Intermuscular Differences in Leg Muscle Protein Quality in Human Diabetic Neuropathy

Abstract

The magnetization transfer (MT) ratio, derived from magnetic resonance (MR) imaging, has been used to non-invasively evaluate pathological changes in the central nervous system. Use of MT imaging has been recently extended to evaluate muscle protein quality in natural adult aging, and in some clinical populations with neuromuscular disease. Peripheral neuropathy due to diabetes is related to loss of strength, motor axon loss, muscle denervation and subsequent atrophy of skeletal muscle. PURPOSE: To assess whether individuals with a diabetic neuropathy (DN) have a reduced muscle protein quality in the flexor and extensor leg muscles compared to age-matched control subjects. METHODS: Using a 3T MR scanner, MT images of the tibialis anterior (TA), soleus (SOL) and gastrocnemius (GA) muscles were recorded from 8 individuals (5 men) with DN (∼60y) and 7 (4 men) age and sex-matched controls. Using image analysis software, a magnetization transfer ratio (MTR) was calculated offline from pairs of images with (MT) and without (M0) an off-resonance prepulse as: [(M0-MT)/M0]. Outside the MR scanner, maximal dorsiflexion strength and voluntary activation were assessed using an ankle joint dynamometer. Absolute maximal dorsiflexion strength was normalized to TA muscle volume in a subset (n=9; 4 DN vs. 5 control) of each group. RESULTS: From MTR calculations, the muscle protein quality of the TA, SOL and GA were significantly reduced (∼13%, ∼5%, ∼5%, respectively) in DN subjects compared to controls. MTR values from an average of all 3 leg muscles were significantly lower in DN subjects (0.28 ± 0.02 vs. 0.30 ± 0.02 p.u.) compared to control. Despite equal voluntary activation abilities, absolute maximal dorsiflexion strength was significantly lower in the DN (∼29%) group. When normalized to muscle tissue volume, dorsiflexion strength was significantly lower in DN (∼34%) compared to control. CONCLUSIONS: In addition to reductions in overall leg muscle protein quality, these findings indicate preferential decline in the structural integrity and contractile quality of the extensor (TA) leg muscles when compared with the flexors (SOL, GA). Thus, for those with DN, muscle weakness may primarily be due to a loss of muscle mass, and reduction of contractile quality per volume of viable muscle tissue. Supported by NSERC