Mechanism of Action of Inhaled Insulin on Whole Body Glucose Metabolism in Subjects with Type 2 Diabetes Mellitus

In the current study we investigate the mechanisms of action of short acting inhaled insulin Exubera (R), on hepatic glucose production (HGP), plasma glucose and free fatty acid (FFA) concentrations. 11 T2D (Type 2 Diabetes) subjects (age = 53 +/- 3 years) were studied at baseline (BAS) and after 16-weeks of Exubera (R) treatment. At BAS and after 16-weeks subjects received: measurement of HGP (3-H-3-glucose); oral glucose tolerance test (OGTT); and a 24-h plasma glucose (24-h PG) profile. At end of study (EOS) we observed a significant decrease in fasting plasma glucose (FPG, 215 +/- 15 to 137 +/- 11 mg/dl), 2-hour plasma glucose (2-h PG, 309 +/- 9 to 264 +/- 11 mg/dl), glycated hemoglobin (HbA1c, 10.3 +/- 0.5% to 7.5 +/- 0.3%,), mean 24-h PG profile (212 +/- 17 to 141 +/- 8 mg/dl), FFA fasting (665 +/- 106 to 479 +/- 61 mu M), post-OGTT (433 +/- 83 to 239 +/- 28 mu M), and triglyceride (213 +/- 39 to 120 +/- 14 mg/dl), while high density cholesterol (HDL-C) increased (35 +/- 3 to 47 +/- 9 mg/dl). The basal HGP decreased significantly and the insulin secretion/insulin resistance (disposition) index increased significantly. There were no episodes of hypoglycemia and no change in pulmonary function at EOS. After 16-weeks of inhaled insulin Exubera (R) we observed a marked improvement in glycemic control by decreasing HGP and 24-h PG profile, and decreased FFA and triglyceride concentrations.