Understanding the Genetic Basis of Type 2 Diabetes: Implications for Precision Medicine and Novel Therapeutic Approaches

Authors

  • Hassam Gul International Islamic University, Islamabad, Pakistan.
  • Farhat Joya Bolan Medical Complex, Quetta, Baluchistan, Pakistan.
  • Ahmar Zafar Department of Rehabilitation Sciences, Move Better, Faisalabad, Pakistan.
  • Suleman Sikander Islamic International Medical College, Riphah University, Pakistan.
  • Hamna Akhlaq Islamic International Medical College, Riphah University, Pakistan.

DOI:

https://doi.org/10.70749/ijbr.v3i3.864

Keywords:

Type 2 Diabetes, Genetic Awareness, General Practitioners, Precision Medicine, Genetic Integration, T2D Management, Snowball Sampling, Genetics in Healthcare

Abstract

This research tries to quantify awareness, integration, and uptake of genetic ideas in Type 2 Diabetes (T2D) management by Punjab general practitioners (GPs). The research used a quantitative research design, whereby a self-report questionnaire was used to collect data from 110 GPs via snowball sampling. This research explores three main aims: (1) to measure the awareness of general practitioners with regard to the genetic cause of T2D, (2) to measure the extent to which genetic considerations are incorporated into T2D management, and (3) to determine predictors of the uptake of genetic information in T2D management. Descriptive statistics, Chi-square tests, and t-tests were employed for statistical analyses. Findings reveal a level of mixed awareness among GPs where 18.18% very familiar, 45.45% somewhat familiar, and 36.36% not familiar with genetic concepts of T2D. Significant gap was discovered in applying genetic factors in clinical practice where most GPs (54.55%) rarely apply genetics in managing T2D. Despite positive attitude scores for the uptake of genetic knowledge (54.55% agreeing or strongly agreeing), an extreme level of resistance to the incorporation of genetic knowledge into practice was observed. Chi-square analysis revealed that a significant association between knowledge of genetic terms and how often T2D management is thought about in relation to genetic factors existed. In addition, t-tests revealed that the difference between agreeing to use genetic knowledge and disagreeing was significant. The research emphasizes the importance of enhanced genetic education and support systems, such as genetic counselors, to assist GPs in applying genetic knowledge to practice. Future implications suggest that greater genetic literacy among health professionals and the availability of genetic testing can facilitate more personalized and effective management of T2D.

Downloads

Download data is not yet available.

References

Ahmad, O. S., Morris, J. A., Mujammami, M., Forgetta, V., Leong, A., Li, R., Turgeon, M., Greenwood, C. M., Thanassoulis, G., Meigs, J. B., Sladek, R., & Richards, J. B. (2015). A mendelian randomization study of the effect of type-2 diabetes on coronary heart disease. Nature Communications, 6(1). https://doi.org/10.1038/ncomms8060

Baye, T. M., Abebe, T., & Wilke, R. A. (2010). Genotype–environment interactions and their translational implications. Personalized Medicine, 8(1), 59-70. https://doi.org/10.2217/pme.10.75

Bonnefond, A., & Froguel, P. (2015). Rare and common genetic events in type 2 diabetes: What should biologists know? Cell Metabolism, 21(3), 357-368. https://doi.org/10.1016/j.cmet.2014.12.020

Boutsouris, K., Poumpouridou, N., Katsarou, M., GOURZI, S.-F., TENTOLOURIS, K., LIAPI, C., & DRAKOULIS, N. (2016). Frequency distribution of TCF7l2, MTNR1B, CDKAl1, SLC30A8 and FTO gene polymorphisms predisposing to type II diabetes mellitus and/or obesity in a greek population and their impact in personalized medicine. Arch Balk Med Union, 51, 157-163. https://umbalk.org/wp-content/uploads/2016/12/2016-2-157.pdf

Brunetti, A., Chiefari, E., & Foti, D. (2014). Recent advances in the molecular genetics of type 2 diabetes mellitus. World Journal of Diabetes, 5(2), 128. https://doi.org/10.4239/wjd.v5.i2.128

