To evaluate whether diabetic polyneuropathy (DPN) follows the hypothesis for the course of nerve fiber damage reflected by symptoms progressing from pure small through mixed to large nerve fiber symptoms with or without symptoms of loss of function of small nerve fibers. RESEARCH DESIGN AND METHODSRepeated assessments of nerve fiber-specific symptoms were obtained in 518 participants of the ADDITION-Denmark study from the time of a screeningbased diagnosis of type 2 diabetes using specific items of the Michigan Neuropathy Screening Instrument questionnaire. DPN was clinically assessed 13 years after inclusion. The course of symptoms reflecting dysfunction of specific nerve fibers was evaluated, and the association between symptoms and DPN was estimated using logistic regression models. RESULTSAn overall stable, yet heterogeneous course of symptoms was seen. According to the hypothesis of symptom progression, 205 (40%) participants remained free of symptoms and 56 (11%) had stable, 114 (23%) progressing, and 132 (26%) improving symptoms. Cross-sectional estimates showed a higher risk of DPN (odds ratios between 2.1 and 4.1) for participants with mixed or large nerve fiber symptoms with or without symptoms of loss of function of small nerve fibers compared with participants without symptoms. CONCLUSIONSThere was no evidence for a progressive development of nerve fiber damage in DPN reflected by symptoms going from pure small through mixed to large nerve fiber symptoms with or without symptoms of loss of function of small nerve fibers. Yet overall, neuropathic symptoms were prospectively associated with a higher risk of DPN.Diabetic polyneuropathy (DPN) is one of the most common complications of type 2 diabetes, with 10-15% of patients having signs of neuropathy already at the time of diabetes diagnosis (1-3). DPN has pivotal consequences because it is associated with a higher morbidity of affected people (1,2). Although previous studies have mainly

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