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.”

References

1. Narayan KM et al., Lifetime risk for diabetes mellitus in the United States. JAMA. 2003 Oct 8;290:1884-90.

2. Pearson, E.R., et al., Variation in TCF7L2 influences therapeutic response to sulfonylureas: a GoDARTs study. Diabetes, 2007. 56(8): p. 2178-82.

3. Pearson ER, D.L., Doney A, , Variation in TCF7L2 influences glycemic response to sulfonylureas. American Diabetes Association 67th Scientific Sessions, 2007.1.

4. Florez, et. al., “TCF7L2 Polymorphisms and Progression to Diabetes in the Diabetes Prevention Program”

(U.S., multiple ethnicities). N Engl J Med 2006; 355:241-250

5. Wang, J., et al., Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion. Diabetologia, 2007; 50(6):1192-1200.

6. Diabetes Prevention Program Research Group. Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. N Engl J Med 2002; 346:393-403

7. Zeggini, Eleftheria et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008 May;40(5):638-45. Epub 2008 Mar 30. PMID: 18372903

8. Voight, Benjamin F et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet. 2010 Jul;42(7):579-89. PMID: 20581827

9. Dupuis, Josee et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010 Feb;42(2):105-16. Epub 2010 Jan 17. PMID: 20081858

10. Bi, Mark et al. Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease: the ARIC Study. PLoS One. 2010 Jul 22;5(7):e11690. PMID: 20661421

11. Onuma, Hiroshi et al. The GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population. J Hum Genet. 2010 Sep;55(9):600-4. Epub 2010 Jun 24. PMID: 20574426

12. Qi, Q et al. Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population. Diabetologia. 2009 May;52(5):834-43. Epub 2009 Feb 25. PMID: 19241058

13. Sparso, T et al. The GCKR rs780094 polymorphism is associated with elevated fasting serum triacylglycerol, reduced fasting and OGTT-related insulinaemia, and reduced risk of type 2 diabetes. Diabetologia. 2008 Jan;51(1):70-5. Epub 2007 Nov 16. PMID: 18008060

14. Saxena, Richa et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010 Feb;42(2):142-8. Epub 2010 Jan 17. PMID: 20081857

15. Weedon, M N. The importance of TCF7L2. Diabet Med. 2007 Oct;24(10):1062-6. PMID: 17888129

16. Saxena, Richa et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science. 2007 Jun 1;316(5829):1331-6. Epub 2007 Apr 26. PMID: 17463246

17. Zeggini, Eleftheria et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007 Jun 1;316(5829):1336-41. Epub 2007 Apr 26. PMID: 17463249

18. Scott, Laura J et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007 Jun 1;316(5829):1341-5. Epub 2007 Apr 26. PMID: 17463248

19. Omori, Shintaro et al. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes. 2008 Mar;57(3):791-5. Epub 2007 Dec 27. PMID: 18162508

20. Ng, Maggie C Y et al. Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes. 2008 Aug;57(8):2226-33. Epub 2008 May 9. PMID: 18469204

21. Chauhan, Ganesh et al. Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians. Diabetes. 2010 Aug;59(8):2068-74. Epub 2010 Apr 27. PMID: 20424228

22. Han, Xueyao et al. Implication of genetic variants near SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, FTO, TCF2, KCNQ1, and WFS1 in type 2 diabetes in a Chinese population. BMC Med Genet. 2010 May 28;11:81. PMID: 20509872

23. Tabara, Yasuharu et al. Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening. Diabetes. 2009 Feb;58(2):493-8. Epub 2008 Nov 25. PMID: 19033397

24. Wu, Ying et al. Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes. 2008 Oct;57(10):2834-42. Epub 2008 Jul 15. PMID: 18633108

25. Horikawa, Yukio et al. Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. J Clin Endocrinol Metab. 2008 Aug;93(8):3136-41. Epub 2008 May 13. PMID: 18477659

26. Huang, Qiong et al. IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population. Acta Pharmacol Sin. 2010 Jun;31(6):709-17. PMID: 20523342

27. Ruchat, Stephanie-May et al. Combining genetic markers and clinical risk factors improves the risk assessment of impaired glucose metabolism. Ann Med. 2010 Apr;42(3):196-206. PMID: 20384434

28. van Hoek, Mandy et al. Genetic variant in the IGF2BP2 gene may interact with fetal malnutrition to affect glucose metabolism. Diabetes. 2009 Jun;58(6):1440-4. Epub 2009 Mar 3. PMID: 19258437

