Comparison of the effects on glucose and lipid metabolism of equipotent doses of insulin detemir and NPH insulin with a 16-h euglycaemic clamp.
OBJECTIVE
The association of insulin detemir with non-esterified fatty acid binding sites on albumin may limit its transfer from the circulation into the extravascular extracellular space in adipose tissue and muscle, due to the capillary endothelial cell barrier. In the liver, the open sinusoids may expose hepatocytes to insulin detemir, enabling it to have a greater effect in the liver than in peripheral tissues.


METHODS
We investigated the effects of equipotent doses of insulin detemir and NPH insulin on hepatic glucose rate of appearance (Ra), peripheral glucose rate of disposal (Rd) and glycerol Ra (a measure of lipolysis) using stable isotope techniques. We also investigated the effects of these insulins on NEFA concentrations in seven healthy volunteers during a 16-h euglycaemic clamp. A higher dose of insulin detemir was also studied.


RESULTS
There was no difference in the glucose infusion profile between insulin detemir and NPH. Insulin detemir had a greater effect on mean suppression of glucose Ra (mean difference 0.24 mg kg(-1) min(-1); CI 0.09-0.39; p<0.01), and minimum glucose Ra, with minimum low dose detemir -0.10+/-0.15 mg.kg(-1).min(-1) and minimum NPH 0.17+/-0.10 mg.kg(-1).min(-1) (p<0.02). However, it had a lesser effect on mean suppression of NEFA concentrations (mean difference -0.10 mmol/l; CI -0.03 to -0.17; ANOVA, p<0.02) than NPH. The effect of insulin detemir on glucose Rd and glycerol Ra was not different from NPH. Following high-dose detemir, total glucose infused and maximum glucose Rd were higher (p<0.02, p<0.03) and plasma NEFA concentrations lower (p<0.01) than with low-dose determir.


CONCLUSIONS
This study suggests that insulin detemir, when compared to NPH insulin, has a greater effect on the liver than on peripheral tissues and thus has the potential to restore the physiological insulin gradient.
Hordern
S V M
SV
Department of Diabetes and Endocrinology, Post Graduate Medical School, University of Surrey, Guildford, Surrey, UK.
Wright
J E
JE
Umpleby
A M
AM
Shojaee-Moradie
F
F
Amiss
J
J
Russell-Jones
D L
DL
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000069057:Insulin Detemir; D007336:Insulin, Isophane / Q000494:pharmacology*; D049528:Insulin, Long-Acting; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir; D007336:Insulin, Isophane; D005947:Glucose
Dan Med Bull. 1991 Aug;38(4):337-46
1914533
Br J Anaesth. 2000 Jul;85(1):69-79
10927996
Pharm Res. 2004 Aug;21(8):1498-504
15359587
News Physiol Sci. 1999 Jun;14:117-121
11390834
Exp Clin Endocrinol Diabetes. 2000;108(2):100-5
10826516
Diabetes Care. 2000 Aug;23(8):1124-9
10937509
Acta Diabetol. 1995 Jun;32(2):131-4
7579535
Horm Res. 1993;40(1-3):68-79
8300053
Am J Physiol. 1956 Sep;187(1):15-24
13362583
Clin Endocrinol (Oxf). 2000 Jan;52(1):1-9
10651746
Diabetes Res Clin Pract. 1989 May 15;6(4):S3-15; discussion S15-6
2666060
Diabetologia. 1985 Mar;28(3):167-71
3888759
Nutr Rev. 1991 Feb;49(2):46-8
2017320
J Mass Spectrom. 1996 Sep;31(9):961-6
8831149
Biochem J. 1995 Dec 15;312 ( Pt 3):725-31
8554512
Diabetes Care. 1999 Mar;22 Suppl 2:B109-13
10097910
Clin Ther. 2004 May;26(5):724-36
15220016
Diabet Med. 1999 Apr;16(4):332-8
10220208
Diabetes Care. 2003 Mar;26(3):590-6
12610006
Am J Clin Nutr. 1995 Nov;62(5 Suppl):1096S-1100S
7484927
Diabetologia. 2000 Jul;43(7):946-52
10952470
J Chromatogr B Biomed Sci Appl. 2000 Jul 7;744(1):47-54
10985565
Diabetologia. 1979 Nov;17(5):291-5
499686
Diabetes. 1987 Aug;36(8):914-24
3297886