TY - JOUR
T1 - Mechanism of action of inhaled insulin on whole body glucose metabolism in subjects with type 2 diabetes mellitus
AU - Mehta, Rucha J.
AU - Gastaldelli, Amalia
AU - Balas, Bogdana
AU - Ricotti, Andrea
AU - Defronzo, Ralph A.
AU - Tripathy, Devjit
N1 - Funding Information:
Funding: The present study was supported, in part, by Pfizer Inc. U.S.A., research grant to R.A.D.
Funding Information:
Acknowledgments: The authors wish to thank the nurses of the General Clinical Research Center for their diligent care of our patients. We gratefully acknowledge the technical assistance of Kathy Camp. Lorrie Albarado and Amy Richardson provided skilled secretarial support in the preparation of this manuscript. Devjit Tripathy’s salary was supported by South Texas Veterans Health Care system and also supported by FAVHR, Foundation for Advancement of Veterans Health and Research.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - In the current study we investigate the mechanisms of action of short acting inhaled insulin Exubera®, 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®treatment. At BAS and after 16-weeks subjects received: measurement of HGP (3-3 H-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 µM), post-OGTT (433 ± 83 to 239 ± 28 µM), 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®we observed a marked improvement in glycemic control by decreasing HGP and 24-h PG profile, and decreased FFA and triglyceride concentrations.
AB - In the current study we investigate the mechanisms of action of short acting inhaled insulin Exubera®, 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®treatment. At BAS and after 16-weeks subjects received: measurement of HGP (3-3 H-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 µM), post-OGTT (433 ± 83 to 239 ± 28 µM), 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®we observed a marked improvement in glycemic control by decreasing HGP and 24-h PG profile, and decreased FFA and triglyceride concentrations.
KW - Disposition index
KW - Hepatic glucose production
KW - Inhaled insulin
KW - OGTT
KW - Tracers
KW - Whole body glucose metabolism
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U2 - 10.3390/ijms20174230
DO - 10.3390/ijms20174230
M3 - Article
C2 - 31470605
AN - SCOPUS:85071781384
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 17
M1 - 4230
ER -