TYPE 5 DIABETES MELLITUS: PATHOPHYSIOLOGY, Β-CELL RECOVERY AND LOW GLYCAEMIC INDEX DIETARY MANAGEMENT
DOI:
https://doi.org/10.56238/revgeov17n5-056Keywords:
Type 5 Diabetes Mellitus, Malnutrition-Related Diabetes, Β-Cell Recovery, Pancreatic Plasticity, Low Glycaemic Index, Nutritional RehabilitationAbstract
Background: Type 5 diabetes mellitus (T5DM), officially recognized in 2025 by the International Diabetes Federation, represents a distinct diabetes phenotype associated with chronic undernutrition and low body mass index (BMI <18.5 kg/m²). T5DM affects approximately 15–25 million individuals globally, predominantly in South Asia, Sub-Saharan Africa, and resource-limited settings.
Objectives: To synthesize current evidence on (1) physiological changes during recovery from chronic undernutrition, (2) the capacity for pancreatic β-cell recovery after nutritional rehabilitation, and (3) dietary management strategies emphasizing low glycaemic index (GI) feeding patterns.
Methods: Narrative synthesis of clinical studies, experimental models, and systematic reviews (2016–2025, with selective inclusion of seminal earlier works) addressing malnutrition-related diabetes, pancreatic plasticity, and low-GI dietary interventions. Literature was searched in PubMed/MEDLINE, Scopus, and Web of Science. Search terms combined: (“type 5 diabetes” OR “malnutrition-related diabetes”) AND (“beta-cell recovery” OR “pancreatic plasticity”) AND (“low glycemic index” OR “nutritional rehabilitation”).
Results: Three main findings emerged: (1) Chronic malnutrition induces persistent metabolic adaptations (elevated NEFA, reduced BCAA, hormonal dysregulation) that persist beyond weight restoration; (2) Pancreatic β-cells demonstrate remarkable plasticity through four mechanisms: neogenesis from progenitor cells, proliferation, transdifferentiation of α-cells, and redifferentiation of dedifferentiated cells. A critical temporal window (3–6 months in children, narrower in adults) exists for maximal recovery; (3) Low-GI dietary patterns reduce HbA1c by 0.3–0.5% and postprandial glycaemia by 20–30% in diabetes populations. Micronutrient repletion enhances β-cell recovery.
Conclusions: T5DM represents a potentially reversible diabetes phenotype when early, adequate nutritional rehabilitation is implemented. Gradual caloric reintroduction combined with micronutrient repletion and low-GI dietary patterns may optimize β-cell recovery.
Downloads
References
1. Selim, S. (2025). Type 5 diabetes mellitus: Global recognition of a previously overlooked subtype. Bangladesh Journal of Endocrinology and Metabolism, 4, 59–60.
2. International Diabetes Federation. (2025). IDF Diabetes Atlas (11th ed.). International Diabetes Federation.
3. Misra, A. (2024). Malnutrition-related diabetes mellitus: Current evidence and evolving concepts. Diabetes Research and Clinical Practice, 205, 110857.
4. Vial-Dahmer, D., Rosa-Santos, C. A., Silva, L. R., Arantes, V. C., Reis, M. A. B., Milanski, M., et al. (2021). Protein malnutrition early in life increases apoptosis but does not alter β-cell mass during gestation. British Journal of Nutrition, 125(10), 1111–1124.
5. Cheng, C. W., Villani, V., Buono, R., Wei, M., Kumar, S., Yilmaz, O. H., et al. (2017). Fasting-mimicking diet promotes Ngn3-driven β-cell regeneration to reverse diabetes. Cell, 168(5), 775–788.
6. Chernysheva, M. B., Ruchko, E. S., Karimova, M. V., Vorotelyak, E. A., & Vasiliev, A. V. (2024). Development, regeneration, and physiological expansion of functional β-cells: Cellular sources and regulators. Frontiers in Cell and Developmental Biology, 12, 1424278. https://doi.org/10.3389/fcell.2024.1424278
7. Hosseini, A., Shafiee-Nick, R., & Ghorbani, A. (2015). Pancreatic beta cell protection/regeneration with phytotherapy. Brazilian Journal of Pharmaceutical Sciences, 51(1), 1–13. https://doi.org/10.1590/S1984-82502015000100001
8. Rosyid, F. N. (2022). Micronutrient deficiency in type 1 and 2 diabetes mellitus: Diagnosis and therapy. International Journal of Research in Medical Sciences, 10(4), 973–979. https://doi.org/10.18203/2320-6012.ijrms20221035
9. Kiprotich, D., Yegon, N. C., & Walekhwa, M. N. (2021). Level of micronutrients affects pathophysiology of diabetes mellitus: A scoping review. European Journal of Medical and Health Sciences, 3(5), 98–116.
