Description:
The pathogenesis of diabetic neuropathy is complex, and various pathogenic pathwayshave been proposed. A better understanding of the pathophysiology is warranted for developingnovel therapeutic strategies. Here, we summarize recent evidence from experiments using animalmodels of type 1 and type 2 diabetes showing that low-grade intraneural inflammation is a facetof diabetic neuropathy. Our experimental data suggest that these mild inflammatory processesare a likely common terminal pathway in diabetic neuropathy associated with the degenerationof intraepidermal nerve fibers. In contrast to earlier reports claiming toxic effects of high-ironcontent, we found the opposite, i.e., nutritional iron deficiency caused low-grade inflammationand fiber degeneration while in normal or high non-heme iron nutrition no or only extremely mildinflammatory signs were identified in nerve tissue. Obesity and dyslipidemia also appear to triggermild inflammation of peripheral nerves, associated with neuropathy even in the absence of overtdiabetes mellitus. Our finding may be the experimental analog of recent observations identifyingsystemic proinflammatory activity in human sensorimotor diabetic neuropathy. In a rat model oftype 1 diabetes, a mild neuropathy with inflammatory components could be induced by insulintreatment causing an abrupt reduction in HbA1c. This is in line with observations in patients withsevere 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 andintervention studies, anti-inflammatory compounds with different modes of action may becomecandidates for the treatment or prevention of diabetic neuropathy.