Candidate Genes for Type 2 Diabetes

  • William L. LoweJr.
Part of the Endocrine Updates book series (ENDO, volume 10)


The pathogenesis of type 2 diabetes is complex, but is characterized by hyperglycemia secondary to a combination of insulin resistance and pancreatic 0-cell dysfunction that is manifest as inadequate insulin secretion in the face of insulin resistance and hyperglycemia (see Chapters 7 and 8) (1,2). Previous studies have established a clear genetic predisposition for type 2 diabetes (3, 4, 5). The concordance rate among monozygotic twins is 50 to 90% compared to 25 to 35% for dizygotic twins (6). Similarly —30% of offspring of affected individuals develop either type 2 diabetes or impaired glucose tolerance (3, 4, 5). Together, these data are consistent with a significant genetic contribution to the development of type 2 diabetes, but the lack of 100% concordance among monozygotic twins suggests that environmental influences are also important. Moreover, mathematical modeling has suggested that type 2 diabetes is polygenic, i.e., it is inherited in a non-Mendelian fashion and onset of the disease requires the simultaneous presence of a subset of susceptibility genes whose gene products affect insulin production, secretion or sensitivity (3, 4, 5). This has complicated efforts to identify diabetes susceptibility genes for several reasons: (1) the relative contributions of insulin resistance and altered insulin secretion to the pathogenesis of type 2 diabetes probably vary between individuals; (2) because of the above heterogeneity, susceptibility genes likely differ between and within populations; and (3) the effect of any single susceptibility gene on disease risk may be small, making identification of susceptibility genes difficult. Furthermore, environmental factors that still have not been fully defined, but include diet and physical activity, contribute to the development of type 2 diabetes (7, 8, 9). Thus, susceptibility genes for type 2 diabetes may be present in unaffected individuals because they lack a required complement of susceptibility genes or needed environmental factors to induce diabetes.


Insulin Secretion Missense Mutation Insulin Receptor Insulin Gene Amino Acid Polymorphism 
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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • William L. LoweJr.
    • 1
  1. 1.Northwestern University Medical SchoolChicagoUSA

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