10. Mostafaei, Z., Paknahad, Z., Feizi, A., & Hovsepian, S. (2025). Dietary antioxidant minerals (Cr, Mg, Cu, Se, Zn) in diabetic children and their relationship with fasting and postprandial blood glucose. International Journal of Preventive Medicine, 16, 24. https://doi.org/10.4103/ijpvm.ijpvm_181_24
11. Sun, L., Goh, H. J., Govindharajulu, P., Leow, M. K., & Henry, C. J. (2022). Low-glycemic index diets as an intervention in metabolic diseases: A systematic review and meta-analysis. Nutrients, 14(2), 307. https://doi.org/10.3390/nu14020307
12. Jenkins, D. J., Willett, W. C., Yusuf, S., Hu, F. B., Glenn, A. J., Liu, S., et al. (2024). Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: A meta-analysis of megacohorts of more than 100 000 participants. Lancet Diabetes & Endocrinology, 12(2), 107–118.
13. Livesey, G., Taylor, R., Livesey, H. F., Buyken, A. E., Jenkins, D. J. A., Augustin, L. S. A., Sievenpiper, J. L., Barclay, A. W., Vinoy, S., Loughman, G., Tosh, S. M., Wolever, T. M. S., Stevenson, L., Trichopoulou, A., Meek, J., Dahal, A., Middleton, D., Brouns, F. J., & Brand-Miller, J. C. (2019). Dietary glycemic index and load and the risk of type 2 diabetes: Assessment of causal relations. Nutrients, 11(6), 1280. https://doi.org/10.3390/nu11061280
14. Page, L., McCain, E., & Freemark, M. (2025). Adaptive responses in severe acute malnutrition: Endocrinology, metabolomics, mortality, and growth. Nutrients, 17(17), 2864. https://doi.org/10.3390/nu17172864
15. Semba, R. D., Trehan, I., Gonzalez-Freire, M., Kraemer, K., Moaddel, R., Ordiz, M. I., et al. (2016). Perspective: The potential role of essential amino acids and the mechanistic target of rapamycin complex 1 (mTORC1) pathway in the pathogenesis of child stunting. Advances in Nutrition, 7(5), 853–865.
16. Thompson, D. S., Hoang, T. T., Arredondo, B. P., Brickman, C. M., Mwakamui, S., Vos, M. B., Dedhia, M., Soleimani, B., Ladesic, O., Spratlen, M. J., Freemark, M., Manary, M. J., Ilkayeva, O., Sharma, R., Wyce, A., Bain, J. R., Williams, S. M., Stein, A. D., Martorell, R., & Stein, C. R. (2020). Childhood severe acute malnutrition is associated with metabolomic changes in adulthood. JCI Insight, 5(24), e141316. https://doi.org/10.1172/jci.insight.141316
17. Ferdous, F., Filteau, S., Schwartz, N. B., Gumede-Moyo, S., & Cox, S. E. (2023). Association of postnatal severe acute malnutrition with pancreatic exocrine and endocrine function in children and adults: A systematic review. British Journal of Nutrition, 129(4), 576–609. https://doi.org/10.1017/S0007114522001416
18. Portha, B., Chavey, A., & Movassat, J. (2011). Early-life origins of type 2 diabetes: Fetal programming of the beta-cell mass. Experimental Diabetes Research, 2011, 105076. https://doi.org/10.1155/2011/105076
19. Fernandez-Twinn, D. S., Hjort, L., Novakovic, B., Ozanne, S. E., & Saffery, R. (2019). Intrauterine programming of obesity and type 2 diabetes. Diabetologia, 62(10), 1789–1801. https://doi.org/10.1007/s00125-019-4951-9
20. Gehrig, J. L., Venkatesh, S., Chang, H. W., Hibberd, M. C., Kung, V. L., Cheng, J., Chen, R. Y., Subramanian, S., Cowardin, C. A., Meier, M. F., O'Donnell, D., Talcott, M., Spears, L. D., Semenkovich, C. F., Henrissat, B., Giannone, R. J., Hettich, R. L., Ilkayeva, O., Muehlbauer, M., Newgard, C. B., Sawyer, C., Head, R. D., Rodionov, D. A., Arzamasov, A. A., Leyn, S. A., Osterman, A. L., & Gordon, J. I. (2019). Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Science, 365(6449), eaau4732. https://doi.org/10.1126/science.aau4732
21. Fazeli, P. K., & Klibanski, A. (2018). Effects of anorexia nervosa on bone metabolism. Endocrine Reviews, 39(6), 895–910. https://doi.org/10.1210/er.2018-00063
22. Zheng, J., Xiao, X., Zhang, Q., Yu, M., Xu, J., & Wang, Z. (2014). DNA methylation: The pivotal interaction between early-life nutrition and glucose metabolism in later life. British Journal of Nutrition, 112(11), 1850–1857. https://doi.org/10.1017/S0007114514002827
23. Sandovici, I., Hammerle, C. M., Ozanne, S. E., & Constância, M. (2013). Developmental and environmental epigenetic programming of the endocrine pancreas: Consequences for type 2 diabetes. Cellular and Molecular Life Sciences, 70(9), 1575–1595. https://doi.org/10.1007/s00018-012-1190-8
