EFFECT OF MEDIUM CHAIN TRIGLYCERIDE-KETOGENIC DIET ON THE LUNGS OF TYPE 2 DIABETIC MALE NEW ZEALAND RABBITS
Abstract
Type 2 diabetes mellitus is a metabolic disorder that results in impairment of the lungs, associated with both structural and functional alterations. Ketogenic diet is a high-fat, moderate-protein and low-carbohydrate dietary regimen, with the potential of ameliorating diabetic lung complications. This study evaluated the effects of medium chain triglyceride-ketogenic diet (MCT-KD) on the lungs of type 2 diabetic male New Zealand rabbits. Type 2 diabetes was induced by feeding the rabbits formulated high fat diet for ten weeks. Twenty rabbits were divided into five groups of four rabbits each: Group I was a normoglycemic group fed with normal diet; Group II was a normoglycemic group fed with a MCT-KD; Group III was a diabetic group fed with normal diet; Group IV was a diabetic group fed with MCT-KD while Group V was a diabetic group fed with normal diet and oral administration of 4 mg/kg pioglitazone. There was a significant increase (p < 0.05) in cellular infiltration of total white blood cells, lymphocytes, neutrophils and macrophages into the bronchoalveolar lavage fluid of diabetic lungs. However, feeding with MCT-KD and administration of 4 mg/kg pioglitazone significantly decreased (p < 0.05) total white blood cells and the differential components in the diabetic lungs. The MCT-KD was observed to reduce the lung weight of the diabetic rabbits, however, no change was observed in the relative lung weight. Cellular infiltration, reduced alveolar spaces, distorted bronchial epithelium and oedema were observed in the lungs. These were observed to be alleviated after feeding with MCT-KD.
References
Ali, M. O. (2014). Pulmonary Complication in Diabetes Mellitus. Mymensingh Medical Journal, 23(3), 603-605. https://pubmed.ncbi.nlm.nih.gov/25178621.
Almeida, R. S., De Malo, C., Chaves, M. S. S., Baptista, G. M., Margotto, S. S., & Andrade, L. J. (2016). Diabetic Pneumopathy. Brazilian Journal of Medicine and Human Health, 4(1), 21-28. https://doi.org/10.17267/2317-3386bjmhh.v4i1.791. DOI: https://doi.org/10.17267/2317-3386bjmhh.v4i1.791
Amal, I. A., Hamdy, G., Amin, M., & AlaaRashad, A. (2013). Pulmonary function changes in diabetic lung. Egyptian Journal of Chest Diseases, 62(3), 513-517. https://doi.org/10.1016/j.ejcdt.2013.07.006. DOI: https://doi.org/10.1016/j.ejcdt.2013.07.006
American Diabetes Association. (2009). Classification and Diagnosis of Diabetes. Diabetes Care, 40 (1), 11-24. https://doi.org/10.2337/dc09-S062. DOI: https://doi.org/10.2337/dc17-S005
Augustin, K., Khabbush, A., Williams, S., Eaton, S., Orford, M., & Cross, J. H. (2018). Mechanism of action of Medium chain triglyceride-ketogenic diet in neurological and metabolic disorders. The Lancet Neurology, 17, 84-93. https://doi.org/10.1016/S1474-4422(17)30408-8. DOI: https://doi.org/10.1016/S1474-4422(17)30408-8
Baker, E.H., & Baines, D. L. (2018). Airway glucose homeostasis: a new target in the prevention and treatment of pulmonary infection. Chest, 153, 507514. https://doi.org/10.1016/j.chest.2017.05.031 DOI: https://doi.org/10.1016/j.chest.2017.05.031
Bankroft, D. J., & Stevens, A. (1990). Theory and Practice of Histopathological Techniques. (3rd Ed.). Churchill Livingstone. https://knustmeltsa.wordpress.com/wp-content/uploads/2020/08/bancrofts-theory-and-practice-of-histological-techniques-7th-edition-0702042269autosaved1.pdf.
