Effect of pramlintide on postprandial glucose fluxes in type 1 diabetes

Context: Early postprandial hyperglycemia and delayed hypoglycemia remain major problems in current management of type 1 diabetes (T1D). Objective: Our objective was to investigate the effects of pramlintide, known to suppress glucagon and delay gastric emptying, on postprandial glucose fluxes in T1D. Design: This was a single-center, inpatient, randomized, crossover study. Patients: Twelve patients with T1D who completed the study were analyzed. Interventions: Subjects were studied on two occasions with or without pramlintide. Triple tracer mixed-meal method and oral minimal model were used to estimate postprandial glucose turnover and insulin sensitivity (S-1). Integrated liver insulin sensitivity was calculated based on glucose turnover. Plasma glucagon and insulin were measured. Main Outcome Measure: Glucose turnover and S, were the main outcome measures. Results: With pramlintide, 2-hour postprandial glucose, insulin, glucagon, glucose turnover, and S, indices showed: plasma glucose excursions were reduced (difference in incremental area under the curve [iAUC], 444.0 mMmin, P = .0003); plasma insulin concentrations were lower (difference in iAUC, 7642.0 pMmin; P = .0099); plasma glucagon excursions were lower (difference in iAUC, 1730.6 pg/mImin; P = .0147); meal rate of glucose appearance was lower (difference in lAUC: 1196.2 mu M/kg fat free mass [FF[W]; P = .0316), endogenous glucose production was not different (difference in iAUC: 105.5 mu M/kg FFM; P = .5842), rate of glucose disappearance was lower (difference in iAUC: 1494.2 mu M/kg FFM; P = .0083). S-i and liver insulin sensitivity were not different between study visits (P > .05).