New Treatment Strategies of Type 1 Diabetes Mellitus

Qand Agha Nazari

doi:10.62810/jns.v7i3.63

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Abstract

Diabetes mellitus is a serious metabolic disorder characterized by elevated blood glucose levels resulting from either autoimmune destruction of β-cells in the pancreatic islets or insulin resistance. Type 1 diabetes mellitus is currently managed with insulin therapy; however, long-term treatment is often associated with chronic complications such as limb amputation, blindness, and kidney failure. This review explores innovative therapeutic strategies for Type 1 diabetes mellitus based on a comprehensive literature search using PubMed and relevant keywords. The findings highlight several promising approaches, including gene therapy, trans-differentiation, enhancing the self-replication of β-cells, stem cell therapies, immunomodulatory agents, and herbal medicines, all of which show potential for improving disease management and reducing complications.

Keywords

B Cells Gene Therapy Stem Cells Type1 Diabetes Mellitus Trans-Differentiation

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Nazari, Q. A. (2024). New Treatment Strategies of Type 1 Diabetes Mellitus. Journal of Natural Sciences – Kabul University, 7(3), 81–96. https://doi.org/10.62810/jns.v7i3.63

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References

Abed, A., Critchlow, C., Flatt, P. R., McClenaghan, N. H., & Kelly, C. (2012). Directed differentiation of progenitor cells towards an islet-cell phenotype. Am J Stem Cells, 1(3), 196-204.
Al-Khawaldeha, O. A., Al-Hassanb, M. A.,& Froelicherc, E. S. (2012). Self-efficacy, self-management, and glycemic control in adults with type 2 diabetes mellitus. J of Diab and Its Comp, 26, 10–16, doi:10.1016/j.jdiacomp.2011.11.002.
Antuna-Puente, B., Disse, E., Rabasa-Lhoret, R., Laville, M., Capeau, J., & Bastard, J. P. (2011). How can we measure insulin sensitivity/resistance? Diabetes Metab, 37(3), 179-88. doi: 10.1016/j.diabet.2011.01.002.
Association, A. D. (2018). Economic Costs of Diabetes in the U.S. in 2017. Diabetes Care, 41(5), 917-928. doi: 10.2337/dci18-0007.
Avogaro, A., & Fadini, G. P. (2019). Microvascular complications in diabetes: A growing concern for cardiologists. Int J Cardiol, 291, 29-35. doi: 10.1016/j.ijcard.2019.02.030.
Bianchi, C., Lorella, B. L., Michele, A. , Cristina, L., Serena, O., & Matilde, R. (2017). Prescribing exercise for prevention and treatment of gestational diabetes: review of suggested recommendations. Gynecol Endocrinol, 33(4), 254-260. doi: 10.1080/09513590.2016.1266474.
Calne, R. Y., Gan, S. U., & Lee K. O. (2010). Stem cell and gene therapies for diabetes mellitus. Nat Rev Endocrinol, 6(3), 173-7. doi: 10.1038/nrendo.2009.276.
Chellappan, D. K., Sivam, N. S., Teoh, K. X., Leong, W. P., Fui, T. Z., & Chooi, K. (2018). Gene therapy and type 1 diabetes mellitus. Biomed Pharmacother, 108, 1188-1200. doi: 10.1016/j.biopha.2018.09.138.
Chen, N. F. K., Wong, J. S., Kee, I. H. C., Lai, S. H., Thng, C. H., & Ng, W. N. (2008). Nonvirally modified autologous primary hepatocytes correct diabetes and prevent target organ injury in a large preclinical model. PLoS One, 3(3), e1734. doi: 10.1371/journal.pone.0001734.
DiMeglio, L. A., Evans-Molina, C., & Oram, R. A. (2018). Type 1 diabetes. Lancet, 391, 2449–62.
Forouhi, N. G., & Wareham, N. J. (2019). Epidemiology of diabetes. Medicine, 47(1), 22-27, https://doi.org/10.1016/j.mpmed.2018.10.004.
Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., & Uribe, K .B. (2020). Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci, 21(17), 6275. doi: 10.3390/ijms21176275.
Izadi, M., Nejad, A. S. H., Moazenchi, M., Masoumi, S., Rabbani, A., & Kompani, F. (2022). Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial. Stem Cell Res Ther, 13(1), 264. doi: 10.1186/s13287-022-02941-w.
Jiang, R., Han, Z., Zhuo, G., Qu, X., Li, X., Wang, X., & Shao, Y. (2011). Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med, 5(1), 94-100. doi: 10.1007/s11684-011-0116-z.
Karimi, A., Majlesi, M., & Rafieian-Kopaei, M. (2015). Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol, 4(1), 27-30.
Kaur, G., Invally, M., Khan, M. K., & Jadhav, P. (2018). A nutraceutical combination of Cinnamomum cassia &Nigella sativa for Type 1 diabetes mellitus. J Ayurveda Integr Med, 9(1), 27-37. doi: 10.1016/j.jaim.2017.02.005.
Kim, H. S., & Lee, M. K. (2016). β-Cell regeneration through the transdifferentiation of pancreatic cells: Pancreatic progenitor cells in the pancreas. J Diabetes Investig, 7(3), 286-96. doi: 10.1111/jdi.12475.
