Pharmacology of Insulin Injected With Jet-injection in Diabetes

• BG-AUC0-2h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion. [ Time Frame: 2 days (2 hours per day) ] [ Designated as safety issue: No ]
  based on plasma glucose levels during the first two hours of the 6-hour post-meal study duration
  
  

• BGmax (mmol/l): maximal glucose excursion after insulin injection and meal ingestion [ Time Frame: 2 days (6 hours each day) ] [ Designated as safety issue: No ]
  Maximal plasma glucose value after the standardised meal
  
  
• T-BGmax (min): time to maximal glucose excursion after insulin injection and meal ingestion [ Time Frame: 2 days (6 hours per day) ] [ Designated as safety issue: No ]
  Time until maximal glucose value after the standardised meal and insulin injection
  
  
• BG-AUC0-6h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 6 h after insulin injection and meal ingestion [ Time Frame: 2 days (6 hours each day) ] [ Designated as safety issue: No ]
  Based on glucose concentration measurements for the total 6 hours of the study
  
  
• T-BGBL (min): time until plasma glucose has returned to baseline values after insulin injection and meal ingestion [ Time Frame: 2 days (6 hours per day) ] [ Designated as safety issue: No ]
  based on glucose level measurements during the total 6 hours of the study
  
  
• T-INSmax (min): time to maximal insulin concentration (C-INSmax) [ Time Frame: 2 days (6 hours per day) ] [ Designated as safety issue: No ]
  Maximal insulin concentration after insulin injection
  
  
• INSAUC (pmol•min-1•l-1): area under the insulin concentration curve (from timepoint 0) [ Time Frame: 2 days (6 hours per day) ] [ Designated as safety issue: No ]
  Based on insulin concentration measurements during the total 6 hours of the study
  
  
• T-INSAUC50% (min): time until 50% of insulin absorption (mean residence time, MRT) [ Time Frame: 2 days (6 hours each day) ] [ Designated as safety issue: No ]
  Based on insulin concentration measurements during the total 6 hours of the study
  
  
• Number of patients requiring exogenous glucose infusion to prevent postprandial hypoglycaemia after insulin injection and meal ingestion [ Time Frame: 2 days ] [ Designated as safety issue: Yes ]
  This will be assessed for the individual patient after every test. After completion of the experiments all cases of hypoglycemia will be assessed
  
  
• Amount of exogenous glucose required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion [ Time Frame: 2 days ] [ Designated as safety issue: Yes ]
  This will be assessed for the individual patient after every test. After completion of the experiments the total amount of glucose infused will be calculate for each device
  
  
• Duration of time that exogenous glucose is required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion [ Time Frame: 2 days ] [ Designated as safety issue: Yes ]
  This will be assessed for the individual patient after every test. After completion of the experiments the total amount of time will be calculate for each device
  
  
• BG-AUC0-1h [ Time Frame: 2 days (6 hours per day) ] [ Designated as safety issue: No ]
  the area under the baseline-subtracted plasma glucose concentration time-curve during the first hour
  
  

A previous study showed that absorption and glucose-lowering action of rapid-acting insulin analogues occurred twice as fast when these analogues were administered by jet injection technology rather than by conventional insulin pen in healthy non-diabetic subjects. This study investigates if the rapid-acting insulin analogue aspart (Novorapid®) injected with jet-injection or a conventional insulin pen prior to a standardised meal in patients with diabetes (type 1 and type 2) shows the same difference in the pharmacokinetic and pharmacodynamic profile.The pharmacokinetic and pharmacodynamic profile of insulin aspart will be derived from the time-action profiles of insulin and glucose, respectively, in response to insulin injected directly prior to a standardised meal. All patients will be investigated twice, where on one occasion the jet-injector device will be used to inject an individualised dose of insulin and a conventional insulin pen to inject a placebo solution, and on the other occasion insulin will be injected with the conventional pen and placebo with the jet-injector. The order of these occasions will be randomised and blinded to both the investigator and the participating patient. The primary endpoint is the hyperglycaemic burden as reflected by area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion (BG-AUC0-2h). Secondary study endpoints are the area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 6 h (BG-AUC0-6h), maximal glucose excursion (BGmax), time to maximal glucose excursion (T-BGmax), time until plasma glucose has returned to baseline (T-BGBL), maximal insulin concentration (C-INSmax), time to maximal insulin concentration (T-INSmax), area under the insulin concentration curve (INSAUC) and time until 50% of insulin absorption (T-INSAUC50%) after insulin injection and meal ingestion.