deCODE T2™
Detects risk of type 2 diabetes independent of family history and obesity. Identifies prediabetics at high near-term risk of conversion to T2D. Predicts responsiveness to major classes of diabetes drugs.
Screening and prevention
How deCODE T2™ can help.
Identifies those at increased risk of T2D.
High-risk individuals may benefit most from aggressive lifestyle modification efforts and/or drug treatment.
Provides more complete risk information.
The genetic risk detected by the deCODE T2™ test is largely independent of any other risk factors that a patient may have. The risk conferred by these other factors can simply be multiplied by the test results to yield a comprehensive risk assessment.
Identifies prediabetics who are at high risk of developing full-blown T2D.
With deCODE T2™ physicians can identify those prediabetic patients who are at a 50-70% likelihood of becoming diabetic within the next 3 to 4 years compared to the baseline risk of 30% in overweight or obese prediabetics.
Enables personalized drug treatment and prevention.
Large-scale, published studies have shown that patients who have the high-risk TCF7L2 genotype detected by the test are likely to respond better to metformin than sulfonylureas. The 2010 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.”
Highly significant, well validated risk factors
deCODE T2™ is a reference laboratory test that measures DNA markers which have been widely replicated as risk factors for T2D. In the case of patients of European descent the test looks at 21 markers(7-75) (main references: 1,3,8,9,26,28,56,63,67 others give further support); for those of East Asian descent, 9 markers (8,15-28,34-38,41-68,73-75) (main references: 19,34,58,62,74 others give further support) and for those of African descent, 2 markers(8,15,20,26,42,48-59,73-75) (main references: 56,73). deCODE T2™ tests only for markers whose association with risk of T2D has been confirmed in multiple studies of multiple cohorts and in meta analysis studies of many thousands of patients and controls. This validation criteria must be fulfilled for each different continental ancestry. Not all markers have yet been validated in all continental ancestries, which partly explains why at the present time there are a different number of validated markers for people of different ethnicities.
deCODE T2™ includes the deCODE TCF7L2 marker, SNP rs7903146, located within the transcription factor 7-like 2 (TCF7L2) gene, the strongest genetic risk factor yet known for T2D(15). The deCODE TCF7L2 marker correlates with lower insulin secretion in response to oral glucose. deCODE T2™ combines the risk due to TCF7L2 with the 20 other widely validated genetic risk markers. The deCODE T2 genetic profile derived for each patient is therefore based on a reference set of tens of thousands of patients and controls in over 40 populations from several continents(7-75).
Among the deCODE T2™ risk variants that multiply with the TCF7L2 risk are markers in or near the CDKAL1, CDKN2A, and PPARG genes. All have been shown to significantly contribute to the risk of T2D, but contributing less risk than TCF7L2. Of these, the CDKAL1 variant was found to correlate with lower insulin response to glucose which is consistent with its expression in pancreatic beta cells.(34).
No studies have demonstrated any overlap between the risk conferred by these markers with commonly recognized risk factors such as obesity, family history or even prediabetes. This makes the deCODE T2™ test useful for all of these categories of patients, complementing risk due to family history, body weight or fasting blood sugar measurements. This allows us to multiply the risk of individual markers together to obtain a overall genetic risk; and this can in turn be used to multiply the risk conferred by, for example, obesity and family history.
deCODE T2™ and prediabetes
According to two prospective clinical trials, the Diabetes Prevention Program (DPP) and the Diabetes Prevention Study (DPS) overweight or obese patients of European descent who already have impaired fasting glucose and impaired glucose tolerance (a condition called prediabetes) have a 30 to 35% general risk for progressing to type 2 diabetes over a 3 to 4 year period(76,77).
The deCODE TCF7L2 marker is one of the strongest risk factors known for predicting increased likelihood of conversion from prediabetes to T2D. The 10% of prediabetics of European descent with two copies of the risk variant at TCF7L2 were found to be at 1.8 to 2.0-fold the population average risk of converting to diabetes. This translated into a 50-70% absolute risk of converting to T2D within 3-4 years if no effective intervention was made by lifestyle management or metformin treatment(4,5).
Genotyping of the DPP and DPS study cohorts(4,5) showed that for people of European descent, lifestyle intervention or metformin therapy are equally effective if not more effective for patients with increased genetic risk of conversion. Lifestyle intervention and metformin use decreased the conversion rate to T2D in patients of European descent 58% and 31%, respectively. Metformin is even more effective in those of these patients younger than 45 (43% decrease in conversion rate)(78).
Not all prediabetics progress to diabetes and many develop normal fasting glucose spontaneously without intervention. The TCF7L2 marker included in the deCODE T2™ test is the strongest known risk factor for conversion in overweight or obese prediabetics. The test may therefore help to target patients at highest risk for more aggressive prevention strategies which can compensate for most if not all of the genetic risk. Metformin is also recommended in the 2010 ADA (American Diabetes Association) guidelines as an option for obese prediabetics younger than 60 who have other risk factors and who fail to lose weight.
deCODE T2™ and drug response
Studies in two populations of European descent show that T2D patients who are homozygous TT at TCF7L2 have much lower response to sulfonylureas compared to those who are not TT homozygous. Among TT homozygotes only 36% meet the HbA1C target of 7% or lower, versus 62% of those who were not TT homozygous(2,3). Metformin response, on the other hand, did not depend on the TCF7L2 genotype, meaning that patients who have the TT TCF7L2 genotype were likely to respond better to metformin than sulfonylureas.
The deCODE T2™ test is done using the llumina I-select BeadChip method. This highly reliable method has greater than 99.9% accuracy and is based on a proprietary Illumina technology using DNA amplification, hybridization and fluorescent detection.
This content was last reviewed on March 16, 2011.