A randomized clinical trial comparing the effect of basal insulin and inhaled mealtime insulin on glucose variability and oxidative stress

Diabetes Obes Metab. 2009 Jul;11(7):709-14. doi: 10.1111/j.1463-1326.2009.01037.x.

Abstract

Aim: To assess the effect of three times daily mealtime inhaled insulin therapy compared with once daily basal insulin glargine therapy on 72-h glucose profiles, glucose variability and oxidative stress in type 2 diabetes patients.

Methods: In an inpatient crossover study, 40 subjects with type 2 diabetes were randomized to receive 9 days of inhaled insulin three times daily before meals or 9 days of glargine administered in the morning before breakfast in a randomized order. During the last 72 h in each phase, glucose was measured with continuous glucose monitoring. Activation of oxidative stress was measured by determining the 15(S)-8-iso-PGF(2alpha)-secretion in 24-h urine samples.

Results: Inhaled insulin improved overall and postprandial glucose control significantly better than insulin glargine (p < 0.0001). There was a trend towards a greater reduction in glucose variability (8-9%) in the inhaled group [p = 0.1430 and p = 0.3298 for mean amplitude of glycaemic excursions (MAGEs) and mean of daily differences respectively]. Oxidative stress, estimated by determining the urinary isoprostane excretion (15(S)-8-iso-PGF(2alpha)), was equally reduced from baseline by both treatments. No correlation was found between glucose variability and oxidative stress in both groups.

Conclusions: This study showed a mealtime insulin approach to improve glycaemic control more than a basal insulin approach. These findings indicate also that lowering glucose using insulin treatment lowers oxidative stress over time, at least for the study period of 9 days, in type 2 diabetes patients. Contrary to earlier data, we found no correlation between glucose variability (MAGE) and oxidative stress (15(S)-8-iso-PGF(2alpha)) in this study.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin / administration & dosage*
  • Insulin / analogs & derivatives*
  • Insulin Glargine
  • Insulin, Long-Acting
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Prospective Studies
  • Treatment Outcome

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Insulin Glargine