Spectral analysis of blood components in diabetic patients with neuropathic complications: Exploring the diagnostic potential of extracellular vesicles

Background\r\nDiabetic sensorimotor peripheral neuropathy (DSPN) is the most prevalent neuropathic complication of diabetes mellitus (DM), significantly impacting the patient's quality of life and correlating with increased mortality. Early intervention is key to slowing down the progression of DSPN, underscoring the importance of a timely diagnosis, currently based on patients' medical history and physical examinations. In this study, we aim to identify novel markers of DSPN in type 1 DM (T1DM) patients by investigating several blood components, including plasma, red blood cells (RBCs), RBC-ghosts (RBC-G), and plasma-extracellular vesicles (pEVs).\r\nResults\r\nTo this end, we utilized Fourier-transform infrared (FTIR) spectroscopy, a rapid and cost-effective technique capable of providing characteristic spectral fingerprints of biological samples. Samples were obtained from 72 T1DM patients, of which 50 showed no signs of neuropathy, and 22 were diagnosed with DSPN. Interestingly, we observed statistically significant differences between the two groups in the spectral signatures of pEV samples, including the amide I and II, lipid ester, and CH3-stretching bands. Additionally, a combined marker was obtained through logistic regression and ROC analysis by exploiting the intensity of the amide I peak and the disease duration. This marker demonstrated good capability in identifying T1DM patients with DSPN (AUC = 0.88, 95 % CI 0.74–1).\r\nSignificance\r\nAlthough pEVs have been widely investigated in diabetes, their biochemical composition has rarely been explored through label-free vibrational spectroscopy, and no previous studies have analyzed patients with neuropathic complications. This work applies FTIR-spectroscopy to characterize blood-derived pEVs and reveals distinctive spectral alterations associated with DSPN. The developed combined marker, leveraging amide I intensity and disease duration, showed strong discriminatory power, supporting the potential of this approach for developing novel screening methods for diabetic neuropathic complications.