Intravenous glargine and regular insulin have similar effects on endogenous glucose output and peripheral activation/deactivation kinetic profiles.
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.


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/m(2) [mean +/- SE]) received a primed continuous intravenous infusion of 40 mU/m(2) 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-(3)H]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 (R(d)) to half-maximum insulin-stimulated R(d), 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.
VA San Diego Healthcare System, La Jolla, California 92161, USA.
Sunder
S
Mudaliar
Pharis
P
Mohideen
Reena
R
Deutsch
Theodore P
TP
Ciaraldi
Debra
D
Armstrong
Bo
B
Kim
Xue
X
Sha
Robert R
RR
Henry
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000493:pharmacokinetics*; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D014316:Tritium
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D014316:Tritium; D000069036:Insulin Glargine; D005947:Glucose