Reply to Drs. Sacco et al
Journal of applied physiology
TO THE EDITOR: We read with interest the comments from Sacco et al. (4) on our manuscript. We feel clarification on their points is necessary to reflect the entirety of the literature on the subject. Although there may be some early effects on motorrelated issues in diabetes (DM), based on small focused studies it is clear that duration and severity is the major factor that determines progression of neuropathy and the significant motor impairment associated with this progression (5). In large
... ion (5). In large prospective trials, the general and clinically relevant progression of diabetes polyneuropathy (DPN) included early sensory findings with later onset of motor dysfunction (2, 3, 5). This latter event is associated with motor axon loss most often seen as reduction in compound muscle action potential amplitude in clinical electromyography laboratories. This change correlates to severity of DPN and greater disability. Our opinion is that Sacco and colleagues may mislead in their assertion that "motor involvements are not related to DPN duration or severity." This leads the reader to believe that clinically relevant motor impairment occurs along with early sensory dysfunction. This is not the message we want to impart, particularly to the clinician, because early sensory phenomena precede significant clinical motor dysfunction and provide the greatest opportunity for detection and intervention in DPN. Sacco and colleagues indicate that many previous investigations have found an increased proportion of type II muscle fibers in the skeletal muscle of human with diabetes as well as animal models of DM. We agree with that point. However, our paper focused on diabetic DPN rather than DM alone. This is a critical difference, because moderate to severe DPN is associated with significant motor axon retraction and loss of motor units with neuromuscular remodeling. This is a process that is not ongoing in DM alone and is a potentially robust driver of skeletal muscle properties. Thus the papers cited by Sacco and colleagues are not necessarily applicable to the discussion of moderate to severe DPN. Investigations studying moderate to severe DPN have shown reduced torque per volume of muscle, reduced rate of torque development in voluntary and evoked contractions, prolonged relaxation of evoked contractions, and reduced motor unit firing rates (for review, see 1). These findings are certainly not definitive of a preferential loss of large, fast motor units, but they may reflect that process. Furthermore, to our knowledge, no muscle biopsy studies to date have explored this question in humans with moderate to severe diabetic neuropathy. We agree with the Sacco et al. regarding their emphasis of our points focusing on exercise therapy management in prevention and management of diabetic polyneuropathy. With limited space available for our review, we chose to focus on more general exercise regimens to focus on more preventative strategies. Certainly there are a number of studies applicable to improving later complications of DPN and to exercise therapies in diabetes in general that deserve attention. We focused on more preventive strategies as our opinion is that prevention of DPN and its progression is the primary clinical goal but acknowledging there are very important management strategies in later disease. DISCLOSURES No conflicts of interest, financial or otherwise, are declared by the authors. final version of manuscript. REFERENCES 1. Allen MD, Doherty TJ, Rice CL, Kimpinski K. Physiology in Medicine: neuromuscular consequences of diabetic neuropathy. . Dyck PJ, Davies JL, Wilson DM, Service FJ, Melton LJ III, O'Brien PC. Risk factors for severity of diabetic polyneuropathy: intensive longitudinal assessment of the Rochester Diabetic Neuropathy Study cohort. . 4. Sacco ICN, Suda EY, Gomes AA. Management of neuropathy musculoskeletal deficits is much more than general global exercises: physiotherapybased programs for diabetes long-term complications.