Increased Systemic Th17 Cytokines Are Associated with Diastolic Dysfunction in Children and Adolescents with Diabetic Ketoacidosis

Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6–12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-08-27

• Fields of study

  Medicine

• Identifiers
  DOI 10.1371/journal.pone.0071905PMID 24013901PMCID 3754936
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Burn enhances toll-like receptor induced responses by circulating leukocytes.

  2012cited by this paper
• Diabetic cardiomyopathy: pathophysiology and clinical features

  2012cited by this paper
• Macrophage diversity in cardiac inflammation: a review.

  2012influential reference
• IL-17 Silencing Does Not Protect Nonobese Diabetic Mice from Autoimmune Diabetes

  2012cited by this paper
• Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies.

  2012cited by this paper
• Angiotensin II Induces TSLP via an AT1 Receptor/NF-KappaB Pathway, Promoting Th17 Differentiation

  2012cited by this paper
• Cardiac Geometry and Function in Diabetic or Prediabetic Adolescents and Young Adults

  2011cited by this paper
• Fractalkine in human inflammatory cardiomyopathy

  2011cited by this paper
• Hypertension despite dehydration during severe pediatric diabetic ketoacidosis

  2011cited by this paper
• Reduced Degradation of the Chemokine MCP-3 by Matrix Metalloproteinase-2 Exacerbates Myocardial Inflammation in Experimental Viral Cardiomyopathy

  2011cited by this paper
• RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation

  2011influential reference
• Th17 response promotes angiotensin II-induced atherosclerosis.

  2011cited by this paper
• TLR activation enhances C5a-induced pro-inflammatory responses by negatively modulating the second C5a receptor, C5L2

  2011cited by this paper
• Diversity of Myocardial Interstitial Proteolytic Pathways: Gene Deletion Reveals Unexpected Consequences

  2011cited by this paper
• Free fatty acids in the presence of high glucose amplify monocyte inflammation via Toll-like receptors.

  2011cited by this paper
• Cytokine response to diabetic ketoacidosis (DKA) in children with type 1 diabetes (T1DM).

  2011influential reference
• Critical Cytokine Pathways to Cardiac Inflammation

  2011cited by this paper
• Direct Gene Transfer with IP-10 Mutant Ameliorates Mouse CVB3-Induced Myocarditis by Blunting Th1 Immune Responses

  2011cited by this paper
• Glycaemic control and incidence of heart failure in 20,985 patients with type 1 diabetes: an observational study.

  2011cited by this paper
• Cutting Edge: Increased IL-17–Secreting T Cells in Children with New-Onset Type 1 Diabetes

  2010cited by this paper
• Cytokine Interactions with Adrenal Medullary Chromaffin Cells

  2010cited by this paper
• Left Ventricular Diastolic Dysfunction in Adolescents with Type 1 Diabetes Reflects the Long- but Not Short- Term Metabolic Control

  2010cited by this paper
• IL-17 Immunity in Human Type 1 Diabetes

  2010cited by this paper
• Mechanisms of IFNγ regulation of autoimmune myocarditis.

  2010cited by this paper
• Evidence for a cross-talk between human neutrophils and Th17 cells.

  2010cited by this paper
• Oxidative stress: a key contributor to diabetic cardiomyopathy.

  2010cited by this paper
• Suppressive Effect of Insulin Infusion on Chemokines and Chemokine Receptors

  2010cited by this paper
• Increased expression of cardiac IL-17 after burn

  2010cited by this paper
• Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4

  2010influential reference
• Toll-like receptor 2 signaling in CD4(+) T lymphocytes promotes T helper 17 responses and regulates the pathogenesis of autoimmune disease.

  2010cited by this paper
• The pattern of inflammatory/anti-inflammatory cytokines and chemokines in type 1 diabetic patients over time

  2010cited by this paper
• Myocardial perfusion imaging using technetium-99m sestamibi in asymptomatic diabetic patients

  2010cited by this paper
• Interleukin-17A Is Dispensable for Myocarditis but Essential for the Progression to Dilated Cardiomyopathy

  2010cited by this paper
• Interleukin 17 Promotes Angiotensin II–Induced Hypertension and Vascular Dysfunction

  2010cited by this paper
• Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function.

  2010cited by this paper
• Contribution of Impaired Myocardial Insulin Signaling to Mitochondrial Dysfunction and Oxidative Stress in the Heart

  2009cited by this paper
• Complement promotes the development of inflammatory T-helper 17 cells through synergistic interaction with Toll-like receptor signaling and interleukin-6 production.

  2009cited by this paper
• Attenuation of experimental autoimmune myocarditis by blocking T cell activation through 4-1BB pathway.

  2009cited by this paper
• Early predictors of myocardial disease in children and adolescents with type 1 diabetes mellitus

  2009cited by this paper
• Attenuation of experimental autoimmune myocarditis by blocking T cell activation through 4-1BB pathway

  2009cited by this paper
• Increased circulating IL-8 is associated with reduced IGF-1 and related to poor metabolic control in adolescents with type 1 diabetes mellitus.

