Associations of serum anti-ganglioside antibodies and inflammatory markers in diabetic peripheral neuropathy

Ge, Shengjie; Xie, Jing; Zheng, Lidan; Yang, Lijuan; Zhu, Hong; Xingbo, Cheng; Shen, Feixia

doi:10.1016/j.diabres.2016.02.005

Cited by 26 publications

(20 citation statements)

References 37 publications

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“…The finding for IL-6 not only corroborates the report from the KORA F4 study (8) but also is in line with other cross-sectional studies investigating DSPN or impaired nerve conduction (5,17). By contrast, associations between higher TNF-a and DSPN or its components have so far been limited to small studies that did not adjust for confounding factors (6,7,9,15,31), whereas no associations were found in studies that considered confounders (5,8). From a mechanistic point of view, it is important to note that IL-6 and TNFa are functionally related: TNF-a activates the transcription factor nuclear factor-kB and thereby induces IL-6 expression.…”

Section: Il-6 Tnf-a and Incident Dspnsupporting

confidence: 79%

“…However, the crosssectional design of almost all clinical and epidemiological studies (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) so far precludes inferences regarding the temporal relationship between inflammation and DSPN, which are essential for any conclusions about causality. One small prospective study assessed plasma levels of soluble adhesion molecules in 28 individuals with diabetes during a 5-year study period and suggested that endothelial activation is associated with nerve conduction slowing (18).…”

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confidence: 99%

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Proinflammatory Cytokines Predict the Incidence and Progression of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study

et al. 2017

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OBJECTIVEExperimental and epidemiological studies have implicated inflammatory processes in the pathogenesis of distal sensorimotor polyneuropathy (DSPN), but prospective studies are lacking. We hypothesized that biomarkers of inflammation predict the development and progression of DSPN in a population-based cohort. RESEARCH DESIGN AND METHODSThis study was based on participants aged 62-81 years from the Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort, with a mean follow-up of 6.5 years. The predictive value of systemic levels of eight biomarkers of inflammation was assessed for incident DSPN in 133 incident case subjects and 397 individuals without incident DSPN, and for DSPN progression in 57 patients with prevalent DSPN at both time points. RESULTSHigher hs-CRP, interleukin (IL)-6, tumor necrosis factor (TNF)-a, IL-1 receptor antagonist (IL-1RA), and soluble intercellular adhesion molecule (sICAM-1) and lower adiponectin levels were associated with incident DSPN in age-and sexadjusted analysis; IL-18 and omentin were not. IL-6 (odds ratio 1.31 [95% CI 1.00-1.71]) and TNF-a (odds ratio 1.31 [95% CI 1.03-1.67]) remained associated with incident DSPN after adjusting for known DSPN risk factors. The addition of both cytokines to a clinical risk model improved model fit and reclassification. sICAM-1 and IL-1RA were positively associated with progression of DSPN. CONCLUSIONSSystemic subclinical and vascular inflammation predicted both the onset and progression of DSPN over 6.5 years in an older general population. Thus modulation of inflammatory processes may be relevant to prevent and/or treat diabetic neuropathy.Distal sensorimotor polyneuropathy (DSPN) is the most frequent neurological complication of type 2 diabetes (1). The pathomechanisms leading to the onset and progression of DSPN are not completely understood, which profoundly limits current prevention and treatment. Advanced age and diabetes duration represent the most important known risk factors, but there is increasing evidence that height,

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Section: Il-6 Tnf-a and Incident Dspnsupporting

confidence: 79%

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confidence: 99%

Proinflammatory Cytokines Predict the Incidence and Progression of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study

et al. 2017

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“…Previous studies identified clinical parameters, such as ageing, long duration of diabetes [ 29 ], high HbA1c and GA [ 30 ], raised body mass index, hypertension, dyslipidaemia [ 31 ], insulin resistance [ 32 ], low serum total bilirubin [ 33 ], elevated serum cystatin C [ 34 ], C-peptide and vitamin D deficiency [ 35 , 36 ], high thyroid-stimulating hormone [ 37 ], increased urinary albumin and decreased glomerular filtration rate (GFR) [ 38 ], anaemia [ 39 ] and arterial stiffness [ 40 ], as potential risk factors for DPN. Moreover, inflammatory markers, i.e., white blood cell parameters [ 41 ], tumour necrosis factor-α [ 42 ], serum C-reactive protein (CRP) [ 42 ], etc., have been observed to be related to diabetic neuropathy. Furthermore, endoplasmic reticulum stress also plays a vital role in the development of DPN [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

