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Article Abstract
Background: Cardiovascular autonomic neuropathy (CAN) and inflammation predict more severe outcomes in type 1 diabetes (T1D). However, the link between CAN and inflammation in T1D remains unclear. We examined associations between CAN measures and inflammatory biomarkers in individuals with T1D.
Methods And Results: In a cross-sectional study, we measured cardiovascular autonomic reflex tests and heart rate variability (established CAN measures) and a panel of 39 inflammatory biomarkers, including soluble urokinase plasminogen activator receptor (suPAR), in T1D participants of the TINSAL-T1DN (Targeting Inflammation with Salsalate in Individuals with T1D Neuropathy) trial (n=57, discovery), and the PERL (Preventing Early Renal Loss in Diabetes) trial (n=468, validation). Amongst 39 inflammatory biomarkers measured in TINSAL-T1DN, suPAR levels had the strongest negative correlations with CAN measures: expiration/inspiration (=-0.48), Valsalva (=-0.28), 30:15 (=-0.37), SD of the normal RR interval (=-0.37), and root mean square of differences of successive RR intervals (=-0.31) (all <0.05). Findings were validated in PERL. In unadjusted analyses, median suPAR levels significantly differed between the lowest and highest SD of the normal RR interval tertiles (3.79 versus 3.12 ng/mL, <0.001) and root mean square of differences of successive RR intervals (3.76 versus 3.17 ng/mL, <0.001). After adjusting for covariates (age, sex, hemoglobin A1c, and estimated glomerular filtration rate), median suPAR values remained significantly elevated in the lowest tertiles of SD of the normal RR interval (=0.004) and root mean square of differences of successive RR intervals (=0.006).
Conclusions: Amongst several inflammatory biomarkers, suPAR, an immune-mediated glycoprotein, has a singular association with CAN measures. The potential of targeting suPAR as a disease-modifying approach for CAN in T1D warrants further exploration.
Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02936843, NCT02017171.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054404 | PMC |
| http://dx.doi.org/10.1161/JAHA.124.036787 | DOI Listing |
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