Histopathological Changes In Lung Tissue Caused By Diabetes: A Review

Abstract

Diabetes mellitus associated with oxidative stress and inflammation can affect many organs. While the effects of diabetes on many organs are well known and documented, its mechanisms of action on the lung are known far less. Hyperglycemia can lead to lung damage by increasing oxidative stresses and inflammation. Diabetes may be a trigger for pulmonary fibrosis, as studies suggest that there may be an important link between pulmonary fibrosis and diabetes. In this review, the histopathological changes caused by diabetes in the lung tissue were summarized. In addition, changes in the lung due to inflammation, oxidative stress and pulmonary fibrosis mechanisms were evaluated.

Keywords

• : Lung
• Diabetes mellitus
• fibrosis
• inflammation
• oxidative stress

References

1. 1. Goldman MD. Lung dysfunction in diabetes. Diabetes care. 2003;26(6):1915-8.
2. 2. Pitocco D, Fuso L, Conte EG, Zaccardi F, Condoluci C, Scavone G, et al. The diabetic lung-a new target organ? Rev Diabet Stud 2012;9(1):23.
3. 3. Erdoğan BB, Uzaslan E. Diabetes and lung. Journal of Uludag University Faculty of Medicine 2005. 31;(1):71-74.
4. 4. Ramachandran A, Snehalatha C, Nanditha A. Classification and diagnosis of diabetes. In Holt RICockram CSFlyvbjerg A, Goldstein BJ, editors. Textbook of diabetes. 5th ed. Oxford, UK: Wiley-Blackwell; 2017. p. 23–8.
5. 5. Zhang RH, Cai YH, Shu LP, Yang J, Qi L, Han M, et al. Bidirectional relationship between diabetes and pulmonary function: a systematic review and meta-analysis. Diabetes Metab. 2020:101186.
6. 6. Nathan DM. Diabetes: advances in diagnosis and treatment. Jama 2015;314(10):1052-62.
7. 7. Khateeb J, Fuchs E, Khamaisi M. Diabetes and lung disease: a neglected relationship Rev Diabet Stud 2019;15:1.
8. 8. Kinney GL, Black-Shinn JL, Wan ES, Make B, Regan E, Lutz S, et al. Pulmonary function reduction in diabetes with and without chronic obstructive pulmonary disease. Diabetes care 2014;37(2):389-95.

