Elevated levels of interleukin-12/23p40 may serve as a potential indicator of dysfunctional heart rate variability in type 2 diabetes

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Abstract

Background

Systemic inflammatory processes plausibly contribute to the development of cardiovascular complications, causing increased morbidity and mortality in type 2 diabetes. Circulating inflammatory markers, i.e., interleukin (IL)-6 and tumour necrosis factor-α, are associated with neurocardiac measures. We examined a broad panel of various inflammatory and inflammation-related serum markers to obtain more detailed insight into the possible neuro-immune interaction between cardiovascular regulation and systemic level of inflammation.

Methods

Serum samples from 100 participants with type 2 diabetes were analysed. Heart rate variability, cardiovascular autonomic reflex tests, and cardiac vagal tone tests were performed based on electrocardiographic readings. Data regarding covariates (demographic-, diabetes-, and cardiovascular risk factors) were registered.

Results

Increased serum levels of IL-12/IL-23p40 (p < 0.01) and intercellular adhesion molecule (ICAM)-1 (p < 0.007) were associated with diminished heart rate variability measures. After all adjustments, the associations between IL-12/23p40, SDANN and VLF persisted (p = 0.001). Additionally, serum levels of vascular endothelial growth factor (VEGF)-C were associated with response to standing (p = 0.005).

Discussion

The few but robust associations between neurocardiac regulation and serum markers found in this study suggest systemic changes in proinflammatory, endothelial, and lymphatic function, which collectively impacts the systemic cardiovascular function. Our results warrant further exploration of IL-12/IL-23p40, ICAM-1, and VEGF-C as possible cardiovascular biomarkers in T2D that may support future decisions regarding treatment strategies for improved patient care.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12933-021-01437-w.

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Most cited references 37

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2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020

(2019)

The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee (https://doi.org/10.2337/dc20-SPPC), a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

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Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017

Thomas R Einarson, Annabel Acs, Craig Ludwig … (2018)

Background Cardiovascular disease (CVD) is a common comorbidity in type 2 diabetes (T2DM). CVD’s prevalence has been growing over time. Purpose To estimate the current prevalence of CVD among adults with T2DM by reviewing literature published within the last 10 years (2007–March 2017). Methods We searched Medline, Embase, and proceedings of major scientific meetings for original research documenting the prevalence of CVD in T2DM. CVD included stroke, myocardial infarction, angina pectoris, heart failure, ischemic heart disease, cardiovascular disease, coronary heart disease, atherosclerosis, and cardiovascular death. No restrictions were placed on country of origin or publication language. Two reviewers independently searched for articles and extracted data, adjudicating results through consensus. Data were summarized descriptively. Risk of bias was examined by applying the STROBE checklist. Results We analyzed data from 57 articles with 4,549,481 persons having T2DM. Europe produced the most articles (46%), followed by the Western Pacific/China (21%), and North America (13%). Overall in 4,549,481 persons with T2DM, 52.0% were male, 47.0% were obese, aged 63.6 ± 6.9 years old, with T2DM duration of 10.4 ± 3.7 years. CVD affected 32.2% overall (53 studies, N = 4,289,140); 29.1% had atherosclerosis (4 studies, N = 1153), 21.2% had coronary heart disease (42 articles, N = 3,833,200), 14.9% heart failure (14 studies, N = 601,154), 14.6% angina (4 studies, N = 354,743), 10.0% myocardial infarction (13 studies, N = 3,518,833) and 7.6% stroke (39 studies, N = 3,901,505). CVD was the cause of death in 9.9% of T2DM patients (representing 50.3% of all deaths). Risk of bias was low; 80 ± 12% of STROBE checklist items were adequately addressed. Conclusions Globally, overall CVD affects approximately 32.2% of all persons with T2DM. CVD is a major cause of mortality among people with T2DM, accounting for approximately half of all deaths over the study period. Coronary artery disease and stroke were the major contributors.

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The inflammatory reflex.

Kevin J. Tracey (2002)

Inflammation is a local, protective response to microbial invasion or injury. It must be fine-tuned and regulated precisely, because deficiencies or excesses of the inflammatory response cause morbidity and shorten lifespan. The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded our understanding of how the nervous system modulates immune responses. The nervous system reflexively regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. The opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.

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Author and article information

Contributors

C. Brock: christina.brock@rn.dk

Journal

Journal ID (nlm-ta): Cardiovasc Diabetol

Journal ID (iso-abbrev): Cardiovasc Diabetol

Title: Cardiovascular Diabetology

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-2840

Publication date (Electronic): 6 January 2022

Publication date PMC-release: 6 January 2022

Publication date Collection: 2022

Volume: 21

Electronic Location Identifier: 5

Affiliations

[1 ]GRID grid.5117.2, ISNI 0000 0001 0742 471X, Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital and Clinical Institute, , Aalborg University, ; Aalborg, Denmark

[2 ]GRID grid.27530.33, ISNI 0000 0004 0646 7349, Thisted Research Unit, , Aalborg University Hospital Thisted, ; Thisted, Denmark

[3 ]GRID grid.27530.33, ISNI 0000 0004 0646 7349, Department of Cardiology, , Aalborg University Hospital, ; Aalborg, Denmark

[4 ]GRID grid.27530.33, ISNI 0000 0004 0646 7349, Steno Diabetes Center North Denmark, , Aalborg University Hospital, ; Aalborg, Denmark

[5 ]GRID grid.27530.33, ISNI 0000 0004 0646 7349, Department of Endocrinology, , Aalborg University Hospital, ; Aalborg, Denmark

[6 ]GRID grid.419658.7, ISNI 0000 0004 0646 7285, Steno Diabetes Center Copenhagen, ; Gentofte, Denmark

Author information

A. M. Wegeberg http://orcid.org/0000-0002-8323-4843

Article

Publisher ID: 1437

DOI: 10.1186/s12933-021-01437-w

PMC ID: 8739720

PubMed ID: 34991588

SO-VID: c1ba7514-b636-4638-8236-e566bbb1a72e

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 24 September 2021

Date accepted : 17 December 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100002702, Aalborg Universitet;

Funded by: Region Nordjyllands Sundhedsvidenskabelige Forskningsfond

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ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: diabetes mellitus, type 2,cardiovascular diseases,inflammation

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ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: diabetes mellitus, type 2, cardiovascular diseases, inflammation

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Elevated levels of interleukin-12/23p40 may serve as a potential indicator of dysfunctional heart rate variability in type 2 diabetes

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Abstract

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Discussion

Supplementary Information

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Journal of the ASEAN Federation of Endocrine Societies

Most cited references 37

2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020

Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017

The inflammatory reflex.

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Cited by 6

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