Display options
Cite
Pop-Busui R, Backlund JC, Bebu I, et al. Utility of using electrocardiogram measures of heart rate variability as a measure of cardiovascular autonomic neuropathy in type 1 diabetes patients. J Diabetes Investig. 2021;13(1):125-133doi: 10.1111/jdi.13635.
Pop-Busui, R., Backlund, J. C., Bebu, I., Braffett, B. H., Lorenzi, G., White, N. H., Lachin, J. M., Soliman, E. Z. (2022). Utility of using electrocardiogram measures of heart rate variability as a measure of cardiovascular autonomic neuropathy in type 1 diabetes patients. Journal of diabetes investigation, 13(1), 125-133. https://doi.org/10.1111/jdi.13635
Pop-Busui, Rodica, et al. "Utility of using electrocardiogram measures of heart rate variability as a measure of cardiovascular autonomic neuropathy in type 1 diabetes patients." Journal of diabetes investigation vol. 13,1 (2022): 125-133. doi: https://doi.org/10.1111/jdi.13635
Pop-Busui R, Backlund JC, Bebu I, Braffett BH, Lorenzi G, White NH, Lachin JM, Soliman EZ. Utility of using electrocardiogram measures of heart rate variability as a measure of cardiovascular autonomic neuropathy in type 1 diabetes patients. J Diabetes Investig. 2022 Jan;13(1):125-133. doi: 10.1111/jdi.13635. Epub 2021 Aug 14. PMID: 34309223.
Copy Download .nbib Format: NLM
Share it on

J Diabetes Investig. 2022 Jan;13(1):125-133. doi: 10.1111/jdi.13635. Epub 2021 Aug 14.

Utility of using electrocardiogram measures of heart rate variability as a measure of cardiovascular autonomic neuropathy in type 1 diabetes patients.

Journal of diabetes investigation

Rodica Pop-Busui, Jye-Yu C Backlund, Ionut Bebu, Barbara H Braffett, Gayle Lorenzi, Neil H White, John M Lachin, Elsayed Z Soliman,

Affiliations

  1. Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan, USA.
  2. Biostatistics Center, The George Washington University, Rockville, Maryland, USA.
  3. University of California San Diego, La Jolla, California, USA.
  4. Washington University, St. Louis, Missouri, USA.
  5. Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
  6. Department of Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
  7. Institute of Global Health and Human Ecology, School of Science and Engineering, American University in Cairo, Cairo, Egypt.

PMID: 34309223 DOI: 10.1111/jdi.13635

Abstract

AIMS/INTRODUCTION: Cardiovascular autonomic neuropathy (CAN) is a predictor of cardiovascular disease and mortality. Cardiovascular reflex tests (CARTs) are the gold standard for the diagnosis of CAN, but might not be feasible in large research cohorts or in clinical care. We investigated whether measures of heart rate variability obtained from standard electrocardiogram (ECG) recordings provide a reliable measure of CAN.

MATERIALS AND METHODS: Standardized CARTs (R-R response to paced breathing, Valsalva, postural changes) and digitized 12-lead resting ECGs were obtained concomitantly in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications participants (n = 311). Standard deviation of normally conducted R-R intervals (SDNN) and the root mean square of successive differences between normal-to-normal R-R intervals (rMSSD) were measured from ECG. Sensitivity, specificity, probability of correct classification and Kappa statistics evaluated the agreement between ECG-derived CAN and CARTs-defined CAN.

RESULTS: Participants with CARTs-defined CAN had significantly lower SDNN and rMSSD compared with those without CAN (P < 0.001). The optimal cut-off points of ECG-derived CAN were <17.13 and <24.94 ms for SDNN and rMSSD, respectively. SDNN plays a dominant role in defining CAN, with an area under the curve of 0.73, indicating fair test performance. The Kappa statistic for SDNN was 0.41 (95% confidence interval 0.30-0.51) for the optimal cut-off point, showing fair agreement with CARTs-defined CAN. Combining SDNN and rMSSD optimal cut-off points does not provide additional predictive power for CAN.

CONCLUSIONS: These analyses are the first to show the agreement between indices of heart rate variability derived from ECGs and the gold standard CARTs, thus supporting potential use as a measure of CAN in clinical research and clinical care.

© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Keywords: Cardiovascular autonomic neuropathy; Cardiovascular reflex tests; Heart rate variability

References

  1. Pop-Busui R, Low PA, Waberski BH, et al. Effects of prior intensive insulin therapy on cardiac autonomic nervous system function in type 1 diabetes mellitus: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC). Circulation 2009; 119: 2886-2893. - PubMed
  2. Pop-Busui R, Cleary PA, Braffett BH, et al. Association between cardiovascular autonomic neuropathy and left ventricular dysfunction: DCCT/EDIC study (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications). J Am Coll Cardiol 2013; 61: 447-454. - PubMed
  3. Pop-Busui R. Cardiac autonomic neuropathy in diabetes: a clinical perspective. Diabetes Care 2010; 33: 434-441. - PubMed
  4. Pop-Busui R, Braffett BH, Zinman B, et al. Cardiovascular autonomic neuropathy and cardiovascular outcomes in the diabetes control and complications trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study. Diabetes Care 2017; 40: 94-100. - PubMed
  5. Pop-Busui R, Evans GW, Gerstein HC, et al. Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 2010; 33: 1578-1584. - PubMed
  6. Ziegler D, Zentai CP, Perz S, et al. Prediction of mortality using measures of cardiac autonomic dysfunction in the diabetic and nondiabetic population: the MONICA/KORA Augsburg Cohort Study. Diabetes Care 2008; 31: 556-561. - PubMed
  7. Pop-Busui R, Boulton AJ, Feldman EL, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care 2017; 40: 136-154. - PubMed
  8. Task Force of the European Society of Cardiology and the North AmericanSociety of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Circulation 1996; 93: 1043-1065. - PubMed
  9. The DCCT Research Group. The Diabetes Control and Complications Trial (DCCT). Design and methodologic considerations for the feasibility phase. Diabetes. 1986; 35: 530-545. - PubMed
  10. The DCCT/EDIC Research Group. Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care. 1999; 22: 99-111. - PubMed
  11. The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977-986. - PubMed
  12. Spallone V, Ziegler D, Freeman R, et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev 2011; 27: 639-653. - PubMed
  13. Martin CL, Albers JW, Pop-Busui R, DCCT/EDIC Research Group. Neuropathy and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care 2014; 37: 31-38. - PubMed
  14. Braffett BH, Gubitosi-Klug RA, Albers JW, et al. Risk factors for diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in the diabetes control and complications trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study. Diabetes 2020; 69: 1000-1010. - PubMed
  15. Paterson AD, Rutledge BN, Cleary PA, et al. The effect of intensive diabetes treatment on resting heart rate in type 1 diabetes: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Diabetes Care 2007; 30: 2107-2112. - PubMed
  16. Snedecor GWCW. Statistical methods, 7th edn. Iowa State University Press, Ames, 1980. - PubMed
  17. Lachin J. Biostatistical Methods: The Assessment of Relative Risks, 2nd edn. Wiley, Hoboken, NJ, 2011. - PubMed
  18. SAS Institute Inc. Logistic Regression Examples Using the SAS System, 1st edn. SAS Institute, Cary, NC, 1995. - PubMed
  19. O'Neal WT, Chen LY, Nazarian S, et al. Reference ranges for short-term heart rate variability measures in individuals free of cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA). J Electrocardiol 2016; 49: 686-690. - PubMed
  20. Mather KJ, Bebu I, Baker C, et al. Prevalence of microvascular and macrovascular disease in the Glycemia Reduction Approaches in Diabetes - a Comparative Effectiveness (GRADE) Study cohort. Diabetes Res Clin Pract 2020; 165: 108235. - PubMed
  21. Andersen ST, Witte DR, Dalsgaard EM, et al. Risk factors for incident diabetic polyneuropathy in a cohort with screen-detected type 2 diabetes followed for 13 years: ADDITION-Denmark. Diabetes Care 2018; 41: 1068-1075. - PubMed
  22. Pop-Busui R, Lu J, Brooks MM, et al. Impact of glycemic control strategies on the progression of diabetic peripheral neuropathy in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Cohort. Diabetes Care 2013; 36: 3208-3215. - PubMed
  23. Herman W, Pop-Busui R, Braffett B, et al. Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in Type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications. Diabetes Med 2012; 29: 934-944. - PubMed
  24. Mizokami-Stout KR, Li Z, Foster NC, et al. The Contemporary prevalence of diabetic neuropathy in type 1 diabetes: findings from the T1D exchange. Diabetes Care 2020; 43: 806-812. - PubMed
  25. Jeyam A, McGurnaghan SJ, Blackbourn LAK, et al. Diabetic neuropathy is a substantial burden in people withtype 1 diabetes and is strongly associated with socioeconomic disadvantage: a population-representative study from Scotland. Diabetes Care 2020; 43: 734-742. - PubMed

Publication Types

Grant support