Sympathovagal imbalance contributes to prehypertension status and cardiovascular risks attributed by insulin resistance, inflammation, dyslipidemia and oxidative stress in first degree relatives of type 2 diabetics.

Thierry Alquier,Thiyagarajan Durgadevi,Pravati Pal,Tarun Kumar Dutta,Avupati Naga Syamsunder,Gopal Krushna Pal,Palghat Hariharan Ananthanarayanan,Nivedita Nanda,Venugopal Lalitha,Chandrasekaran Adithan

doi:10.1371/journal.pone.0078072

Abstract

BackgroundThough cardiovascular (CV) risks are reported in first-degree relatives (FDR) of type 2 diabetics, the pathophysiological mechanisms contributing to these risks are not known. We investigated the association of sympathovagal imbalance (SVI) with CV risks in these subjects.Subjects and MethodsBody mass index (BMI), basal heart rate (BHR), blood pressure (BP), rate-pressure product (RPP), spectral indices of heart rate variability (HRV), autonomic function tests, insulin resistance (HOMA-IR), lipid profile, inflammatory markers, oxidative stress (OS) marker, rennin, thyroid profile and serum electrolytes were measured and analyzed in subjects of study group (FDR of type 2 diabetics, n = 72) and control group (subjects with no family history of diabetes, n = 104).ResultsBMI, BP, BHR, HOMA-IR, lipid profile, inflammatory and OS markers, renin, LF-HF (ratio of low-frequency to high-frequency power of HRV, a sensitive marker of SVI) were significantly increased (p<0.0001) in study group compared to the control group. SVI in study group was due to concomitant sympathetic activation and vagal inhibition. There was significant correlation and independent contribution of markers of insulin resistance, dyslipidemia, inflammation and OS to LF-HF ratio. Multiple-regression analysis demonstrated an independent contribution of LF-HF ratio to prehypertension status (standardized beta 0.415, p<0.001) and bivariate logistic-regression showed significant prediction (OR 2.40, CI 1.128–5.326, p = 0.002) of LF-HF ratio of HRV to increased RPP, the marker of CV risk, in study group.ConclusionSVI in FDR of type 2 diabetics occurs due to sympathetic activation and vagal withdrawal. The SVI contributes to prehypertension status and CV risks caused by insulin resistance, dyslipidemia, inflammation and oxidative stress in FDR of type 2 diabetics.

Highlights

It has been reported that Asian Indian phenotype is exceptionally predisposed to develop diabetes because of strong familial aggregation and abrupt change in lifestyle [1]
Body mass index (BMI) and CV Parameters There was no significant difference in age (p = 0.4419) between the subjects of control group and study group (Table 1)
Metabolic Biomarkers Fasting blood glucose (FBG), insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly increased (p,0.0001), all lipid parameters and lipid risk factors were significantly increased (p,0.0001) in study group compared to the control group (Table 2)

Summary

Subjects and Methods

Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), rate-pressure product (RPP), spectral indices of heart rate variability (HRV), autonomic function tests, insulin resistance (HOMA-IR), lipid profile, inflammatory markers, oxidative stress (OS) marker, rennin, thyroid profile and serum electrolytes were measured and analyzed in subjects of study group (FDR of type 2 diabetics, n = 72) and control group (subjects with no family history of diabetes, n = 104)

Results

Introduction

Methods

Discussion