Diabetic peripheral neuropathy: A clinicopathologic and immunohistochemical analysis of sural nerve biopsies

Younger, David S.; Rosoklija, Gorazd; Hays, Arthur P.; Trojaborg, W.; Latov, Norman

doi:10.1002/(sici)1097-4598(199606)19:6<722::aid-mus6>3.0.co;2-c

Cited by 114 publications

(10 citation statements)

References 27 publications

(1 reference statement)

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“…In diabetic patients (type I and II) with peripheral neuropathy, approximatively 25 times more CD3+ T cells were counted per section in sural nerve biopsies compared to control patients. The infiltrated T cells were mostly CD8+ T cells and CD25+ cells, an indication of CD4+ or CD8+ Treg (Younger et al, 1996). However, the contribution of T cells to diabetic painful neuropathy has not been investigated yet.…”

Section: Contribution Of T Cells To the Transition From Acute To Chromentioning

confidence: 99%

T Cells as an Emerging Target for Chronic Pain Therapy

Laumet

Robison

et al. 2019

Front. Mol. Neurosci.

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The immune system is critically involved in the development and maintenance of chronic pain. However, T cells, one of the main regulators of the immune response, have only recently become a focus of investigations on chronic pain pathophysiology. Emerging clinical data suggest that patients with chronic pain have a different phenotypic profile of circulating T cells compared to controls. At the preclinical level, findings on the function of T cells are mixed and differ between nerve injury, chemotherapy, and inflammatory models of persistent pain. Depending on the type of injury, the subset of T cells and the sex of the animal, T cells may contribute to the onset and/or the resolution of pain, underlining T cells as a major player in the transition from acute to chronic pain. Specific T cell subsets release mediators such as cytokines and endogenous opioid peptides that can promote, suppress, or even resolve pain. Inhibiting the pain-promoting functions of T cells and/or enhancing the beneficial effects of pro-resolution T cells may offer new disease-modifying strategies for the treatment of chronic pain, a critical need in view of the current opioid crisis.

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Section: Contribution Of T Cells To the Transition From Acute To Chromentioning

confidence: 99%

T Cells as an Emerging Target for Chronic Pain Therapy

Laumet

Robison

et al. 2019

Front. Mol. Neurosci.

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“…If we can find diabetic peripheral neuropathy early, actively and effectively control blood sugar and give symptomatic treatment [ 4 ], and carry out some necessary foot care, serious consequences such as ulcer, gangrene, and amputation of the foot may be avoided [ 5 ]. In view of this research problem, Younger and others reported that the course of diabetes is the influencing factor of DPN [ 6 ]. Studies by Dixit et al show that hyperglycemia is one of the most important causes of DPN.…”

Section: Introductionmentioning

confidence: 99%

Balance Analysis of Peripheral Neuropathy in Type 2 Diabetes Mellitus Based on Logistic Regression Equation

Zhang¹,

Du²,

Yao³

et al. 2022

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This paper analyzes the factors of peripheral neuropathy in type 2 diabetes mellitus and puts forward a balanced analysis of peripheral neuropathy in type 2 diabetes mellitus based on logistic regression equation. A total of 1192 eligible patients were selected as the study subjects. All selected patients underwent 75 g oral glucose tolerance test to measure fasting blood glucose and insulin and 2-hour postprandial blood glucose and 2-hour postprandial insulin, as well as neuroelectrophysiological examination. The results showed that the OR values of age, course of disease, fingertip blood glucose immediately after admission, and 2-hour blood glucose were greater than 1, and the P values were all less than 0.05, which were the risk factors of diabetic peripheral neuropathy. OR value of β cell function index (HBCI) is less than 1. P is less than 0.05, and it is a protective factor of diabetic peripheral neuropathy. Laboratory indicators are as follows: 75 g OGTT: 0-hour blood glucose, 2-hour blood glucose, and glycosylated hemoglobin; serum creatinine; glutamate transaminase; fibrinogen; ten items of hemoglobin; and indexes reflecting islet function: islet β is thin, and there are significant differences in cell function index, insulin resistance index, and insulin secretion index between the non-DPN group and DPN group. Age, course of disease, fingertip blood glucose immediately after admission, and blood glucose within 2 hours after admission were the risk factors for diabetic peripheral neuropathy. Islet β cell function index (HBCI) is a protective factor of diabetic peripheral neuropathy.

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“…Our results relate a higher percentage of CD4 + T cells to lower NCV. Early histological studies demonstrated an abundant presence of T cells in nerves of patients with DSPN, [23][24][25] but it remained unclear to what extent this observation would be relevant to the pathophysiology of DSPN. In this context, it is important to note that we previously identified the proinflammatory cytokines IL-6 and TNF-α as independent predictors of DSPN.…”

Section: Associations Between Leukocyte Subsets and Dspnmentioning

confidence: 99%

“…39 Direct cell contact between B cells and peripheral nerves appears unlikely given the absence of B cells in sural nerve biopsies in histological studies. 25 However, existing nerve damage may lead to danger signals being transferred via lymphatics to draining lymph nodes, where B cells capture and present free-floating antigen coming from the tissue and where B cell/T cell interaction mainly happens. With respect to cytokine release and antibody production, it was shown that B cells are involved in the pathophysiology of different inflammatory neuropathies, 26 40 but whether similar processes operate in DSPN is unclear.…”

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confidence: 99%

Associations of cells from both innate and adaptive immunity with lower nerve conduction velocity: the Maastricht Study

Maalmi

Wouters

Savelberg

et al. 2021

BMJ Open Diab Res Care

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IntroductionDistal sensorimotor polyneuropathy (DSPN) is common in people with diabetes but is also found in pre-diabetes. Peripheral nerve myelin damage, which can be assessed by reduced nerve conduction velocity (NCV), is an essential feature of DSPN. Emerging evidence indicates that the development of DSPN may involve the activation of the immune system. However, available studies have mainly investigated circulating immune mediators, whereas the role of immune cells remains unclear. Therefore, we aimed to test whether leukocyte subsets are associated with NCV.Research design and methodsThis cross-sectional study analyzed data from 850 individuals (of whom 252 and 118 had type 2 diabetes and pre-diabetes, respectively) of the Maastricht Study. NCV was measured in the peroneal and tibial motor nerves and the sural sensory nerve and summed to calculate a standardized NCV sum score. Associations between percentages of leukocyte subsets and NCV sum scores were estimated using linear regression models adjusted for demographic, lifestyle, metabolic and clinical covariates.ResultsAfter adjustment for covariates, higher percentages of basophils and CD4+ T cells were associated with lower NCV (p=0.014 and p=0.005, respectively). The percentage of CD8+ T cells was positively associated with NCV (p=0.022). These associations were not modified by glucose metabolism status (all pinteraction >0.05). No associations were found for monocytes, eosinophils, neutrophils, lymphocytes, total T cells, Treg cells and B cells.ConclusionsThe associations of basophils, CD4+ and CD8+ T cells with NCV suggest that cell types from both innate and adaptive immunity may be implicated in the development of DSPN.

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Diabetic peripheral neuropathy: A clinicopathologic and immunohistochemical analysis of sural nerve biopsies

Cited by 114 publications

References 27 publications

T Cells as an Emerging Target for Chronic Pain Therapy

T Cells as an Emerging Target for Chronic Pain Therapy

Balance Analysis of Peripheral Neuropathy in Type 2 Diabetes Mellitus Based on Logistic Regression Equation

Associations of cells from both innate and adaptive immunity with lower nerve conduction velocity: the Maastricht Study

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