The effects of nerve dysfunction upon blood vessels in diabetes.

INTERVENTION: The intervention is remote ischaemic conditioning (RIC): a single session of 4 repeated cycles of 5 minute blood pressure cuff inflation to 200mmHg followed by 5 minutes of cuff deflation on the non‐dominant upper arm. The RIC exposure will be applied by a general practitioner member of the research team with >10 years of clinical experience, or a suitably trained researcher, at either the Sport UNE Exercise Physiology laboratory at the University of New England (UNE), or the University Medical Centre at the UNE. The RIC involves the use of a standard pneumatic blood pressure cuff and sphygmomanometer. The researcher will be present throughout the intervention. Ischaemia will be confirmed by absence of the radial pulse and pulse oximetry on the cuffed arm during each cuff inflation. Participants will be asked to avoid alcohol, caffeine and minimise physical exercise for 24 hours prior to the study until study completion. CONDITION: Diabetes Diabetic neuropathy Peripheral Arterial Disease PRIMARY OUTCOME: Change in plasma levels of calcitonin gene‐related peptide in peripheral venous blood (ELISA assay) Change in plasma levels of vascular endothelial growth factor in peripheral venous blood (ELISA assay) Change in serum levels of apolipoprotein A‐1 in peripheral venous blood. SECONDARY OUTCOME: Change in serum C reactive protein in peripheral venous blood Change in serum glucose in peripheral venous blood Changes in arterial blood pressure (mmHg) using non‐invasive continuous blood pressure monitoring of the dominant arm, measured by Finometer® Midi Model‐2 (Finapres Medical Systems B.V., Amsterdam, The Netherlands) Changes in heart rate variability assessed with use of an ambulatory Holter monitor INCLUSION CRITERIA: Type 2 diabetic participants, with or without diabetic neuropathy