Kono, T. M., Sims, E. K., Moss, D. R., Yamamoto, W., Ahn, G., & Diamond, J. (2014). Human adipose-derived stromal/stem cells protect against STZ-induced hyperglycemia: analysis of hASC-derived paracrine effectors. Stem Cells, 32(7), 1831-42. doi: 10.1002/stem.1676.
Kulkarni, R. N., Mizrachi, E. B., Ocana, A. G., & Stewart, A. F. (2012). Human β-cell proliferation and intracellular signaling: driving in the dark without a road map. Diabetes, 61(9), 2205-13. doi: 10.2337/db12-0018.
Kurup, S. B & Mini, S. (2017). Averrhoa bilimbi fruits attenuate hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats. J Food Drug Anal, 25(2), 360-368. doi: 10.1016/j.jfda.2016.06.007.
Lake, D., Corrêa, S. A. L., & Müller, J. (2016). Negative feedback regulation of the ERK1/2 MAPK pathway. Cell Mol Life Sci, 73(23), 4397-4413. doi: 10.1007/s00018-016-2297-8.
Lee, P. G. & Halter, J. B. (2017). The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations. Diabetes Care, 40, 40:444–452 | DOI: 10.2337/dc16-1732.
Levesque, C. (2017). Therapeutic Lifestyle Changes for Diabetes Mellitus. Nurs Clin North Am, 52(4), 679-692. doi: 10.1016/j.cnur.2017.07.012.
Li, H., Li, X., Lam, K. S. L., Tam, S., Xiao, W., & Xu R. (2008). Adeno-associated virus-mediated pancreatic and duodenal duodenal homeobox gene-1 expression enhanced differentiation of hepatic oval stem cells to insulin-producing cells in diabetic rats. J Biomed Sci, 15(4), 487-97. doi: 10.1007/s11373-008-9233-3.
Lovic, D., Piperidou, A., Zografou, I., Grassos, H., Pittaras, A. &, Manolis, A. (2020). The Growing Epidemic of Diabetes Mellitus. Curr Vasc Pharmacol, 18(2), 104-109. doi: 10.2174/1570161117666190405165911.
Millman, J. R., Xie, C., Dervort, A. V., Gürtler, M., Pagliuca, F. W., Melton, D. A. (2016). Generation of stem cell-derived β-cells from patients with type 1 diabetes. Nat Commun, 7, 11463. doi: 10.1038/ncomms11463.
Nakayasu, E. S., Qian, W., Evans-Molina, C., Mirmira, R. G., Eizirik, D. L., & Metz T. O. (2019). The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes. Expert Rev Proteomics, 17(7), 569-582. doi: 10.1080/14789450.2019.1634548.
Papatheodorou, K.,Papanas, N., & Banach M. (2016, Sep). Complications of Diabetes 2016. J of Diab Res, 6989453, 3 pages.
Redondo, M. J., Geyer, S., Steck, A. K., Sharp, S., Wentworth, J. M., & Weedon, M. N. (2018). A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk. Diabetes Care, 41(9), 1887-1894. doi: 10.2337/dc18-0087.
Rewers, M., & Ludvigsson, J. (2016). Environmental risk factors for type 1 diabetes. Lancet, 387(10035), 2340-2348. doi: 10.1016/S0140-6736(16)30507-4.
Richardson, S. J., & Morgan, N. G. (2018). Enteroviral infections in the pathogenesis of type 1 diabetes: new insights for therapeutic intervention. Curr Opin Pharmacol, 43, 11-19. doi: 10.1016/j.coph.2018.07.006.
Sheehy, D. F., Quinnell, S. P. &, Vegas, A. J. (2019). Targeting Type 1 Diabetes: Selective Approaches for New Therapies. Biochemistry, 58(4), 214-233. doi: 10.1021/acs.biochem.8b01118.
Sionov, R. S., & Ahdut-HaCohen, R. (2023). A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome. Biomedicines, 11(9), 2558. doi: 10.3390/biomedicines11092558.
Skyler, J. S., Bakris, G. L., Bonifacio, E., Darsow, T., Eckel, R. H., & Groop, L. (2017). Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis. Diabetes, 66(2), 241-255. doi: 10.2337/db16-0806.
Tan, S. Y., Mei, W. J. L, Sim, Y. J., Wong, S. S., Mohamed, E. S. A., & Tan, S.H,. (2019). Type 1 and 2 diabetes mellitus: A review on current treatment approach and gene therapy as potential intervention. Diabetes Metab Syndr, 13(1), 364-372. doi: 10.1016/j.dsx.2018.10.008.
Thomas, P. B., Robertson, D. H., & Chawla, N. V. (2018). Predicting onset of complications from diabetes: a graph based approach. Appl Netw Sci, 3(1), 48. doi: 10.1007/s41109-018-0106-z.
Vinayagam, R., Jayachandran, M., Chung, S. M., & Xu, B. (2018). Guava leaf inhibits hepatic gluconeogenesis and increases glycogen synthesis via AMPK/ACC signaling pathways in streptozotocin-induced diabetic rats. Biomed Pharmacother, 103, 1012-1017. doi: 10.1016/j.biopha.2018.04.127.
Xu, G. K., Qin, Xiao., Wang, G., Xie, G., Li, X., Sun, C., Liu, B. &, Qin, M. (2017). Antihyperglycemic, antihyperlipidemic and antioxidant effects of standard ethanol extract of Bombax ceiba leaves in high-fat-diet- and streptozotocin-induced Type 2 diabetic rats. Chin J Nat Med, 15(3), 168-177. doi: 10.1016/S1875-5364(17)30033-X.
Yaribeygi, H., Farrokhi, F. R., Butler, A.E., & Sahebkar, A. (2019). Insulin resistance: Review of the underlying molecular mechanisms. J Cell Physiol, 234(6), 8152-8161. doi: 10.1002/jcp.27603.

