title: Type 1 diabetes mellitus is an independent risk factor for pulmonary fibrosis.
abstract: The objective of this study was to assess the clinical and histopathological relationship between pulmonary fibrosis and type 1 diabetes. We examined clinical pulmonary function parameters and transbronchial lung biopsies to assess associated histopathological changes in 12 type 1 diabetic patients presenting with dyspnea. Lung CT images pulmonary function tests from 12 diabetic patients without dyspnea and from 12 matched normal subjects served as controls. A similar histopathological analysis, including cytokine levels and pro-fibrotic markers, was performed on lung tissues in mice after the induction of experimental diabetes in an attempt to strengthen the link between diabetes and pulmonary fibrosis. Pulmonary function parameters (FVC, FEV1, TLC, and DLco/VA) were significantly reduced in diabetic patients with dyspnea and without dyspnea, compared to controls. Both patient groups also had increased lung CT scores and symptoms compared to normal controls, though the greatest increases were in the diabetic patients with dyspnea. Chronic hyperglycemia induced in mice led to histopathological changes in the lungs that were similar to those found in the human diabetic subjects and included alveoli compression by hyperplastic interstitium infiltrated with inflammatory cells and fibrotic in nature. Two inflammatory related genes, TNF-α and PAI-1, and two fibrosis-related genes, CTGF and fibronectin, demonstrated increased mRNA and protein expression in diabetic mouse lungs. In conclusion, there were significant clinical and histopathological correlations between pulmonary fibrosis and the presence of type 1 diabetes. Diabetes was clinically associated with pulmonary fibrosis and dysfunction in humans, and diabetes induction led to a similar pulmonary fibrosis in an experimental model. These clinical and non-clinical data suggest that diabetes is an independent risk factor for pulmonary fibrosis.
authors.affiliation: Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, 130041, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhongsen
authors.initials: Z
authors.lastname: Ma
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Guo
authors.forename: Fenglian
authors.initials: F
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.forename: Junling
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000150:complications*; D012307:Risk Factors