The pathogenesis of diabetic neuropathy is complex, and various pathogenic pathways
have been proposed. A better understanding of the pathophysiology is warranted for developing
novel therapeutic strategies. Here, we summarize recent evidence from experiments using animal
models of type 1 and type 2 diabetes showing that low-grade intraneural inflammation is a facet
of diabetic neuropathy. Our experimental data suggest that these mild inflammatory processes
are a likely common terminal pathway in diabetic neuropathy associated with the degeneration
of intraepidermal nerve fibers. In contrast to earlier reports claiming toxic effects of high-iron
content, we found the opposite, i.e., nutritional iron deficiency caused low-grade inflammation
and fiber degeneration while in normal or high non-heme iron nutrition no or only extremely mild
inflammatory signs were identified in nerve tissue. Obesity and dyslipidemia also appear to trigger
mild inflammation of peripheral nerves, associated with neuropathy even in the absence of overt
diabetes mellitus. Our finding may be the experimental analog of recent observations identifying
systemic proinflammatory activity in human sensorimotor diabetic neuropathy. In a rat model of
type 1 diabetes, a mild neuropathy with inflammatory components could be induced by insulin
treatment causing an abrupt reduction in HbA1c. This is in line with observations in patients with
severe diabetes developing a small fiber neuropathy upon treatment-induced rapid HbA1c reduction.
If the inflammatory pathogenesis could be further substantiated by data from human tissues and
intervention studies, anti-inflammatory compounds with different modes of action may become
candidates for the treatment or prevention of diabetic neuropathy.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89483 |
| Date | 02 February 2024 |
| Creators | Baum, Petra, Toyka, Klaus V., Blüher, Matthias, Kosacka, Joanna, Nowicki, Marcin |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 10835 |
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