Endocrine alterations in myotonic dystrophy type 1 and type 2 : correlation with markers of muscle fiber atrophy

DM1 and DM2 are progressive multisystem genetic disorders that share a similar pathogenetic mechanism and clinical manifestations. The endocrine features include insulin resistance and testicular failure. Some clinical studies showed how hypogonadism do not correlate to muscle weakness in DM1 but there are no studies that evaluate directly the contribution of endocrine disorders (as hypogonadism and insulin resistance) on atrophy on muscle fibers. Atrogin1 and MuRF1 belong to the ubiquitin proteasome pathway (UPP) and their gene expression have been observed in a wide range of in vivo models of skeletal muscle atrophy including diabetes, cancer, renal failure and denervation. The aim of the study is to evaluate the influence of gonadic function, insulin resistance to muscle fiber atrophy in myotonic dystrophies. The study has been carried out on 18 male patients, 10 DM1 (age 49+/-8,1years) and 8 DM2 (age 55*/-7,9years). Patients under 18 and over 65 years were excluded. Other exclusion criteria were testosterone and statin therapy, cardiac failure (stage 3 and 4 NYHA). Muscle strength was measured by manual muscle testing (MRC score) and QMA (Gainesville, Giorgia). Gonadic function was evaluated by measurement of total testosterone, free testosterone, and gonadotropin (LH,FSH) levels. HOMA-IR as index of insulin resistance was calculated from fasting glucose and insulin level. Body composition was measured by bioelectric impedance analysis and DEXA. Biceps brachii biopsy has been performed in all patients. Atrophy and hypertrophy factors of muscle fibres have been calculated on fast or slow myosin immunostained muscle sections. The correlations between metabolic alteration and muscle fibre atrophy/hypertrophy and the expression of atrogin1 evaluated by western blot on frozen muscle will be presented.