Diabetic peripheral neuropathy may not be as its name suggests

Abstract

Diabetic peripheral neuropathy (DPN) affects up to 50% of patients with diabetes and is a major cause of morbidity and increased mortality. Its clinical manifestations include distressing painful neuropathic symptoms and insensitivity to trauma that result in foot ulcerations and amputations. Several recent studies have implicated poor glycemic control, duration of diabetes, hyperlipidemia (particularly hypertryglyceridaemia), elevated albumin excretion rates, and obesity as risk factors for the development of DPN. However, similar data are not available for painful DPN. Moreover, although there is now strong evidence for the importance of peripheral nerve microvascular disease in the pathogenesis of DPN, peripheral structural biomarkers of painful DPN are lacking. However, there is now emerging evidence for the involvement of the central nervous system in both painful and painless DPN afforded by magnetic resonance imaging. This review will focus on this emerging evidence for central changes in DPN, hitherto considered a peripheral nerve disease only.

Fish oil and wheat germ oil supplementation modulates brain injury in streptozotocin‐induced diabetic rats

“…Tumor necrosis factor‐α signaling induces a number of intracellular signaling pathways, including the NF‐κB, p38, c‐Jun N‐terminal kinase (JNK), and ceramide/sphingomyelinase signaling pathways, resulting in inflammation, proliferation, cell migration, apoptosis, and necrosis . Therefore, TNF‐α plays a key role in the pathogenesis of DPN and its inhibition can be a useful therapeutic strategy for the treatment and/or prevention of DPN symptoms . In this context, the present study revealed a marked increase in brain TNF‐α and overexpression of NF‐κB in the cerebral cells of diabetic rats.…”

“…There results are in accordance with a previous study in which the use of n‐3 PUFA increased the availability of ACh in central cholinergic synapses. In addition, centrally acting AChE inhibitors can reduce microglial production of TNF‐α and enhance the peripheral cholinergic anti‐inflammatory pathway via central muscarinic receptors . Shevalye et al found that diabetic mice fed FO and treated with daily injections of resolvin for 6 weeks have improved nerve health in terms of density and sensory signal transmission and stimulated nerve cell growth.…”

“…Although DPN is considered a disease of the peripheral nerves, there are many changes within the central nervous system (CNS) that may be concomitant with the evolution of DPN. A recent study demonstrated atrophy in the primary sensory cortex, the part of the brain responsible for the sense of touch, in patients with diabetes . The investigators also reported that changes in blood supply to the thalamus and a reduction in the brain’s gray matter, where somatosensory perception is processed, can contribute to DPN …”

“…Peripheral inflammation is controlled by the cholinergic anti‐inflammatory pathway, which involves inhibition of innate immune responses by ACh released from the vagus nerve. This mechanism is dependent on inhibition of the nuclear translocation of NF‐κ B and suppresses cytokine release by monocytes and macrophages . Cytokines are key mediators of chronic neuroinflammation that drives progressive tissue damage in the brain and progression of neurodegenerative diseases.…”

Declining Skeletal Muscle Function in Diabetic Peripheral Neuropathy

“…137–140 More recent work has shown that DTI can be used for diagnosis of neuropathy, 141 as well as bring new insights into the involvement of central nervous system in DPN. 142,143 …”