Inflammatory Mechanisms in Diabetic Peripheral Neuropathy

Inflammatory Mechanisms in the Pathophysiology of Diabetic Peripheral Neuropathy (DN)—New Aspects 🔗

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.

This article explores the inflammatory mechanisms contributing to diabetic peripheral neuropathy (DN). It emphasizes various factors including inflammation, iron intake, rapid blood glucose lowering, and dyslipidemia as key elements in the development of DN. The study is structured into several sections, covering the neuropathogenic roles of these factors and concluding with implications for future research and clinical practices.

Key Factors in DN: Inflammation, iron intake, rapid blood glucose reduction, and dyslipidemia are critical.
Focus on Inflammation: The article highlights inflammation as a primary mechanism affecting nerve health in diabetes.
Clinical Implications: Understanding these mechanisms may guide future therapies and management strategies for DN.

What is the main focus of the article?

The article focuses on the inflammatory mechanisms that contribute to diabetic peripheral neuropathy and discusses various factors affecting its development.

How does inflammation relate to diabetic peripheral neuropathy?

Inflammation is identified as a key neuropathogenic factor, impacting nerve health and potentially leading to the progression of diabetic peripheral neuropathy.

What are the implications for future research?

The findings suggest that further understanding of these inflammatory mechanisms could lead to better treatment and management strategies for diabetic peripheral neuropathy.