Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

Background and Aims. Since hyperglycemia promotes inflammation by different pathways and inflammation participates in the development of chronic diabetes complications, we investigated the association between the leukotriene (LT) pathway and microvascular diabetes complications. Methods and Results. Quantitative polymerase chain reaction was employed to quantify the expression of ALOX5 (encodes 5-lipoxygenase), LTB4R (encodes one of the LTB4 receptors), and MYD88 in peripheral blood mononuclear cells from 164 type 1 diabetes (T1D) individuals presenting or not diabetes kidney disease, retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy (CAN); 26 nondiabetic subjects were included as controls. LTB4 plasmatic concentrations were also evaluated. The expression of LTB4R was significantly higher in T1D individuals than in controls. T1D individuals with microvascular complications presented lower MYD88 mRNA expression when compared to those without microvascular complications. Higher LTB4 concentrations were found in individuals with CAN versus without CAN. The observation of two distinct subgroups of T1D individuals in the correlation analyses motivated us to evaluate the characteristics of each one of these groups separately. The group presenting higher expression of ALOX5 and of LTB4R also presented higher values of HbA1C, of fructosamine, and of plasmatic LTB4. Conclusion. In the diabetes setting, the LT pathway is not only activated by hyperglycemia but is also modulated by the status of the autonomic nervous system.

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Can the most frequent DRB1* gene's alleles be associated with cardiovascular autonomic neuropathy among patients with type 1 diabetes mellitus? A case - control pilot study

Endocrine Abstracts ◽

10.1530/endoabs.49.ep550 ◽

2017 ◽

Author(s):

Dovile Razanskaite-Virbickiene ◽

Vilma Vezbaviciene ◽

Erika Skrodeniene ◽

Rimantas Zalinkevicius

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Pilot Study ◽

Type 1 Diabetes Mellitus ◽

Autonomic Neuropathy ◽

Case Control ◽

Cardiovascular Autonomic Neuropathy

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322-OR: Risk Factors for Peripheral and Cardiovascular Autonomic Neuropathy in Type 1 Diabetes: Thirty Years of Follow-Up in DCCT/EDIC

Diabetes ◽

10.2337/db19-322-or ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 322-OR

Author(s):

BARBARA BRAFFETT ◽

ROSE GUBITOSI-KLUG ◽

JAMES W. ALBERS ◽

EVA L. FELDMAN ◽

CATHERINE MARTIN ◽

...

Keyword(s):

Risk Factors ◽

Type 1 Diabetes ◽

Autonomic Neuropathy ◽

Cardiovascular Autonomic Neuropathy

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Diabetic cardiovascular autonomic neuropathy in children

European Heart Journal ◽

10.1093/ehjci/ehaa946.3200 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

O.L.G.A Gumeniuk ◽

N Bolotova ◽

A Averianov ◽

I.U Chernenkov

Keyword(s):

Heart Rate ◽

Type 1 Diabetes ◽

Autonomic Neuropathy ◽

Hba1c Level ◽

Diabetes Duration ◽

Cardiovascular Autonomic Neuropathy ◽

Deep Breath ◽

Group I ◽

Diabetic Cardiovascular Autonomic Neuropathy

Abstract Diabetic cardiovascular autonomic neuropathy (CAN) encompasses damage to the autonomic nerve fibers innervating the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. Clinical symptoms associated with CAN include resting tachycardia, postural hypotension, dizziness, syncope, exercise intolerance, silent myocardial infarction. The earliest finding of CAN, even at the subclinical stage, is a decrease in heart rate variability (HRV) Purpose To study CAN prevalence and understand the diagnostic capabilities of HRV - tests of diabetic cardiovascular autonomic neuropathy in children with type 1 diabetes. Methods 100 children with type 1 diabetes were assessed for CAN (age 15.2 yrs [9.0–17.8], duration 6.5 yrs [4.0–10.6], HbA1c 8.1% 6.3–9.7]). The degree of compensation of diabetes was estimated according to criteria ISPAD Consensus Guidelines, 2018. Optimal level (HbA1c <7.0%) of compensation was revealed in 62% of children (group I) and nonoptimal in 38% of children (group II). For evaluation of the CAN we used HRV - tests: RR 30:15 ratio, ΔRR quiet breath, ΔRR deep breath, BP response to standing. Results Diabetic cardiovascular autonomic neuropathy was diagnosed in 41 children: in group I – in 6 (29%) and in group II – 35 (71%) children (p=0.00001). The prevalence of DCN correlated with HbA1c level in children and adolescents (groups I and II): ΔRR quiet breath r=−0.47 & r=−0.9; ΔRR deep breath r=−0.65 & r=−0.85; RR30:15 r=−0.77 & r=−0.88 respectively. Prevalence of CAN increased parallel to type 1 diabetes duration (p<0.01). Conclusions Diabetic cardiovascular autonomic neuropathy in children with type 1 diabetes was diagnosed in 41%. Prevalence of diabetic cardiovascular autonomic neuropathy increases parallel to type 1 diabetes duration (p<0.01). In this study we found an association between HRV indexes and HbA1c level. This provides support for HRV - testing to assess diabetic cardiovascular autonomic neuropathy in children. Funding Acknowledgement Type of funding source: None

