Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Mader, JK; Birngruber, T; Korsatko, S; Deller, S; Köhler, G; Boysen, S; Augustin, T; Mautner, SI; Sinner, F; Pieber, TR; AP@home Consortium.
Enhanced absorption of insulin aspart as the result of a dispersed injection strategy tested in a randomized trial in type 1 diabetic patients.
Diabetes Care. 2013; 36(4):780-785
Doi: 10.2337/dc12-1319
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- Führende Autor*innen der Med Uni Graz
- Birngruber Thomas
- Mader Julia
- Pieber Thomas
- Co-Autor*innen der Med Uni Graz
- Deller Sigrid
- Köhler Gerd
- Korsatko Stefan
- Mautner Selma
- Sinner Frank Michael
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- Abstract:
- We investigated the impact of two different injection strategies on the pharmacokinetics and pharmacodynamics of insulin aspart in vivo in an open-label, two-period crossover study and verified changes in the surface-to-volume ratio ex vivo. Before the clinical trial, insulin aspart was injected ex vivo into explanted human abdominal skin flaps. The surface-to-volume ratio of the subcutaneous insulin depot was assessed by microfocus computed tomography that compared 1 bolus of 18 IU with 9 dispersed boluses of 2 IU. These two injection strategies were then tested in vivo, in 12 C-peptide-negative type 1 diabetic patients in a euglycemic glucose clamp (glucose target 5.5 ± 1.1 mmol/L) for 8 h after the first insulin administration. The ex vivo experiment showed a 1.8-fold higher mean surface-to-volume ratio for the dispersed injection strategy. The maximum glucose infusion rates (GIR) were similar for the two strategies (10 ± 4 vs. 9 ± 4; P = 0.5); however, times to reach maximum GIR and 50% and 10% of the maximum GIR were significantly reduced by using the 9 × 2 IU strategy (68 ± 33 vs. 127 ± 93 min; P = 0.01; 38 ± 9 vs. 49 ± 16 min; P < 0.01; 23 ± 6 vs. 30 ± 10 min; P < 0.05). For 9 × 2 IU, the area under the GIR curve was greater during the first 60 min (219 ± 89 vs. 137 ± 75; P < 0.01) and halved until maximum GIR (242 ± 183 vs. 501 ± 396; P < 0.01); however, it was similar across the whole study period (1,361 ± 469 vs. 1,565 ± 527; P = 0.08). A dispersed insulin injection strategy enhanced the effect of a fast-acting insulin analog. The increased surface-to-volume ratio of the subcutaneous insulin depot can facilitate insulin absorption into the vascular system.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- C-Peptide - blood
- Diabetes Mellitus, Type 1 - blood
- Diabetes Mellitus, Type 1 - drug therapy
- Female -
- Humans -
- Insulin Aspart - administration & dosage
- Insulin Aspart - pharmacokinetics
- Insulin Aspart - therapeutic use
- Male -
- Young Adult -