Frequently Asked Questions

What is deCODE T2™?
deCODE T2™ is a reference laboratory DNA test for assessing an inherited risk factors for T2D.
The test detects versions of four SNPs (single nucleotide polymorphism), one letter variations in the sequence of the genome in or near genes that have been linked to increased risk of T2D. The variants included in deCODE T2™ are located in or near the following genes: TCF7L2, PPARG, CDKAL1, and CDKN2A..

What is this test based on?
The test is based on deCODE genetics and others discoveries of genetic variants that carry with them increased risk for the development of T2D. Multiple research studies by independent researchers have validated the results in tens of thousands of people from populations around the globe.

What is a genetic risk factor for a common disease, and why is understanding inherited risk important?
A genetic risk factor for a common disease is a specific version of a marker in the sequence of the genome that causes or correlates with an increased likelihood of developing a given disease. Common diseases such as T2D occur at the interface of genes and the environment, as both genetic as well as lifestyle and other health risk factors play important roles in the disease process. As a result, it is important to understand what carrying an inherited risk variant for a common disease means, and how that information can be used to support implementation of strategies that can reduce the likelihood of an individual ever developing the disease.

In basic terms, carrying a genetic risk variant for a common disease does not mean that one will necessarily develop the disease; and not having a certain risk variant does not eliminate the possibility of getting the disease. Rather, for the common diseases, genetic risk variants impact the likelihood that one may develop the disease. Understanding this inherited risk is empowering information* with potentially important clinical utility. This is particularly true in a disease like T2D, in which specific lifestyle and health factors are known to play such an important part. By understanding inherited risk, it may be possible to take action through lifestyle modification or by taking certain medications to reduce or minimize the likelihood of developing T2D. This is similar to the approach that is taken to address other risk factors for common diseases, such as high cholesterol, which is commonly treated using statin drugs to reduce the risk of heart disease.

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Should test results be interpreted differently for different ethnic groups?
Only the TCF7L2 associated risks have been validated in multiple races and show similar effect in whites, Africans, Hispanics, and Asian populations. CDKAL1 and CDKN2 seem to have equivalent effects in whites (European descent) and Asians.  PPARG has so far only been validated in whites.
Both deCODE’s studies and many studies of independent research groups have shown that the association of the TCF7L2 gene variant and the likelihood of developing diabetes is quite similar across a wide variety of ethnic groups. However, the average frequency of carrying two copies, a positive result for the test, appears to vary according to ethnicity. For instance, approximately 8-9% of general populations of European or African ancestry studied carry two copies, (Helgason et al, Nat Genet 2007; 39:218-225), compared to only 1% of Japanese studied (Horikoshi et al, Diabetologia 2007; 50:747-751). As a consequence ethnicity has an effect on the likelihood of testing positive for carrying two copies of the variant, but no significant impact on the magnitude of risk conferred by the variant.

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Why is understanding genetic risk important for T2D?
The increasing prevalence of T2D is believed to be due in large measure to well known, modifiable lifestyle and health factors, including obesity and to more sedentary lifestyles in general. Yet while obesity, lack of exercise and high-calorie diet are all major known risk factors, it has long been recognized that certain individuals are more susceptible to developing T2D than others, even after accounting for shared lifestyle and health factors. This differential is the hallmark of the impact of genetic risk factors. One of the risk variants included in deCODE T2™, the TCF7L2 gene variant, discovered by deCODE in 2005, is the first widely-replicated, common variant ever found to associate with substantial increased risk of T2D as a public health problem.

Despite measuring four widely confirmed genetic risk variants, deCODE T2™ does not measure other risk factors for T2D such as obesity, prediabetes, age or family history, gestational diabetes or ethnicity (such as African-Americans, Pacific Islanders, American-Indians, and Hispanics) each of which can be multiplied by the genetic risk identified by the test. Furthermore, the deCODE T2™ test does not measure all possible gene variants contributing to T2D, many of which have not yet been discovered.

As a physician, you likely have many patients who need to lose weight, get more exercise and improve their diet. As you know, many of these patients are at increased risk of developing T2D. You probably also have patients who are prediabetic, with fasting plasma glucose levels of between 100 and 125 mg/dL, who are at even higher risk. You know that your efforts to get your patients to change their lifestyle and address known risk factors for T2D are not always successful. But additional information on which of your patients might be at highest risk could provide you and your patients with added incentive to implement and stick to lifestyle modification regimes that can reduce the risk of T2D, possibly including certain existing medications aimed at slowing the progression from prediabetes to T2D.

deCODE T2™ is a risk prediction test, meaning that patients at higher risk, based on their genetic profile, are not destined to develop T2D and patients with relatively lower genetic risk are not immune from T2D.   These risks need to put in the context of other clinical risk factors and vigorous attention to management of modifiable risk factors remains important.

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Who might benefit from having this test and why?
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.