  2009cited by this paper
• Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells

  2009cited by this paper
• Inhibition of Th17 Cells Regulates Autoimmune Diabetes in NOD Mice

  2009cited by this paper
• Inhibition of Th 17 cells regulates autoimmune diabetes in NOD mice Running Title : A role for Th 17 cells in autoimmune diabetes

  2009cited by this paper
• Faculty Opinions recommendation of IL-21 and TGF-beta are required for differentiation of human T(H)17 cells.

  2008cited by this paper
• IL-21 and TGF-β are required for differentiation of human TH17 cells

  2008cited by this paper
• High Glucose Induces Toll-Like Receptor Expression in Human Monocytes

  2008cited by this paper
• Recent insights into the role of autoimmunity in idiopathic dilated cardiomyopathy.

  2008cited by this paper
• Cardiovascular impairment in children, adolescents, and young adults with type 1 diabetes mellitus (T1DM)

  2008cited by this paper
• Biomarkers in cardiovascular diabetology: interleukins and matrixins.

  2008cited by this paper
• IL-12p40: an inherently agonistic cytokine.

  2007cited by this paper
• Diabetic cardiomyopathy revisited.

  2007cited by this paper
• An 18‐yr prospective study of pediatric diabetic ketoacidosis: an approach to minimizing the risk of brain herniation during treatment

  2007influential reference
• Neutralization of IL‐17 by active vaccination inhibits IL‐23‐dependent autoimmune myocarditis

  2006cited by this paper
• The effect of acute hypertension on left ventricular diastolic pressures in a canine model of left ventricular dysfunction with a preserved ejection fraction and elevated left ventricular filling pressures.

  2006cited by this paper
• Asymptomatic Cardiomyopathy in Children and Adolescents with Type 1 Diabetes Mellitus: Association of Echocardiography Indicators with Duration of Diabetes Mellitus and Metabolic Parameters

  2006influential reference
• T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17

  2006cited by this paper
• Mechanisms of [Ca2+]i transient decrease in cardiomyopathy of db/db type 2 diabetic mice.

  2006cited by this paper
• Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes.

  2006cited by this paper
• Expression of immunological molecules by cardiomyocytes and inflammatory and interstitial cells in rat autoimmune myocarditis.

  2005cited by this paper
• Protection against experimental autoimmune myocarditis is mediated by interleukin-10-producing T cells that are controlled by dendritic cells.

  2005influential reference
• IL-23 drives a pathogenic T cell population that induces autoimmune inflammation

  2005cited by this paper
• Diabetic ketoacidosis increases extracellular levels of the major inducible 70-kDa heat shock protein.

  2005cited by this paper
• Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes—the EURODIAB Prospective Complications Study

  2005cited by this paper
• Inflammatory and anti‐inflammatory cytokines in chronic heart failure: Potential therapeutic implications

  2005cited by this paper
• Intensive insulin therapy protects the endothelium of critically ill patients.

  2005cited by this paper
• Left ventricular function and specific diabetic complications in other target organs in young insulin-dependent diabetics: An echocardiographic study

  2005cited by this paper
• Complement activation in diabetic ketoacidosis and its treatment.

  2005cited by this paper
• Differential distribution of allelic variants in cytokine genes among African Americans and White Americans.

  2004cited by this paper
• The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.

  2004cited by this paper
• Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications.

  2004cited by this paper
• Diabetic ketoacidosis induces in vivo activation of human T-lymphocytes.

  2004cited by this paper
• Female children and adolescents with type 1 diabetes have more pronounced early echocardiographic signs of diabetic cardiomyopathy.

  2004cited by this paper
• Insulin Treatment Improves the Systemic Inflammatory Reaction to Severe Trauma

  2004cited by this paper
• The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents

  2004cited by this paper
• IL‐12 and IL‐23: master regulators of innate and adaptive immunity

  2004cited by this paper
• Plasma C-reactive protein levels in severe diabetic ketoacidosis.

  2003cited by this paper
• Diabetic Ketoacidosis Promotes a Prothrombotic State

  2003cited by this paper
• Delayed dilated cardiomyopathy for major burn injuries.

  2003cited by this paper
• Oxidized low density lipoprotein and innate immune receptors

  2003cited by this paper
• Corrigendum to “Cytokines and neuro-immune–endocrine interactions: a role for the hypothalamic–pituitary–adrenal revolving axis” [J. Neuroimmunol. 133 (2002) 1–19]

  2003cited by this paper
• Cytokine response to diabetic ketoacidosis and its treatment.

  2003influential reference
• Cardiac Mass and Function, Carotid Artery Intima-Media Thickness and Lipoprotein (a) Levels in Children and Adolescents with Type I Diabetes Mellitus of Short Duration

  2002cited by this paper
• Lipid peroxidation and antioxidant vitamins prior to, during, and after correction of diabetic ketoacidosis.

