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Background Sensitive imaging modalities in the diagnosis of microcircular complications of the lower extremities induced by metabolic diseases are becoming a focus of interest. Purpose To investigate the [99mTc]HMPAO uptake of the legs in type 2 diabetes mellitus (T2DM) and obesity, and to search for associations with clinical parameters and nerve conducting studies. Material and Methods A total of 57 patients with controlled T2DM and 46 obese participants without DM were enrolled in the study. [99mTc]HMPAO SPECT/CT examinations were performed to evaluate the radiopharmaceutical accumulation of the legs. For the quantitative assessment of tracer uptake, standardized uptake value (SUVpeak) was measured in fixed spheric volumes of interest placed on both sural muscles on the attenuation-corrected images. Measurement of current perception threshold applying Neurometer (NM-01/CPT) was used to evaluate peripheral nerve dysfunction. Laboratory parameters assessing the glucose homeostasis of the study participants were also measured. Results In the diabetic group, significantly lower leg SUV values were detected compared to the non-DM obese group (median: 0.517 vs. 0.607; P Conclusion We assume that [99mTc]HMPAO uptake of leg muscles is associated with microcirculation, so quantitative [99mTc]HMPAO SPECT/CT might be a sensitive method for evaluating lower limb microvascular alterations. BMI, age, HbA1c, and glucose level may be significant predictors of peripheral vascular abnormalities triggered by metabolic disturbances.