Chan, I. S., & Ginsburg, G. S. (2011). Personalized medicine: Progress and promise. Annual Review of Genomics and Human Genetics, 12(1), 217-244. https://doi.org/10.1146/annurev-genom-082410-101446

Cox, R. D., & Church, C. D. (2011). Mouse models and the interpretation of human GWAS in type 2 diabetes and obesity. Disease Models & Mechanisms, 4(2), 155-164. https://doi.org/10.1242/dmm.000414

De Rosa, S., Arcidiacono, B., Chiefari, E., Brunetti, A., Indolfi, C., & Foti, D. P. (2018). Type 2 diabetes mellitus and cardiovascular disease: Genetic and epigenetic links. Frontiers in Endocrinology, 9. https://doi.org/10.3389/fendo.2018.00002

Doria, A., Patti, M., & Kahn, C. R. (2008). The emerging genetic architecture of type 2 diabetes. Cell Metabolism, 8(3), 186-200. https://doi.org/10.1016/j.cmet.2008.08.006

Dziewulska, A., Dobosz, A. M., & Dobrzyn, A. (2018). High-throughput approaches onto uncover (Epi)Genomic architecture of type 2 diabetes. Genes, 9(8), 374. https://doi.org/10.3390/genes9080374

Engwa, G. A., Nweke, F. N., Karngong, G. N., Afiukwa, C. A., & Nwagu, K. E. (2020). Understanding the pathogenesis, therapeutic targets/Drug action and Pharmacogenetics of type 2 diabetes: Is there a future for personalised medicine? Endocrine, Metabolic & Immune Disorders - Drug Targets, 20(10), 1569-1589. https://doi.org/10.2174/1871530320666200425202312

Florez, J. C., Udler, M. S., & Hanson, R. L. (2021). Genetics of type 2 diabetes. https://europepmc.org/article/nbk/nbk567998

Frayling, T. M. (2007). Genome–wide association studies provide new insights into type 2 diabetes aetiology. Nature Reviews Genetics, 8(9), 657-662. https://doi.org/10.1038/nrg2178

Galiero, R., Caturano, A., Vetrano, E., Monda, M., Marfella, R., Sardu, C., Salvatore, T., Rinaldi, L., & Sasso, F. C. (2023). Precision medicine in type 2 diabetes mellitus: Utility and limitations. Diabetes, Metabolic Syndrome and Obesity, 16, 3669-3689. https://doi.org/10.2147/dmso.s390752

Glotov, O. S., Chernov, A. N., & Glotov, A. S. (2023). Human Exome sequencing and prospects for predictive medicine: Analysis of international data and own experience. Journal of Personalized Medicine, 13(8), 1236. https://doi.org/10.3390/jpm13081236

Gloyn, A. L. (2003). The search for type 2 diabetes genes. Ageing Research Reviews, 2(2), 111-127. https://doi.org/10.1016/s1568-1637(02)00061-2

Gouda, H. N., Sagoo, G. S., Harding, A., Yates, J., Sandhu, M. S., & Higgins, J. P. (2010). The association between the Peroxisome proliferator-activated receptor-γ2 (PPARG2) Pro12Ala gene variant and type 2 diabetes mellitus: A huge review and meta-analysis. American Journal of Epidemiology, 171(6), 645-655. https://doi.org/10.1093/aje/kwp450

Grant, R. W., Moore, A. F., & Florez, J. C. (2009). Genetic architecture of type 2 diabetes: Recent progress and clinical implications. Diabetes Care, 32(6), 1107-1114. https://doi.org/10.2337/dc08-2171

Groop, L., & Pociot, F. (2014). Genetics of diabetes – Are we missing the genes or the disease? Molecular and Cellular Endocrinology, 382(1), 726-739. https://doi.org/10.1016/j.mce.2013.04.002

Hara, K., Kadowaki, T., & Odawara, M. (2015). Genes associated with diabetes: Potential for novel therapeutic targets? Expert Opinion on Therapeutic Targets, 20(3), 255-267. https://doi.org/10.1517/14728222.2016.1098618

