In vivo whole-body resting energy expenditure and insulin action in human malignant hyperthermia

Background: Malignant hyperthermia (MH) is a pharmacogenetic disease trigge red by volatile anesthetics or succinylcholine. The disorder is heterogenet ic and caused by abnormal calcium regulation within skeletal muscle cells. No clear metabolic differences have been found in MH-susceptible (MHS) pers ons in vivo while not having MH episodes, but some reported signs suggest t hat insulin action and energy turnover might be altered in muscle of MHS pe rsons. Methods: In fasting and insulin-stimulated conditions, using the glucose cl amp technique and indirect calorimetry, we assessed in vivo resting energy expenditure (REE) and nutrient utilization rates in 10 MHS, 5 MH-equivocal (MHE) and 10 MH-negative (MHN) persons from 14 families. With a model using the persons' fat-free mass, fat mass, age, and gender, we calculated their predicted REE and compared it with measured REE in 10 MHS and 10 MHN perso ns (measured - predicted = residual REE). Results: In vitro measured REE and glucose disposal rates were similar in 1 0 MHS and 10 MHN persons. Only during insulin stimulation was residual REE greater in MHS persons (6.4%; P = 0.013). Conclusions: In vivo insulin action is unimpaired in MHS persons. Although the absolute values of whole-body REE are the same in MHS and MHN persons, the part of REE independent of the determinants fat-free mass, fat mass, ag e, and gender is moderately grater in MHS than in MHN persons during insuli n exposure. This suggests that MH susceptibility might influence insulin-st imulated energy turnover in muscle.