Insulin Detemir Compared to NPH Insulin: A Study to Explore Whether Differences Exist in the Response to Hypoglycaemia Induced After Subcutaneous Injection in Subjects with Type 1 Diabetes.

Insulin detemir is an intermediate acting basal insulin bound to albumin via its 14C fatty acid side chain. Insulin detemir may have a more physiological action because it is believed that compared to NPH insulin (Neutral Protamine Hagedorn) it is preferentially cleared by the liver. This increased clearance may occur due to the open sinusoids of the endothelial membrane in the liver allowing the passage of larger molecules, such as the albumin bound insulin detemir, when compared to the tight endothelial junction in the periphery. This theory may explain why there is less hypoglycaemia and less weight gain observed in clinical trials when used as part of a basal bolus regime in comparison to NPH insulin. The glucose lowering effect of insulin detemir compared to NPH insulin administered subcutaneously to subjects with type 1 diabetes was investigated in a randomised, double blind, cross over study. The first five individuals received 0.4 Units/kg. The insulin dose was increased for the subsequent 18 subjects to 0.5 Units/Kg to achieve more consistent hypoglycaemia. The glucose lowering effect of each insulin was compared along with symptoms of hypoglycaemia, effects on cognitive and autonomic function and counterregulatory responses (adrenaline, noradrenaline, glucagon, cortisol, growth hormone, IGFBP1 and NEFA). The effect on endogenous glucose production and peripheral glucose uptake were also compared using stable isotope techniques. The data analysis was performed on 14 subjects who achieved adequate hypoglycaemia when dosed at 0.5 units/Kg. The glucose lowering effect of both NPH and insulin detemir were equivalent, no significant differences were observed in symptoms of hypoglycaemia, effects on cognitive or autonomic function or counterregulatory hormone responses. At or below a glucose concentration of 3.5 mmol/1 suppression of endogenous glucose production was shown to be greater with insulin detemir than NPH insulin (p=0.001) and stimulation of peripheral glucose uptake was shown to be greater with NPH insulin when compared to insulin detemir (p=0.005). This would suggest that insulin detemir had a greater effect on the liver than in the periphery when compared to NPH insulin.