Hasanzad, M., Sarhangi, N., Meybodi, H. R. A., Nikfar, S., Khatami, F., & Larijani, B. (2019). Precision medicine in non communicable diseases. International Journal of Molecular and Cellular Medicine, 8(Suppl1), 1. https://pmc.ncbi.nlm.nih.gov/articles/PMC7175610/

Imamura, M., & Maeda, S. (2011). Genetics of type 2 diabetes: The GWAS era and future perspectives [Review]. Endocrine Journal, 58(9), 723-739. https://doi.org/10.1507/endocrj.ej11-0113

Kalniņa, I. (2014). Susceptibility variants for obesity and type 2 diabetes mellitus in the population of Latvia. https://dspace.lu.lv/dspace/handle/7/4955

Kim, D. S., Gloyn, A. L., & Knowles, J. W. (2021). Genetics of type 2 diabetes: Opportunities for precision medicine. Journal of the American College of Cardiology, 78(5), 496-512. https://doi.org/10.1016/j.jacc.2021.03.346

Kingsmore, S. F., Lindquist, I. E., Mudge, J., Gessler, D. D., & Beavis, W. D. (2008). Genome-wide association studies: Progress and potential for drug discovery and development. Nature Reviews Drug Discovery, 7(3), 221-230. https://doi.org/10.1038/nrd2519

Kreienkamp, R. J., Voight, B. F., Gloyn, A. L., & Udler, M. S. (2023). Genetics of type 2 diabetes. Diabetes in America [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK597726/

Kullo, I. J., & Ding, K. (2007). Mechanisms of disease: The genetic basis of coronary heart disease. Nature Clinical Practice Cardiovascular Medicine, 4(10), 558-569. https://doi.org/10.1038/ncpcardio0982

Kwak, S. H., & Park, K. S. (2016). Recent progress in genetic and epigenetic research on type 2 diabetes. Experimental & Molecular Medicine, 48(3), e220-e220. https://doi.org/10.1038/emm.2016.7

Laakso, M., & Fernandes Silva, L. (2022). Genetics of type 2 diabetes: Past, present, and future. Nutrients, 14(15), 3201. https://doi.org/10.3390/nu14153201

Lindgren, C. M., & McCarthy, M. I. (2008). Mechanisms of disease: Genetic insights into the etiology of type 2 diabetes and obesity. Nature Clinical Practice Endocrinology & Metabolism, 4(3), 156-163. https://doi.org/10.1038/ncpendmet0723

Mao, H., Li, Q., & Gao, S. (2012). Meta-analysis of the relationship between common type 2 diabetes risk gene variants with gestational diabetes mellitus. PLoS ONE, 7(9), e45882. https://doi.org/10.1371/journal.pone.0045882

Fitipaldi, H., McCarthy, M. I., Florez, J. C., & Franks, P. W. (2018). A global overview of precision medicine in type 2 diabetes. Diabetes, 67(10), 1911-1922. https://doi.org/10.2337/dbi17-0045

Meigs, J. B., Shrader, P., Sullivan, L. M., McAteer, J. B., Fox, C. S., Dupuis, J., Manning, A. K., Florez, J. C., Wilson, P. W., D'Agostino, R. B., & Cupples, L. A. (2008). Genotype score in addition to common risk factors for prediction of type 2 diabetes. New England Journal of Medicine, 359(21), 2208-2219. https://doi.org/10.1056/nejmoa0804742

Moore, A. F., & Florez, J. C. (2008). Genetic susceptibility to type 2 diabetes and implications for Antidiabetic therapy. Annual Review of Medicine, 59(1), 95-111. https://doi.org/10.1146/annurev.med.59.090706.135315

Muller, G. (2012). Personalized strategies for the diagnosis and therapy of type II diabetes and obesity. Immunology Endocrine & Metabolic Agents - Medicinal Chemistry, 12(2), 80-109. https://doi.org/10.2174/187152212800388950

