title: Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof-of-concept study.
abstract: BACKGROUND
  Effective glycaemic control in type 1 diabetes mellitus usually requires two or more insulin injections daily. Inhaled intrapulmonary delivery of insulin offers a potential new way to deliver meal-related insulin, eliminating the need for preprandial injections.
  
  
  METHODS
  73 patients with type 1 diabetes mellitus were studied in an open-label, proof-of-concept, parallel-group randomised trial. Patients in the experimental group received preprandial inhaled insulin plus a bedtime subcutaneous ultralente insulin injection. Patients in the control group received their usual insulin regimen of two to three injections per day. Participants monitored their blood glucose four times daily, and adjusted insulin doses weekly to achieve preprandial glucose targets of 5.6-8.9 mmol/L. The primary outcome measure was change in glycosylated haemoglobin (HbA1c) after 12 weeks. Secondary outcomes were fasting and postprandial glucose response to a mixed meal; hypoglycaemia frequency and severity; pulmonary function; and patients' satisfaction.
  
  
  RESULTS
  Changes in HbA1c were indistinguishable between groups (difference 0.2% [95% CI -0.2 to 0.5]). Changes in fasting and postprandial glucose concentrations, and occurrence and severity of hypoglycaemia were also similar between groups. Inhaled insulin was well tolerated and had no effect on pulmonary function (ie, spirometry, lung volumes, diffusion capacity, and oxygen saturation).
  
  
  CONCLUSIONS
  This proof-of-concept study shows that preprandial insulin can be given by inhalation in individuals with insulin-deficient type 1 diabetes as a less invasive alternative to conventional preprandial insulin injections.
authors.affiliation: Department of Medicine, University of Miami School of Medicine,  FL, USA. jskyler@miami.edu
authors.forename: J S
authors.initials: JS
authors.lastname: Skyler
authors.forename: W T
authors.initials: WT
authors.lastname: Cefalu
authors.forename: I A
authors.initials: IA
authors.lastname: Kourides
authors.forename: W H
authors.initials: WH
authors.lastname: Landschulz
authors.forename: C C
authors.initials: CC
authors.lastname: Balagtas
authors.forename: S L
authors.initials: SL
authors.lastname: Cheng
authors.forename: R A
authors.initials: RA
authors.lastname: Gelfand
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001786:Blood Glucose; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D006441:Hemoglobin A / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D015656:Respiratory Mechanics / Q000187:drug effects; D018709:Statistics, Nonparametric
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D006441:Hemoglobin A