Bharucha, Adil

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.

Constipation is common in the palliative population. Opioid medications, which are frequently prescribed to this cohort, represent a significant risk factor for this condition. Opioid-induced constipation may be of such severity that opioid doses are reduced or missed, and analgesia and quality of life are therefore reduced. However, underlying chronic constipation, local and systemic disease effects, and other medications may also precipitate constipation in this population. The assessment and treatment of constipation in a palliative individual should be undertaken in a fashion similar to that used in non-palliative patients. Initial management should include minimising exposure to predisposing factors and general measures such as encouraging hydration, fibre intake and mobility. Pharmacological treatment should commence with a stool softener and a stimulant laxative. Recently published literature demonstrates that newer laxatives, including lubiprostone (a chloride channel activator) and prucalopride (a 5-HT4 receptor agonist) can effectively treat opioid-induced constipation. For patients not responding to laxatives, opioid antagonists (non-specific or peripherally acting μ-opioid receptor antagonists) can be co-prescribed with laxatives. These agents have also proven efficacy in treating opioid-induced constipation. This review discusses the recent literature regarding the management of opioid-induced constipation and provides a rational approach to assessing and managing constipation in the palliative population.