Subclinical inflammation and endothelial dysfunction are linked to cardiac autonomic neuropathy in type 2 diabetes

  • Pooja Bhati
  • Rizwan Alam
  • Jamal Ali Moiz
  • M. Ejaz HussainEmail author
Research article



The present study aimed to examine association between inflammatory and endothelial function biomarkers and indices of cardiac autonomic control in T2DM patients.


50 T2DM patients were recruited for this study. For cardiac autonomic function, cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV) analysis was performed. Blood samples were collected for evaluating inflammatory and endothelial function biomarkers. Multivariable linear regression analysis adjusted for diabetes duration, glycemic control, waist circumference, hypertension, dyslipidemia, metformin, and statins was performed to examine the association between the biomarkers and cardiac autonomic function parameters.


Interleukin-6 was inversely related to total power (p = .009) and low frequency power (p = .04). Interleukin-18 and high sensitivity C-reactive protein inversely correlated with measures of cardiac vagal control (p < .05). Both nitric oxide and endothelial nitric oxide synthase were positively linked with cardiac vagal control indices (p < .05) whereas endothelin-1 did not show any independent association with cardiac autonomic function parameters.


Biomarkers of inflammation and endothelial function are associated with measures of cardiac vagal control and global HRV which suggest that there is some pathophysiological link between subclinical inflammation, endothelial dysfunction and cardiac autonomic dysfunction in T2DM.


Vascular endothelium Biomarkers Diabetes Autonomic dysfunction Interleukins 



Cardiac autonomic neuropathy


Type 2 diabetes mellitus






high sensitivity C-reactive protein


Nitric oxide


Endothelial nitric oxide synthase




Cardiovascular disease


Heart rate variability


Heart rate


Deep breathing test


Valsalva Maneuvre


Head-up tilt


Blood Pressure


Hand grip test

30/15 ratio

ratio of largest and shortest R-R interval at 30th and 15th second of head-up tilt test




Fast Fourier transform

mean NN

average of N-N intervals


Standard deviation of N-N intervals


Root mean square of successive differences between adjacent R-R intervals


percentage of consecutive N-N intervals that vary by more than 50 ms


Total power


Low frequency power


High frequency power

LF/HF ratio

Ratio of low and high frequency power


Coefficient of variability


Glycosylated hemoglobin


Waist circumference


Confidence intervals


Variance inflation factor


Type 1 diabetes mellitus


Cardiovascular autonomic reflex tests


Autonomic nervous system



Authors would like to admit gratitude to University Grants Commission (UGC), India for providing fellowship to the author PB during this study. A sincere thank to Jamia Millia Islamia (A Central University) and UGC for providing adequate financial help during the study.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest

Supplementary material

40200_2019_435_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 11 kb)
40200_2019_435_MOESM2_ESM.docx (20 kb)
Supplementary material 2 (DOCX 20 kb)
40200_2019_435_MOESM3_ESM.docx (19 kb)
Supplementary material 3 (DOCX 19 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Diabetes Research Group, Centre for Physiotherapy and Rehabilitation SciencesJamia Millia Islamia (A Central University)New DelhiIndia
  2. 2.Deen Dayal Upadhyay Kaushal KendraJamia Millia Islamia (A Central University)New DelhiIndia

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