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Pulse pressure and cardiovascular autonomic neuropathy according to duration of type 1 diabetes

Diabetes/Metabolism Research and Reviews ◽

10.1002/dmrr.969 ◽

2009 ◽

Vol 25 (5) ◽

pp. 442-451 ◽

Cited By ~ 18

Author(s):

J. C. Philips ◽

M. Marchand ◽

A. J. Scheen

Keyword(s):

Type 1 Diabetes ◽

Autonomic Neuropathy ◽

Pulse Pressure ◽

Cardiovascular Autonomic Neuropathy

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Left ventricular remodelling and cardiac chamber sizes in long-term, normoalbuminuric type 1 diabetes patients with and without cardiovascular autonomic neuropathy

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2018.10.007 ◽

2019 ◽

Vol 33 (2) ◽

pp. 171-177 ◽

Cited By ~ 1

Author(s):

Henrik Ø. Hjortkjær ◽

Tonny Jensen ◽

Jannik Hilsted ◽

Ulrik M. Mogensen ◽

Helle Corinth ◽

...

Keyword(s):

Type 1 Diabetes ◽

Autonomic Neuropathy ◽

Left Ventricular ◽

Cardiovascular Autonomic Neuropathy ◽

Ventricular Remodelling ◽

Left Ventricular Remodelling ◽

Cardiac Chamber ◽

Diabetes Patients

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Type 1 diabetes alters lipid handling and metabolism in human fibroblasts and peripheral blood mononuclear cells

PLoS ONE ◽

10.1371/journal.pone.0188474 ◽

2017 ◽

Vol 12 (12) ◽

pp. e0188474 ◽

Cited By ~ 5

Author(s):

Albert R. Jones IV ◽

Emily L. Coleman ◽

Nicholas R. Husni ◽

Jude T. Deeney ◽

Forum Raval ◽

...

Keyword(s):

Type 1 Diabetes ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Human Fibroblasts ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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Glutathione peroxidase 4 functional variant rs713041 modulates the risk for cardiovascular autonomic neuropathy in individuals with type 1 diabetes

Diabetes and Vascular Disease Research ◽

10.1177/1479164118820641 ◽

2019 ◽

Vol 16 (3) ◽

pp. 297-299 ◽

Cited By ~ 2

Author(s):

Sharon Nina Admoni ◽

Daniele Pereira Santos-Bezerra ◽

Ricardo Vesoni Perez ◽

Thiago Andrade Patente ◽

Maria Beatriz Monteiro ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glutathione Peroxidase ◽

Autonomic Neuropathy ◽

Microvascular Complications ◽

Diabetic Complication ◽

Cardiac Autonomic Neuropathy ◽

Inverse Association ◽

Gene Encoding ◽

Functional Variant

Cardiac autonomic neuropathy is a neglected diabetic chronic complication for which genetic predictors are rarely reported. Oxidative stress is implicated in the pathogenesis of microvascular complications, and glutathione peroxidase 4 is involved in the detoxification of peroxides and of reactive oxygen species. Thus, the association of a functional variant in the gene encoding glutathione peroxidase 4 (rs713041) with this diabetic complication was investigated in 341 individuals with type 1 diabetes evaluated for cardiac autonomic neuropathy status (61.7% women, 34 [27–42] years old; diabetes duration: 21 [15–27] years; HbA1c: 8.3% [7.4–9.4]; as median [interquartile interval]). Cardiac autonomic neuropathy was present in 29% of the participants. There was an inverse association of the minor T allele of rs713041 with cardiac autonomic neuropathy (odds ratio = 0.39; 95% confidence interval = 0.17–0.90; p = 0.0271) after adjustment for potential confounders. The functional glutathione peroxidase 4 variant rs713041 modulated the risk for cardiac autonomic neuropathy in the studied population with type 1 diabetes.

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