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Practiceupdateadc2018 ‘There Is More to Neuropathy Than Hyperglycemia Alone in T2D’ BY THE PRACTICEUPDATE EDITORIAL TEAM ne of America’s top neurologists says that the “This told us that we have to move away from the underlying pathogenesis of neuropathy in glucose-centric idea that neuropathy in type 2 dia- type 2 diabetes (T2D) is likely the metabolic betes is just caused by hyperglycemia,” Professor Osyndrome, rather than solely hyperglycemia. Feldman said. As such, consuming healthy foods and increasing In Australia, approximately half of all patients with T2D exercise may be the answer to preventing neuropa- are thought to have diabetic neuropathy. thy brought on by the metabolically induced changes “We know that neuropathy is the leading predictor of in peripheral nerves of patients with type 2 diabetes, mortality in a patient with diabetes, and that it leads said Eva Feldman, MD, PhD, Professor of Neurology to poor quality of life, pain, depression, and ulcers at the University of Michigan in Ann Arbor, Michigan. and amputation. “We know that in type 1 diabetes, there is a clear “In the US alone, diabetic neuropathy costs the US decrease in the incidence and prevalence of diabetic government about $60 billion annually in healthcare neuropathy with good glucose control. But in patients costs,” Professor Feldman said. with type 2 diabetes, controlling glucose has very little efect on neuropathy. Metabolic reprogramming of nerve bioenergetics “And what we saw is that the more components of the In a simple clinical trial conducted at the University of metabolic syndrome a patient has, the more likely Michigan, Professor Feldman and her team recruited they are to have neuropathy. patients in the early stages of T2D and placed them on a diet and exercise intervention. Almost all of the patients were obese and had the … it’s likely that there’s metabolic metabolic syndrome, and experienced discomfort " reprogramming of nerve bioenergetics in their feet. The primary aim of the study was to assess the efects gone awry – there is energy failure, of diet and exercise on the small unmyelinated nerve especially at the distal nerve. COPYRIGHTfibers that are important for sensation and pain. " Each patient was assigned his or her own exercise physiologist and dietician during the first year of follow-up. Comment At the end of year 1, patients who were compliant with the intervention loss 7 kg of their body weight and BY JOSEPHINE FORBES PhD had a clear increase in the number of intraepidermal nerve fibers. Professor Forbes is Program Leader in Chronic Disease at Mater Research Institute–The University However, when these patients were followed for an of Queensland in Brisbane, Australia. additional 2 years, during which they did not have access to the physiologist or dietician, they gained rofessor Eva Feldman, a world-renowned back the weight lost. neurologist, has also observed changes in cellular energy production and use by “When we re-biopsied their skin, we saw that with the ELSEVIERPperipheral nerves during the development of return of pain in their feet they had also loss the intraep- diabetic neuropathy. idermal nerve fiber density gained” at the end of year 1. “So this was a nice clinical proof-of-concept that Professor Josephine Forbes Her studies identified that, if caught early enough, these energetic changes in nerve func- showed us the importance of controlling aspects of tion and their symptoms were best reversed by increasing exercise and the metabolic syndrome,” Professor Feldman said. by weight loss of at least 7 kg. “The underlying pathogenesis of type 2 diabetes is She, however, cautioned against rapid reductions in HbA1c, which, in not simply glucose, it’s the metabolic syndrome. And some individuals with diabetes, can induce a painful and irreversible it’s likely that there’s metabolic reprogramming of peripheral neuropathy. nerve bioenergetics gone awry – there is energy failure, especially at the distal nerve. Professor Feldman suggested that the nerves in a diabetic environment need time to adjust their use of fuels and that reducing blood glucose in “We really need future studies to target these new a short timeframe did not allow for this, resulting in activation of neural mechanisms in our patients with early intervention,” pathways involved in pain. she added. Her clinical advice – slowly, slowly! www.practiceupdate.com/c/73015 16 PRACTICEUPDATE CONFERENCE SERIES • ADC 2018.
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