Inflammatory Markers and Measures of Cardiovascular Autonomic Neuropathy in Type 1 Diabetes
Year: 2024
Type: 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 ( r =−0.48), Valsalva ( r =−0.28), 30:15 ( r =−0.37), SD of the normal RR interval ( r =−0.37), and root mean square of differences of successive RR intervals ( r =−0.31) (all P <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, P <0.001) and root mean square of differences of successive RR intervals (3.76 versus 3.17 ng/mL, P <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 ( P =0.004) and root mean square of differences of successive RR intervals ( P =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.
Institutions: University of Michigan, Michigan Medicine, New York University, The University of Texas Medical Branch at Galveston, University of Washington, Beaumont Hospital, Royal Oak, Corewell Health William Beaumont University Hospital, VA Ann Arbor Healthcare System, Ann Arbor VA Medical Center, Joslin Diabetes Center, Oregon Health & Science University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,700
Awards: PERL: A multi-center clinical trial of allopurinol to prevent GFR loss in T1D, G301048564, G3803894709, G4358553630, Extracorporeal SuPAR Extraction to Prevent COVID-19-associated Acute Kidney Injury, G591338366, G6194337726, G643119639, UroEDIC Bladder: Bladder Dysfunction in Type 1 Diabetes, Michigan Diabetes Research Center (MDRC), Diabetes Research Center, NIDDK Diabetic Foot Consortium Clinical Research Unit, Multidisciplinary Cardiovascular Research Training, Support to Adopt and Retain Technology (StART) CGM: A pilot study to support continuous glucose monitoring in primary care
OpenAlex ID: W4405829473