In normal physiology insulin is secreted by beta cells into the portal vein. There have been a number of purported benefits among long-term intraperitoneal insulin users. In the present study we will inject ultra-rapid acting insulin into the upper and lower peritoneum under ultrasound guidance and compare it to subcutaneous injection. We will measure glucose, insulin and glucagon following these injections, to assess for benefits in counter-regulatory hormone production and insulin pharmacokinetics.
The eventual goal of this line of work is an implanted insulin pump that delivers insulin automatically into the peritoneum based on continuous glucose data. All prior intraperitoneal pharmacokinetic studies used only concentrated regular insulin, which may be too slow to provide full closed-loop insulin delivery without meal announcement. A description of intraperitoneal ultra-rapid insulin kinetics, as well as counter-regulatory hormonal factors that may counter hypoglycemia is needed. Upper versus lower peritoneal delivery may also affect insulin kinetics. A possible benefit of intraperitoneal insulin is restoration of glucagon response in longstanding diabetes and clearance of insulin by the liver, both of which could provide hypoglycemic rescue in automated insulin delivery systems.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
16
Following 0.5-3 hours of insulin suspension from insulin pump, participants will receive insulin injection in respective locations (separated by at least 1 week) and then have serial lab measurements (YSI glucose, insulin and glucagon) taken during induced hypoglycemia.
Stanford University
Stanford, California, United States
Glucagon Response to Induced Hypoglycemia
For each injection site we will assess the peak concentration of glucagon at time of the first induced hypoglycemic nadir. Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal). Participants must have achieved induced hypoglycemia to be evaluable for the primary outcome.
Time frame: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max
Insulin Maximum Concentration in Plasma
We will assess the maximum concentration of circulating insulin for each injection site after a median injection of 40% of each participant's total daily dose (approximately 0.25 units per kilogram of body weight). Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal).
Time frame: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max
Hypoglycemic Treatments Required as a Measure of Glucose Values
We will compare the number of rescue treatments (2.5ml/kg 10% Dextrose) required to treat hypoglycemia \<50mg/dl for each injection location of approximately 0.25u/kg ultra-rapid insulin. Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal).
Time frame: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max
Time Until Maximum Insulin Concentration in Plasma
We will assess time until the maximum concentration of circulating insulin for each injection site after a median injection of 40% of each participant's total daily dose (approximately 0.25 units per kilogram of body weight). Analysis includes reporting groups for each type of injection, and upper and lower peritoneal injections combined (Injection- All Peritoneal).
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Time frame: Peritoneal: Every 5 minutes for 180 minutes max; Subcutaneous: Every 15 minutes for 360 minutes max