References

Abed, A., Critchlow, C., Flatt, P. R., McClenaghan, N. H., & Kelly, C. (2012). Directed differentiation of progenitor cells towards an islet-cell phenotype. Am J Stem Cells, 1(3), 196-204.

Al-Khawaldeha, O. A., Al-Hassanb, M. A.,& Froelicherc, E. S. (2012). Self-efficacy, self-management, and glycemic control in adults with type 2 diabetes mellitus. J of Diab and Its Comp, 26, 10–16, doi:10.1016/j.jdiacomp.2011.11.002.

Antuna-Puente, B., Disse, E., Rabasa-Lhoret, R., Laville, M., Capeau, J., & Bastard, J. P. (2011). How can we measure insulin sensitivity/resistance? Diabetes Metab, 37(3), 179-88. doi: 10.1016/j.diabet.2011.01.002.

Association, A. D. (2018). Economic Costs of Diabetes in the U.S. in 2017. Diabetes Care, 41(5), 917-928. doi: 10.2337/dci18-0007.

Avogaro, A., & Fadini, G. P. (2019). Microvascular complications in diabetes: A growing concern for cardiologists. Int J Cardiol, 291, 29-35. doi: 10.1016/j.ijcard.2019.02.030.

Bianchi, C., Lorella, B. L., Michele, A. , Cristina, L., Serena, O., & Matilde, R. (2017). Prescribing exercise for prevention and treatment of gestational diabetes: review of suggested recommendations. Gynecol Endocrinol, 33(4), 254-260. doi: 10.1080/09513590.2016.1266474.

