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Exp Clin Endocrinol Diabetes 2007; 115(7): 461-467
DOI: 10.1055/s-2007-976512
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

Proportional Dose-Response Relationship and Lower Within-Patient Variability of Insulin Detemir and NPH Insulin in Subjects With Type 1 Diabetes Mellitus

A. Wutte 1 , J. Plank 1 , M. Bodenlenz 2 , C. Magnes 2 , W. Regittnig 1 , F. Sinner 2 , B. Rønn 3 , M. Zdravkovic 3 , T. R. Pieber 1 , 2
  • 1Department of Internal Medicine, Diabetes and Metabolism, Medical University of Graz, Austria
  • 2Institute of Medical Technologies and Health Management, Joanneum Research, Graz, Austria
  • 3Novo Nordisk A/S, Bagsvaerd, Denmark
Further Information

Publication History

received 12.2.2007 first decision 6.3.2007

accepted 27.3.2007

Publication Date:
23 July 2007 (online)

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Abstract

Aims: This study was conducted to evaluate the dose ratio of insulin detemir and neutral protamine Hagedorn (NPH) insulin over a range of therapeutically relevant subcutaneous doses.

Methods: The study was a randomized, double-blind, crossover 24-h-iso-glycemic clamp trial in 12 C-peptide-negative type 1 diabetic patients. Each subject received, by an incomplete block design selection, two of three possible doses of insulin detemir (0.15, 0.3, 0.6 U/kg) and NPH insulin (0.15, 0.3, 0.6 IU/kg), respectively. A detailed assessment of endogenous glucose production (EGP) and glucose uptake was performed, by use of stable isotopic labeled glucose tracer (D-[6,6-2H2] glucose).

Results: Dose proportionality was observed within the tested dose range. Regarding unit dose ratio, 0.68 U insulin detemir equals 1 IU NPH insulin (95% CI [0.35; 1.30]). There was no statistically significant difference in effect on the area under the curve (AUC) of glucose infusion rate (GIR) (AUCGIR) and the maximal GIR (GIRmax) values, when comparing U (insulin detemir) to IU (NPH insulin). The pharmacodynamic within-subject profile was lower with insulin detemir in regard to AUCGIR 0-24 h, GIRmax and duration of action (P<0.05). There was a tendency for a greater reduction of EGP with insulin detemir than with NPH insulin in regard to the area over the curve (AOC) of EGP in 24 hours (AOCEGP 0-24 h) (P=0.07) and minimal EPG (EGPmin) (P=0.02).

Conclusions: These data show that insulin detemir is dose-proportional to NPH insulin in type 1 diabetic patients at clinically relevant doses. The data indicate that insulin detemir has a lower degree of within-subject variability.

Key words

Glucose uptake - glucose production - glucose clamp - tracer infusion technique

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Correspondence

A. WutteMSc 

Medical University of Graz

Department of Internal Medicine

Diabetes and Metabolism

Stiftingtalstr 24/1. OG

A-8010 Graz

Austria

Phone: +43/316/385 72 83 5

Fax: +43/316/385 72 83 9

Email: andrea.wutte@healthsite.at

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