Incident diabetic neuropathy was defined by clinical and electrophysiological criteria according to the consensus of the American Association of Neurology, the American Academy of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation (15 (link)). Based on this consensus, incident case definition generally required the presence of electrophysiological polyneuropathy as defined by abnormality of three or more parameters in two or more nerves in combination with the presence of more than one neuropathic symptom or sign of peripheral neuropathy. This same criterion was used to both exclude the presence of diabetic neuropathy at baseline and to define incident neuropathy during follow-up.
For the electrophysiological component of incident case definition, evaluation of the unilateral median, ulnar, peroneal, tibial, and sural nerves was performed at baseline and subsequent examinations were performed using standardized nerve conduction studies (16 (link)). These were performed using the Counterpoint instrument (Natus Medical, San Carlos, CA) according to the standards of the American Association for Neuromuscular and Electrodiagnostic Medicine and the Canadian Society of Clinical Neurophysiology. Low interobserver and intraobserver variabilities have been observed for these measurements using the techniques described (17 (link)). Individual nerve conduction parameters were scored as normal or abnormal according to laboratory reference values.