Personalized therapy of type 2 diabetes mellitus

Abstract

Currently, the contribution of genetic factors to the development of type 2 diabetes is becoming more obvious. Despite the available nine classes of hypoglycemic drugs, only 35–40 % of patients achieve an adequate glycemic control. One the reasons may be the genetic heterogeneity of diabetes mellitus. An increasing number of studies indicates that an individual set of gene polymorphisms can determine the therapeutic response to a particular drug and cause the development of undesirable effects. The article presents an overview of a new direction in the diagnosis and treatment of diabetes mellitus – personalized medicine. The pathogenetic mechanisms of the development of the disease, its heterogeneity and the difficulties of choosing the most effective hypoglycemic therapy are described. Data on the pharmacogenetic features of metformin are presented.

Keywords

diabetes mellitus / personalized medicine / pharmacogenetics

References

[1] Mannino G.C., Andreozzi F., Sesti G. Pharmacogenetics of type 2 diabetes mellitus, the route toward tailored medicine. Diabetes Metab Res Rev. 2019; 35 (3): 3109. DOI: 10.1002/dmrr.3109

[2] Imamovic Kadric S., Kulo Cesic A., Dujic T. Pharmacogenetics of new classes of anti-diabetic drugs. Bosn J Basic Med Sci. 2021; 21 (6): 659–671. DOI: 10.17305/bjbms.2021.5646

[3] Imamovic Kadric S., Kulo Cesic A., Dujic T. Pharmacogenetics of new classes of antidiabetic drugs. Bosn J Basic Med Sci. 2021; 21 (6): 659–671. DOI: 10.17305/bjbms.2021.5646

[4] Global report on diabetes. Geneva: World Health Organization, 2018. License: CC BY-NC-SA (in Russian).

[5] Глобальный доклад по диабету. Женева: Всемирная организация здраво-охранения, 2018. Лицензия: CC BY-NC-SA 3.0 IGO.

[6] Dedov I.I., Shestakova M.V. Personalized therapy for diabetes mellitus: the path from disease to the patient. Terapevticheskii arkhiv 2014; 86 (10): 4–9 (in Russian).

[7] Дедов И.И., Шестакова М.В. Персонализированная терапия сахарного диабета: путь от болезни к больному. Терапевтический архив 2014; 86 (10): 4–9.

[8] Smushkin G., Vella A. Genetics of type 2 diabetes. Current Opinion in Clinical Nutrition and Metabolic Care 2010; 13 (4): 471–477. DOI: http://dx.doi.org/10.1097/MCO.0b013e32833a558d

[9] Smushkin G., Vella A. Genetics of type 2 diabetes. Current Opinion in Clinical Nutrition and Metabolic Care. 2010; 13 (4): 471–477. DOI: http://dx.doi.org/10.1097/MCO.0b013e32833a558d

[10] Voight B.F., Scott L.J., Steinthorsdottir V., et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet. 2010; 42 (7): 579–589. DOI: 10.1038/ng.609

[11] Vujkovic M., Keaton J.M., Lynch J.A., et al. Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis. Nat Genet. 2020; 52 (7): 680–691. DOI: 10.1038/s41588-020-0637-y

[12] Vujkovic M., Keaton J.M., Lynch J.A.,

[13] McCarthy M.I. Painting a new picture of personalised medicine for diabetes. Diabetologia 2017; 60 (5): 793–799. DOI: 10.1007/s00125-017-4210-x

[14] et al. Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multiancestry meta-analysis. Nat Genet. 2020; 52 (7): 680–691. DOI: 10.1038/s41588-020-0637-y

[15] Pearson E.R. Type 2 diabetes: a multifaceted disease. Diabetologia 2019; 62 (7): 1107–1112. DOI: 10.1007/s00125-019-4909-y

[16] McCarthy M.I. Painting a new picture of personalised medicine for diabetes. Diabetologia 2017; 60 (5): 793–799. DOI: 10.1007/s00125-017-4210-x

[17] Kononenko I.V., Mayorov A.Yu., Koksharova E.O., Shestakova M.V. Pharmacogenetics of hypoglycemic agents. Diabetes mellitus. 2015; 18 (4): 28–34. DOI: 10.14341/DM7681 (in Russian).

[18] Pearson E.R. Type 2 diabetes: a multifaceted disease. Diabetologia 2019; 62 (7), 1107–1112. DOI: 10.1007/s00125-019-4909-y

[19] Becker M.L., Pearson E.R., Tkáč I. Pharmacogenetics of oral antidiabetic drugs. Int J Endocrinol. 2013: 686315. DOI: 10.1155/2013/686315

[20] Кононенко И.В., Майоров А.Ю., Кокшарова Е.О., Шестакова М.В. Фармакогенетика сахароснижающих препаратов. Сахарный диабет 2015; 18 (4): 28–34. DOI: 10.14341/DM7681

[21] Dawed A.Y., Zhou K., Pearson E.R. Pharmacogenetics in type 2 diabetes: influence on response to oral hypoglycemic agents. Pharmgenomics Pers Med. 2016; 9: 17–29. DOI: 10.2147/PGPM.S84854

[22] Becker M.L., Pearson E.R., Tkáč I. Pharmacogenetics of oral antidiabetic drugs. Int J Endocrinol. 2013: 686315. DOI: 10.1155/2013/686315

[23] Wild H. The economic rationale for adherence in the treatment of type 2 diabetes mellitus. Am J Manag Care. 2012; 18 (3): S43–S48.

