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

Sharad Purohit, Paul Minh Huy Tran, Lynn Kim Hoang Tran, Khaled Bin Satter, Mingfang He, Wenbo Zhi, Shan Bai, Diane Hopkins, Melissa Gardiner, Chandramohan Wakade, Jennifer Bryant, Risa Bernard, John Morgan, Bruce Bode, John Chip Reed, Jin Xiong She

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number654233
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - Mar 31 2021

Keywords

  • autoimmunity
  • chronic inflammation
  • cytokines
  • peripheral neuropathy
  • receptors
  • type-1 diabetes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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