What is deCODE T2™?
deCODE T2™ is a reference laboratory test that measures four DNA markers which are widely replicated genetic risk factors for type 2 diabetes (T2D). It defines genetic risk for T2D, independent of family history and obesity, that ranges from 0.6 to 2.2 fold the general population risk.
deCODE T2™, like other DNA based tests for common disease, is a risk assessment test as it measures DNA risk markers that are not determinative but associate with the disease in certain proportion of the patients. Patients with higher genetic risk are not destined to develop T2D and conversely, patients with lower genetic risk are not immune from diabetes. There are other risk factors not measured by the deCODE T2™ test. DNA markers for common disease simply are risk markers comparable to biomarkers such as LDL-cholesterol and PSA that predict risk for cardiovascular diseases and prostate cancer respectively.
By knowing and understanding genetic risk, it may be possible to take actions that reduce or minimize the likelihood of an individual developing diabetes. In addition to predicting or recalculating the remaining lifetime risk of developing T2D, the deCODE T2™ results can predict the likelihood of prediabetes converting to full blown T2D and which patients may benefit the most from preventive management.
deCODE T2™ offers new means to help physicians decide which prediabetic patients are at 50 to 70% absolute risk for converting T2D within 3 to 4 years compared to the baseline risk of 30% in overweight or obese prediabetics. These high-risk patients therefore may benefit the most from more aggressive management either through lifestyle modification or drug treatment. The 2008 ADA recommendations on management of prediabetics state: “In addition to lifestyle counseling, metformin may be considered in those who are at very high risk (combined IFG and IGT plus other risk factors) and who are obese and under 60 years of age.” deCODE T2™ is one of the strongest risk factors for conversion.
Prediabetic patients with higher genetic risk for T2D, may be more compliant with weight loss recommendations by their physicians. For patients who fail to lose significant weight within 6 months, high risk prediabetics may benefit the most from nutritional advice and more aggressive lifestyle intervention. Finally, high risk prediabetics who still fail to respond to lifestyle intervention, would be prime candidates for metformin as suggested by the latest ADA recommendations.
Regarding patients who already have T2D studies in two populations show that those who have two copies of the risk variant at TCF7L2, one of the genes included in deCODE T2™, have much lower response to sulfonylurea, with only 36% meeting HbA1C target of 7% or lower, versus 62% of those who do not have two copies (Pearson, E.R., et al., Diabetes, 2007. 56(8): p. 2178-82 and American Diabetes Association 67th Scientific Sessions, 2007). Metformin response on the other hand did not depend on the TCF7L2 genotype, meaning that patients who have the high-risk TCF7L2 genotype are likely to respond better to metformin than sulfonylureas.
The DNA markers included in deCODE T2™ are located in or near the following genes: TCF7L2, PPARG, CDKAL1, and CDKN2A and have each been widely replicated in 10 to 40 independent populations. TCF7L2 is the strongest genetic risk factor discovered so far for Type 2 diabetes and has been validated in over 40 populations spanning several ethnicities. The TCF7L2 marker correlates with lower insulin secretion in response to oral glucose. deCODE T2™ combines the risk due to TCF7L2 with the three other widely validated genes. The T2 genetic profile derived for each patient is based on a reference set of tens of thousands of patients and controls. This genetic profile defines risk ranges from 0.6 to 2.2 compared to the risk in the general population. About 40 % of the population has a genotype combination of the tested markers that have an increased relative risk (>1) over the general population, about 8% of the population have 1.5 to 2.2 relative risk, about 3% of the population have genotype combinations that confer a 1.8 to 2.2 fold relative risk.
Further reading: The deCODE T2™ gene markers
The deCODE T2™ genetic risk profile is independent of other risk factors for type 2 diabetes such as family history, obesity, prediabetes, and ethnicity. The genetic risk can be multiplied by the other risk factors not measured by this test to derive a composite risk relative to that in the general population. Therefore, this test is useful for patients with or without family history of T2D.
The deCODE T2™ test report includes the risk of T2D relative to the general population and provides a lookup table (see below) based on epidemiologic studies to calculate the remaining lifetime risk of T2D based on the current age of the patient. (see a sample deCODE T2™ result report).