29. Altshuler, D et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000 Sep;26(1):76-80. PMID: 10973253

30. Sanghera, Dharambir Kaur et al. PPARG and ADIPOQ gene polymorphisms increase type 2 diabetes mellitus risk in Asian Indian Sikhs: Pro12Ala still remains as the strongest predictor. Metabolism. 2010 Apr;59(4):492-501. Epub 2009 Oct 20. PMID: 19846176

31. Kilpelainen, Tuomas O et al. SNPs in PPARG associate with type 2 diabetes and interact with physical activity. Med Sci Sports Exerc. 2008 Jan;40(1):25-33. PMID: 18091023

32. Sandhu, Manjinder S et al. Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet. 2007 Aug;39(8):951-3. Epub 2007 Jul 1. PMID: 17603484

33. Fawcett, Katherine A et al. Detailed investigation of the role of common and low-frequency WFS1 variants in type 2 diabetes risk. Diabetes. 2010 Mar;59(3):741-6. Epub 2009 Dec 22. PMID: 20028947

34. Steinthorsdottir, Valgerdur et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet. 2007 Jun;39(6):770-5. Epub 2007 Apr 26. PMID: 17460697

35. Cauchi, Stephane et al. Post genome-wide association studies of novel genes associated with type 2 diabetes show gene-gene interaction and high predictive value. PLoS One. 2008 May 7;3(5):e2031. PMID: 18461161

36. Horikoshi, M et al. Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population. Diabetologia. 2007 Dec;50(12):2461-6. Epub 2007 Oct 10. PMID: 17928989

37. Chidambaram M et al. Replication of recently described type 2 diabetes gene variants in a South Indian population. Metabolism. 2010 Jun 24. PMID: 20580033

38. Dehwah, M A S et al. CDKAL1 and type 2 diabetes: a global meta-analysis. Genet Mol Res. 2010 Jun 15;9(2):1109-20. PMID: 20568056

39. An, Ping et al. Epistatic interactions of CDKN2B-TCF7L2 for risk of type 2 diabetes and of CDKN2B-JAZF1 for triglyceride/high-density lipoprotein ratio longitudinal change: evidence from the Framingham Heart Study. BMC Proc. 2009 Dec 15;3 Suppl 7:S71. PMID: 20018066

40. Omori, S et al. Replication study for the association of new meta-analysis-derived risk loci with susceptibility to type 2 diabetes in 6,244 Japanese individuals. Diabetologia. 2009 Aug;52(8):1554-60. Epub 2009 May 20. PMID: 19455301

41. Sladek, Robert et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007 Feb 22;445(7130):881-5. Epub 2007 Feb 11. PMID: 17293876

42. Lin, Ying et al. Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population. BMC Med Genet. 2010 Jun 15;11:97. PMID: 20550665

43. Lee, Yong-Ho et al. Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet. 2008;53(11-12):991-8. Epub 2008 Nov 11. PMID: 18991055

44. Jing YL et al. SLC30A8 polymorphism and type 2 diabetes risk: Evidence from 27 study groups. Nutr Metab Cardiovasc Dis. 2010 Feb 16. PMID: 20167458

45. Cauchi, Stephane et al. Meta-analysis and functional effects of the SLC30A8 rs13266634 polymorphism on isolated human pancreatic islets. Mol Genet Metab. 2010 May;100(1):77-82. Epub 2010 Jan 15. PMID: 20138556

46. Xiang, Jie et al. Zinc transporter-8 gene (SLC30A8) is associated with type 2 diabetes in Chinese. J Clin Endocrinol Metab. 2008 Oct;93(10):4107-12. Epub 2008 Jul 15. PMID: 18628523

47. Grarup, Niels et al. Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies. Diabetes. 2007 Dec;56(12):3105-11. Epub 2007 Sep 7. PMID: 17827400

48. Wen, Jie et al. Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort. PLoS One. 2010 Feb 10;5(2):e9153. PMID: 20161779

49. Gori, Francesca et al. Common genetic variants on chromosome 9p21 are associated with myocardial infarction and type 2 diabetes in an Italian population. BMC Med Genet. 2010 Apr 19;11:60. PMID: 20403154

50. Hertel, J K et al. Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study). Diabetologia. 2008 Jun;51(6):971-7. Epub 2008 Apr 24. PMID: 18437351

51. Duesing, K et al. Strong association of common variants in the CDKN2A/CDKN2B region with type 2 diabetes in French Europids. Diabetologia. 2008 May;51(5):821-6. Epub 2008 Mar 27. PMID: 18368387

52. Grant, Struan F A et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006 Mar;38(3):320-3. Epub 2006 Jan 15. PMID: 16415884

53. Helgason, Agnar et al. Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nat Genet. 2007 Feb;39(2):218-25. Epub 2007 Jan 7. PMID: 17206141

