Insulin detemir causes increased symptom awareness during hypoglycaemia compared to human insulin

Aim: The long-acting insulin analogue detemir (Levemir®) has structural and physicochemical properties which differ from human insulin. The aim of the present study was to test whether this leads to altered hormone and symptom response during hypoglycaemia. Methods: 12 healthy subjects [6f/6m, age 32 ± 6 years (mean ± s.d.), body mass index (BMI) 24.2 ± 2.5 kg/m2] underwent a 200-min stepwise hypoglycaemic clamp (45 min steps of 4.4, 3.7, 3.0 and 2.3 mmol/l) with either detemir or human insulin in random order. A bolus of detemir (660 mU/kg) or human insulin (60 mU/kg) was given before insulin was infused at a rate of 5 (detemir) or 2 (human insulin) mU/kg/min. Blood was drawn and a semi-quantitative symptom questionnaire was administered before and after each plateau of the hypoglycaemic clamp. Cognitive function was assessed during each step. Results: Blood glucose levels and glucose infusion rates were comparable with detemir and human insulin. The total symptom score was higher with detemir during the 3 and 2.3 mmol glucose step compared to human insulin (p = 0.048). Especially sweating was increased with detemir (p = 0.02) with an earlier and faster increase during the clamp (interaction insulin × time: p = 0.04). No significant differences between detemir and human insulin in cortisol, norepinephrine, epinephrine, glucagon, growth hormone, lactate or free fatty acid (FFA) levels during hypoglycaemia were observed, and there were no significant differences in cognitive function tests. Conclusions: Insulin detemir increased symptom awareness during hypoglycaemia compared to human insulin in healthy individuals, whereas counter-regulatory hormone response and cognitive function were unaltered.