Feasibility Study of the Effect of Intra-Dermal Insulin Injection on Blood Glucose Levels After Eating

• Maximal BG (BGmax) [ Time Frame: Approximately 4 hours per injection ] [ Designated as safety issue: No ]
• Total BG-AUC0-4 h [ Time Frame: Approximately 4 hrs per injection ] [ Designated as safety issue: No ]
• Minimal BG (BGmin, time to BGmin (tBGmin) [ Time Frame: Approximately 4 hrs per injection ] [ Designated as safety issue: No ]
• Insulin pharmacokinetics [ Time Frame: Approximately 4 hrs per injection ] [ Designated as safety issue: No ]
• Number and seriousness of adverse events [ Time Frame: Approximately 4 hrs per injections ] [ Designated as safety issue: Yes ]
• Vital signs, examination of insulin application [ Time Frame: Approximately 4 hrs per injection ] [ Designated as safety issue: No ]
• Time to BGmax (tBGmax) [ Time Frame: Approximately 4 hours per injection ] [ Designated as safety issue: No ]

This study is to determine the effect of intra-dermal (ID) administration of regular and of rapid-acting insulin, before eating, on blood glucose levels for several hours after a standard meal (a mixed, liquid meal). Insulin will also be given normally, subcutaneously, for control or comparison purposes. The hypothesis or expectation is that ID insulin will work more quickly and control blood glucose levels better than SC injection.

Previous studies have shown that intra-dermal (ID) insulin administration results in a more rapid onset of action in comparison to subcutaneous (SC) administration as measured by glucose infusion rate (GIR) under glucose clamp conditions.The aim of this study is to investigate whether ID administration of regular human insulin or rapid-acting insulin analogue leads to reduced postprandial glycemic excursions in comparison to SC application under highly standardized experimental conditions. Effects on the occurrence of hypoglycemia will also be investigated, as well as pK and pD comparisons between different insulin formulations administered ID. This is a mono-center, open-label, randomized, 5-period crossover study in patients with type 1 diabetes

• Drug: Regular insulin (Humulin)
  Insulin will be given either subcutaneously or intra-dermally, and at two different times prior to the liquid meal (T zero). At -17 mins, regular insulin will be given either SC or ID. At -2 mins, regular insulin will be given ID; also insulin lispro will be given either SC or ID. Each patient will receive 1 injection on 5 different study days.
  Other Name: Regular insulin (Humulin)
• Drug: Insulin lispro (Humalog)
  Insulin will be given either subcutaneously or intra-dermally, and at two different times prior to the liquid meal (T zero). At -17 mins, regular insulin will be given either SC or ID. At -2 mins, regular insulin will be given ID; also insulin lispro will be given either SC or ID. Each patient will receive 1 injection on 5 different study days.
  Other Name: Insulin lispro (Humalog)

• Active Comparator: 1
  Regular insulin SC at -17 mins
  Intervention: Drug: Regular insulin (Humulin)
• Active Comparator: 2
  Regular insulin ID at -17 mins
  Intervention: Drug: Regular insulin (Humulin)
• Active Comparator: 3
  Regular insulin ID at -2 mins
  Intervention: Drug: Regular insulin (Humulin)
• Active Comparator: 4
  Insulin lispro given SC at -2 mins
  Intervention: Drug: Insulin lispro (Humalog)
• Experimental: 5
  Insulin lispro given ID at -2 mins
  Intervention: Drug: Insulin lispro (Humalog)

Inclusion Criteria:

• Type 1 diabetes for 1-15 years, on multiple daily injections (MDI) or insulin pump (CSII) in stable control with HbA1c <= 9.0%.
• Able to attend clinic for 5 different days

Exclusion Criteria:

• BMI > 32 kg/m2
• Evidence of gastroparesis or impaired renal function or lipodystrophy