Abstract
Background/Objectives: Type 2 Diabetes Mellitus (T2DM) represents a significant global health burden, frequently leading to severe complications such as peripheral neuropathy and both micro- and macrovascular dysfunctions. These complications are integral to the pathology of diabetic foot ulcers (DFUs) and are associated with an elevated risk of lower limb amputations. This study investigated lower extremity skeletal muscle perfusion in patients with T2DM and DFUs using [(15)O]H(2)O PET imaging, in comparison to healthy controls. Methods: A total of 10 healthy controls and 26 patients with T2DM and DFUs were enrolled. Resting skeletal muscle perfusion was quantified using [(15)O]H(2)O PET. Regional perfusion was assessed in multiple lower leg and foot muscle groups. Distal blood pressure was measured, and foot/leg perfusion ratios were calculated. Results: Patients with T2DM and DFUs exhibited a 58% higher median global foot resting perfusion compared to healthy controls. At the individual muscle level, median perfusion in the flexor hallucis brevis was elevated by up to 210% in the ulcerated foot compared to controls. No significant differences in perfusion were observed in the non-ulcerated foot. The foot/leg perfusion ratio was up to 58% higher in the ulcerated limb of T2DM patients compared to the controls. Conclusions: This study demonstrates localized alterations in skeletal muscle perfusion in patients with T2DM and DFUs, characterized by elevated resting foot perfusion in muscles adjacent to ulcerations. Understanding these perfusion dynamics may contribute to refined DFU management strategies. However, further research is needed to validate the clinical utility of [(15)O]H(2)O PET imaging in guiding interventions and predicting treatment outcomes for DFUs.