PMID- 21875362
OWN - NLM
STAT- MEDLINE
DCOM- 20120502
LR  - 20221207
IS  - 1557-8593 (Electronic)
IS  - 1520-9156 (Linking)
VI  - 14
IP  - 1
DP  - 2012 Jan
TI  - Trough insulin levels in bronchoalveolar lavage following inhaled human insulin 
      (Exubera) in patients with diabetes mellitus.
PG  - 50-8
LID - 10.1089/dia.2011.0148 [doi]
AB  - BACKGROUND/AIM: 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((R)) [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.
FAU - Mendivil, Carlos O
AU  - Mendivil CO
AD  - Molecular and Integrative Physiological Sciences Program, Department of 
      Environmental Health, Harvard School of Public Health, Boston, Massachusetts 
      02115, USA.
FAU - Teeter, John G
AU  - Teeter JG
FAU - Finch, Gregory L
AU  - Finch GL
FAU - Schwartz, Pamela F
AU  - Schwartz PF
FAU - Riese, Richard J
AU  - Riese RJ
FAU - Brain, Joseph D
AU  - Brain JD
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20110829
PL  - United States
TA  - Diabetes Technol Ther
JT  - Diabetes technology & therapeutics
JID - 100889084
RN  - 0 (Exubera)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
SB  - IM
MH  - Administration, Inhalation
MH  - Adult
MH  - *Bronchoalveolar Lavage Fluid
MH  - Bronchoscopy
MH  - Diabetes Mellitus, Type 1/*drug therapy/metabolism
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Female
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/*metabolism
MH  - Insulin/administration & dosage/*metabolism
MH  - Lung/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
EDAT- 2011/08/31 06:00
MHDA- 2012/05/04 06:00
CRDT- 2011/08/31 06:00
PHST- 2011/08/31 06:00 [entrez]
PHST- 2011/08/31 06:00 [pubmed]
PHST- 2012/05/04 06:00 [medline]
AID - 10.1089/dia.2011.0148 [doi]
PST - ppublish
SO  - Diabetes Technol Ther. 2012 Jan;14(1):50-8. doi: 10.1089/dia.2011.0148. Epub 2011 
      Aug 29.