Belvisi, M. G., Hele, D. J., & Birrell, M. A. (2006). Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation. European Journal of Pharmacology, 533, 101109. https://doi.org/10.1016/j.ejphar.2005.12.048. DOI: https://doi.org/10.1016/j.ejphar.2005.12.048
Bhargava, P., & Lee, C. H. (2012). Role and function of macrophages in the metabolic syndrome. Biochemical Journal, 442, 25362. https://doi.org/10.1042/BJ20111708. DOI: https://doi.org/10.1042/BJ20111708
Casqueiro, J., Casqueiro, J., & Alves, C. (2012). Infections in patients with diabetes mellitus: A review of pathogenesis. Indian Journal of Endocrinology and Metabolism, 16, 27-36. https://doi.org/10.4103/2230-8210.94253. DOI: https://doi.org/10.4103/2230-8210.94253
Chaudhari, B., Jagdele, P., Raissudin, S., Thiparti, S. S., Shukla, M., & Singh, K.P. (2011). Histological studies of murine model of asthma. Journal of Applied Pharmaceutical Sciences, 1(10), 77-84. URL: https://www.japsonline.com/admin/php/uploads/302_pdf.pdf.
Cheesbrough, M. (1999). District Laboratory Practice in Tropical Countries Part I. (1st ed.). Cambridge University Press. www.cambridge.org/9780521676304.
Dawud, F.A., Dubo, A. B., Yusuf, N. Y., & Umar, I. A. (2016). Effects of aqueous extract of Allium cepa (red onion) on ovalbumin induced allergic asthma in Wistar rats. Bayero Journal of Pure and Applied Sciences, 9(2), 95101. https://doi.org/10.4314/bajopas.v9i2.19. DOI: https://doi.org/10.4314/bajopas.v9i2.19
De Nucci, S., Bonfiglio, C., Donvito, R., Di Chito, M., Cerabino, N., Rinaldi, R., Sila, A., Shahini, E., Giannuzzi, V., Pesole, P.L., Coletta, S., Lanzilotta, E., Piazzolla, G., Cozzolongo, R., Giannelli, G., & De Pergola, G. (2023). Effects of an Eight Week Very Low-Calorie Ketogenic Diet (VLCKD) on White Blood Cell and Platelet Counts in Relation to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Subjects with Overweight and Obesity. Nutrients, 15(20), 4468-4489. https://doi.org/10.3390/nu15204468. DOI: https://doi.org/10.3390/nu15204468
Dubo, A. B., Dawud, F. A., Umar, I. A., Alex, E. A., Baiyekusi, S., & Farrau, U. (2019). Lauric Acid Alleviates inflammation and Structural Changes in the Lungs of Type II Diabetic Male Wistar Rats. Journal of African Association of Physiological Sciences, 7(2), 88-96. https://www.ajol.info/index.php/jaaps/article/view/192646.
Eidangbe, G. O. (2025). Antioxidant and Anti-Inflammatory Activities of Stevia Rebaudiana Leaf Extract in Diabetic Rats. FUDMA Journal of Sciences, 9(1), 301 - 306. https://oi.Org/10.33003/Fjs-2025-0901-2944. DOI: https://doi.org/10.33003/fjs-2025-0901-2944
Fernndez-Real, J.M., Valds, S., Manco, M., Chico, B., Botas, P., Campo, A., Casamitjana, R., Delgado, E., Salvador, J., Fruhbeck, G., Mingrone, G., & Ricart, W. (2010). Surfactant protein d, a marker of lung innate immunity, is positively associated with insulin sensitivity. Diabetes Care, 33, 847853 https://doi.org/10.2337/dc09-0542. DOI: https://doi.org/10.2337/dc09-0542
Hallberg, S.J., McKenzie, A.L., Williams, P.T., Bhanpuri, N.H., Peters, A.L., Campbell, W.W., Hazbun, T.L., Volk, B.M., McCarter, J.P., Phinney, S.D., & Volek, J.S. (2018). Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study. Journal of Diabetes Therapy, 9(2), 583-612. https://doi.org/10.1007/s13300-018-0373-9. DOI: https://doi.org/10.1007/s13300-018-0373-9
Hussain, M., & Liu, G. (2024). Eosinophilic Asthma: Pathophysiology and Therapeutic Horizons. Cells, 13(5), 384. https://doi.org/10.3390/cells13050384. DOI: https://doi.org/10.3390/cells13050384
Huttenlocher, P. R., Wilbourn, A. J., & Signore, J. M. (1971). Medium chain triglycerides as a therapy for intractable childhood epilepsy. Neurobiology, 21, 1097-1103. https://doi.org/10.1212/wnl.21.11.1097. DOI: https://doi.org/10.1212/WNL.21.11.1097