9. 9. Matsubara T, Hara F. The pulmonary function and histopathological studies of the lung in diabetes mellitus. Nihon Ika Daigaku Zasshi 1991;58(5):528-36.
10. 10. Ehrlich SF, Quesenberry CP, Van Den Eeden SK, Shan J, Ferrara A. Patients diagnosed with diabetes are at increased risk for asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and pneumonia but not lung cancer. Diabetes care 2010;33(1):55-60.
11. 11. Chen CM, Juan SH, Pai MH, Chou HC. Hyperglycemia induces epithelial–mesenchymal transition in the lungs of experimental diabetes mellitus. Acta histochem 2018;120(6):525-33.
12. 12. Honiden S, Gong MN. Diabetes, insulin, and development of acute lung injury. Crit. Care Med 2009;37(8):2455.
13. 13. Mannino DM, Ford ES, Redd SC. Obstructive and restrictive lung disease and markers of inflammation: data from the Third National Health and Nutrition Examination. Am J Med 2003;114(9):758-62.
14. 14. Di Naso FC, Forgiarini Júnior LA, Forgiarini LF, Porawski M, Dias AS, Marroni NAP. Aminoguanidine reduces oxidative stress and structural lung changes in experimental diabetes mellitus. J Bras Pneumol 2010; 36, 485-489.
15. 15. Klein O, Krishnan J, Glick S, Smith L. Systematic review of the association between lung function and Type 2 diabetes mellitus. Diabetic Med 2010;27(9):977-87.
16. 16. Hsia CC, Raskin P. Lung function changes related to diabetes mellitus. Diabetes Technol. Ther. 2007;9(S1):S-73-S-82.
17. 17. Onk D, Onk OA, Erol HS, Özkaraca M, Çomaklı S, Ayazoğlu TA, et al. Effect of melatonin on antioxidant capacity, ınflammation and apoptotic cell death in lung tissue of diabetic rats. Acta Cir. Bras 2018;33:375-85.
18. 18. Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C, et al. Diabetes is a risk factor for the progression and prognosis of COVID‐19. Diabetes Metab. Res. Rev 2020;36(7):e3319.
19. 19. Al-Kuraishy HM, Al-Gareeb AI, Alblihed M, Cruz-Martins N, Batiha GE-S. COVID-19 and risk of acute ischemic stroke and acute lung injury in patients with type ii diabetes mellitus: the anti-inflammatory role of metformin. Front. Med 2021;8:110.
20. 20. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia–a systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr 2020;14(4):395-403.
21. 21. Wang CM, Hsu CT, Niu HS, Chang CH, Cheng JT, Shieh JM. Lung damage induced by hyperglycemia in diabetic rats: The role of signal transducer and activator of transcription 3 (STAT3). J. Diabetes Complicat 2016;30(8):1426-33.
22. 22. Alireza S, Leila N, Siamak S, Mohammad-Hasan KA, Behrouz I. Effects of vitamin E on pathological changes induced by diabetes in rat lungs. Respir Physiol Neurobiol 2013;185(3):593-9.
23. 23. Mexas AM, Hess RS, Hawkins EC, Martin LD. Pulmonary lesions in cats with diabetes mellitus. J. Vet. Intern. Med 2006;20(1):47-51.
24. 24. Davis TM, Knuiman M, Kendall P, Vu H, Davis WA. Reduced pulmonary function and its associations in type 2 diabetes: the Fremantle Diabetes Study. Diabetes Res. Clin. Pract 2000;50(2):153-9.
25. 25. Weynand B, Jonckheere A, Frans A, Rahier J. Diabetes mellitus induces a thickening of the pulmonary basal lamina. Respiration 1999;66(1):14-9.
26. 26. Medeiros TDD, Pereira AT, Silva FSD, Bortolin RH, Taveira KVM, et al. Ethanol extract of Cissampelos sympodialis ameliorates lung tissue damage in streptozotocin-induced diabetic rats. Braz. J. Pharm. Sci 2020;56.
27. 27. Lazarus R, Sparrow D, Weiss ST. Handgrip strength and insulin levels: cross-sectional and prospective associations in the Normative Aging Study. Metabolism 1997;46(11):1266-9.
28. 28. Ofuwe AF, Kida K, Thurlbeck WM. Experimental diabetes and the lung. Am Rev Respir Dis. 1988; 137(1),162-66.
29. 29. Klein OL, Kalhan R, Williams M, Tipping M, Lee J, Peng J, et al. Lung spirometry parameters and diffusion capacity are decreased in patients with Type 2 diabetes. Diabetic Med 2012;29(2):212-9.
30. 30. Rajasurya V, Gunasekaran K, Surani S. Interstitial lung disease and diabetes. World J. Diabetes 2020;11(8):351.
31. 31. Zhang X, Liu Y, Shao R, Li W. Cdc42-interacting protein 4 silencing relieves pulmonary fibrosis in STZ-induced diabetic mice via the Wnt/GSK-3β/β-catenin pathway. Exp. Cell Res 2017;359(1):284-90.
32. 32. Li Y, Ma J, Zhu H, Singh M, Hill D, Greer PA, et al. Targeted inhibition of calpain reduces myocardial hypertrophy and fibrosis in mouse models of type 1 diabetes. Diabetes 2011;60(11):2985-94.
33. 33. Chilosi M, Poletti V, Zamò A, Lestani M, Montagna L, Piccoli P, et al. Aberrant Wnt/β-catenin pathway activation in idiopathic pulmonary fibrosis. Am. J. Clin. Pathol 2003;162(5):1495-502.
34. 34. Flozak AS, Lam AP, Russell S, Jain M, Peled ON, Sheppard KA, et al. β-catenin/T-cell factor signaling is activated during lung injury and promotes the survival and migration of alveolar epithelial cells. J. Biol. Chem 2010;285(5):3157-67.
35. 35. Kneidinger N, Yildirim AON, Callegari J, Takenaka S, Stein MM, Dumitrascu R, et al. Activation of the WNT/β-catenin pathway attenuates experimental emphysema. Am. J. Respir. Crit. Care Med 2011;183(6):723-33.
36. 36. van Noort M, Meeldijk J, van der Zee R, Destree O, Clevers H. Wnt signaling controls the phosphorylation status of β-catenin. J. Biol. Chem 2002;277(20):17901-5.
37. 37. Chen X, Shi C, Meng X, Zhang K, Li X, Wang C, et al. Inhibition of Wnt/β-catenin signaling suppresses bleomycin-induced pulmonary fibrosis by attenuating the expression of TGF-β1 and FGF-2. Exp. Mol. Pathol 2016;101(1):22-30.
38. 38. Lee J-Y, Jeon I, Lee JM, Yoon J-M, Park SM. Diabetes mellitus as an independent risk factor for lung cancer: a meta-analysis of observational studies. Eur J Cancer 2013;49(10):2411-23.
39. 39. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005;54(6):1615-25.
40. 40. Haskins K, Bradley B, Powers K, Fadok V, Flores S, Ling X, et al. Oxidative stress in type 1 diabetes. Ann. N. Y. Acad. Sci 2003;1005(1):43-54.
41. 41. Lange P, Parner J, Schnohr P, Jensen G. Copenhagen City Heart Study: longitudinal analysis of ventilatory capacity in diabetic and nondiabetic adults. Eur Respir J 2002;20(6):1406-12.
42. 42. Lee WL, Downey GP. Neutrophil activation and acute lung injury. Curr Opin Crit Care 2001;7(1):1-7.
43. 43. Reinhart PG, Bassett DJ, Bhalla DK. The influence of polymorphonuclear leukocytes on altered pulmonary epithelial permeability during ozone exposure. Toxicology. 1998;127(1-3):17-28.
44. 44. Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. International journal of physiology, pathophysiology and pharmacology. 2019;11(3):45.
45. 45. Tiengo A, Fadini G, Avogaro A. The metabolic syndrome, diabetes and lung dysfunction. Diabetes Metab 2008;34(5):447-54.
46. 46. Sonnenberg GE, Krakower GR, Kissebah AH. A novel pathway to the manifestations of metabolic syndrome. Obes Res 2004;12(2):180-6.
47. 47. Gumieniczek A, Hopkała H, Wójtowicz Z, Wysocka M. Changes in antioxidant status of lung tissue in experimental diabetes in rabbits. Clin. Biochem 2002;35(2):147-9.
48. 48. Forgiarini Junior LA, Kretzmann NA, Tieppo J, Picada JN, Dias AS, Marroni NAP. Lung alterations in a rat model of diabetes mellitus: effects of antioxidant therapy. J. Bras. Pneumol 2010;36:579-87.