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Differences in Effect of Insulin Detemir and NPH Insulin on Glucose and Lipid Metabolism.

Hodern, Sara Victoria Margaret. (2004) Differences in Effect of Insulin Detemir and NPH Insulin on Glucose and Lipid Metabolism. Doctoral thesis, University of Surrey (United Kingdom)..

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Abstract

Insulin detemir has a 14C fatty acid chain, which associates with free fatty acid binding sites on albumin. Capillary endothelial cells in adipose tissue and muscle may limit transfer of insulin detemir from the circulation into the extravascular extracellular space. In the liver, the open sinusoids may expose hepatocytes to insulin detemir enabling it to have greater effect on the liver than' on the periphery. We investigated the effects of two doses of insulin detemir and one dose of NPH insulin on hepatic glucose output (Ra), peripheral glucose uptake (Rd), glycerol Ra using stable isotope techniques and on NEFA, IGF-1, IGFBP-1, C-peptide, and glucagon concentrations in 7 healthy volunteers, 6 volunteers with type 1 diabetes and 6 volunteers with type 2 diabetes during a 16h euglycaemic clamp. In healthy volunteers we demonstrated that 9nmol/kg insulin detemir had greater effect on suppression of glucose Ra than an equipotent dose of NPH (0.3iu/kg or 1.8nmol/kg). In subjects with type 1 and type 2 diabetes 18nmol/kg insulin detemir was equipotent to 0.6 iu/kg (3.6 nmol/kg) NPH, with a similar time action profile. In subjects with type 1 diabetes we were unable to demonstrate differences in the effect of insulin detemir on glucose Ra but demonstrated small but significant differences in effect on glucose Rd compared to the equipotent dose of NPH. The suppression of NEFA concentrations by insulin detemir was less than with an equipotent dose of NPH, both in healthy subjects and to a lesser extent in those with type 1 diabetes. We were unable to demonstrate a statistical difference in effect on glucose or lipid metabolism in subjects with type 2 diabetes. There were no differences in the effect of these two insulins on glycerol Ra, IGF-1, IGFBP-1, glucagon or c-peptide concentrations in any of our three subject groups. We demonstrated a dose response effect for insulin detemir. This study suggests that when equipotent doses of insulin detemir are compared to NPH insulin, detemir has greater effect on the liver than peripheral tissues and thus the potential to restore the normal insulin gradient.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Hodern, Sara Victoria Margaret.
Date : 2004
Additional Information : Thesis (M.D.)--University of Surrey (United Kingdom), 2004.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 11:53
Last Modified : 06 May 2020 11:53
URI: http://epubs.surrey.ac.uk/id/eprint/855527

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