Study: NCT05724134

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Insulin human
Description: Insulin infusion rate (IIR) will be determined empirically first to maintain mean basal fasting plasma glucose, and then either maintained at the basal rate (MH protocol) or be reduced stepwise toward euinsulinemia (RE protocol).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Insulin human
Description: Insulin infusion rate (IIR) will be determined empirically first to maintain mean basal fasting plasma glucose, and then either maintained at the basal rate (MH protocol) or be reduced stepwise toward euinsulinemia (RE protocol).

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Octreotide Acetate
Description: Octreotide will be infused at 30 ng/kg/min to suppress endogenous insulin, glucagon, and growth hormone secretion. Co-administered with glucagon and rhGH.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Octreotide Acetate
Description: Octreotide will be infused at 30 ng/kg/min to suppress endogenous insulin, glucagon, and growth hormone secretion. Co-administered with glucagon and rhGH.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Glucagon
Description: Glucagon will be replaced at a constant rate of up to 0.65 ng/kg/min to maintain baseline counterregulatory response. Co-administered with octreotide and rhGH.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Glucagon
Description: Glucagon will be replaced at a constant rate of up to 0.65 ng/kg/min to maintain baseline counterregulatory response. Co-administered with octreotide and rhGH.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Growth Hormone, Human
Description: Recombinant human growth hormone (rhGH) will be replaced at a constant rate of up to 3 ng/kg/min to maintain baseline counterregulatory response. Co-administered with octreotide and glucagon.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Growth Hormone, Human
Description: Recombinant human growth hormone (rhGH) will be replaced at a constant rate of up to 3 ng/kg/min to maintain baseline counterregulatory response. Co-administered with octreotide and glucagon.

Intervention type: OTHER
Group type: ACTIVE_COMPARATOR
Intervention: [6,6-2H2] D-glucose
Description: Stable isotope tracer administered to calculate glucose kinetics during pancreatic clamp.

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: [6,6-2H2] D-glucose
Description: Stable isotope tracer administered to calculate glucose kinetics during pancreatic clamp.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: 20% D-glucose (aq)
Description: 20% D-glucose (aq) (D20W) will be administered to counteract hypoglycemia or strongly downward blood glucose trends, as needed.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: 20% D-glucose (aq)
Description: 20% D-glucose (aq) (D20W) will be administered to counteract hypoglycemia or strongly downward blood glucose trends, as needed.

Intervention type: DIETARY_SUPPLEMENT
Group type: ACTIVE_COMPARATOR
Intervention: BOOST Plus
Description: Nutritional supplement will be administered to provide three standardized mixed meals on the day before the pancreatic clamp.

Intervention type: DIETARY_SUPPLEMENT
Group type: EXPERIMENTAL
Intervention: BOOST Plus
Description: Nutritional supplement will be administered to provide three standardized mixed meals on the day before the pancreatic clamp.

Intervention type: DIETARY_SUPPLEMENT
Group type: ACTIVE_COMPARATOR
Intervention: CORE Bar
Description: Energy bar used as a standardized snack on the day before the pancreatic clamp.

Intervention type: DIETARY_SUPPLEMENT
Group type: EXPERIMENTAL
Intervention: CORE Bar
Description: Energy bar used as a standardized snack on the day before the pancreatic clamp.

Intervention type: DEVICE
Group type: ACTIVE_COMPARATOR
Intervention: Harvard Apparatus PHD ULTRA CP syringe pump
Description: Syringe pump used for highly precise administration of insulin, octreotide/glucagon/rhGH, and D20W (as needed) even at low infusion rates.

Intervention type: DEVICE
Group type: EXPERIMENTAL
Intervention: Harvard Apparatus PHD ULTRA CP syringe pump
Description: Syringe pump used for highly precise administration of insulin, octreotide/glucagon/rhGH, and D20W (as needed) even at low infusion rates.

Intervention type: DEVICE
Group type: ACTIVE_COMPARATOR
Intervention: Yellow Springs Instruments (YSI) 2500 Biochemistry Glucose/Lactate Analyzer
Description: Glucose oxidase analyzer used to detect plasma glucose levels at the point of care. YSI have been the gold standard in clamp studies for many years. Two machines will run in parallel to ensure accuracy of results.

Intervention type: DEVICE
Group type: EXPERIMENTAL
Intervention: Yellow Springs Instruments (YSI) 2500 Biochemistry Glucose/Lactate Analyzer
Description: Glucose oxidase analyzer used to detect plasma glucose levels at the point of care. YSI have been the gold standard in clamp studies for many years. Two machines will run in parallel to ensure accuracy of results.