Nasykhova, Y. A., Barbitoff, Y. A., Serebryakova, E. A., Katserov, D. S., & Glotov, A. S. (2019). Recent advances and perspectives in next generation sequencing application to the genetic research of type 2 diabetes. World Journal of Diabetes, 10(7), 376-395. https://doi.org/10.4239/wjd.v10.i7.376

Palmer, N. D., McDonough, C. W., Hicks, P. J., Roh, B. H., Wing, M. R., An, S. S., Hester, J. M., Cooke, J. N., Bostrom, M. A., Rudock, M. E., Talbert, M. E., Lewis, J. P., Ferrara, A., Lu, L., Ziegler, J. T., Sale, M. M., Divers, J., & Bowden, D. W. (2012). A genome-wide association search for type 2 diabetes genes in African Americans. PLoS ONE, 7(1), e29202. https://doi.org/10.1371/journal.pone.0029202

Parikh, H. (2009). Integrating bioinformatics and physiology to describe genetic effects in complex polygenic diseases (Vol. 2009, No. 9). Lund University. https://lup.lub.lu.se/search/files/3638163/1275367.pdf

Pintérová, D. (2009). Molecular aspects of genetic predisposition to type 2 diabetes mellitus and its monogenic forms. https://dspace.cuni.cz/handle/20.500.11956/23901

Prasad, R., & Groop, L. (2015). Genetics of type 2 diabetes—Pitfalls and possibilities. Genes, 6(1), 87-123. https://doi.org/10.3390/genes6010087

Prasad, R. B., & Groop, L. (2016). Genetic architecture of type 2 diabetes. Textbook of Diabetes, 187-204. https://doi.org/10.1002/9781118924853.ch14

Prokopenko, I., McCarthy, M. I., & Lindgren, C. M. (2008). Type 2 diabetes: New genes, new understanding. Trends in Genetics, 24(12), 613-621. https://doi.org/10.1016/j.tig.2008.09.004

Rabbani, B., Nakaoka, H., Akhondzadeh, S., Tekin, M., & Mahdieh, N. (2016). Next generation sequencing: Implications in personalized medicine and pharmacogenomics. Molecular BioSystems, 12(6), 1818-1830. https://doi.org/10.1039/c6mb00115g

Roberts, R. (2008). Personalized medicine: A reality within this decade. Journal of Cardiovascular Translational Research, 1(1), 11-16. https://doi.org/10.1007/s12265-007-9001-1

Sanghera, D. K., & Blackett, P. R. (2012). Type 2 diabetes genetics: Beyond GWAS. Journal of Diabetes & Metabolism, 03(05). https://doi.org/10.4172/2155-6156.1000198

Sayed, S., & Nabi, A. H. (2020). Diabetes and genetics: A relationship between genetic risk alleles, clinical phenotypes and therapeutic approaches. Advances in Experimental Medicine and Biology, 457-498. https://doi.org/10.1007/5584_2020_518

Siddiqui, K., & Tyagi, S. (2015). Genetics, genomics and personalized medicine in type 2 diabetes: A perspective on the Arab region. Personalized Medicine, 12(4), 417-431. https://doi.org/10.2217/pme.15.11

Silvia, P., Simona, Z., Ernesto, M., & Raffaella, B. (2020). “H” for heterogeneity in the algorithm for type 2 diabetes management. Current Diabetes Reports, 20(5). https://doi.org/10.1007/s11892-020-01297-w

Sithara, S., Crowley, T. M., Walder, K., & Aston-Mourney, K. (2017). Gene expression signature: A powerful approach for drug discovery in diabetes. Journal of Endocrinology, 232(2), R131-R139. https://doi.org/10.1530/joe-16-0515

Srinivasan, S., & Todd, J. (2022). The genetics of type 2 diabetes in youth: Where we are and the road ahead. The Journal of Pediatrics, 247, 17-21. https://doi.org/10.1016/j.jpeds.2022.05.044

Stalbow, L. (2023). A Genotype First Approach to Diabetes (Doctoral dissertation, Icahn School of Medicine at Mount Sinai).

