Evidence mapPaperPMID 39727210Full record

Trial reportJournal of the American Heart Association2025

Inflammatory Markers and Measures of Cardiovascular Autonomic Neuropathy in Type 1 Diabetes.

Lynn Ang, Sejal Gunaratnam, Yiyuan Huang, Brendan R Dillon, Catherine L Martin, Aaron Burant, Jacob Reiss, Pennelope Blakely, Alexi Vasbinder, Lili Zhao and 8 more

2 registry-linked trialsAbstract readClinical Trial, Phase IIClinical Trial, Phase IIIMulticenter Study
In one paragraph

Trial report in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02017171 phase3completednot on this map

PERL: A Multicenter Clinical Trial of Allopurinol to Prevent GFR Loss in T1D

TypeinterventionalSponsorAlessandro DoriaRan2014 to 2019Enrolled530ConditionsDiabetic Nephropathies, Coronary Artery DiseaseArmsAllopurinol, Placebo
NCT02936843 phase2 / phase3completednot on this map

Targeting Inflammation With Salsalate in Type 1 Diabetes Neuropathy-TINSAL -T1DN

TypeinterventionalSponsorUniversity of MichiganRan2016 to 2023Enrolled61ConditionsType 1 Diabetes, Peripheral NeuropathyArmsSalsalate, PLACEBO
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Observational
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Lynn AngDepartment of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes University of Michigan Ann Arbor MI USA.ORCID 0000-0001-7133-9886
Sejal GunaratnamLife Science Informatics University of Michigan Ann Arbor MI USA.
Yiyuan HuangDepartment of Biostatistics University of Michigan Ann Arbor MI USA.ORCID 0000-0001-5568-8517
Brendan R DillonDepartment of Medicine NYU Grossman School of Medicine New York NY USA.
Catherine L MartinDepartment of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes University of Michigan Ann Arbor MI USA.
Aaron BurantDepartment of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes University of Michigan Ann Arbor MI USA.
Jacob ReissQuality Department University of Michigan Ann Arbor MI USA.
Pennelope BlakelyDepartment of Internal Medicine, Division of Cardiology University of Texas Medical Branch Galveston TX USA.ORCID 0000-0002-9677-3010
Alexi VasbinderBiobehavioral Nursing and Health Informatics University of Washington School of Nursing Seattle WA USA.ORCID 0000-0002-1380-5364
Lili ZhaoCorewell Health William Beaumont University Hospital Royal Oak MI USA.ORCID 0000-0002-6366-8206
Kara Mizokami-StoutDepartment of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes University of Michigan Ann Arbor MI USA.ORCID 0000-0002-6933-2586
Yaling TangDepartment of Epidemiology Joslin Diabetes Center Boston MA USA.
Eva L FeldmanDepartment of Neurology University of Michigan Ann Arbor MI USA.
Alessandro DoriaDepartment of Epidemiology Joslin Diabetes Center Boston MA USA.ORCID 0000-0002-3830-4304
Cathie SpinoDepartment of Biostatistics University of Michigan Ann Arbor MI USA.ORCID 0000-0002-6157-6738
Mousumi BanerjeeDepartment of Biostatistics University of Michigan Ann Arbor MI USA.ORCID 0000-0001-5901-822X
Salim S HayekDepartment of Internal Medicine, Division of Cardiology University of Texas Medical Branch Galveston TX USA.ORCID 0000-0003-0180-349X
Rodica Pop-BusuiDepartment of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes University of Michigan Ann Arbor MI USA.ORCID 0000-0002-2042-1350

Funding

PILOT STUDY--SECRETORY TARGETING IN PANCREATIC B CELLSP30DK036836 · JOSLIN DIABETES CENTER · 1986 to 2025
$12.1M
Pilot and Feasibility ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 to 2025
$4.9M
TRAINING IN MOLECULAR AND CELLULAR CARDIOLOGYT32HL007853 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1996 to 2025
$2.8M
NIDDK Diabetic Foot Consortium Clinical Research UnitU01DK119083 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$727k
Support to Adopt and Retain Technology (StART) CGM: A pilot study to support continuous glucose monitoring in primary careK23DK131296 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$194k
NHLBI NIH HHS R01 HL153384NHLBI NIH HHS T32 HL007853NIDDK NIH HHS K23 DK131296NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK036836NIDDK NIH HHS R01 DK107956NIDDK NIH HHS R01 DK116723NIDDK NIH HHS R01 DK128012NIDDK NIH HHS U01 DK119083NIDDK NIH HHS UC4 DK101108
6 · The paper itself

Abstract

backgroundCardiovascular 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

resultsIn 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 (

conclusionsAmongst 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.

Indexed as

BiomarkersDiabetes Mellitus, Type 1Diabetic NeuropathiesHeart RateInflammationReceptors, Urokinase Plasminogen ActivatorAdultAutonomic Nervous SystemAutonomic Nervous System DiseasesCardiovascular DiseasesCardiovascular SystemCross-Sectional StudiesFemaleHumansInflammation MediatorsMaleBiomarkersInflammation MediatorsPLAUR protein, humanReceptors, Urokinase Plasminogen Activatorbiomarkerscardiovascular autonomic neuropathycardiovascular autonomic reflex testsheart rate variabilityinflammationsoluble urokinase plasminogen activator receptortype 1 diabetes

Identifiers

PMID39727210
PMCPMC12054404

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.