Objective: We aimed to assess the role of chronic inflammation in the pathogenesis of cardiovascular autonomic neuropathy (CAN) , a serious complication of type 1 diabetes (T1D) .

Methods: We leveraged an ongoing randomized, placebo-controlled clinical trial targeting inflammation with salsalate in individuals with T1D, to measure a panel of 40 inflammatory markers (Figure) in baseline samples. Measures of CAN included standardized cardiovascular autonomic reflex tests (CARTs) (E/I, Valsalva, 30/15 ratios) and indices of heart rate variability (HRV) . We used Spearman-rank to assess the correlations between inflammatory markers and CAN measures, and linear regression to adjust for age and hemoglobin A1c.

Results: The Figure displays the correlation between biomarkers and CAN measures in 58 T1D participants (mean age 51 ± 13 years, and HbA1c 8.4 ± 1.8%) . Amongst all biomarkers, we noted a singular negative correlation between soluble urokinase plasminogen activator receptor (suPAR) and measures of CAN, which remained significant in multivariable analysis (E/I ratio p=0.005, Valsalva p=0.037, RFA p=0.019, LFA p=0.023) .

Conclusion: Amongst a large panel of inflammatory markers, we found suPAR to have a notable association with CAN. SuPAR is an immune-mediated signaling glycoprotein which levels are strong predictors of risk in patients with diabetes, thus its role in CAN warrants further exploration.


L.Ang: None. L.Zhao: None. E.L.Feldman: None. S.Hayek: n/a. R.Pop-busui: Advisory Panel; Averitas Pharma, Inc., Boehringer Ingelheim International GmbH, Nevro Corp., Novo Nordisk, Reata Pharmaceuticals, Inc., Regenacy Pharmaceuticals, Inc. S.V.G.Gunaratnam: None. Y.Huang: None. K.R.Mizokami-stout: None. C.Martin: Advisory Panel; Nevro Corp. J.Reiss: n/a. A.Burant: None. A.Vasbinder: None. C.Launius: None.



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