Calne, R. Y., Gan, S. U., & Lee K. O. (2010). Stem cell and gene therapies for diabetes mellitus. Nat Rev Endocrinol, 6(3), 173-7. doi: 10.1038/nrendo.2009.276.

Chellappan, D. K., Sivam, N. S., Teoh, K. X., Leong, W. P., Fui, T. Z., & Chooi, K. (2018). Gene therapy and type 1 diabetes mellitus. Biomed Pharmacother, 108, 1188-1200. doi: 10.1016/j.biopha.2018.09.138.

Chen, N. F. K., Wong, J. S., Kee, I. H. C., Lai, S. H., Thng, C. H., & Ng, W. N. (2008). Nonvirally modified autologous primary hepatocytes correct diabetes and prevent target organ injury in a large preclinical model. PLoS One, 3(3), e1734. doi: 10.1371/journal.pone.0001734.

DiMeglio, L. A., Evans-Molina, C., & Oram, R. A. (2018). Type 1 diabetes. Lancet, 391, 2449–62.

Forouhi, N. G., & Wareham, N. J. (2019). Epidemiology of diabetes. Medicine, 47(1), 22-27, https://doi.org/10.1016/j.mpmed.2018.10.004.

Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., & Uribe, K .B. (2020). Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci, 21(17), 6275. doi: 10.3390/ijms21176275.

Izadi, M., Nejad, A. S. H., Moazenchi, M., Masoumi, S., Rabbani, A., & Kompani, F. (2022). Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial. Stem Cell Res Ther, 13(1), 264. doi: 10.1186/s13287-022-02941-w.

Jiang, R., Han, Z., Zhuo, G., Qu, X., Li, X., Wang, X., & Shao, Y. (2011). Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med, 5(1), 94-100. doi: 10.1007/s11684-011-0116-z.

Karimi, A., Majlesi, M., & Rafieian-Kopaei, M. (2015). Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol, 4(1), 27-30.

Kaur, G., Invally, M., Khan, M. K., & Jadhav, P. (2018). A nutraceutical combination of Cinnamomum cassia &Nigella sativa for Type 1 diabetes mellitus. J Ayurveda Integr Med, 9(1), 27-37. doi: 10.1016/j.jaim.2017.02.005.

Kim, H. S., & Lee, M. K. (2016). β-Cell regeneration through the transdifferentiation of pancreatic cells: Pancreatic progenitor cells in the pancreas. J Diabetes Investig, 7(3), 286-96. doi: 10.1111/jdi.12475.

Kono, T. M., Sims, E. K., Moss, D. R., Yamamoto, W., Ahn, G., & Diamond, J. (2014). Human adipose-derived stromal/stem cells protect against STZ-induced hyperglycemia: analysis of hASC-derived paracrine effectors. Stem Cells, 32(7), 1831-42. doi: 10.1002/stem.1676.

Kulkarni, R. N., Mizrachi, E. B., Ocana, A. G., & Stewart, A. F. (2012). Human β-cell proliferation and intracellular signaling: driving in the dark without a road map. Diabetes, 61(9), 2205-13. doi: 10.2337/db12-0018.

Kurup, S. B & Mini, S. (2017). Averrhoa bilimbi fruits attenuate hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats. J Food Drug Anal, 25(2), 360-368. doi: 10.1016/j.jfda.2016.06.007.

Lake, D., Corrêa, S. A. L., & Müller, J. (2016). Negative feedback regulation of the ERK1/2 MAPK pathway. Cell Mol Life Sci, 73(23), 4397-4413. doi: 10.1007/s00018-016-2297-8.

Lee, P. G. & Halter, J. B. (2017). The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations. Diabetes Care, 40, 40:444–452 | DOI: 10.2337/dc16-1732.

Levesque, C. (2017). Therapeutic Lifestyle Changes for Diabetes Mellitus. Nurs Clin North Am, 52(4), 679-692. doi: 10.1016/j.cnur.2017.07.012.

Li, H., Li, X., Lam, K. S. L., Tam, S., Xiao, W., & Xu R. (2008). Adeno-associated virus-mediated pancreatic and duodenal duodenal homeobox gene-1 expression enhanced differentiation of hepatic oval stem cells to insulin-producing cells in diabetic rats. J Biomed Sci, 15(4), 487-97. doi: 10.1007/s11373-008-9233-3.

