Alterations in cardiovascular and respiratory reflexes in diabetes are probably one of the first applications of heart rate variability in clinical medicine. Despite significant progress in diabetes care, these abnormalities are still considered the result of anatomical neural damage. Recent research from our group showed that what had been called “neuropathy” is also in part a functional abnormality. This “dysfunction” can be induced by several factors, including tissue hypoxia, hence strictly connected to respiratory abnormalities, but potentially reversible. Therefore, methods aimed at diagnosing these abnormalities in diabetes need to take into account the many possible covariates of heart rate variability, like arterial and tissue oxygenation, the integrated control of breathing and of the cardiovascular system.