Insulin Detemir Compared to NPH Insulin: A Study to Explore Whether Differences Exist Between Glucose Flux, Lipolysis, Pharmacokinetics and Brain Function During Hyperglycaemia in Type 1 Diabetes.

In spite of major developments in insulin production and methods of delivery, problems remain in the day to day management of insulin treated diabetes. One striking difference between currently available insulin treatments is the relative difference in weight gain and hypoglycaemia frequency. With the use of stable isotope technology the differential effects of 0.5units/kg of subcutaneous insulin detemir and NPH insulin on glucose flux, lipid metabolism and brain function during hyperglycaemia were investigated. Two protocols were designed, a protocol to look at the action of insulin following a period of insulin withdrawal and a second protocol using the gold standard euglycaemic and hyperglycaemic hyperinsulinaemic clamp methodology. Following a period of insulin withdrawal, suppression of endogenous glucose production (glucose Ra) was similar with subcutaneous insulin detemir and NPH insulin treatment. With glucose concentration decreasing from 9 to 6mmol/l, glucose Ra decreased from 8.2±0.9 to 5.8±0.5 and 8.2±0.5 to 6.3±0.6pmol/kg/min respectively. However, peripheral glucose uptake (glucose Rd) was greater with NPH insulin when compared with insulin detemir at the same glucose concentration. With glucose concentration decreasing from 9 to 6mmol/l, insulin detemir was consistently lower at 11.0±0.6 to 9.5±0.7 and 11.5±0.6 to 11.4±0.4pmol/kg/min with NPH insulin. Suppression of lipolysis was delayed with insulin detemir compared to NPH insulin. While eliciting comparable effects on glucose flux and lipolysis during the clamp study, insulin detemir compared with NPH insulin showed a distinct negative shift in EEG DC-potentials. (ANOVA P=0.03) Insulin detemir had a lesser effect on peripheral glucose uptake and delayed suppression of lipolysis when compared to NPH insulin. Insulin detemir may also affect brain function to a greater extent than NPH insulin suggesting that enhanced insulin signalling to the brain may be an important mechanism behind the limitation of weight gain observed in people with type 1 diabetes receiving subcutaneous detemir treatment