Association of Diabetes Related Complications with Heart Rate Variability among a Diabetic Population in the UAE

PLOS ONE, Dec 2019

Microvascular, macrovascular and neurological complications are the key causes of morbidity and mortality among type II diabetes mellitus (T2DM) patients. The aim of this study was to investigate the alterations of cardiac autonomic function of diabetic patients in relation to three types of diabetes-related complications. ECG recordings were collected and analyzed from 169 T2DM patients in supine position who were diagnosed with nephropathy (n = 55), peripheral neuropathy (n = 64) and retinopathy (n = 106) at two hospitals in the UAE. Comparison between combinations of patients with complications and a control diabetic group (CONT) with no complication (n = 34) was performed using time, frequency and multi-lag entropy measures of heart rate variability (HRV). The results show that these measures decreased significantly (p<0.05) depending on the presence and type of diabetic complications. Entropy, (median, 1st- 3rd interquartile range) for the group combining all complications (1.74,1.37–2.09) was significantly lower than the corresponding values for the CONT group (1.77, 1.39–2.24) with lag-1 for sequential beat-to-beat changes. Odds ratios (OR) from the entropy analysis further demonstrated a significantly higher association with the combination of retinopathy and peripheral neuropathy versus CONT (OR: 1.42 at lag 8) and an even OR for the combination of retinopathy and nephropathy (OR: 2.46 at lag 8) compared to the other groups with complications. Also, the OR of low frequency power to high frequency power ratio (LF/HF) showed a higher association with these diabetic-related complications compared to CONT, especially for the patient group combining all complications (OR: 4.92). This study confirms that the type of microvascular or peripheral neuropathy complication present in T2DM patients have different effects on heart rate entropy, implying disorders of multi-organ connectivity are directly associated with autonomic nervous system dysfunction. Clinical practice may benefit from including multi-lag entropy for cardiac rhythm analysis in conjunction with traditional screening methods in patients with diabetic complications to ensure better preventive and treatment outcomes in the Emirati Arab population.

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Association of Diabetes Related Complications with Heart Rate Variability among a Diabetic Population in the UAE

January Association of Diabetes Related Complications with Heart Rate Variability among a Diabetic Population in the UAE Ahsan H. Khandoker 0 1 2 Haitham M. Al-Angari 0 2 Kinda Khalaf 0 1 2 Sungmun Lee 0 1 2 Wael Almahmeed 0 2 Habiba S. Al Safar 0 1 2 Herbert F. Jelinek 0 2 0 University of Science, Technology and Research 1 Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates, 2 Khalifa University Center of Biotechnology, Abu Dhabi, United Arab Emirates, 3 Institute of Cardiac Science, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates, 4 Heart and Vascular Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates, 5 School of Community Health, Charles Sturt University , Albury, New South Wales , Australia , 6 Australian School of Advanced Medicine, Macquarie University , Sydney, New South Wales , Australia 2 Editor: Suresh Kumar Verma, Temple University , UNITED STATES Microvascular, macrovascular and neurological complications are the key causes of morbidity and mortality among type II diabetes mellitus (T2DM) patients. The aim of this study was to investigate the alterations of cardiac autonomic function of diabetic patients in relation to three types of diabetes-related complications. ECG recordings were collected and analyzed from 169 T2DM patients in supine position who were diagnosed with nephropathy (n = 55), peripheral neuropathy (n = 64) and retinopathy (n = 106) at two hospitals in the UAE. Comparison between combinations of patients with complications and a control diabetic group (CONT) with no complication (n = 34) was performed using time, frequency and multi-lag entropy measures of heart rate variability (HRV). The results show that these measures decreased significantly (p<0.05) depending on the presence and type of diabetic complications. Entropy, (median, 1st- 3rd interquartile range) for the group combining all complications (1.74,1.37±2.09) was significantly lower than the corresponding values for the CONT group (1.77, 1.39±2.24) with lag-1 for sequential beat-to-beat changes. Odds ratios (OR) from the entropy analysis further demonstrated a significantly higher association with the combination of retinopathy and peripheral neuropathy versus CONT (OR: 1.42 at lag 8) and an even OR for the combination of retinopathy and nephropathy (OR: 2.46 at lag 8) compared to the other groups with complications. Also, the OR of low frequency power to high frequency power ratio (LF/HF) showed a higher association with these diabetic-related complications compared to CONT, especially for the patient group combining all complications (OR: 4.92). This study confirms that the type of microvascular or peripheral neuropathy complication present in T2DM patients have different effects on heart rate entropy, implying disorders of multi-organ connectivity are directly associated with autonomic nervous system dysfunction. Clinical practice may benefit from including multi-lag entropy for cardiac rhythm analysis in conjunction with traditional screening methods in patients with diabetic complications to ensure better preventive and treatment outcomes in the Emirati Arab population. - Competing Interests: The authors have declared that no competing interests exist. Abbreviations: ANS, Autonomic nervous system; ALL-C, T2DM patients with retinopathy, nephropathy and DPN; BGL, Blood Glucose Level; BMI, Body Mass Index; CAN, Cardiac autonomic neuropathy; CONT, T2DM patients with no retinopathy, nephropathy or DPN; DBP, Diastolic Blood Pressure; DPN, Diabetic peripheral neuropathy; DPNn, T2DM patients with DPN; HbA1c, Glycated Hemoglobin Level; HDL, High Density Lipoprotein; HF, High frequency power of HRV; HRV, Heart rate variability; LDL, Low Density Lipoprotein; LF, Low frequency power of HRV; mRR, Mean of normal RR intervals; NNp, T2DM patients with DPN and nephropathy; Np, T2DM patients with nephropathy; OR, Odds ratio; PI, Percentage index of changes in successive RR intervals; R, T2DM patient with retinopathy; RN, T2DM patients with retinopathy and DPN; RNp, T2DM patients with retinopathy and nephropathy; SBP, Systolic Blood Pressure; SD1, SD2, Standard descriptors of the Poincare plot; SDNN, Standard deviation of normal RR intervals; T2DM, Type 2 Diabetes Mellitus; TC, Total Cholesterol. Introduction Type II diabetes mellitus (T2DM) is a multifactorial disease characterized by altered glucose metabolism that can affect organ function either directly or indirectly through oxidative stress and inflammatory mechanisms linked to hyperglycemia [ 1 ]. Oxidative stress and inflammation are considered as the main causative factors of diabetes complications including renal, retinal vascular and neurological impairments [ 2, 3 ]. However, the mechanisms for the development of diabetic related complications are most likely multifactorial and involve in addition to oxidative stress and inflammation, environmental and lifestyle factors, as well as genetic predisp (...truncated)


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Ahsan H. Khandoker, Haitham M. Al-Angari, Kinda Khalaf, Sungmun Lee, Wael Almahmeed, Habiba S. Al Safar, Herbert F. Jelinek. Association of Diabetes Related Complications with Heart Rate Variability among a Diabetic Population in the UAE, PLOS ONE, 2017, Volume 12, Issue 1, DOI: 10.1371/journal.pone.0168584