Active Comparator: Maintenance hyperinsulinemia (MH) protocol
The basal insulin infusion rate (IIR) necessary to maintain participants’ mean basal fasting plasma glucose (mbFPG) will be determined during the basal titration period. Then, during the intervention period, the IIR will remain at 100% of basal for the full duration (225 min). The IIR and resulting insulin levels are expected to be relatively high (cf. hyperinsulinemia) because of underlying insulin resistance.
Drug: Insulin human
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).
Drug: Octreotide Acetate
Octreotide will be infused at 30 ng/kg/min to suppress endogenous insulin, glucagon, and growth hormone secretion. Co-administered with glucagon and rhGH.
Drug: Glucagon
Glucagon will be replaced at a constant rate of 0.65 ng/kg/min to maintain baseline counterregulatory response. Co-administered with octreotide and rhGH.
Other Name: GlucaGen
Drug: Growth Hormone, Human
Recombinant human growth hormone (rhGH) will be replaced at a constant rate of 3 ng/kg/min to maintain baseline counterregulatory response. Co-administered with octreotide and glucagon.
Other Name: Humatrope
Other: [6,6-2H2] D-glucose
Stable isotope tracer administered to calculate glucose kinetics during pancreatic clamp.
Other Name: D2-glucose, D2G
Drug: 20% D-glucose (aq)
20% D-glucose (aq) (D20W) will be administered to counteract hypoglycemia or strongly downward blood glucose trends, as needed.
Other Name: D20W
Dietary Supplement: BOOST Plus
Nutritional supplement will be administered to provide three standardized “mixed meals” on the day before the pancreatic clamp.
Device: Harvard Apparatus PHD ULTRA CP syringe pump
Syringe pump used for highly precise administration of insulin, octreotide/glucagon/rhGH, and D20W (as needed) even at low infusion rates.
Device: Yellow Springs Instruments (YSI) 2500 Biochemistry Glucose/Lactate Analyzer
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.
Source: View full study details on ClinicalTrials.gov
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