Glargine metabolism over 24 h following its subcutaneous injection in patients with type 2 diabetes mellitus: a dose-response study.
Nutr Metab Cardiovasc Dis
; 24(7): 709-16, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24702815
ABSTRACT
BACKGROUND AND AIMS:
After subcutaneous injection insulin glargine is rapidly metabolized to M1 and M2. In vitro, both M1 and M2 have metabolic effects and bind to IGF-1R similarly to human insulin, whereas glargine exhibits a higher affinity for the IGF-1R and greater mitogenetic effects. The present study was specifically designed to establish the dose-response metabolism of glargine over 24 h following s.c. injection in T2DM subjects on long-term use of glargine. METHODS ANDRESULTS:
Ten subjects with T2DM were studied during 24 h after s.c. injection of 0.4 (therapeutic) and 0.8 (high dose) U/kg of glargine on two separate occasions during euglycaemic clamps (cross-over design). Glargine, M1 and M2 over 24 h period were determined in appropriately processed plasma samples by a specific liquid chromatography-tandem mass spectrometry assay. Plasma M1 concentration (AUC0-24 h) was detected in all subjects and increased by increasing the glargine dose from therapeutic to high dose (p = 0.008). Glargine was detectable in 6 (therapeutic dose) and 9 (high dose) out of the 10 subjects and also increased by increasing the dose (p = 0.031). However, glargine concentration (AUC0-24 h--high dose) represented at most only 9.7% (4.6-15%) of the total amount of insulin measured in the blood. M2 was not detected at all.CONCLUSION:
In T2DM people on long-term use of insulin glargine, even with higher doses (0.8 U/kg), glargine is nearly totally metabolized to the active metabolite M1. Glargine is often detectable in plasma, but its concentration remains well below that needed in vitro to potentiate IGF-1R binding and mitogenesis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Insulina de Ação Prolongada
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Diabetes Mellitus Tipo 2
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Hipoglicemiantes
Tipo de estudo:
Clinical_trials
Limite:
Aged
/
Humans
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article