Lovic, D., Piperidou, A., Zografou, I., Grassos, H., Pittaras, A. &, Manolis, A. (2020). The Growing Epidemic of Diabetes Mellitus. Curr Vasc Pharmacol, 18(2), 104-109. doi: 10.2174/1570161117666190405165911.

Millman, J. R., Xie, C., Dervort, A. V., Gürtler, M., Pagliuca, F. W., Melton, D. A. (2016). Generation of stem cell-derived β-cells from patients with type 1 diabetes. Nat Commun, 7, 11463. doi: 10.1038/ncomms11463.

Nakayasu, E. S., Qian, W., Evans-Molina, C., Mirmira, R. G., Eizirik, D. L., & Metz T. O. (2019). The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes. Expert Rev Proteomics, 17(7), 569-582. doi: 10.1080/14789450.2019.1634548.

Papatheodorou, K.,Papanas, N., & Banach M. (2016, Sep). Complications of Diabetes 2016. J of Diab Res, 6989453, 3 pages.

Redondo, M. J., Geyer, S., Steck, A. K., Sharp, S., Wentworth, J. M., & Weedon, M. N. (2018). A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk. Diabetes Care, 41(9), 1887-1894. doi: 10.2337/dc18-0087.

Rewers, M., & Ludvigsson, J. (2016). Environmental risk factors for type 1 diabetes. Lancet, 387(10035), 2340-2348. doi: 10.1016/S0140-6736(16)30507-4.

Richardson, S. J., & Morgan, N. G. (2018). Enteroviral infections in the pathogenesis of type 1 diabetes: new insights for therapeutic intervention. Curr Opin Pharmacol, 43, 11-19. doi: 10.1016/j.coph.2018.07.006.

Sheehy, D. F., Quinnell, S. P. &, Vegas, A. J. (2019). Targeting Type 1 Diabetes: Selective Approaches for New Therapies. Biochemistry, 58(4), 214-233. doi: 10.1021/acs.biochem.8b01118.

Sionov, R. S., & Ahdut-HaCohen, R. (2023). A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome. Biomedicines, 11(9), 2558. doi: 10.3390/biomedicines11092558.

Skyler, J. S., Bakris, G. L., Bonifacio, E., Darsow, T., Eckel, R. H., & Groop, L. (2017). Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis. Diabetes, 66(2), 241-255. doi: 10.2337/db16-0806.

Tan, S. Y., Mei, W. J. L, Sim, Y. J., Wong, S. S., Mohamed, E. S. A., & Tan, S.H,. (2019). Type 1 and 2 diabetes mellitus: A review on current treatment approach and gene therapy as potential intervention. Diabetes Metab Syndr, 13(1), 364-372. doi: 10.1016/j.dsx.2018.10.008.

Thomas, P. B., Robertson, D. H., & Chawla, N. V. (2018). Predicting onset of complications from diabetes: a graph based approach. Appl Netw Sci, 3(1), 48. doi: 10.1007/s41109-018-0106-z.

Vinayagam, R., Jayachandran, M., Chung, S. M., & Xu, B. (2018). Guava leaf inhibits hepatic gluconeogenesis and increases glycogen synthesis via AMPK/ACC signaling pathways in streptozotocin-induced diabetic rats. Biomed Pharmacother, 103, 1012-1017. doi: 10.1016/j.biopha.2018.04.127.

Xu, G. K., Qin, Xiao., Wang, G., Xie, G., Li, X., Sun, C., Liu, B. &, Qin, M. (2017). Antihyperglycemic, antihyperlipidemic and antioxidant effects of standard ethanol extract of Bombax ceiba leaves in high-fat-diet- and streptozotocin-induced Type 2 diabetic rats. Chin J Nat Med, 15(3), 168-177. doi: 10.1016/S1875-5364(17)30033-X.

Yaribeygi, H., Farrokhi, F. R., Butler, A.E., & Sahebkar, A. (2019). Insulin resistance: Review of the underlying molecular mechanisms. J Cell Physiol, 234(6), 8152-8161. doi: 10.1002/jcp.27603.

New Treatment Strategies of Type 1 Diabetes Mellitus

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