DOI: http://dx.doi.org/10.18203/2394-6040.ijcmph20210250

Epigenetic modifications and their role in the development and disease progression of type 2 diabetes

Abhijeet Roy

Abstract


Type 2 Diabetes is one of the major public health issues and a complex metabolic disorder strongly associated with genetic predisposition influenced by environmental factors and epigenetic regulation. This review paper illustrated the role of epigenetics in the pathogenesis, progression, and detection of Type 2 Diabetes. A review study was performed for the articles published in English from 2000-2019 using Pub Med, and Google Scholar databases. Main underlining mechanisms of Type 2 Diabetes were identified; insulin resistance in the peripheral tissue, and disintegrate insulin secretion. Genome Wide Association Studies suggested that epigenetic regulation such as DNA methylation, Histone modification, Non-coding RNA, microRNA is strongly related with the development of Type 2 Diabetes. Altered DNA methylation patterns in pancreatic islets, skeletal muscle, adipose tissue, from diabetic subjects compare to normal subjects was also found. Other risk factors like; obesity, age, gender, impaired glucose tolerance, periconception and intrauterine environment may also have been linked with the possibilities of epigenetic changes. Epigenetics plays a crucial role by modifying the gene expression and establish a relationship between the environment and genetic factors. Understanding the epigenetic mechanisms contributing to the development of Type 2 Diabetes is still limited.


Keywords


DNA methylation, Epigenetics, Epigenetic modifications, Type 2 diabetes

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References


Saeedi P, Petersohn I, Salpea P. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Research and Clinical Practice. 2019;157.

Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. The Lancet. 2017;389(10085):2239-51.

Misra A, Gopalan H, Jayawardena R, et al. Diabetes in developing countries. J Diabetes. 2019;11(7):522-39.

American Diabetes Association. Diabetes Ready Reference for Nurse Practitioners: Clear, Concise Guidelines for Effective Patient Care. American Diabetes Association; 2013.

Desiderio A, Spinelli R, Ciccarelli M, et al. Epigenetics: spotlight on type 2 diabetes and obesity. Journal of endocrinological investigation. 2016;39(10):1095-1103.

Bird A. Perceptions of epigenetics. Nature. 2007;447(7143):396.

Rönn T, Ling C. DNA methylation as a diagnostic and therapeutic target in the battle against Type 2 diabetes. Epigenomics. 2015;7(3):451-60.

Dayeh T, Ling C. Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes? Biochemistry and Cell Biol. 2015;93(5):511-521.

Sterns JD, Smith CB, Steele JR, Stevenson KL, Gallicano GI. Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition. Frontiers in cell and developmental Biol. 2014;2:15.

Volkmar M, Dedeurwaerder S, Cunha DA, et al. DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. The EMBO J. 2012;31(6):1405-26.

dos Santos JM, Moreli ML, Tewari S, Benite-Ribeiro SA. The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: An epigenetic perspective. Metabolism. 2015;64(12):1619-28.

Kaul N, Ali S. Genes, genetics, and environment in type 2 diabetes: implication in personalized medicine. DNA and cell Biol. 2016;35(1):1-12.

Kwak SH, Park KS. Recent progress in genetic and epigenetic research on type 2 diabetes. Experimental & Molecular Medic. 2016;48(3):e220.

Hales CN, Barker D. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. International J Epidemiol. 2013;42(5):1215-22.

Ahmed M, de Winther MP, Van den Bossche J. Epigenetic mechanisms of macrophage activation in type 2 diabetes. Immunobiol. 2017;222(10):937-43.

Vaag A, Brøns C, Gillberg L. Genetic, nongenetic and epigenetic risk determinants in developmental programming of type 2 diabetes. Acta obstetricia et gynecologica Scandinavica. 2014;93(11):1099-1108.

Ma RC, Tutino GE, Lillycrop KA, Hanson MA, Tam WH. Maternal diabetes, gestational diabetes and the role of epigenetics in their long term effects on offspring. Progress in biophysics and molecular Biol. 2015;118(1-2):55-68.

Burgio E, Lopomo A, Migliore L. Obesity and diabetes: from genetics to epigenetics. Molecular biology reports. 2015;42(4):799-818.

Hadaegh F, Zabetian A, Harati H, Azizi F. Waist/height ratio as a better predictor of type 2 diabetes compared to body mass index in Tehranian adult men-a 3.6-year prospective study. Experimental and Clinical Endocrinol & Diabetes. 2006;114(06):310-5.

Dayeh T, Volkov P, Salö S, et al. Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion. PLoS Genet. 2014;10(3):e1004160.

Ling C, Rönn T. Epigenetic markers to further understand insulin resistance. Diabetologia. 2016;59(11):2295-7.

Bergman RN, Ader M. Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends in Endocrinology & Metabolism. 2000;11(9):351-6.

Villeneuve LM, Natarajan R. The role of epigenetics in the pathology of diabetic complications. American J Physiology-Renal Physiol. 2010;299(1):F14-25.

Gillberg L, Ling C. The potential use of DNA methylation biomarkers to identify risk and progression of type 2 diabetes. Frontiers in Endocrinol. 2015;6:43.

Hidalgo B, Irvin MR, Sha J, et al. Epigenome-wide association study of fasting measures of glucose, insulin, and HOMA-IR in the Genetics of Lipid Lowering Drugs and Diet Network study. Diabetes. 2014;63(2):801-7.

Willmer T, Johnson R, Louw J, Pheiffer C. Blood-based DNA methylation biomarkers for type 2 diabetes: potential for clinical applications. Frontiers in endocrinol. 2018;9:744.

Nilsson E, Jansson PA, Perfilyev A, et al. Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes. Diabetes. 2014;63(9):2962-76.

Dayeh T, Tuomi T, Almgren P, et al. DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk. Epigenetics. 2016;11(7):482-8.