Course of nerve fiber damage underlying diabetic polyneuropathy remains unclear
medwireNews: Danish researchers monitoring hundreds of patients with type 2 diabetes for more than a decade say they have been unable to find clear support for the widely argued “one-way street” hypothesis of how nerve damage progresses in diabetic polyneuropathy (DPN).
The hypothesis proposes that damage originates in small, unmyelinated nerve fibers and is reflected in symptoms such as pain and prickling sensations. It then progresses to small myelinated nerve fibers before ultimately causing damage to large myelinated nerve fibers, with the loss of the initial symptoms as small nerve fibers lose function, explain Signe Andersen (Aarhus University) and co-workers in Diabetes Care.
In their study, Andersen and colleagues found that the course of neuropathic symptoms followed a stable, yet heterogeneous phenotype from screening-based diagnosis of type 2 diabetes to when DPN was clinically assessed 13 years later, with 40% of the 518 participants studied remaining symptom free, while symptoms remained stable in 11%, progressed in 23%, and improved in 26%.
Nonetheless, individuals with any neuropathic symptoms at baseline were more likely than others to be among the 150 individuals with clinically confirmed DPN at 13 years, defined as abnormal nerve conduction and the presence of clinical signs or symptoms of neuropathy.
Participants with mixed-fiber symptoms at baseline were a significant three times as likely as those with no symptoms to be later identified with DPN, while those with large-fiber symptoms had a 2.1-fold increased likelihood of DPN, irrespective of whether they had symptoms indicating the loss of small fiber function.
Older age at baseline was additionally associated with an elevated likelihood of DPN after 13 years, increasing the risk by 6% with each additional year.
At the 13-year follow-up, each of the three symptom categories was associated with an increased likelihood of DPN. Small fiber symptoms were associated with a 2.1-fold increased risk, mixed-fiber symptoms with a 4.1-fold increased risk, and large-fiber symptoms with a 2.5-fold increased risk.
Therefore, “this study can neither confirm nor refute the hypothesis for the course of nerve fiber damage in DPN,” says the team.
The findings come from a nested, case-control analysis of the ADDITION-Denmark trial, which compared the effect of intensive diabetes treatment to routine care on cardiovascular endpoints among 1533 individuals with screen-detected type 2 diabetes.
The researchers conclude: “Prospective studies investigating concurrent dysfunction of small and large nerve fibers and neuropathic symptoms are needed to clarify the course of DPN.”
By Anita Chakraverty
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