Jimoh, A., Tanko, Y., Ahmed, A., Mohammed, A., & Ayo, J. O. (2015). Protective effect of resveratrol coadministration with high fat diet on blood glucose homeostasis and thyroid function in New Zealand rabbits. Cell Biology, 3(1), 19-24. https://doi.org/10.11648/j.cb.20150301.13. DOI: https://doi.org/10.11648/j.cb.20150301.13
Kaparianos, A., Argyropoulou, E., Sampsonas, F., Karkoulias, K., Tsiamita, M., & Spiropoulos, K. (2008). Pulmonary complications in diabetes mellitus. Chronic Respiratory Disease, 5, 101-108. https://doi.org/10.1177/1479972307086313. DOI: https://doi.org/10.1177/1479972307086313
Kloc, M., Ghobrial, R. M., Lewicki, S., & Kubiak, J.Z. (2020). Macrophages in diabetes mellitus (DM) and COVID-19: do they trigger DM? Journal of Diabetes & Metabolic Disorders, 19, 20452048. https://doi.org/10.1007/s40200-020-00665-3. DOI: https://doi.org/10.1007/s40200-020-00665-3
Kolahian, S., Leiss, V., & Nrnberg, B. (2019). Diabetic lung disease: fact or fiction? Reviews in Endocrine and Metabolic Disorders, 20(3), 303-319. https://doi.org/10.1007/s11154-019-09516-w. DOI: https://doi.org/10.1007/s11154-019-09516-w
Kossoff, E. H., McGrogan, J. R., Bluml, R. M., Pillas, D. J., Rubenstein, J. E., & Vining, E. P. (2006). A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsia, 47(2), 421424. https://doi.org/10.1111/j.1528-1167.2006.00438.x. DOI: https://doi.org/10.1111/j.1528-1167.2006.00438.x
Kuziemski, K., Specjacski, K., & Jassem, E. (2011). Diabetic Pulmonary Microangiopathy - fact or fiction? Journal of Endocrinology, 62(2), 171-175. https://pubmed.ncbi.nlm.nih.gov/21528480.
Li, Z., & Heber, D. (2020). Ketogenic Diets. Journal of the American Medical Association, 323(4),386-402. https://doi.org/10.1001/jama.2019.18408. DOI: https://doi.org/10.1001/jama.2019.18408
Lima, R.C.P., Camerino, S.R.A.S., Frana, T.C.L., Rodrigues, D.S.A., Gouveia, M.G.S., Ximenes-da-Silva, A., Bassini, A., Prado, E.S., & Cameron, L.C. (2017). Keto analogues and amino acids supplementation induce a decrease of white blood cell counts and a reduction of muscle damage during intense exercise under thermoneutral conditions. Food and Function, 8(4), 1519-1525. https://doi.org/10.1039/c7fo00189d. DOI: https://doi.org/10.1039/C7FO00189D
Liu, C., Liu, R., Fu, H., Li, J., Wang, X., Cheng, L., Korantzopoulos, P., Tse, G., Li, G., & Liu, T. (2017). Pioglitazone attenuates atrial remodeling and vulnerability to atrial fibrillation in alloxan-induced diabetic rabbits. Cardiovascular Therapy, 35(5). https://doi.org/10.1111/1755-5922.12284. DOI: https://doi.org/10.1111/1755-5922.12284
Liu, Y. C., & Wang, H.-S. (2013). Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets. Biomedical Journal, 36(1), 915. https://doi.org/10.4103/2319-4170.107154. DOI: https://doi.org/10.4103/2319-4170.107154
Machado, L. M. Q., Serra, D. S., Neves, T. G., Cavalcante, F. S. A., Cecattao, V. M., Leal-Cardoso, J.S., Zin, W. A., & Morreira-Gomez, M.D. (2021). Pulmonary impairment in type 2 diabetic rats and its improvement by exercise. Acta Physiologica, https://doi.org/10.1111/apha.13708. DOI: https://doi.org/10.1111/apha.13708
Mahmood, A., Ahmed, S. T., Hameed, A., Bhagwani, A. R., & Borges, K. J. J. (2024). Exploring the Streptozotocin-Nicotinamide Mouse Model in Balb/C Mice: Gaining Insights into Diabetic Pneumopathy. Pakistan Journal of Physiology, 20 (3), 31-36. https://doi.org/10.69656/pjp.v20i3.1673 DOI: https://doi.org/10.69656/pjp.v20i3.1673
Masood, W., Annamaraju, P., & Uppaluri, K. R. (2021). Ketogenic Diet. Starpearl, 1(1), 1-5. URL: https://www.ncbi.nlm.nih.gov/books/NBK499830.
