Christian Lunetta1, Andrea Lizio2, Lucio Tremolizzo3, Massimiliano Ruscica4, Chiara Macchi4, Nilo Riva5, Patrick Weydt6, Ettore Corradi7, Paolo Magni4, Valeria Sansone2,8. 1. NEuroMuscular Omnicentre (NEMO), ASST Grande Ospedale Metropolitano Niguarda, Fondazione Serena Onlus, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy. christian.lunetta@centrocliniconemo.it. 2. NEuroMuscular Omnicentre (NEMO), ASST Grande Ospedale Metropolitano Niguarda, Fondazione Serena Onlus, Piazza Ospedale Maggiore, 3, 20162, Milan, Italy. 3. Neurology Unit, San Gerardo Hospital, ALS Clinic, University of Milano-Bicocca, Monza, Italy. 4. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy. 5. Neuropathology Unit, Division of Neuroscience, Department of Neurology, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Milan, Italy. 6. Department of Neurology, Ulm University, Ulm, Germany. 7. Clinical Nutritional Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 8. Department Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
Abstract
INTRODUCTION: The progression of amyotrophic lateral sclerosis (ALS) leads to a decline of the nutritional status that represents an independent prognostic factor for survival. Recent studies recognize the muscle tissue as an endocrine organ able to release several molecules, called myokines. Among them, irisin seems to be involved in the regulation of metabolism, body weight and development and function of the nervous system. OBJECTIVES: (1) To evaluate irisin serum levels in patients with ALS, with comparison to healthy subjects; (2) to assess the possible association of circulating irisin levels of ALS patients with the metabolic status, clinical and biochemical features. METHODS: We performed an observational, cross-sectional study in 50 ALS patients and 32 age- and sex-comparable healthy controls. Patients underwent to a complete set of neurological, pulmonary and nutritional evaluations. Serum irisin concentration was measured by enzyme immunoassay. According to indirect calorimetry, ALS patients were divided into a normo-metabolic patient group (n = 24) and a hyper-metabolic patient group (n = 26). RESULTS: ALS patients showed significantly higher serum irisin levels compared to healthy subjects (51.0 ± 37.8 vs 13.1 ± 2.2 ng/mL, p < 0.0001). Hyper-metabolic ALS patients displayed higher serum irisin levels compared to normo-metabolic ALS patients and healthy controls (p < 0.0009 and p < 0.0001, respectively). Serum irisin levels showed significant association with the ALSFRS-R (β=-1.18, p = 0.042), Forced Vital Capacity (β = - 0.64, p = 0.013), Fat Mass (β=-1.44, p = 0.034), pCO2 arterial blood levels (β = 2.67, p = 0.003), HCO3- arterial blood levels (β = 5.44, p = 0.001) and Free Fat Mass (β = 1.07, p = 0.025) adjusted for sex, age and metabolic status. CONCLUSIONS: ALS patients with impaired metabolic status showed higher serum irisin levels compared to normo-metabolic ALS patients and healthy subjects. Irisin levels were also negatively correlated with the extent of functional and respiratory impairment, due to as yet unknown causes, being more elevated in patients with greater disability.
INTRODUCTION: The progression of amyotrophic lateral sclerosis (ALS) leads to a decline of the nutritional status that represents an independent prognostic factor for survival. Recent studies recognize the muscle tissue as an endocrine organ able to release several molecules, called myokines. Among them, irisin seems to be involved in the regulation of metabolism, body weight and development and function of the nervous system. OBJECTIVES: (1) To evaluate irisin serum levels in patients with ALS, with comparison to healthy subjects; (2) to assess the possible association of circulating irisin levels of ALSpatients with the metabolic status, clinical and biochemical features. METHODS: We performed an observational, cross-sectional study in 50 ALSpatients and 32 age- and sex-comparable healthy controls. Patients underwent to a complete set of neurological, pulmonary and nutritional evaluations. Serum irisin concentration was measured by enzyme immunoassay. According to indirect calorimetry, ALSpatients were divided into a normo-metabolic patient group (n = 24) and a hyper-metabolicpatient group (n = 26). RESULTS:ALSpatients showed significantly higher serum irisin levels compared to healthy subjects (51.0 ± 37.8 vs 13.1 ± 2.2 ng/mL, p < 0.0001). Hyper-metabolic ALSpatients displayed higher serum irisin levels compared to normo-metabolic ALSpatients and healthy controls (p < 0.0009 and p < 0.0001, respectively). Serum irisin levels showed significant association with the ALSFRS-R (β=-1.18, p = 0.042), Forced Vital Capacity (β = - 0.64, p = 0.013), Fat Mass (β=-1.44, p = 0.034), pCO2 arterial blood levels (β = 2.67, p = 0.003), HCO3- arterial blood levels (β = 5.44, p = 0.001) and Free Fat Mass (β = 1.07, p = 0.025) adjusted for sex, age and metabolic status. CONCLUSIONS:ALSpatients with impaired metabolic status showed higher serum irisin levels compared to normo-metabolic ALSpatients and healthy subjects. Irisin levels were also negatively correlated with the extent of functional and respiratory impairment, due to as yet unknown causes, being more elevated in patients with greater disability.
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