Sternberg, R. J., & Sternberg, K. (2006). Cognitive psychology (pp. 200-204). Belmont, CA: Thomson/Wadsworth.

Tallapragada, D. S., Bhaskar, S., & Chandak, G. R. (2015). New insights from monogenic diabetes for “common” type 2 diabetes. Frontiers in Genetics, 6. https://doi.org/10.3389/fgene.2015.00251

Thomsen, S. K., & Gloyn, A. L. (2017). Human genetics as a model for target validation: Finding new therapies for diabetes. Diabetologia, 60(6), 960-970. https://doi.org/10.1007/s00125-017-4270-y

Travers, M. E., & McCarthy, M. I. (2011). Type 2 diabetes and obesity: Genomics and the clinic. Human Genetics, 130(1), 41-58. https://doi.org/10.1007/s00439-011-1023-8

Turner, S. T., Schwartz, G. L., & Boerwinkle, E. (2007). Personalized medicine for high blood pressure. Hypertension, 50(1), 1-5. https://doi.org/10.1161/hypertensionaha.107.087049

Venkatachalapathy, P., Padhilahouse, S., Sellappan, M., Subramanian, T., Kurian, S. J., Miraj, S. S., Rao, M., Raut, A. A., Kanwar, R. K., Singh, J., Khadanga, S., Mondithoka, S., & Munisamy, M. (2021). Pharmacogenomics and personalized medicine in type 2 diabetes mellitus: Potential implications for clinical practice. Pharmacogenomics and Personalized Medicine, 14, 1441-1455. https://doi.org/10.2147/pgpm.s329787

Viraj, T. (2023). GENETIC PREDISPOSITION AND NUTRITION IN RELATION TO TYPE 2 DIABETES.

Volkmar, M., Dedeurwaerder, S., Cunha, D. A., Ndlovu, M. N., Defrance, M., Deplus, R., Calonne, E., Volkmar, U., Igoillo-Esteve, M., Naamane, N., Del Guerra, S., Masini, M., Bugliani, M., Marchetti, P., Cnop, M., Eizirik, D. L., & Fuks, F. (2012). DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. The EMBO Journal, 31(6), 1405-1426. https://doi.org/10.1038/emboj.2011.503

Webb, C. P., Thompson, J. F., Littman, B. H., Bleavins, M., Carini, C., Jurima-Romet, M., & Rahbari, R. (2010). Redefining disease and pharmaceutical targets through molecular definitions and personalized medicine. BIOMARKERS IN DRUG DEVELOPMENT, 593.

Witka, B. Z., Oktaviani, D. J., Marcellino, M., Barliana, M. I., & Abdulah, R. (2019).

Type 2 diabetes-associated genetic polymorphisms as potential disease Predictors

. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 12, 2689-2706. https://doi.org/10.2147/dmso.s230061

Zeggini, E., Weedon, M. N., Lindgren, C. M., Frayling, T. M., Elliott, K. S., Lango, H., Timpson, N. J., Perry, J. R., Rayner, N. W., Freathy, R. M., Barrett, J. C., Shields, B., Morris, A. P., Ellard, S., Groves, C. J., Harries, L. W., Marchini, J. L., Owen, K. R., Knight, B., … Hattersley, A. T. (2007). Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science, 316(5829), 1336-1341. https://doi.org/10.1126/science.1142364

Zolotov, S., Ben Yosef, D., Rishe, N. D., Yesha, Y., & Karnieli, E. (2011). Metabolic profiling in personalized medicine: Bridging the gap between knowledge and clinical practice in type 2 diabetes. Personalized Medicine, 8(4), 445-456. https://doi.org/10.2217/pme.11.36

Downloads

Published

2025-03-29

How to Cite

Gul, H., Joya, F., Zafar, A., Sikander, S., & Akhlaq, H. (2025). Understanding the Genetic Basis of Type 2 Diabetes: Implications for Precision Medicine and Novel Therapeutic Approaches. Indus Journal of Bioscience Research, 3(3), 559-573. https://doi.org/10.70749/ijbr.v3i3.864