(194) Epidermal Axon Changes in Patients with Prediabetes: The PACMAN Study

Pain is a tremendous health care burden associated with prediabetes and diabetes. However, not everyone with prediabetes or diabetes develops pain and the factors that increase susceptibility to painful neuropathy remain elusive. The epidermis is innervated by both peptidergic and nonpeptidergic axons and our studies in mice reveal that mechanical allodynia induced by consuming a high fat diet increases peptidergic epidermal axons. We hypothesize that patients with prediabetes and painful neuropathy have an abnormal proportion of epidermal peptidergic axons. We are carrying out an ongoing clinical study in which patients are recruited into 3 groups based on their metabolic status: 1) normal (n=6), 2) prediabetes (n=7), or 3) prediabetes with neuropathic symptoms (n=5). Metabolic status (healthy vs. prediabetic) is determined using the 2016 American Diabetes Association (ADA) Guidelines associated with A1c (5.7-6.4%), fasting glucose (100-125 mg/dl), or oral glucose tolerance (140-199 mg/dl). Data (vitals, demographic, social/lifestyle, medical history) is collected, and fasting patients undergo a blood draw (insulin, lipid panel, hematocrit, hemoglobin, and HBA1c) and a glucose tolerance test and to identify their metabolic status. In a second visit, patients undergo a clinical evaluation of their sensory status (Brief Pain Inventory for Diabetic Neuropathy (BPI-DPN), Michigan Neuropathy Screening Instrument, Utah Early Neuropathy Scale) and an ankle skin biopsy is obtained to quantify intraepidermal nerve fiber density (IENFD). PGP 9.5 is used to identify all axons, and TrkA+ fibers are used to identify peptidergic axons. Our primary analysis will compare differences in peptidergic fiber measures to neuropathy symptoms among the 3 groups. Our goal is to identify risk factors that modify peripheral innervation and increase the risk of pain associated with neuropathy. The status of this ongoing clinical study will be presented at the meeting and include discussions of the translational approaches driving this clinical study. Pain is a tremendous health care burden associated with prediabetes and diabetes. However, not everyone with prediabetes or diabetes develops pain and the factors that increase susceptibility to painful neuropathy remain elusive. The epidermis is innervated by both peptidergic and nonpeptidergic axons and our studies in mice reveal that mechanical allodynia induced by consuming a high fat diet increases peptidergic epidermal axons. We hypothesize that patients with prediabetes and painful neuropathy have an abnormal proportion of epidermal peptidergic axons. We are carrying out an ongoing clinical study in which patients are recruited into 3 groups based on their metabolic status: 1) normal (n=6), 2) prediabetes (n=7), or 3) prediabetes with neuropathic symptoms (n=5). Metabolic status (healthy vs. prediabetic) is determined using the 2016 American Diabetes Association (ADA) Guidelines associated with A1c (5.7-6.4%), fasting glucose (100-125 mg/dl), or oral glucose tolerance (140-199 mg/dl). Data (vitals, demographic, social/lifestyle, medical history) is collected, and fasting patients undergo a blood draw (insulin, lipid panel, hematocrit, hemoglobin, and HBA1c) and a glucose tolerance test and to identify their metabolic status. In a second visit, patients undergo a clinical evaluation of their sensory status (Brief Pain Inventory for Diabetic Neuropathy (BPI-DPN), Michigan Neuropathy Screening Instrument, Utah Early Neuropathy Scale) and an ankle skin biopsy is obtained to quantify intraepidermal nerve fiber density (IENFD). PGP 9.5 is used to identify all axons, and TrkA+ fibers are used to identify peptidergic axons. Our primary analysis will compare differences in peptidergic fiber measures to neuropathy symptoms among the 3 groups. Our goal is to identify risk factors that modify peripheral innervation and increase the risk of pain associated with neuropathy. The status of this ongoing clinical study will be presented at the meeting and include discussions of the translational approaches driving this clinical study.