Pleiotropic role of IGF-I in obesity hypoventilation syndrome

Abstract

Context Obesity hypoventilation syndrome (OHS) is defined by the association between obesity and daytime arterial hypercapnia. The syndrome includes in variable proportion impaired diaphragmatic weakness, decreased central ventilatory drive and nearly systematically occurrence of sleep apnea. An increased cardio-vascular risk has been demonstrated compared to normocapnic obesity. IGF-I has a pleiotropic role in metabolism, ventilatory control, muscle function and cardiovascular protection. Objectives and design We performed a case control study comparing somatotropic axis changes including IGF-I in obese with or without OHS. Methods Patients underwent respiratory function tests, CO 2 ventilatory responses, polysomnography and somatotropic axis exploration (GH, IGF-I and IGFBP-3). Results 15 OHS (BMI: 41 ± 5.6 kg/m 2, PaCO 2: 6.13 ± 0.39 kPa, age: 55.6 ± 5.9 years) and 15 matched obese without hypercapnia (BMI: 42 ± 6.7 kg/m 2, PaCO 2: 5.13 ± 0.27 kPa, age: 55.0 ± 7.5 years) were compared. IGF-I and IGFBP-3 were significantly lowered in OHS, and negatively correlated with PaCO 2 ( r = −0.615; P < 0.001 and r = −0.452; P = 0.016, respectively). Inspiratory capacity and forced vital capacity reflecting respiratory muscle strength decreased significantly with IGF-I ( r = 0.408; P = 0.038). Triglycerides levels were higher in OHS (1.64 ± 0.58 versus 1.13 ± 0.56 g/L; P < 0.01), and negatively associated with IGF-I ( r = −0.418; P = 0.027). Conclusion A low IGF-I level is associated with hypercapnia presumably by reducing ventilatory drive and favouring muscle weakness. The relationship between increased triglycerides and low IGF-I may represent one of mechanisms involved in the OHS increased cardio-vascular risk.