[24] Dawed A.Y., Zhou K., Pearson E.R. Pharmacogenetics in type 2 diabetes: influence on response to oral hypoglycemic agents. Pharmgenomics Pers Med. 2016; 9: 17–29. DOI: 10.2147/PGPM.S84854

[25] Singh S., Usman K., Banerjee M. Pharmacogenetic studies update in type 2 diabetes mellitus. World J Diabetes. 2016; 7 (15): 302–315. DOI: 10.4239/wjd.v7.i15.302

[26] Wild H. The economic rationale for adherence in the treatment of type 2 diabetes mellitus. Am J Manag Care. 2012; 18 (3): S43–S48.

[27] Yan, Q. Pharmacogenomics in drug discovery and development. Humana Press 2010; 504.

[28] Singh S., Usman K., Banerjee M. Pharmacogenetic studies update in type 2 diabetes mellitus. World J Diabetes. 2016; 7 (15): 302–315. DOI: 10.4239/wjd.v7.i15.302

[29] Deenen M.J., Cats A., Beijnen J.H., Schellens J.H. Part 1: background, methodology, and clinical adoption of pharmacogenetics. Oncologist 2011; 16 (6): 811–819. DOI: 10.1634/theoncologist.2010-0258

[30] Yan Q. Pharmacogenomics in drug discovery and development. Humana Press 2010; 504.

[31] Pernicova I., Korbonits M. Metformin-mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014; 10 (3): 143–156. DOI: 10.1038/nrendo.2013.256

[32] Deenen M.J., Cats A., Beijnen J.H., Schellens J.H. Part 1: background, methodology, and clinical adoption of pharmacogenetics. Oncologist 2011; 16 (6): 811–819. DOI: 10.1634/theoncologist.2010-0258

[33] Miller R.A., Chu Q., Xie J., Foretz M., Viol-let B., Birnbaum M.J. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature. 2013; 494 (7436): 256–260. DOI: 10.1038/nature11808

[34] Pernicova I., Korbonits M. Metformin-mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014; 10 (3): 143–156. DOI: 10.1038/nrendo.2013.256

[35] Viollet B., Guigas B., Sanz Garcia N., Leclerc J., Foretz M., Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012; 122 (6): 253–270. DOI: 10.1042/CS20110386

[36] Miller R.A., Chu Q., Xie J., Foretz M., Viollet B., Birnbaum M.J. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature 2013; 494 (7436): 256–260. DOI: 10.1038/nature11808

[37] Gong L., Goswami S., Giacomini K.M., Altman R.B., Klein T.E. Metformin path-ways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2012; 22 (11): 820–827. DOI: 10.1097/FPC.0b013e3283559b22

[38] Viollet B., Guigas B., Sanz Garcia N., Leclerc J., Foretz M., Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond) 2012; 122 (6): 253–270. DOI: 10.1042/CS20110386

[39] Madiraju A.K., Erion D.M., Rahimi Y. et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014; 510 (7506): 542–546. DOI: 10.1038/nature13270

[40] Gong L., Goswami S., Giacomini K.M., Altman R.B., Klein T.E. Metformin path-ways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics. 2012; 22 (11): 820–827. DOI: 10.1097/FPC.0b013e3283559b22

[41] GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group; Wellcome Trust Case Control Consortium 2, Zhou K., et al. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet. 2011; 43 (2): 117–120. DOI: 10.1038/ng.735

[42] Madiraju A.K., Erion D.M., Rahimi Y.,

[43] DeGorter M.K., Xia C.Q., Yang J.J., Kim R.B. Drug transporters in drug efficacy and toxicity. Annu Rev Pharmacol Toxicol. 2012; 52: 249–273. DOI: 10.1146/annurev-pharmtox-010611-134529

[44] et al. Metformin suppresses gluconeo-genesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 2014; 510 (7506): 542–546. DOI: 10.1038/nature13270

[45] Umamaheswaran G., Praveen R.G., Damodaran S.E., Das A.K., Adithan C. Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients. Clin Exp Med. 2015; 15 (4): 511–517. DOI: 10.1007/s10238-014-0322-564

[46] GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group; Wellcome Trust Case Control Consortium 2, Zhou K., et al. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet. 2011; 43 (2): 117–120. DOI: 10.1038/ng.735

[47] Dujic T., Zhou K., Donnelly L.A., Tavendale R., Palmer C.N., Pearson E.R. Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. Diabetes. 2015; 64 (5): 1786–1793. DOI: 10.2337/db14-1388

[48] DeGorter M.K., Xia C.Q., Yang J.J., Kim R.B. Drug transporters in drug efficacy and toxicity. Annu Rev Pharmacol Toxicol. 2012; 52: 249–273. DOI: 10.1146/annurev-pharmtox-010611-134529

[49] Umamaheswaran G., Praveen R.G., Damodaran S.E., Das A.K., Adithan C. Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients. Clin Exp Med. 2015; 15 (4): 511–517. DOI: 10.1007/s10238-014-0322-564

[50] Dujic T., Zhou K., Donnelly L.A., Tavendale R., Palmer C.N., Pearson E.R. Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. Diabetes 2015; 64 (5): 1786–1793. DOI: 10.2337/db14-1388

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