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Autonomic control during acute hypoglycemia in type 1 diabetes mellitus

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Abstract

Purpose

We hypothesized that adults with type 1 diabetes mellitus (T1DM) would exhibit impaired heart rate variability (HRV), QT interval, T-wave amplitude, and baroreflex sensitivity (BRS) when compared with healthy controls. In addition, we hypothesized that acute hypoglycemia would result in further adverse changes in measures of autonomic and cardiovascular function.

Methods

A single 180-min hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic (~3.3 umol/mL) clamp was completed in 10 healthy adults and 13 adults with T1DM. Counterregulatory hormones were assessed and measures of heart rate (electrocardiogram) and blood pressure (intra-arterial catheter or finger photoplethysmography) were analyzed at baseline and during the hypoglycemic clamp for measures of HRV, QT interval, T-wave amplitude, and spontaneous cardiac BRS (sCBRS).

Results

Baseline measures of HRV, sCBRS, and T-wave amplitude were blunted in adults with T1DM when compared with healthy controls. Hypoglycemia resulted in significant reductions in HRV, sCBRS, and T-wave amplitude and prolonged QT intervals; these changes were not different between adults with T1DM and healthy controls.

Conclusions

Results from the current study show that adults with T1DM exhibit impaired autonomic and cardiovascular function. Additionally, novel findings highlight an effect of acute hypoglycemia to further reduce measures of autonomic and cardiovascular function similarly between adults with T1DM and healthy controls. These results suggest that acute hypoglycemia may worsen impairments in autonomic and cardiovascular control in patients with T1DM, thus increasing the risk of ventricular arrhythmias and cardiovascular mortality.

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References

  1. (1996) Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation 93:1043–1065

  2. Adler GK, Bonyhay I, Failing H, Waring E, Dotson S, Freeman R (2009) Antecedent hypoglycemia impairs autonomic cardiovascular function: implications for rigorous glycemic control. Diabetes 58:360–366

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Bazett HC (1920) An analysis of time-relations of the electrocardiogram. Heart 7:353–370

    Google Scholar 

  4. Bellavere F, Balzani I, De Masi G, Carraro M, Carenza P, Cobelli C, Thomaseth K (1992) Power spectral analysis of heart-rate variations improves assessment of diabetic cardiac autonomic neuropathy. Diabetes 41:633–640

    Article  CAS  PubMed  Google Scholar 

  5. Davis SN, Mann S, Briscoe VJ, Ertl AC, Tate DB (2009) Effects of intensive therapy and antecedent hypoglycemia on counterregulatory responses to hypoglycemia in type 2 diabetes. Diabetes 58:701–709

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R, Band MM, Reekie G, Leese GP (2005) Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study. Diabet Med 22:749–755

    Article  CAS  PubMed  Google Scholar 

  7. Ewing DJ, Neilson JM, Shapiro CM, Stewart JA, Reid W (1991) Twenty four hour heart rate variability: effects of posture, sleep, and time of day in healthy controls and comparison with bedside tests of autonomic function in diabetic patients. Br Heart J 65:239–244

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Frattola A, Parati G, Gamba P, Paleari F, Mauri G, Di Rienzo M, Castiglioni P, Mancia G (1997) Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus. Diabetologia 40:1470–1475

    Article  CAS  PubMed  Google Scholar 

  9. Freeman R, Saul JP, Roberts MS, Berger RD, Broadbridge C, Cohen RJ (1991) Spectral analysis of heart rate in diabetic autonomic neuropathy. A comparison with standard tests of autonomic function. Arch Neurol 48:185–190

    Article  CAS  PubMed  Google Scholar 

  10. Huang CL, Liu CC, Tseng HC, Wang YP, Tsai SK (2000) Comparison of invasive and non-invasive measurement of spontaneous baroreflex during anesthesia. Acta Anaesthesiol Sin 38:149–153

    CAS  PubMed  Google Scholar 

  11. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ (1987) Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59:256–262

    Article  CAS  PubMed  Google Scholar 

  12. Koivikko ML, Salmela PI, Airaksinen KE, Tapanainen JS, Ruokonen A, Makikallio TH, Huikuri HV (2005) Effects of sustained insulin-induced hypoglycemia on cardiovascular autonomic regulation in type 1 diabetes. Diabetes 54:744–750

    Article  CAS  PubMed  Google Scholar 

  13. Laitinen T, Huopio H, Vauhkonen I, Camaro C, Hartikainen J, Laakso M, Niskanen L (2003) Effects of euglycaemic and hypoglycaemic hyperinsulinaemia on sympathetic and parasympathetic regulation of haemodynamics in healthy subjects. Clin Sci Lond 105:315–322

