Diabetic Pulmopathy: A New Clinical Challenge for Diabetology

Breathlessness is a frequent symptom in patients with diabetes [1]. The first diseases which have to be excluded are coronary heart disease and inflammatory diseases of the upper respiratory tract [2]. However, epidemiological studies have long shown that patients with diabetes mellitus are overrepresented among the group of patients with idiopathic pulmonary fibrosis (IPF) [3] [4]. These patients are characterized by a more severe disease progression compared to IPF patients without diabetes [4] [5]. Thus, the speculation arises that pulmonary fibrosis might be associated with diabetes.

Since the lung is the organ with the most extreme exposure to oxygen and consecutive oxidative stress, this organ is prone to be also a target of metabolic abnormalities in diabetes [6] [7] [8]. Diabetes by itself is associated with an increase in reactive oxygen species, leading to inflammation, cell destruction and finally to fibrosis – also in the lung [7] [9] [10]. Furthermore, it’s well known that antioxidant defense mechanisms are reduced in diabetes, as are defense mechanisms against dicarbonyl stress [11]. Therefore it is surprising that pulmonary dysfunction in diabetes has been neglected for so long time. However, before the term diabetic pulmopathy can be established, mechanistic studies proving cause-effect-relationship between diabetes and pulmonary fibrosis are mandatory. The first data indicate that indeed pulmonary fibrosis might be a consequence of diabetes [12] [13] [14].

• References

• 1 Kopf S, Groener JB, Kender Z. et al. Breathlessness and restrictive lung disease: An important diabetes-related feature in patients with type 2 diabetes. Respiration 2018; 96: 29-40
• 2 Berliner D, Schneider N, Welte T. et al. The differential diagnosis of dyspnea. Deutsches Arzteblatt International 2016; 113: 834-845
• 3 Kreuter M, Ehlers-Tenenbaum S, Palmowski K. et al. Impact of comorbidities on mortality in patients with idiopathic pulmonary fibrosis. PloS One 2016; 11: e0151425
• 4 Kim YJ, Park JW, Kyung SY. et al. Clinical characteristics of idiopathic pulmonary fibrosis patients with diabetes mellitus: The national survey in Korea from 2003 to 2007. J Korean Med Sci 2012; 27 : 756-760
• 5 Kishaba T, Nagano H, Nei Y. et al. Clinical characteristics of idiopathic pulmonary fibrosis patients according to their smoking status. J Thorac Dis 2016; 8: 1112-1120
• 6 Sosulski ML, Gongora R, Danchuk S. et al. Deregulation of selective autophagy during aging and pulmonary fibrosis: The role of TGFbeta1. Aging Cell 2015; 14: 774-783
• 7 Sinha K, Das J, Pal PB. et al. Oxidative stress: The mitochondria-dependent and mitochondria-independent pathways of apoptosis. ArchToxicol 2013; 87: 1157-1180
• 8 Sandler M. Is the lung a ‘target organ’ in diabetes mellitus?. Arch Intern Med 1990; 150: 1385-1388
• 9 Paravicini TM, Touyz RM. NADPH oxidases, reactive oxygen species, and hypertension: Clinical implications and therapeutic possibilities. Diabetes Care 2008; 31 (Suppl. 02) S170-S180
• 10 Jagadapillai R, Rane MJ, Lin X. et al. Diabetic microvascular disease and pulmonary fibrosis: The contribution of platelets and systemic inflammation. Int J Mol Sci 2016; 17: pii: E1853
• 11 Groener JB, Oikonomou D, Cheko R. et al. Methylglyoxal and advanced glycation end products in patients with diabetes - What we know so far and the missing links. Exp Clin Endocrinol Diabetes 2017;
• 12 Zhang X, Liu Y, Shao R. et al. Cdc42-interacting protein 4 silencing relieves pulmonary fibrosis in STZ-induced diabetic mice via the Wnt/GSK-3beta/beta-catenin pathway. Exp Cell Res 2017; 359: 284-290
• 13 Oztay F, Sancar-Bas S, Gezginci-Oktayoglu S. etal. Exendin-4 partly ameliorates - hyperglycemia-mediated tissue damage in lungs of streptozotocin-induced diabetic mice. Peptides 2018; 99: 99-107
• 14 Kumar V, Fleming T, Terjung S. et al. Homeostatic nuclear RAGE-ATM interaction is essential for efficient DNA repair. Nucleic Acids Res 2017; 45: 10595-10613
• 15 Röhling M, Pesta D, Markgraf DF. et al. Metabolic determinants of impaired pulmonary function in patients with newly diagnosed type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2018; 126: 584-589
• 16 Spagnolo P, Kreuter M, Maher TM. et al. Metformin does not affect clinically relevant outcomes in patients with idiopathic pulmonary fibrosis. Respiration 2018; 1-9
• 17 Gaunaurd IA, Gomez-Marin OW, Ramos CF. et al. Physical activity and quality of life improvements of patients with idiopathic pulmonary fibrosis completing a pulmonary rehabilitation program. Respir Care 2014; 59: 1872-1879
• 18 Vainshelboim B. Exercise training in idiopathic pulmonary fibrosis: Is it of benefit?. Breathe (Sheff) 2016; 12: 130-138