Insulin aspart has a shorter duration of action than human insulin over a wide dose-range.

AIMS: Regular human insulin (RHI) at high doses shows prolongation of its duration of action potentially leading to late postprandial hypoglycaemia. This study compared late metabolic activity (4-12 and 6-12 h post-dosing) and duration of action (time to reach late half-maximal activity) over a range of doses between insulin aspart (IAsp) and RHI. METHODS: Pharmacokinetic and pharmacodynamic properties of subcutaneous IAsp and RHI (6, 12 and 24 (I)U) were compared in 16 healthy subjects in this double-blind, randomized, six-way crossover glucose clamp study. RESULTS: With increasing doses of both insulins, metabolic activity, insulin exposure, maximum metabolic effect and maximum serum insulin concentration increased linearly. Late metabolic activity was lower for IAsp than RHI at all doses, reaching statistical significance (p < 0.05) for 12 and 24 (I)U. Likewise, IAsp had a shorter duration of action at all doses (p < 0.01) and reached time to 80% of total metabolic activity earlier at doses of 12 and 24 (I)U (p < 0.05). IAsp, compared with RHI, showed a higher maximum metabolic effect at 12 and 24 (I)U (p < 0.0001) and a stronger early metabolic activity for all three doses (p < 0.05). CONCLUSIONS: IAsp showed a shorter duration of action and, particularly with doses of 12 and 24 (I)U, less late metabolic activity than RHI. These properties might contribute to the lower incidence of hypoglycaemia observed with IAsp versus RHI in clinical trials as lower late metabolic activity should decrease the risk of late postprandial hypoglycaemia.

Renal glucose excretion and tubular reabsorption rate related to blood glucose in subjects with type 2 diabetes with a critical reappraisal of the "renal glucose threshold" model.

Until today a "renal threshold for glucose" is described in most medical textbooks. Notwithstanding, low glucose levels are detectable in urine even under euglycaemic conditions - a phenomenon which was observed already in 1904 and labelled as "basal glucosuria". We aimed to characterise renal glucose transport during various steady-state blood glucose levels. Twenty-two subjects with type 2 diabetes and normal renal function underwent two 5-period hyperglycaemic glucose-clamps with blood glucose target levels between 7.8 and 13.3 mmol x l(-1). A virtual renal threshold for glucose excretion (VRT (G)) was calculated for every subject as the highest blood glucose concentration during the glucose-clamps associated with a concomitant urinary glucose level of <2.8 mmol x l(-1). VRT (G) of subjects was classified as low, medium, and high. Each urine sample contained a detectable amount of glucose with a minimal urinary glucose concentration of 0.73 mmol x l(-1). Median VRT (G) was 11.0 mmol x l(-1), ranging from 7.8 and 12.1 mmol x l(-1). With increasing blood glucose renal glucose excretion increased in each subject - but varied considerably between subjects. For example, at a blood glucose concentration of 11 mmol x l(-1) renal glucose excretion ranged from 163 micromol x min(-1) to 25 micromol x min(-1) in subjects exhibiting a low to high VRT (G), thus showing a variability >factor 6. This study reinforces the rejection of the concept of a renal threshold for glucose. Instead, this study shows a substantial variability of renal glucose excretion between subjects with type 2 diabetes.