HbA1c variability and diabetic peripheral neuropathy in type 2 diabetic patients

Zhao

Zhang

et al. 2018

Cardiovasc Diabetol

104

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BackgroundDiabetic complications may be associated with impaired time-dependent glycemic control. Therefore, long-term glycemic variability, assessed by variations in haemoglobin A1c (HbA1c), may be a potential risk factor for microvascular complications, such as diabetic peripheral neuropathy (DPN). We investigated the association of HbA1c variability with DPN in patients with type 2 diabetes.MethodsIn this cross-sectional study, 563 type 2 diabetic patients who had been screened for DPN and undergone quarterly HbA1c measurements during the year preceding enrolment were recruited. DPN was confirmed in patients displaying both clinical manifestations of neuropathy and abnormalities in a nerve conduction evaluation. HbA1c variability was assessed by the coefficient of variation of HbA1c (CV-HbA1c), and the mean of HbA1c (M-HbA1c) was calculated. In addition, medical history and clinical data were collected.ResultsAmong the recruited patients, 18.1% (n = 102) were found to have DPN, and these patients also presented with a higher CV-HbA1c than the patients without DPN (p < 0.001). The proportion of patients with DPN increased significantly from 6.9% in the first to 19.1% in the second and 28.5% in the third tertile of CV-HbA1c (p for trend < 0.001). After adjusting for initial HbA1c, M-HbA1c and other clinical factors via multiple logistic regression analysis, the odds ratios (ORs) for DPN in the second and third versus those in the first CV-HbA1c tertile were 3.61 (95% CI 1.62–8.04) and 6.48 (2.86–14.72), respectively. The area under the receiver operating characteristic (ROC) curve of CV-HbA1c was larger than that of M-HbA1c, at 0.711 (95% CI 0.659–0.763) and 0.662 (0.604–0.721), respectively. ROC analysis also revealed that the optimal cutoff value of CV-HbA1c to indicate DPN was 15.15%, and its corresponding sensitivity and specificity were 66.67% and 65.73%, respectively.ConclusionsIncreased HbA1c variability is closely associated with DPN in type 2 diabetic patients and could be considered as a potent indicator for DPN in these patients.

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“…While distal microcirculation of the hallux has been demonstrated to decrease in healthy subjects and those with Type 2 diabetes and intact skin, blood flow velocity on the dorsal foot significantly increased. This may have occurred due to differences in capillary density or due to a local "steal phenomenon" caused by vasodilation of the more proximal medium sized arterioles [35][36][37]. In subjects with a diabetic foot ulceration, distal hallux microcirculation increased after 14 sessions of one hour daily PEMF therapy performed over three-week timeframe.…”

Section: Discussionmentioning

confidence: 99%

A Randomized, Sham-Controlled, Double-Blind Pilot Study of Pulsed Electromagnetic Field Therapy to Evaluate Small Fiber Nerve Growth and Function and Skin Perfusion in Subjects with Painful Peripheral Diabetic Neuropathy

Aj¹,

Rp²,

Muhlenfeld³

et al. 2017

J Diabetic Complications Med

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Abstract:Purpose: The objective of this study was to determine the potential efficacy and safety of dual energy pulsed electromagnetic field therapy (PEMF) on painful distal symmetric diabetic sensorimotor polyneuropathy (DSPN).Methodology: Subjects with Type 2 diabetes and painful DSPN were randomized to receive either an active or sham PEMF device. Objective measures of efficacy (skin biopsy, nerve conduction velocity (NCV) studies, dorsal and plantar foot skin perfusion pressure (SPP) were performed prior to and following 60-days of twice daily 30 minute treatments. Patient reported outcomes included perception of pain, concomitant medication use and adverse events.Major findings: Dorsal foot SPP improved with PEMF (n=11), change from baseline=19.6 mmHg) vs. sham (n=7, change=-17.4 mmHg), p=0.03. Trends in favor of PEMF vs sham were observed for medial nerve (n=4), planter nerve (n=4) and sural nerve (n=15) onset time and amplitude (p>0.05) other than medial planter onset time (p=0.04). Although change in pain scores were similar, compliance with device use was higher in the active group compared to the sham control. The series of tests and long-term use of PEMF was well-tolerated and feasible. No device related adverse effects were recorded.Principal conclusions: Twice daily PEMF therapy was feasible, well-tolerated, and associated with trends suggesting improved nerve function and microcirculation in patients with painful DSPN. Future, large randomized controlled trials are necessary to confirm these findings and evaluate the potential longer term benefits on symptoms and pathology of DSPN.Keywords: Diabetes; Nerve conduction velocity; Peripheral neuropathy; Pulsed electromagnetic field; Skin biopsy; Skin perfusion pressure Key MessagesPainful diabetic neuropathy affects the majority of patients with diabetes during their lifetime. The presence of diabetic neuropathy increases the potential for diabetes-related lower extremity complications.The aim of this randomized, sham-controlled trial was to determine the feasibility and effects of 60 days of treatment with PEMF therapy on skin perfusion, nerve growth and function as well as pain perception, compliance and safety in subjects with painful diabetic neuropathy. Nineteen patients (12 active; 7 sham) participated in this study.This pilot study demonstrated feasibility of use and trends in favor of PEMF in nerve function and skin perfusion of the dorsal foot. Although a reduction in average pain intensity score was not observed, subjects in the active group were relatively more compliant with device use. No device adverse effects were reported.

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Associations of serum anti-ganglioside antibodies and inflammatory markers in diabetic peripheral neuropathy

Cited by 26 publications

References 37 publications

Proinflammatory Cytokines Predict the Incidence and Progression of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study

Proinflammatory Cytokines Predict the Incidence and Progression of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study

HbA1c variability and diabetic peripheral neuropathy in type 2 diabetic patients

A Randomized, Sham-Controlled, Double-Blind Pilot Study of Pulsed Electromagnetic Field Therapy to Evaluate Small Fiber Nerve Growth and Function and Skin Perfusion in Subjects with Painful Peripheral Diabetic Neuropathy

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