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Introduction: Preclinical research suggests a role of Glucagon Like Peptide-1 Receptors (GLP-1R) on the regulation of human bronchial tone. We investigated the effect of GLP-1R agonists on lung function of Type 2 Diabetes Mellitus (T2DM) population without co-existing chronic obstructive respiratory disorders. Methods: This was a prospective cohort study that examined change in lung function measurements over two years of T2DM patients (n = 32) treated with metformin monotherapy (control cohort), metformin plus GLP-1R agonists (GLP-1R agonists cohort), or metformin plus insulin (insulin cohort). Results: After 24 months of treatment, the forced expiratory volume in 1 s (FEV 1 ) significantly (p < 0.05) increased from baseline in the GLP-1R agonists cohort (218 ml [95%CI 88-246]), but not in the control and insulin cohorts (94 ml [95%CI -28 -216] and 26 ml [95%CI -174 -226], respectively; p > 0.05 vs. baseline). The average increase in FEV 1 in the GLP-1R agonists cohort was significantly greater than that in the control and insulin cohorts (delta: 110 ml [95%CI 18-202] and 177 ml [95%CI 85-270], respectively, p < 0.05). The forced vital capacity (FVC) also increased significantly more in the GLP-1R agonists cohort than in the control and insulin cohorts (overall delta FVC: 183 ml [95%CI 72-295], p < 0.05). The maximal expiratory flow at 50-75% significantly (p < 0.05) improved from baseline in the GLP-1R agonists cohort, but not in the control and insulin cohorts (p > 0.05). Conclusion:Our preliminary results suggest a potential new therapeutic perspective to treat airway disorders with GLP-1R agonists.

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Insulin action and often glucose-stimulated insulin secretion are reduced in obesity. In addition, the excessive intake of lipids increases oxidative stress leading to overt type 2 diabetes mellitus (T2DM). Among the antioxidative defense systems, peroxiredoxin 6 (PRDX6) is able to reduce H2O2 and short chain and phospholipid hydroperoxides. Increasing evidences suggest that PRDX6 is involved in the pathogenesis of atherosclerosis and T2DM, but its role in the etiopathology of obesity and its complications is still not known. Therefore, in the present study, we sought to investigate this association by using PRDX6 knockout mice (PRDX6-/-). Metabolic parameters, like carbon dioxide (VCO2) production, oxygen consumption (VO2), and the respiratory exchange ratio (RER), were determined using metabolic cages. Intraperitoneal insulin and glucose tolerance tests were performed to evaluate insulin sensitivity and glucose tolerance, respectively. Liver and pancreas histochemical analyses were also evaluated. The expression of enzymes involved in lipid and glucose metabolism was analyzed by real-time PCR. Following 24 weeks of high-fat-diet (HFD), PRDX6-/- mice showed weight gain and higher food and drink intake compared to controls. VO2 consumption and VCO2 production decreased in PRDX6-/- mice, while the RER was lower than 0.7 indicating a prevalent lipid metabolism. PRDX6-/- mice fed with HFD showed a further deterioration on insulin sensitivity and glucose-stimulated insulin secretion. Furthermore, in PRDX6-/- mice, insulin did not suppress adipose tissue lipolysis with consequent hepatic lipid overload and higher serum levels of ALT, cholesterol, and triglycerides. Interestingly, in PRDX6-/- mice, liver and adipose tissue were associated with proinflammatory gene upregulation. Finally, PRDX6-/- mice showed a higher rate of nonalcoholic steatohepatitis (NASH) compared to control. Our results suggest that PRDX6 may have a functional and protective role in the development of obesity-related metabolic disorders such as liver diseases and T2DM and may be considered a potential therapeutic target against these illnesses.