54. Horikoshi, M et al. A genetic variation of the transcription factor 7-like 2 gene is associated with risk of type 2 diabetes in the Japanese population. Diabetologia. 2007 Apr;50(4):747-51. Epub 2007 Jan 24. PMID: 17245589

55. Florez, Jose C. The new type 2 diabetes gene TCF7L2. Curr Opin Clin Nutr Metab Care. 2007 Jul;10(4):391-6. PMID: 17563454

56. Sale, Michele M et al. Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy. Diabetes. 2007 Oct;56(10):2638-42. Epub 2007 Jun 29. PMID: 17601994

57. Parra, E J et al. Association of TCF7L2 polymorphisms with type 2 diabetes in Mexico City. Clin Genet. 2007 Apr;71(4):359-66. PMID: 17470138

58. Miyake, Kazuaki et al. Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects. J Hum Genet. 2008;53(2):174-80. Epub 2007 Dec 21. PMID: 18097733

59. Gupta, Vipin et al. A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India. Ann Hum Genet. 2010 Jul;74(4):361-8. PMID: 20597906

60. Furukawa, Yasushi et al. Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population. J Clin Endocrinol Metab. 2008 Jan;93(1):310-4. Epub 2007 Oct 30. PMID: 17971426

61. Wang, Fang et al. Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population. Chin Med J (Engl). 2009 Oct 20;122(20):2477-82. PMID: 20079163

62. Yasuda, Kazuki et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet. 2008 Sep;40(9):1092-7. PMID: 18711367

63. Zhou, Jian-Bo et al. Variants in KCNQ1, AP3S1, MAN2A1, and ALDH7A1 and the risk of type 2 diabetes in the Chinese Northern Han population: a case-control study and meta-analysis. Med Sci Monit. 2010 Jun;16(6):BR179-83. PMID: 20512086

64. Shin, Hyoung Doo et al. Association of KCNQ1 polymorphisms with the gestational diabetes mellitus in Korean women. J Clin Endocrinol Metab. 2010 Jan;95(1):445-9. Epub 2009 Oct 22. PMID: 19850681

65. Qi, Qibin et al. Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Hum Mol Genet. 2009 Sep 15;18(18):3508-15. Epub 2009 Jun 25. PMID: 19556355

66. Liu, Y et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes in the population of mainland China. Diabetologia. 2009 Jul;52(7):1315-21. Epub 2009 May 12. PMID: 19448982

67. Hu, C et al. Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population. Diabetologia. 2009 Jul;52(7):1322-5. Epub 2009 Mar 24. PMID: 19308350

68. Tan, Jonathan T et al. Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore. Diabetes. 2009 Jun;58(6):1445-9. Epub 2009 Feb 27. PMID: 19252135

69. Prokopenko, Inga et al. Variants in MTNR1B influence fasting glucose levels. Nat Genet. 2009 Jan;41(1):77-81. Epub 2008 Dec 7. PMID: 19060907

70. Ronn, T et al. A common variant in MTNR1B, encoding melatonin receptor 1B, is associated with type 2 diabetes and fasting plasma glucose in Han Chinese individuals. Diabetologia. 2009 May;52(5):830-3. Epub 2009 Feb 25. PMID: 19241057

71. Kan, M Y et al. Two susceptible diabetogenic variants near/in MTNR1B are associated with fasting plasma glucose in a Han Chinese cohort. Diabet Med. 2010 May;27(5):598-602. PMID: 20536959

72. Sparso, Thomas et al. G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release: studies involving 19,605 Europeans. Diabetes. 2009 Jun;58(6):1450-6. Epub 2009 Mar 26. PMID: 19324940

73. Gudmundsson, Julius et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet. 2007 Aug;39(8):977-83. Epub 2007 Jul 1. PMID: 17603485

74. Wang, Congrong et al. Common variants of hepatocyte nuclear factor 1beta are associated with type 2 diabetes in a Chinese population. Diabetes. 2009 Apr;58(4):1023-7. Epub 2009 Jan 23. PMID: 19168595

75. Stevens, Victoria L et al. HNF1B and JAZF1 genes, diabetes, and prostate cancer risk. Prostate. 2010 May 1;70(6):601-7. PMID: 19998368

76. Tuomilehto, J., et al., Prevention of type 2 diabetes mellitus by changes in lifestyle among patients with impaired glucose tolerance. N Engl J Med, 2001. 344: 1343-50.

77. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care, 2002. 25: 2165-71.

78. Crandall, J., et al., The influence of age on the effects of lifestyle modification and metformin in prevention of diabetes. J Gerontol A Biol Sci Med Sci, 2006. 61(10): p. 1075-81.