Mayer-Davis, E., Kahskoska, A. R., Jefferies, C., Danbelea, D., Balde, N., Gong, C., X. & Aschner, P. (2018). Definition, epidemiology and classification of diabetes in children and adolescents. ISPAD Clinical Practice Consensus Guidelines 2018. https://doi.org/10.1111/pedi.12773. DOI: https://doi.org/10.1111/pedi.12773
Nawale, R. B., Mourya, V. K., & Bhise, S. B. (2006). Non-Enzymatic Glycation of Proteins: A cause for Complications in Diabetes. International Journal of Biochemistry and Biophysics, 43, 337-344. URL: https://pubmed.ncbi.nlm.nih.gov/17285797.
Okoduwa, S. I. R., Umar, I.A., James, D.B., & Inuwa, I.A. (2017). Anti-Diabetic Potential of Ocimumgratissimum Leaf Fractions in Fortified Diet-Fed Streptozotocin Treated Rat Model of Type-2 Diabetes. Medicines, 73(4), 1-21. https://doi.org/10.3390/medicines4040073. DOI: https://doi.org/10.3390/medicines4040073
Rego-Costa, A.C., Rosado, E.L., & Soares-Monta, M. (2012). Influence of the dietary intake of medium chain triglycerides on body composition, energy expenditure and satiety; A systematic review. Nutricion Hospitalaria, 27(1),103-108. doi:10.1590/S0212-16112012000100011.
Sanya, E. O., Soladoye, A. O., Desalu, O. O., Kolo, P. M., Olatunji, L. A., & Olarinoye, J. K. (2016). Antiseizure Effects of Ketogenic Diet on Seizures Induced with Pentylenetetrazole, 4-Aminopyridine and Strychnine in New Zealand rabbits. Nigerian Journal of Physiological Sciences, 115-119. https://pubmed.ncbi.nlm.nih.gov/28262846.
Schreck, K. C., Lwin, M., Strowd, R. E., Henry-Barron, B. J., Blakeley, J. O., & Cervenka, M. C. (2017). Effect of ketogenic diets on leukocyte counts in patients with epilepsy. Nutritional Neuroscience, 22(7), 522527. https://doi.org/10.1080/1028415X.2017.1416740. DOI: https://doi.org/10.1080/1028415X.2017.1416740
Standiford, T. J., Keshamouni, V. G., & Reddy, R. C. (2005). Peroxisome Proliferator-activated Receptor-gamma as a Regulator of Lung Inflammation and Repair. Proceedings of American Thoracic Society, 2, 226-231. https://doi.org/10.1513/pats.200501-010AC. DOI: https://doi.org/10.1513/pats.200501-010AC
Suarez, O. A. X., Lucchesi, A. N., Cataneo, A. J. M., & Spadella, C. T. (2016). Alloxan-Diabetes Causes Oxidative Imbalance and Morphological,Morphometric and Ultrastructural Changes in Rat Lungs. European Journal of Pharmaceutical and Medical Research, 3(12), 1-10. https://doi.org/10.1155/2015/494578. DOI: https://doi.org/10.1155/2015/494578
Vishwakarma, P., Usman, K., Garg, R., Bajpai, J., Sethi, R., & Pradhan, A. (2021). Clinical and Radiological Presentations of Various Pulmonary Infections in Hospitalized Diabetes Mellitus Patients: A Prospective, Hospital-Based, Comparative, Case Series Study. Pulmonary Medicine, 18. https://doi.org/10.1155/2021/8878746. DOI: https://doi.org/10.1155/2021/8878746
World Health Organization. (2024). Global Report on diabetes. Retrieved from: http://apps.who.int/iris/bitstream/10665/204871/1/9789241565257_eng.pdf
Zheng, H., Wu, J., Jin, Z. & Yan, L. (2017). Potential Biochemical Mechanisms of Lung Injury in Diabetes. Aging and Disease, 8(1), 7-16. https://doi.org/10.14336/AD.2016.0627. DOI: https://doi.org/10.14336/AD.2016.0627
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