    Article  CAS  PubMed  Google Scholar 

  14. Limberg JK, Taylor JL, Dube S, Basu R, Basu A, Joyner MJ, Wehrwein EA (2014) Role of the carotid body chemoreceptors in baroreflex control of blood pressure during hypoglycaemia in humans. Exp Physiol 99(4):640–650

    Article  CAS  PubMed  Google Scholar 

  15. Liu D, Moberg E, Kollind M, Lins PE, Adamson U, Macdonald IA (1992) Arterial, arterialized venous, venous and capillary blood glucose measurements in normal man during hyperinsulinaemic euglycaemia and hypoglycaemia. Diabetologia 35:287–290

    Article  CAS  PubMed  Google Scholar 

  16. Lykke JA, Tarnow L, Parving HH, Hilsted J (2008) A combined abnormality in heart rate variation and QT corrected interval is a strong predictor of cardiovascular death in type 1 diabetes. Scand J Clin Lab Invest 68:654–659

    Article  CAS  PubMed  Google Scholar 

  17. Malpas SC, Maling TJ (1990) Heart-rate variability and cardiac autonomic function in diabetes. Diabetes 39:1177–1181

    Article  CAS  PubMed  Google Scholar 

  18. Marques JL, George E, Peacey SR, Harris ND, Macdonald IA, Cochrane T, Heller SR (1997) Altered ventricular repolarization during hypoglycaemia in patients with diabetes. Diabet Med 14:648–654

    Article  CAS  PubMed  Google Scholar 

  19. Parati G, Casadei R, Groppelli A, Di Rienzo M, Mancia G (1989) Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing. Hypertension 13:647–655

    Article  CAS  PubMed  Google Scholar 

  20. Petersen ME, Williams TR, Sutton R (1995) A comparison of non-invasive continuous finger blood pressure measurement (Finapres) with intra-arterial pressure during prolonged head-up tilt. Eur Heart J 16:1641–1654

    CAS  PubMed  Google Scholar 

  21. Pinna GD, La Rovere MT, Maestri R, Mortara A, Bigger JT, Schwartz PJ (2000) Comparison between invasive and non-invasive measurements of baroreflex sensitivity; implications for studies on risk stratification after a myocardial infarction. Eur Heart J 21:1522–1529

    Article  CAS  PubMed  Google Scholar 

  22. Robinson RT, Harris ND, Ireland RH, Macdonald IA, Heller SR (2004) Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes. Diabetologia 47:312–315

    Article  CAS  PubMed  Google Scholar 

  23. Rosengard-Barlund M, Bernardi L, Fagerudd J, Mantysaari M, Af Bjorkesten CG, Lindholm H, Forsblom C, Waden J, Groop PH (2009) Early autonomic dysfunction in Type 1 diabetes: a reversible disorder? Diabetologia 52:1164–1172

    Article  CAS  PubMed  Google Scholar 

  24. Schachinger H, Port J, Brody S, Linder L, Wilhelm FH, Huber PR, Cox D, Keller U (2004) Increased high-frequency heart rate variability during insulin-induced hypoglycaemia in healthy humans. Clin Sci Lond 106:583–588

    Article  PubMed  Google Scholar 

  25. Tu E, Twigg SM, Semsarian C (2010) Sudden death in type 1 diabetes: the mystery of the ‘dead in bed’ syndrome. Int J Cardiol 138:91–93

    Article  PubMed  Google Scholar 

  26. Wehrwein EA, Curry TB, Basu A, Rizza RA, Basu R, Joyner MJ (2012) Do the carotid bodies modulate hypoglycemic counter regulation and baroreflex control of blood pressure in humans? Adv Exp Med Biol 758:129–135

    Article  PubMed Central  PubMed  Google Scholar 

  27. Weston PJ, James MA, Panerai RB, McNally PG, Potter JF, Thurston H (1998) Evidence of defective cardiovascular regulation in insulin-dependent diabetic patients without clinical autonomic dysfunction. Diabetes Res Clin Pract 42:141–148

    Article  CAS  PubMed  Google Scholar 

  28. Weston PJ, Panerai RB, McCullough A, McNally PG, James MA, Potter JF, Thurston H, Swales JD (1996) Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index. Diabetologia 39:1385–1391

    Article  CAS  PubMed  Google Scholar 

  29. Xhyheri B, Manfrini O, Mazzolini M, Pizzi C, Bugiardini R (2012) