Endocrine Abstracts

The study of the genetics of diabetes, in its different forms, has produced a huge amount of data only very recently and new information is becoming available as this text is being written. The question, at this time, is: are they any good to our patients?

As the study of the genetics of a disease progresses, one would expect several clinical applications, the most obvious being improved prediction and diagnosis, as well as tailored treatment of the disease. In diabetes, some of these expectations have been met already and more should be met in the future. This discussion will focus on what is currently available and its clinical relevance.

Monogenic diabetes represents the paradigm of clinical applications of genetic information. Although rare as a whole, certain clinical features should make us suspect this diagnosis, with important implications for the patient. This is especially true for neonatal diabetes and beta-cell defects due to mutations in HNF1A and GCK, where identification may have a huge impact on the choice and effectiveness of treatment. Our main challenge now, as clinicians, is to identify these patients and offer the best treatment available. Non-genetic measurements are being developed to optimise patient selection and genotyping strategy and new whole-genome genotyping methods will soon provide a more efficient diagnosis.

Type 1 diabetes (T1D) is characterised by auto-immune destruction of beta-cells, which leads to the dependence on insulin to survive. Most genes associated with T1D play a relevant role in immune response. HLA, the major gene/region, explains about half of the genetic risk for developing the disease, and high-risk HLA haplotypes are currently being used to select individuals for diabetes prevention trials.

Type 2 diabetes (T2D) is characterised by a combination of beta-cell failure and insulin resistance, often associated with increasing age, inactivity and obesity. The identification of genetic variants influencing disease predisposition have highlighted the importance of beta-cell failure in the pathogenesis of this disease and will probably have an impact on the design of new treatments and preventive measures in the future. The second main potential application of the genetics of T2D, prediction of disease risk for a given individual, is not ready for clinical application yet, though recent studies show promising results.