetes have already been identified. However, common type 2 diabetes is likely to result from the contribution of many genes interacting with different environmental factors to produce wide variation in the clinical course of the disease. Not surprisingly, the etiologic complexity underlying type 2 diabetes has made identification of the contributing genes difficult.

Current therapies in the management of type 2 diabetes include lifestyle intervention through diet modification and exercise, and oral or injected hypoglycemic agents; however, not all individuals with type 2 diabetes respond in the same way to these treatments. Because of variability in the clinical course of the disease and in the responsiveness to pharmacologic therapies, identification and characterization of the genetic variants underlying type 2 diabetes susceptibility will be important in the development of individualized treatment. Findings from linkage analyses, candidate gene studies, and animal models will be valuable in the identification of novel pathways involved in the regulation of glucose homeostasis, and will augment our understanding of the gene-gene and gene-environment interactions, which impact on type 2 diabetes etiology and pathogenesis. In addition, identification of genetic variants that determine differences in antidiabetic drug responsiveness will be useful in assessing a first-line pharmacologie therapy for diabetic patients.


Insulin Secretion Troglitazone Diabetes Susceptibility Monogenic Form Pro12Ala Polymorphism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This review was written during National Institute of Health fellowships for both authors (no funding source). The authors have no conflicts of interest that are directly relevant to the content of this review.


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Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Johanna K. Wolford
    • 1
    Email author
  • Barbora Vozarova de Courten
    • 2
  1. 1.Research Program, Genetic Basis of Human Disease DivisionTranslational Genomics Research InstitutePhoenixUSA
  2. 2.Department of Clinical PhysiologyBaker Heart InstituteMelbourneAustralia

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