Efficacy of Long‐Term Remote Ischemic Conditioning on Vascular and Neuronal Function in Type 2 Diabetes Patients With Peripheral Arterial Disease

BACKGROUND: Peripheral artery disease is a major socioeconomic challenge in the diabetes mellitus community and non‐surgical treatment options are limited. As remote ischemic conditioning (RIC) improves vascular function and attenuates ischemia‐induced tissue damage, we investigated the efficacy of RIC on vascular and neuronal function in type 2 diabetes mellitus patients with peripheral artery disease. METHODS AND RESULTS: We enrolled 36 type 2 diabetes mellitus patients with moderately reduced toe pressure (40–70 mm Hg) in a randomized sham‐controlled double‐masked trial. Patients were allocated to 12 weeks once daily upper arm cuff‐based treatment of either RIC treatment (4 cycles of 5‐minute ischemia followed by 5‐minute reperfusion) or similar sham‐device treatment. Primary outcome was transcutaneous tissue oxygen tension of the instep of the feet. Secondary outcomes were aortic pulse wave velocity, toe pressure and toe‐brachial index. Tertiary outcomes were markers of peripheral and autonomic nerve function. We enrolled 36 patients (83% men). Patients had a mean (SD) age of 70.7 years (6.8), diabetes mellitus duration of 18.4 years (8.3), HbA1c (gycated hemoglobin) of 59.7 mmol/mol (11.2). Eighty percent had peripheral symmetrical neuropathy. The mean difference in change of transcutaneous tissue oxygen tension from baseline between the RIC and sham‐treated groups was −0.03 mm Hg ([95% CI −0.1; 0.04], P=0.438). RIC did not elicit any change in additional outcomes. Three patients experienced transient skin petechiae in the treated arm. CONCLUSIONS: Long‐term repeated remote ischemic conditioning treatment have no effect on tissue oxygenation, vascular or neuronal function in patients with type 2 diabetes mellitus and moderate peripheral artery disease. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02749942.