OR16-4 The Growth Hormone Axis in Relation to Muscle Weakness in the ICU: Effect of Early Macronutrient Deficit

Background: The activity of the growth hormone (GH) axis is altered by critical illness. In the acute phase, GH resistance, as reflected by increased GH and decreased insulin-like growth factor-I (IGF-I), mimics fasting-induced changes in health. Although early full feeding in ICU has long been assumed to prevent muscle wasting and weakness, the EPaNIC RCT observed fewer complications and faster recovery with accepting the macronutrient deficit in the first ICU week, as compared with early full feeding, including less acquired muscle weakness [1,2]. We previously observed that accepting the early macronutrient deficit attenuated rather than aggravated the rise in GH as compared with early full feeding [3]. We have now further characterized its impact on the GH axis, in relation to the risk of acquiring muscle weakness in ICU. Methods: This was a preplanned sub-analysis of the EPaNIC RCT. For 10 matched patients per group, serum GH was quantified every 10 min between 9 PM and 6 AM, followed by deconvolution analyses to estimate GH secretion. For 564 patients per group, matched for baseline characteristics, and for all patients investigated for muscle weakness (n=600), serum IGF-I, IGF binding protein 3 (IGFBP3) and IGFBP1 were measured upon ICU admission, at day 4 (if still in ICU), and on the last ICU day (LD). Matched healthy subjects (n=65) were included as controls. Groups were compared with Wilcoxon test or repeated-measures ANOVA. Associations between changes in concentrations from baseline to day 4 or LD for patients with shorter ICU stay (d4/LD) and risk of muscle weakness were assessed with nominal logistic regression analysis, adjusted for baseline risk factors, baseline hormone concentrations and randomization. Results: Upon ICU admission, patients revealed low IGF-I and IGFBP3 and high IGFBP1 as compared with controls (p<0.001). Tolerating an early macronutrient deficit in ICU decreased basal (non-pulsatile) GH secretion (p=0.005) without affecting pulsatile GH secretion. From admission to d4/LD IGF-I and IGFBP3 increased, whereas IGFBP1 decreased (all p<0.001) in the fully fed group. Compared to full feeding, tolerating the early macronutrient deficit prevented the rise in IGF-I (p<0.001), did not affect IGFBP3 and attenuated the decrease in IGFBP1 (p<0.001). A stronger rise in GH and IGF-I from admission to d4/LD was independently associated with a lower risk of acquiring muscle weakness (OR (95%CI) per ng/ml change 0.88 (0.81-0.96) for GH, p=0.001; 0.98 (0.97-0.99) for IGF-I, p=0.002). Conclusion: Tolerating the early macronutrient deficit suppresses basal but not pulsatile GH secretion and alters IGF-I bioavailability during critical illness. These effects may counteract the protection of the intervention against the development of muscle weakness. 1. Casaer et al. N Engl J Med 2011;365:506-17 2. Hermans et al. Lancet Respir Med 2013;1:621-9 3. Van Dyck et al. ENDO 2018;SUN601