Dataset Information

Serum Levels of Inflammatory Proteins Are Associated With Peripheral Neuropathy in a Cross-Sectional Type-1 Diabetes Cohort.

ABSTRACT: Chronic low-grade inflammation is involved in the pathogenesis of type-1 diabetes (T1D) and its complications. In this cross-section study design, we investigated association between serum levels of soluble cytokine receptors with presence of peripheral neuropathy in 694 type-1 diabetes patients. Sex, age, blood pressure, smoking, alcohol intake, HbA1c and lipid profile, presence of DPN (peripheral and autonomic), retinopathy and nephropathy was obtained from patient's chart. Measurement of soluble cytokine receptors, markers of systemic and vascular inflammation was done using multiplex immunoassays. Serum levels were elevated in in DPN patients, independent of gender, age and duration of diabetes. Crude odds ratios were significantly associated with presence of DPN for 15/22 proteins. The Odds ratio (OR) remained unchanged for sTNFRI (1.72, p=0.00001), sTNFRII (1.45, p=0.0027), sIL2Rα (1.40, p=0.0023), IGFBP6 (1.51, p=0.0032) and CRP (1.47, p=0.0046) after adjusting for confounding variables, HbA1C, hypertension and dyslipidemia. Further we showed risk of DPN is associated with increase in serum levels of sTNFRI (OR=11.2, p<10), sIL2Rα (8.69, p<10^-15), sNTFRII (4.8, p<10^-8) and MMP2 (4.5, p<10^-5). We combined the serum concentration using ridge regression, into a composite score, which can stratify the DPN patients into low, medium and high-risk groups. Our results here show activation of inflammatory pathway in DPN patients, and could be a potential clinical tool to identify T1D patients for therapeutic intervention of anti-inflammatory therapies.

SUBMITTER: Purohit S

PROVIDER: S-EPMC8044415 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Serum Levels of Inflammatory Proteins Are Associated With Peripheral Neuropathy in a Cross-Sectional Type-1 Diabetes Cohort.

Purohit Sharad S Tran Paul Minh Huy PMH Tran Lynn Kim Hoang LKH Satter Khaled Bin KB He Mingfang M Zhi Wenbo W Bai Shan S Hopkins Diane D Gardiner Melissa M Wakade Chandramohan C Bryant Jennifer J Bernard Risa R Morgan John J Bode Bruce B Reed John Chip JC She Jin-Xiong JX

Frontiers in immunology 20210331

Chronic low-grade inflammation is involved in the pathogenesis of type-1 diabetes (T1D) and its complications. In this cross-section study design, we investigated association between serum levels of soluble cytokine receptors with presence of peripheral neuropathy in 694 type-1 diabetes patients. Sex, age, blood pressure, smoking, alcohol intake, HbA1c and lipid profile, presence of DPN (peripheral and autonomic), retinopathy and nephropathy was obtained from patient's chart. Measurement of solu ...[more]

PMID: 33868296

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Project description:BackgroundIncreased serum carcinoembryonic antigen (CEA) levels are reported to be associated with various metabolic and inflammatory diseases. This study assessed whether high-normal serum CEA is related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D).MethodsAll subjects received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate composite Z scores of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum CEA levels and other clinical indices were also synchronously detected. Multivariable linear regression analyses were used to determine the independent effects of serum CEA levels on nerve conduction indices, multivariable logistic regression analyses were used to determine the independent impact of CEA levels on the risk of DPN, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of CEA levels to discriminate DPN.ResultsWe ultimately recruited 402 eligible subjects with normal ranges of serum CEA for this study, and 25.4% (n = 102) were determined to have DPN. After adjusting for other clinical covariates, serum CEA levels were independently associated with the composite Z score for latency (β = 0.132, t = 2.330, p = 0.021), amplitude (β = - 0.164, t = - 2.838, p = 0.005) and NCV (β = - 0.210, t = - 3.662, p < 0.001). Moreover, the prevalence of DPN in the first, second, third and fourth quartiles of CEA level was 12.9%, 19.0%, 29.4% and 40.4%, respectively (p for trend < 0.001); the corresponding adjusted odds ratios and 95% CIs for DPN in CEA quartiles were 1, 1.47 (0.45-4.82), 1.72 (0.54-5.53) and 4.58 (1.39-15.06), respectively. Furthermore, the optimal cut-off value of high-normal serum CEA to discriminate DPN was ≥ 2.66 ng/mL, with a Youden index of 0.28, sensitivity of 66.67% and specificity of 61.00%.ConclusionsIncreased serum CEA levels within the normal range are closely linked to dysfunction of peripheral nerve conduction and the risk of DPN, and high-normal serum CEA levels are a potential risk factor for DPN in T2D.