  2002cited by this paper
• Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary-adrenal revolving axis.

  2002cited by this paper
• Acute hyperglycemia induces an oxidative stress in healthy subjects.

  2001cited by this paper
• Chronic exposure to beta-hydroxybutyrate impairs insulin action in primary cultures of adult cardiomyocytes.

  2001cited by this paper
• Diabetes related cardiomyopathy time dependent echocardiographic evaluation in an experimental rat model.

  2001cited by this paper
• Role of Cytokines in Autoimmune Myocarditis and Cardiomyopathy

  2001cited by this paper
• Ketosis and the generation of oxygen radicals in diabetes mellitus.

  2001cited by this paper
• Acute activation of peripheral lymphocytes during treatment of diabetic ketoacidosis.

  2001cited by this paper
• The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review

  2001influential reference
• Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.

  2000cited by this paper
• Association of lipid metabolism with subclinical diabetic cardiomyopathy in children and adolescents with type 1 diabetes.

  2000cited by this paper
• Acetoacetate and beta-hydroxybutyrate differentially regulate endothelin-1 and vascular endothelial growth factor in mouse brain microvascular endothelial cells.

  1999cited by this paper
• Acetoacetate and β-Hydroxybutyrate Differentially Regulate Endothelin-1 and Vascular Endothelial Growth Factor in Mouse Brain Microvascular Endothelial Cells

  1999cited by this paper
• Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action.

  1999cited by this paper
• Interstitial pulmonary edema in children and adolescents with diabetic ketoacidosis.

  1998influential reference
• Acute pulmonary edema in juvenile diabetic ketoacidosis

  1997cited by this paper
• Hyperglycemia counterbalances the antihypertensive effect of glutathione in diabetic patients: evidence linking hypertension and glycemia through the oxidative stress in diabetes mellitus.

  1997cited by this paper

• The Cardiohepatic Axis in Metabolic Disease

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• Early expression of neuroinflammation in an untreated fatal case of diabetic ketoacidosis

  2024cites this paper
• IL-17 in type II diabetes mellitus (T2DM) immunopathogenesis and complications; molecular approaches.

  2024cites this paper
• Enriched housing differentially alters allostatic load and cardiopulmonary responses to wildfire-related smoke in male and female mice

  2024cites this paper
• Hypophosphatemia: A Common but Overlooked Cause of Cardiac Dysfunction in a Child with DKA

  2023cites this paper
• Serum Troponin I Level in Children with Diabetic Ketoacidosis

  2022cites this paper
• CCL7 as a novel inflammatory mediator in cardiovascular disease, diabetes mellitus, and kidney disease

  2022cites this paper
• Mechanisms and Therapeutic Prospects of Diabetic Cardiomyopathy Through the Inflammatory Response

  2021cites this paper
• Tryptophan, kynurenine pathway, and diabetic ketoacidosis in type 1 diabetes

  2021cites this paper
• Diabetic cardiomyopathy and inflammation: development of hostile microenvironment resulting in cardiac damage.

  2021cites this paper
• Soluble Receptor for Glycation End-products Concentration Increases Following the Treatment of Severe Diabetic Ketoacidosis

  2020cites this paper
• Diabetic ketoacidosis

  2020cites this paper
• Cognitive Function Following Diabetic Ketoacidosis in Children With New-Onset or Previously Diagnosed Type 1 Diabetes

  2020cites this paper
• Molecular pathogenesis of heart failure in diabetes mellitus – new direction for the therapeutic approach

  2020cites this paper
• sRAGE Concentration İncreases Following the Treatment of Severe Diabetic Ketoacidosis Short title: sRAGE and DKA

  2019influential citation
• Intracerebral matrix metalloproteinase 9 in fatal diabetic ketoacidosis.

  2019cites this paper
• Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis

  2018cites this paper
• Cardiopathy and Congestive Heart Failure

  2017cites this paper
• Sinomenine prevents the development of cardiomyopathy in diabetic rats by inhibiting inflammatory responses and blocking activation of NF-κB.

  2017cites this paper
• Markers of immune-mediated inflammation in the brains of young adults and adolescents with type 1 diabetes and fatal diabetic ketoacidosis. Is there a difference?

  2017cites this paper
• Type I Diabetes and Celiac Disease

  2017cites this paper
• Advances in the pharmacotherapy of chronic heart failure with preserved ejection fraction: an ideal opportunity for precision medicine

  2017cites this paper
• Cardiac antibody production to self-antigens in children and adolescents during and following the correction of severe diabetic ketoacidosis

  2016cites this paper
• Improvement of cardiac dysfunction by bilateral surgical renal denervation in animals with diabetes induced by high fructose and high fat diet.

  2016cites this paper
• MCP-1and IL-1β expression in the myocardia of two young patients with Type 1 diabetes mellitus and fatal diabetic ketoacidosis.

  2014cites this paper