According to two prospective clinical trials, the Diabetes Prevention Program (DPP) and the Diabetes Prevention Study (DPS) (Tuomilehto, J., et al., N Engl J Med, 2001. 344: 1343-50.The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care, 2002. 25: 2165-71), overweight or obese patients 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 TCF7L2 is one of the strongest risk factors known for conversion. For the 10% of prediabetic patients with two copies of the risk variants at TCF7L2 there was a 1.8 to 2.0 fold risk of converting to diabetes resulting in 50 to 70% absolute risk of converting to T2D within 3-4 years if no intervention was made by lifestyle management or metformin treatment (Florez, J.C., et al., N Engl J Med, 2006. 355(3): p. 241-50. Wang, J., et al., Diabetologia, 2007; 50(6):1192-1200). Genotyping of the DPP and DPS study cohorts showed that lifestyle intervention or metformin therapy are equally effective if not more effective for patients with increased genetic risk of conversion. Lifestyle intervention or metformin use decreased conversion rate to type 2 diabetes by 58% and 31%, respectively.   Metformin is even more effective in patients younger than 45 (43% decreased rate) (Crandall, J., et al., J Gerontol A Biol Sci Med Sci, 2006. 61(10): p. 1075-81). Moreover, deCODEs work and analysis of data from this clinical trial suggest that this variant is associated with reduced insulin secretion, and not with inhibited uptake or absorption of insulin. Not all prediabetics progress to diabetes and many develop normal fasting glucose spontaneously without intervention.  Therefore, deCODE T2™ may help target patients at highest risk for more aggressive prevention strategies which may compensate for most if not all of the genetic risk.  Metformin is also recommended in the 2008 ADA guidelines as an option for obese prediabetics younger than 60 who have other risk factors and who fail to lose weight (Standards of medical care in diabetes--2008. Diabetes Care, 2008. 31 Suppl 1: S12-54). TCF7L2 is the strongest known risk factor for conversion in overweight or obese prediabetics. 

Studies in two populations show that T2D patients who are homozygous TT at TCF7L2 have much lower response to sulfonylurea compared to those who are not TT homozygous, with only 36% meeting HbA1C target of 7% or lower, versus 62% of those who were not TT homozygous. (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 TT TCF7L2 genotype are likely to respond better to metformin than sulfonylureas.

The deCODE T2™ test may therefore provide a new means to help physicians to decide which prediabetics they wish to treat more aggressively either through lifestyle change or through drug treatment.

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Is deCODE T2™ an FDA approved test?
No, this is a reference laboratory test that has not been cleared or approved by the FDA. deCODE's laboratory in Iceland that conducts the test is registered as a high-complexity laboratory under the Clinical Laboratory Improvement Amendments (CLIA). Using this test as a means of assessing genetic susceptibility to type 2 diabetes, as presented on this site and elsewhere, is based upon published studies by deCODE and independent researchers demonstrating the correlation of the tested variants with increased risk of developing T2D. This correlation has been demonstrated in numerous independent cohorts of patient across multiple populations and ethnic groups from around the world.

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What scientific publications support the value of this test?
deCODE is widely recognized as a world leader in the discovery of genes contributing to risk of developing common diseases. deCODE has also led the way in publishing its discoveries, a commitment that not only drives ongoing research but also enables independent researchers from around the globe to validate the company’s discoveries.
deCODE T2™ risk results conferred by each variant are separately derived from the published results of thousands of patients and controls genotyped in the same way (Grant, S.F., et al., Nat Genet, 2006. 38(3): p. 320-3. Steinthorsdottir, V., et al. Nat Genet, 2007. 39: p. 770-776. Zeggini, E., et al., Science, 2007;  316(5829):1336-1341. Saxena, R., et al., Science, 2007, 316(5829):1331-1336. Scott, L.J., et al., Science, 2007;316(5829):1341-1345.Altshuler, D., et al. Nat Genet, 2000. 26(1): p. 76-80) and have been replicated in numerous published studies in a wide variety of populations and ethnic groups. A list of key publications can be found on our Scientific Publications page.

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How can I order the test?
You can order deCODE T2™ for your patients by following the simple steps outlined in Ordering deCODE T2™.

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Payment and Reimbursement
Payment can be made by any major credit card by the individual or by the ordering physician or clinic, by including the card details on the test request form. Samples submitted anonymously must be accompanied by a valid credit card number from the respective doctor or affiliated health care institution.

deCODE plans to make the deCODE T2™ as widely available as possible and is working with physicians, patients, and their insurers on reimbursement for deCODE T2™. For more information contact customer service at diagnostics@decode.com, or by phone at 1-877-222-6510

How can I get additional information?
If you would like additional information on deCODE T2™, you can contact deCODE at diagnostics@decode.com, or by phone at 1-877-222-6510 and a deCODE representative will respond promptly to your questions.