title: Effect of insulin on airway responsiveness in patients with type 2 diabetes mellitus: a cohort study.
abstract: BACKGROUND
  The correlation between low insulin levels and a decreased sensitivity of the muscarinic receptor has been shown on induced-diabetes animal models. We designed a cohort study with the aim of evaluating the effects of insulin therapy on airway responsiveness (AR) in human patients with type 2 diabetes mellitus.
  
  
  METHODS
  We enrolled 92 patients with type 2 diabetes who had switched from oral anti-diabetic therapy to treatment by insulin subcutaneous injection. Patients were administered the methacholine challenge test (MCT) at time 0 (pre-insulin therapy) and at intervals of 15, 30, 90, 180, and 360 days after insulin treatment. The decline of forced expiratory volume in 1 second (FEV(1))% from baseline (Delta FEV(1)) in response to inhaled methacholine (MCH) was determined to assess airway hyper-responsiveness (AHR).
  
  
  RESULTS
  A total of 81 patients (18 women and 63 men) completed the study. Their mean age was 58 +/- 7 years and the mean duration of disease was 13.5 +/- 7.7 years. The mean decrease of FEV(1) at pre-insulin assessment was 2.96 +/- 2.6%. Compared with the pre-insulin value, a significant increase of Delta FEV(1) was observed at 15, 30, and 90 days after treatment (6.25%, CI 95% 5.4 to 7.2, p = 0.0005; 7.64%, CI 95% 6.6 to 8.1, p < 0.001; 6.45%, CI 95% 5.5 to 7.3, p = 0.0004, respectively), while after 180 and 360 days AR was similar to pre-insulin values (Delta FEV(1), 3.62%, CI 95% 2.7 to 3.5 and 3.11%, CI 95% 7.9 to 9.3, respectively).
  
  
  CONCLUSIONS
  The finding of an increased AR in patients with type 2 diabetes during the first 3 months of insulin therapy may underline the importance of monitoring pulmonary function and respiratory symptoms in patients switching from oral anti-diabetic drugs to insulin therapy, especially in the subset of individuals with respiratory disorders.
authors.affiliation: Department of Cardiovascular and Respiratory Sciences, Respiratory Diseases Unit, Fondazione E. Lorillard Spencer Cenci, Sapienza University of Rome, Italy. cterzano@tin.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Terzano
authors.forename: Susanna
authors.initials: S
authors.lastname: Morano
authors.forename: Daniela
authors.initials: D
authors.lastname: Ceccarelli
authors.forename: Vittoria
authors.initials: V
authors.lastname: Conti
authors.forename: Gregorino
authors.initials: G
authors.lastname: Paone
authors.forename: Angelo
authors.initials: A
authors.lastname: Petroianni
authors.forename: Elda
authors.initials: E
authors.lastname: Graziani
authors.forename: Anna
authors.initials: A
authors.lastname: Carnovale
authors.forename: Mara
authors.initials: M
authors.lastname: Fallarino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gatti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mandosi
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007073:Immunoglobulin E; D007328:Insulin; C517652:hemoglobin A1c protein, human