Intravenous Glargine and Regular Insulin Have Similar Effects on Endogenous Glucose Output and Peripheral Activation/Deactivation Kinetic Profiles
- Sunder Mudaliar, MD12,
- Pharis Mohideen, MD12,
- Reena Deutsch, PHD23,
- Theodore P. Ciaraldi, PHD2,
- Debra Armstrong, BS1,
- Bo Kim, PHARMD4,
- Xue Sha, MD4 and
- Robert R. Henry, MD12
- 1VA San Diego Healthcare System, La Jolla, California
- 2Department of Medicine, University of California, San Diego, La Jolla, California
- 3Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, California
- 4Aventis Pharmaceuticals, Bridgwater, New Jersey
OBJECTIVE—To compare the effects of intravenously administered long-acting insulin analog glargine and regular human insulin on activation and deactivation of endogenous glucose output (EGO) and peripheral glucose uptake.
RESEARCH DESIGN AND METHODS—In this single-center, randomized, double-blind, crossover euglycemic glucose clamp study, 15 healthy male volunteers (aged 27 ± 4 years, BMI 24.2 ± 0.7 kg/m2 [mean ± SE]) received a primed continuous intravenous infusion of 40 mU/m2 of insulin glargine or regular human insulin on 2 different study days in a randomized order. Euglycemia was maintained at 90 mg/dl using a simultaneous variable intravenous infusion of 20% dextrose containing d-[3-3H]glucose. EGO and peripheral glucose disposal kinetics were determined during a 4-h insulin infusion activation period and a 3-h deactivation period.
RESULTS—The results demonstrated no significant difference in activation or deactivation kinetics with respect to EGO and peripheral glucose disposal between insulin glargine and regular human insulin when given intravenously. The mean ± SE time required for 50% suppression of EGO after insulin infusion was 73 ± 23 min for regular insulin and 57 ± 20 min for insulin glargine (NS). The mean maximum rate of glucose disposal was 10.10 ± 0.77 and 9.90 ± 0.85 mg · kg−1 · min−1 for regular insulin and insulin glargine, respectively (NS). The mean time required for 50% suppression of incremental glucose disposal rate (GDR), defined as the time required for activation from the basal glucose disappearance rate (Rd) to half-maximum insulin-stimulated Rd, was 32 ± 5 and 42 ± 10 min for regular insulin and insulin glargine, respectively (NS). The time required for deactivation from maximum insulin-stimulated GDR to half-maximum GDR after cessation of insulin infusion was 63 ± 5 and 57 ± 4 min for regular insulin and insulin glargine, respectively (NS).
CONCLUSIONS—Activation and deactivation kinetics of EGO and peripheral glucose uptake as well as absolute disposal rate are similar between regular human insulin and insulin glargine when administered intravenously. Thus, the various biological actions of these insulin preparations when given subcutaneously are completely due to their different absorption kinetics.
- A50EGO, time required for 50% suppression of endogenous glucose output after insulin infusion
- A50IGDR, time from basal Rd to half-maximum insulin-stimulated Rd
- D50EGO, time required to achieve 50% deactivation from maximum insulin-induced suppression of endogenous glucose output after cessation of insulin infusion
- D50IGDR, time required for deactivation from maximum insulin-stimulated glucose disposal rate to half-maximum glucose disposal rate after cessation of insulin infusion
- ED50, half maximally effective insulin dose
- EGO, endogenous glucose output
- FFA, free fatty acid
- GDR, glucose disposal rate
- hot-GINF, glucose infusion containing d-[3-3H]glucose
- IGDR, incremental GDR
- Ra, glucose appearance
- Rd, glucose disappearance
- Rd max, maximum rate of glucose disposal
Address correspondence and reprint requests to Robert R. Henry, MD, VA San Diego Healthcare System, San Diego (111-G), 3350 La Jolla Village Dr., San Diego, CA 92161. E-mail:.
Received for publication 1 February 2002 and accepted in revised form 31 May 2002.
S.M. and P.M. contributed equally to this work.
P.M. is employed by Bristol-Myers Squibb; T.P.C. has received honoraria from Hoechst Marion Roussel and Aventis Pharmaceuticals; B.K., at the time of study, was employed by Hoeschst Marion Roussel; X.S. is employed by Aventis Pharmaceuticals and Pfizer; and R.R.H. has received honoraria, consulting fees, and research/grant support from Hoechst Marion Roussel and Aventis Pharmaceuticals.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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