title: Trough insulin levels in bronchoalveolar lavage following inhaled human insulin (Exubera) in patients with diabetes mellitus.
abstract: OBJECTIVE
  There are few data regarding insulin levels in the lungs during diabetes therapy with inhaled insulin. We examined the disposition of inhaled human insulin (Exubera(®) [EXU] human insulin [recombinant DNA origin], Pfizer, New York, NY) in the lungs by measuring trough insulin levels in bronchoalveolar lavage (BAL) fluid after 12 weeks of EXU treatment.
  
  
  METHODS
  After a 4-week run-in period of subcutaneous insulin therapy, 24 subjects with type 1 diabetes mellitus (T1DM) and 26 with type 2 diabetes mellitus (T2DM) continued their basal insulin regimen and received premeal subcutaneous (SC) insulin for 13 weeks, followed by 12 weeks of premeal EXU. BAL was performed approximately 12 h after the last insulin dose at (1) baseline, (2) following SC insulin, and (3) following EXU.
  
  
  RESULTS
  Twenty patients with T1DM and 24 patients with T2DM completed all three bronchoscopies. BAL trough insulin levels were undetectable at baseline or following SC insulin. After EXU therapy, they increased to a median of 4.5 nM (1.6-9.0 nM) and 2.3 nM (0.5-9.4 nM) in T1DM and T2DM, respectively. BAL trough insulin levels did not correlate with treatment efficacy, adverse effects, plasma insulin levels, or changes in pulmonary function. A larger proportion of previous EXU doses was present in the BAL in patients with T1DM. We found no correlation between average daily insulin doses and BAL trough insulin levels.
  
  
  CONCLUSIONS
  BAL trough insulin increased following EXU therapy, but this increase did not correlate with other clinical or laboratory parameters, suggesting no significant biological action. Further studies are warranted to better understand inhaled insulin deposition and clearance and possible effects of increased insulin levels on the lungs.
authors.affiliation: Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Mendivil
authors.forename: John G
authors.initials: JG
authors.lastname: Teeter
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Finch
authors.forename: Pamela F
authors.initials: PF
authors.lastname: Schwartz
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Riese
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Brain
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C473734:Exubera