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Genetic susceptibility to type 2 diabetes and implications for therapy
1Center for Human Genetic Research and Diabetes Research Center (Diabetes Unit), Massachusetts General Hospital, Boston, Massachusetts 02114, USA. jcflorez@partners.org
Journal of Diabetes Science and Technology
|February 11, 2010
Summary
Genetic discoveries for type 2 diabetes risk have surged, yet explain little inheritable risk. Current genetic markers offer minimal improvement for individual risk prediction beyond clinical factors.
Area of Science:
- Genetics
- Endocrinology
- Preventive Medicine
Background:
- Numerous genetic determinants for type 2 diabetes (T2D) have been identified since 2000.
- These discoveries raised expectations for personalized medicine in T2D prediction and treatment.
- However, identified genetic loci explain only a small portion of the disease's heritability.
Purpose of the Study:
- To evaluate the clinical utility of current genetic risk factors for type 2 diabetes.
- To assess the impact of genetic discoveries on risk prediction, stratification, and therapeutic decisions.
Main Methods:
- Review of findings from large-scale cohort studies identifying genetic associations with type 2 diabetes.
- Analysis of the predictive power of genetic markers compared to established clinical variables.
- Consideration of the potential for genetic information in targeted surveillance, prevention, and treatment strategies.
Main Results:
- Identified genetic loci are largely associative, often indicating genomic regions rather than causal variants.
- Current genetic markers do not significantly enhance individual type 2 diabetes risk prediction over clinical variables, except possibly in younger individuals.
- The clinical utility of genetic risk information for guiding surveillance, prevention, or therapy requires further rigorous testing.
Conclusions:
- Despite an increase in identified genetic risk factors, their contribution to overall type 2 diabetes heritability and clinical prediction remains limited.
- Genetic information may aid in identifying subgroups for targeted interventions, but its cost-effectiveness and impact on patient outcomes need evaluation.
- Prospective clinical trials are essential to determine if genetic data can effectively guide therapeutic decisions in type 2 diabetes management.
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