Project description:AimsDiabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus. Early identification of individuals at high risk of DPN is essential for successful early intervention. Traditional Chinese medicine (TCM) tongue diagnosis, one of the four diagnostic methods, lacks specific algorithms for TCM symptoms and tongue features. This study aims to develop machine learning (ML) models based on TCM to predict the risk of diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 4723 patients were included in the analysis (4430 with T2DM and 293 with DPN). TFDA-1 was used to obtain tongue images during a questionnaire survey. LASSO (least absolute shrinkage and selection operator) logistic regression model with fivefold cross-validation was used to select imaging features, which were then screened using best subset selection. The synthetic minority oversampling technique (SMOTE) algorithm was applied to address the class imbalance and eliminate possible bias. The area under the receiver operating characteristic curve (AUC) was used to evaluate the model's performance. Four ML algorithms, namely logistic regression (LR), random forest (RF), support vector classifier (SVC), and light gradient boosting machine (LGBM), were used to build predictive models for DPN. The importance of covariates in DPN was ranked using classifiers with better performance.ResultsThe RF model performed the best, with an accuracy of 0.767, precision of 0.718, recall of 0.874, F-1 score of 0.789, and AUC of 0.77. With a value of 0.879, the LGBM model appeared to be the best regarding recall Age, sweating, dark red tongue, insomnia, and smoking were the five most significant RF features. Age, yellow coating, loose teeth, smoking, and insomnia were the five most significant features of the LGBM model.ConclusionsThis cross-sectional study demonstrates that the RF and LGBM models can screen for high-risk DPN in T2DM patients using TCM symptoms and tongue features. The identified key TCM-related features, such as age, tongue coating, and other symptoms, may be advantageous in developing preventative measures for T2DM patients.

Project description:ObjectivesThe aims of this study were to investigate circulating levels of inflammatory markers in adolescents with type 1 diabetes with and without different types of neuropathies and evaluate the association between inflammatory biomarkers, nerve function and clinical parameters.DesignCross-sectional study.SettingHospitals and Steno Diabetes Center in Denmark.ParticipantsAdolescents with more than 5 years of diabetes duration were investigated for large fibre, small fibre and autonomic neuropathy as a part of the T1DANES study. Blood samples from the participants were analysed for inflammatory biomarkers by Meso Scale Discovery multiplexing technology.Primary and secondary outcome measuresInflammatory biomarkers and results of diagnostic nerve tests.ResultsFifty-six adolescents with type 1 diabetes and 23 healthy controls were included. The adolescents with diabetes had significantly higher interferon-gamma, tumour necrosis factor-alpha (TNF-a), interleukin (IL)-10 and soluble urokinase plasminogen activator receptor (suPAR) compared with healthy controls (p values<0.05). TNF-a was higher in the adolescents with large fibre neuropathy (LFN) (p=0.03) compared with those without LFN in the group with diabetes. A negative correlation was seen between TNF-a and conduction velocity in nervus tibialis (p=0.04), and higher TNF-a and IL-6 were associated with higher gastric motility index (TNF-a, p value=0.03; IL-6, p value=0.02). There were no significant associations between inflammatory markers and expressed symptoms, haemoglobin A1c, diabetes duration or body mass index standard derivation score (p values>0.05). The receiver operating characteristic (ROC) curves for the inflammatory markers suggested them as poor screening methods for all types of neuropathies with an area under the curve between 0.47 and 0.67.ConclusionOur results confirm increased low-grade inflammation in adolescents with type 1 diabetes. TNF-a was higher in adolescents with LFN and correlated negatively with nervus tibialis conduction velocity. The other inflammatory biomarkers fail to support differences in those with and without different types of diabetic neuropathies. However, TNF-a and IL-6 were positively correlated to gastric motility index.

Project description:Giant Axon Neuropathy (GAN) is a progressive neurodegenerative disease characterised by involvement of peripheral and central nervous system frequently associated with frizzy hair. The phenotype is caused by bi-allelic variants in the GAN gene, leading to loss of functional gigaxonin proteins.. Thus, far the disease cannot be cured, but a first clinical gene therapy trial in the US was currently completed. So far, there has been no systematic reporting of GAN patients in German-speaking countries. Therefore, we conducted a survey using an e-mail list of German-speaking child neurologists of the so-called DACH region reflecting Germany, Austria and Switzerland. Based on their feedback, clinical, genetic and epidemiological data were collected using a standardised data collection form in turn enabling the collection of comprehensive and detailed epidemiological, clinical and genetic information from a total of 15 patients representing one of the largest cohorts systematically described thus far. Average age of patients was 11.7 years at the time of data collection. In line with the frequency of homozygous variants, the majority were of Syrian origin and of consanguineous relationships. In 14 patients, diagnosis was confirmed by molecular genetics, revealing eight different GAN variants, four being reported as pathogenic in literature. 13 patients had a classical GAN phenotype, one was classified as mild whereas another one was too young to draw final clinical conclusions. Proteomics of white blood cells derived from four patients revealed was conducted to obtain unbiased insights into the underlying pathophysiology and revealed dysregulation of 111 proteins implicated in diverse biological processes. Of note diverse of these proteins are known to be crucial for proper synaptic function and transmission and affection of intermediate filament organization and proteolysis is in line with the known functions of gigaxonin. In view of a potential genetic treatment option, these data on the natural course of the disease are important for study design in preparation for gene therapy trials in Europe and moreover provide a catalogue of proteins serving as minimal invasive but cellular biomarkers.

Dataset Information

Serum Levels of Inflammatory Proteins Are Associated With Peripheral Neuropathy in a Cross-Sectional Type-1 Diabetes Cohort.

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Serum Levels of Inflammatory Proteins Are Associated With Peripheral Neuropathy in a Cross-Sectional Type-1 Diabetes Cohort.

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