---
title: "Heart rate fragmentation and baroreflex coupling in type 2 diabetes with and without CAN"
id: "pubmed-42815531"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42815531"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42815531/"
doi: "10.1088/1361-6579/aeae9f"
published_at: "2026-10-20T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Heart rate fragmentation and baroreflex coupling in type 2 diabetes with and without CAN
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42815531
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42815531/)
- **DOI:** [10.1088/1361-6579/aeae9f](https://doi.org/10.1088%2F1361-6579%2Faeae9f)
- **Published At:** 2026-10-20T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The investigators examined the relationship between ultrafast heart period dynamics, measured as **heart rate fragmentation** (HRF), and baroreflex control in 64 people with **type 2 diabetes mellitus** (T2DM). - Participants were split into T2DM with **cardiovascular autonomic neuropathy** (DMCAN, n = 28, ages 55–62, 17 males) and T2DM without CAN (DMnoCAN, n = 36, ages 49–61, 19 males). - Recordings were obtained during supine resting (REST) and active standing (STAND); HRF used five-beat sequences classified as W0–W3 and a total inflection-point measure (PIP). - Baroreflex indices included cross-spectral measures between HP and systolic arterial pressure (SAP) in LF and HF bands, squared coherence K2HP-SAP(LF/HF), and sequence-method metrics (%SEQ, αSEQ). - At REST the cohort with CAN showed higher W3 compared with those without CAN; W3 rose on STAND for both groups. - At REST %SEQ and K2HP-SAP(HF) were positively associated with W0 and W1, and negatively associated with W3 and PIP — indicating better baroreflex linked to fewer inflection points. - During STAND K2HP-SAP(LF), %SEQ and αSEQ correlated negatively with PIP and W3, suggesting impaired baroreflex during orthostatic challenge relates to increased fast HP changes. - The authors reported that more inflection points in 4-beat words (W3) corresponded to less effective **baroreflex** control, implying impaired baroreflex may raise the likelihood of rapid HP fluctuations in DMCAN. - The abstract does not provide additional methodological details such as recording durations, medication status, exclusion criteria, or full statistical metrics; those items were not reported in the source abstract.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Cardiovascular Physiotherapy Laboratory, Department of Physiotherapy, Federal University of São Carlos, São Carlos, SP, Brazil. * 2 Samsung R&D Institute Brazil-SRBR, Campinas, São Paulo, Brazil. * 3 Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. * 4 Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America. * 5 Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. * 6 Department of Cardiothoracic, Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, San Donato Milanese, Italy. * PMID: **42815531** * DOI: [ 10.1088/1361-6579/aeae9f ](https://doi.org/10.1088/1361-6579/aeae9f) Item in Clipboard # Heart rate fragmentation and its relationship with baroreflex control in type 2 diabetes with and without cardiovascular autonomic neuropathy Gabriela Aguiar Mesquita Galdino et al. Physiol Meas. 2026. Show details Display options Display options Format Abstract PubMed PMID Physiol Meas Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Physiol+Meas%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Physiol+Meas%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42815531/) . 2026 Oct 20;47(10). doi: 10.1088/1361-6579/aeae9f. ### Authors [Gabriela Aguiar Mesquita Galdino](https://pubmed.ncbi.nlm.nih.gov/?term=Galdino+GAM&cauthor_id=42815531)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-1 "Cardiovascular Physiotherapy Laboratory, Department of Physiotherapy, Federal University of São Carlos, São Carlos, SP, Brazil."), [Thomas Beltrame](https://pubmed.ncbi.nlm.nih.gov/?term=Beltrame+T&cauthor_id=42815531)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-1 "Cardiovascular Physiotherapy Laboratory, Department of Physiotherapy, Federal University of São Carlos, São Carlos, SP, Brazil.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-2 "Samsung R&D Institute Brazil-SRBR, Campinas, São Paulo, Brazil."), [Letícia de Souza Sant'Anna](https://pubmed.ncbi.nlm.nih.gov/?term=Sant%27Anna+LS&cauthor_id=42815531)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-1 "Cardiovascular Physiotherapy Laboratory, Department of Physiotherapy, Federal University of São Carlos, São Carlos, SP, Brazil."), [Andréia Machado Santos](https://pubmed.ncbi.nlm.nih.gov/?term=Santos+AM&cauthor_id=42815531)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-1 "Cardiovascular Physiotherapy Laboratory, Department of Physiotherapy, Federal University of São Carlos, São Carlos, SP, Brazil."), [Patrícia Rehder-Santos](https://pubmed.ncbi.nlm.nih.gov/?term=Rehder-Santos+P&cauthor_id=42815531)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-1 "Cardiovascular Physiotherapy Laboratory, Department of Physiotherapy, Federal University of São Carlos, São Carlos, SP, Brazil."), [Étore de Favari Signini](https://pubmed.ncbi.nlm.nih.gov/?term=Signini+%C3%89F&cauthor_id=42815531)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-1 "Cardiovascular Physiotherapy Laboratory, Department of Physiotherapy, Federal University of São Carlos, São Carlos, SP, Brazil."), [Rubens Fazan Jr](https://pubmed.ncbi.nlm.nih.gov/?term=Fazan+R+Jr&cauthor_id=42815531)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-3 "Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil."), [Luiz Eduardo Virgilio Silva](https://pubmed.ncbi.nlm.nih.gov/?term=Silva+LEV&cauthor_id=42815531)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-4 "Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America."), [Alberto Porta](https://pubmed.ncbi.nlm.nih.gov/?term=Porta+A&cauthor_id=42815531)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-5 "Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-6 "Department of Cardiothoracic, Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, San Donato Milanese, Italy."), [Aparecida Maria Catai](https://pubmed.ncbi.nlm.nih.gov/?term=Catai+AM&cauthor_id=42815531)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42815531/#short-view-affiliation-1 "Cardiovascular Physiotherapy Laboratory, Department of Physiotherapy, Federal University of São Carlos, São Carlos, SP, Brazil.") ### Affiliations * 1 Cardiovascular Physiotherapy Laboratory, Department of Physiotherapy, Federal University of São Carlos, São Carlos, SP, Brazil. * 2 Samsung R&D Institute Brazil-SRBR, Campinas, São Paulo, Brazil. * 3 Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. * 4 Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America. * 5 Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. * 6 Department of Cardiothoracic, Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, San Donato Milanese, Italy. * PMID: **42815531** * DOI: [ 10.1088/1361-6579/aeae9f ](https://doi.org/10.1088/1361-6579/aeae9f) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract _Objective._ The link between ultrafast heart period (HP) dynamics and baroreflex is poorly analyzed, especially in pathologies altering autonomic regulation. This study assesses this link via heart rate fragmentation (HRF) analysis in type 2 diabetes mellitus (T2DM) with or without cardiac autonomic neuropathy (CAN)._Approach._ Sixty-four individuals with T2DM, divided into those with CAN (DMCAN,_n_ = 28, 55-62 years, 17 males) and without CAN (DMnoCAN,_n_ = 36, 49-61 years, 19 males), were evaluated at supine resting (REST) and during active standing (STAND). HRF was calculated using sequences of five consecutive HPs categorized as words with zero (_W_ 0), one (_W_ 1), two (_W_ 2), three (_W_ 3) and total (PIP) inflection points. Baroreflex control was assessed from HP and systolic arterial pressure (SAP) variabilities via cross-spectral analyses in low frequency (LF) and high frequency (HF) bands and via sequence method (SEQ). Also squared coherence between HP and SAP in LF and HF bands, namely _K_ 2HP-SAP(LF) and _K_ 2HP-SAP(HF), and percentage of baroreflex sequences (%SEQ) were assessed._Main results. W_ 3was higher in DMCANat REST compared to DMnoCANand W3increased in STAND for both groups. At REST %SEQand _K_ 2HP-SAP(HF) were positively associated with _W_ 0and _W_ 1, while they were negatively associated with _W_ 3and PIP. During STAND _K_ 2HP-SAP(LF), %SEQand αSEQwere negatively correlated with PIP and _W_ 3._Significance_. Greater presence of inflection points in 4-beat words was associated with a less effective baroreflex, thus suggesting that an impaired baroreflex augmented the likelihood of fast HP changes in DMCAN. **Keywords:** baroreflex sensitivity; cardiac control; fast time scales; heart rate variability; type 2 diabetes mellitus. Creative Commons Attribution license. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Influence of age and gender on the phase and strength of the relation between heart period and systolic blood pressure spontaneous fluctuations. ](https://pubmed.ncbi.nlm.nih.gov/29212671/) Milan-Mattos JC, Porta A, Perseguini NM, Minatel V, Rehder-Santos P, Takahashi ACM, Mattiello SM, Catai AM.Milan-Mattos JC, et al.J Appl Physiol (1985). 2018 Mar 1;124(3):791-804. doi: 10.1152/japplphysiol.00903.2017. Epub 2017 Dec 6.J Appl Physiol (1985). 2018.PMID: 29212671 * [ Cardiovascular Variability Analysis and Baroreflex Estimation in Patients with Type 2 Diabetes in Absence of Any Manifest Neuropathy. ](https://pubmed.ncbi.nlm.nih.gov/26987126/) de Moura-Tonello SC, Porta A, Marchi A, de Almeida Fagundes A, Francisco Cde O, Rehder-Santos P, Milan-Mattos JC, Simões RP, Gois Mde O, Catai AM.de Moura-Tonello SC, et al.PLoS One. 2016 Mar 17;11(3):e0148903. doi: 10.1371/journal.pone.0148903. eCollection 2016.PLoS One. 2016.PMID: 26987126Free PMC article. * [ Cardiovascular autonomic modulation and baroreflex control in the second trimester of pregnancy: A cross sectional study. ](https://pubmed.ncbi.nlm.nih.gov/31086378/) Corrêa MDS, Catai AM, Milan-Mattos JC, Porta A, Driusso P.Corrêa MDS, et al.PLoS One. 2019 May 14;14(5):e0216063. doi: 10.1371/journal.pone.0216063. eCollection 2019.PLoS One. 2019.PMID: 31086378Free PMC article. * [ The additional impact of type 2 diabetes on baroreflex sensitivity of coronary artery disease patients might be undetectable in presence of deterioration of mechanical vascular properties. ](https://pubmed.ncbi.nlm.nih.gov/30843124/) de Oliveira Gois M, Porta A, Simões RP, Kunz VC, Driusso P, Hirakawa HS, De Maria B, Catai AM.de Oliveira Gois M, et al.Med Biol Eng Comput. 2019 Jul;57(7):1405-1415. doi: 10.1007/s11517-019-01966-3. Epub 2019 Mar 7.Med Biol Eng Comput. 2019.PMID: 30843124 * [ Heart rate fragmentation is impaired in type 2 diabetes mellitus patients. ](https://pubmed.ncbi.nlm.nih.gov/36529300/) Aguiar Mesquita Galdino G, Eduardo Virgilio Silva L, Cristina Garcia Moura-Tonello S, Cristina Milan-Mattos J, Nogueira Lina
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