Despite its negative impact on quality of life (QoL), diabetic peripheral neuropathy (DPN) remains undertreated, with only half of individuals receiving analgesic treatment and only 28% of them using anticonvulsants or antidepressants, according to Loretta Vileikyte, MD, PhD, University of Manchester, United Kingdom.

Dr. Vileikyte will discuss the psychosocial impact of painful DPN during the session Emerging Directions in Diabetic Neuropathy, which will be held at 4:30 p.m. CT Sunday, June 5, in Great Hall B at the convention center. The session will also be livestreamed for virtual meeting attendees.

“Inadequately treated or untreated DPN often results in impaired physical and mental functioning,” she said. “Worse yet, as the result of inadequate pain control and severe sleep deprivation, more than half of persons with painful DPN report decreased work productivity and even loss of job or early retirement.”

Several cross-sectional and longitudinal studies have defined pathways by which DPN generates depression, thereby providing clinicians with specific intervention points to alleviate emotional distress and improve QoL, Dr. Vileikyte said.

“In these reports, DPN symptoms and related psychosocial factors, including restrictions in activities of daily living, diminished self-worth, perceptions of pain unpredictability, and the lack of treatment control account for nearly half of the variance in depression scores,” she explained. “Pain catastrophizing is another path to increased disability and reduced quality of life in persons with painful DPN.”

While DPN is associated with an elevated risk for depression, it also displays an enduring relationship with anxiety. Other parameters, such as quality of sleep, are also important for successful DPN management.

“While most of the existing treatments to date are focused on pharmacological management of painful DPN, over the past decade there has been a steady increase in studies testing psychological interventions to manage pain in DPN sufferers,” Dr. Vileikyte said.

Cognitive behavioral therapy (CBT) is the leading psychological treatment for painful DPN and focuses on challenging negative thoughts and behaviors, she said. Recent studies have tested various CBT modifications, including mindfulness-based stress reduction, thermal biofeedback-assisted relaxation, and acceptance and commitment therapy.

“Although these are mostly small, pilot studies and have methodological issues, nonetheless, as indicated by systematic reviews, these psychological therapies have a large positive effect on pain severity, pain interference, and a moderate effect on depressive symptoms,” Dr. Vileikyte said. “It is therefore likely that, when pharmacological treatment is augmented with psychological interventions, adults with diabetes can benefit from better painful DPN management.”

Despite extensive research in recent decades, the pathogenesis of DPN remains unclear and there is no treatment beyond tight glycemic regulation, which does not slow or reverse the onset or progression of neuropathy in prediabetes and type 2 diabetes patients, said Stephanie Eid, PhD, University of Michigan.

Dr. Eid will discuss efforts to develop mechanism-based therapies that impact peripheral neuropathy before irreversible nerve damage occurs. She will focus on recent findings suggesting that targeting mitochondria is a promising approach to improve nerve function in prediabetes and type 2 diabetes.

“Our work in clinically relevant in vivo and in vitro peripheral neuropathy models mechanistically supports our central hypothesis that a complex network of metabolic changes in prediabetes and type 2 diabetes, centered on dyslipidemia, predicts the development and progression of peripheral neuropathy,” she said.

While the mechanisms by which dyslipidemia leads to nerve damage are not fully understood, research by Dr. Eid and her team has provided a greater understanding of how altered nerve lipid metabolism intersects with mitochondrial dysfunction to produce nerve damage.

“I will present our data on the mechanistic role of NADPH oxidase 5 (NOX5) in the development of oxidative stress and nerve injury in peripheral neuropathy,” Dr. Eid said. “Our findings highlight the importance of dyslipidemia and nerve lipid overload in inducing mitochondrial injury and oxidative stress in peripheral neuropathy and provide evidence of a previously unrecognized role of NOX5 as a potential mitochondrial site for therapeutic intervention in peripheral neuropathy.”

Also during the session, Lynn Ang, MD, University of Michigan, will discuss the relevance of the autonomic nervous system.

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