Enhanced Absorption of Insulin Aspart as the Result of a Dispersed Injection Strategy Tested in a Randomized Trial in Type 1 Diabetic Patients

  1. on behalf of the AP@home consortium
  1. 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria
  2. 2Joanneum Research GmbH, HEALTH—Institute for Biomedicine and Health Sciences, Graz, Austria
  3. 3Novo Nordisk A/S, Maaloev, Denmark
  1. Corresponding author: Thomas R. Pieber, endo{at}medunigraz.at.
  1. J.K.M. and T.B. contributed equally to this study.

Abstract

OBJECTIVE 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.

RESEARCH DESIGN AND METHODS 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.

RESULTS 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).

CONCLUSIONS 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.

  • Received July 5, 2012.
  • Accepted September 4, 2012.

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This Article

  1. Diabetes Care
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