#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Personalized therapy for diabetes in retrospect and prospect


Authors: Ivan Tkáč
Authors‘ workplace: IV. interná klinika LF UPJŠ a UN L. Pasteura Košice, Slovenská republika, prednosta prof. MUDr. Ivan Tkáč, PhD.
Published in: Vnitř Lék 2014; 60(9): 797-800
Category:

Overview

In recent years, the term “personalized medicine“ has been increasingly mentioned in relation to the endeavours to tailor the pharmaceutical as well as regimen therapy to the needs and requirements of individual patients. The personalization of antidiabetic treatment has undergone a dramatic advancement in relation to the expansion of knowledge about diabetes. From the empirical it moved forward to the phenotypic level which made it possible to differentiate between individual types of diabetes. The pathogenetic personalization which began to be used within Type 2 diabetes in the 1960s, was based on the assumption that while insulin resistance predominates in some patients, others are mainly affected by insulin secretion deficit. Biostatistics-personalized medicine (evidence based medicine) gathered evidence based on which metformin was included in recommendations on the therapy for Type 2 diabetes as a first-line drug. Although randomized studies during the first decade of the 21st century did not prove superiority of any other treatment modality as an adjunctive therapy used with metformin, they brought with them individualization of the goals of glycemic con­trol. At present, personalization is heading towards the pharmacogenetic level that will enable in the near future individualized therapy in terms of choice of first-, second- and third-line drugs depending on the panel of key gene polymorphisms which characterize sensitivity of an individual to specific antidiabetics. Finally, the “tailor-maded therapy“ should be chosen based on a synthesis of pathogenetic, biostatistic and pharmacogenetic knowledge that will reflect the translation of results of the basic biomedical research into the clinical practice.

Key words:
evidence based medicine – pathogenesis – personalized therapy – pharmacogenetics – type 2 diabetes


Sources

1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977–986.

2. Goldner MG, Knattered GL, Prout TE. Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. III. Clinical implications of UGDP results. JAMA 1971; 218(9): 1400–1410.

3. Knatterud GL, Klimt CR, Osborne RK et al. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. V. Evaluation of phenphormin therapy. Diabetes 1975; 24(Suppl 1): 65–184.

4. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352(9131): 837–853.

5. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998 (9131); 352: 854–865.

6. Inzucchi SE, Bergenstal RM, Buse JB et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2012; 55(6): 1577–1596. Erratum in Diabetologia 2013; 56(3): 680

7. Dormandy JA, Charbonnel B, Eckland. DJA et al (PROactive Investigators). Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005; 366(9493): 1279–1289.

8. Nissen SE, Wolski K. Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 2011; 170(14): 1191–1201.

9. Gerstein HC, Miller ME, Byington RP et al (The Action to Control Cardiovascular Risk in Diabetes Study Group). Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358(24): 2545–2559.

10. Patel A, MacMahon S, Chalmers J et al (The ADVANCE Collaborative Group). Intensive blood glucose and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358(24): 2560–2572.

11. Duckworth W, Abraira C, Moritz T et al. for the VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009; 360(2): 129–139. Erratum inN Engl J Med. 2009; 361(10): 1024–1025.

12. Pearson ER, Flechtner I, Njolstad PR et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med 2006; 355(5): 467–477.

13. Feng Y, Mao G, Ren X et al. Ser1369Ala variant in sulfonylurea receptor gene ABCC8 is associated with antidiabetic efficacy of gliclazide in Chinese type 2 diabetic patients. Diabetes Care 2008; 31(10): 1939–1944.

14. Javorsky M, Klimcakova L, Schroner Z et al. KCNJ11 gene E23K variant and therapeutic response to sulfonylureas. Eur J Intern Med 2012; 23(3): 245–249.

15. Pearson ER, Donelly LA, Kimber C et al. Variation in TCF7L2 influences therapeutic response to sulfonylureas. A GoDARTs Study. Diabetes 2007; 56(8): 2178–2182.

16. Javorský M, Babjaková E, Klimčáková L et al. Association between TCF7L2 genotype and glycemic control in diabetic patients treated with gliclazide. Int J Endocrinol 2013; 2013: 374858. Dostupné z DOI: <http://doi: 10.1155/2013/374858>.

17. Zhou K, Donnelly L, Burch L et al. Loss-of-function CYP2C9 variants improve therapeutic response to sulfonylureas in type 2 diabetes: a Go-DARTS study. Clin Pharmacol Ther 2010; 87(1): 52–56.

18. Zhou K, Bellenguez C, Spencer CC et al. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet 2011; 43(2): 117–120.

19. Becker ML, Visser LE, van Schaik RH et al. Genetic variation in the multidrug and toxin extrusion 1 transporter protein influences the glucose-lowering effect of metformin in patients with diabetes: a preliminary study. Diabetes 2009; 58(3): 745–749.

20. Tkáč I, Klimčáková L, Javorský M et al. Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes. Diabetes Obes Metab 2012; 15(2): 189–191.

21. Kang ES, Park SY, Kim HJ et al. Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma2 gene on rosiglitazone response in type 2 diabetes. Clin Pharm Therap 2005; 78(2): 202–208.

22. ‘t Haart LM, Fritsche A, Nijpels G et al. The CTRB1/2 locus affects diabetes susceptibility and treatment via the incretin pathway. Diabetes 2013; 62(9): 3275–3281.

23. Doria A, Wojcik J, Xu R et al. Interaction between poor glycemic control and 9p21 locus on risk of coronary artery disease in type 2 diabetes. JAMA 2008; 300(20): 2389–2397.

24. Cahill LE, Levy AP, Chiuve SE et al. Haptoglobin genotype is a consistent marker of coronary heart disease risk in individuals with elevated glycosylated hemoglobin. J Am Coll Cardiol 2013; 61(7): 728–737.

25. Goldenstein H, Levy NS, Levy AP. Haptoglobin genotype and its role in determining heme-iron mediated vascular disease. Pharmacol Res 2012; 66(1): 1–6.

Labels
Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue 9

2014 Issue 9

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#