Abstract
Abstract: Dietary interventions are promising approaches to treat pain associated with metabolic changes because they impact both metabolic and neural components contributing to painful neuropathy. Here, we tested whether consumption of a ketogenic diet could affect sensation, pain, and epidermal innervation loss in type 1 diabetic mice. C57Bl/6 mice were rendered diabetic using streptozotocin and administered a ketogenic diet at either 3 weeks (prevention) or 9 weeks (reversal) of uncontrolled diabetes. We quantified changes in metabolic biomarkers, sensory thresholds, and epidermal innervation to assess impact on neuropathy parameters. Diabetic mice consuming a ketogenic diet had normalized weight gain, reduced blood glucose, elevated blood ketones, and reduced hemoglobin-A1C levels. These metabolic biomarkers were also improved after 9 weeks of diabetes followed by 4 weeks of a ketogenic diet. Diabetic mice fed a control chow diet developed rapid mechanical allodynia of the hind paw that was reversed within a week of consumption of a ketogenic diet in both prevention and reversal studies. Loss of thermal sensation was also improved by consumption of a ketogenic diet through normalized thermal thresholds. Finally, diabetic mice consuming a ketogenic diet had normalized epidermal innervation, including after 9 weeks of uncontrolled diabetes and 4 weeks of consumption of the ketogenic diet. These results suggest that, in mice, a ketogenic diet can prevent and reverse changes in key metabolic biomarkers, altered sensation, pain, and axon innervation of the skin. These results identify a ketogenic diet as a potential therapeutic intervention for patients with painful diabetic neuropathy and/or epidermal axon loss. [ABSTRACT FROM AUTHOR]