Effect of Pramlintide on Postprandial Glucose Fluxes in Type 1 Diabetes

Abstract

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 (SI). Integrated liver insulin sensitivity was calculated based on glucose turnover. Plasma glucagon and insulin were measured.

Main outcome measure: Glucose turnover and SI were the main outcome measures.

Results: With pramlintide, 2-hour postprandial glucose, insulin, glucagon, glucose turnover, and SI 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/mlmin; P = .0147); meal rate of glucose appearance was lower (difference in iAUC: 1196.2 μM/kg fat free mass [FFM]; P = .0316), endogenous glucose production was not different (difference in iAUC: -105.5 μM/kg FFM; P = .5842), rate of glucose disappearance was lower (difference in iAUC: 1494.2 μM/kg FFM; P = .0083). SI and liver insulin sensitivity were not different between study visits (P > .05).

Conclusions: Inhibition of glucagon and gastric emptying delaying reduced 2-hour prandial glucose excursions in T1D by delaying meal rate of glucose appearance.

Figure 1.

A, Gastric emptying for solids and liquids during triple tracer studies without pramlintide (dashed-open circle) and with pramlintide (solid-closed square) in subjects with type 1 diabetes (T50 gastric emptying for liquids and solids emptying was delayed with pramlintide, P < .001). B, Plasma glucose, insulin, and glucagon concentrations during triple tracer meal studies without pramlintide (dashed-open circle) and with pramlintide (solid-closed square) in subjects with type 1 diabetes. Error bars represent SD.

Figure 2.

A, Rates of meal glucose appearance, endogenous glucose production, and Rd during triple tracer studies without pramlintide (dashed-open circle) and with pramlintide (solid-closed square) in subjects with type 1 diabetes. B, Whole body S_I and S_IL obtained during triple tracer studies without pramlintide and with pramlintide in subjects with type 1 diabetes (left panels). Individual S_I and S_IL are shown (right panels). C, Plasma concentrations of GLP-1, somatostatin, total and active Ghrelin, and pancreatic polypeptide obtained during the studies.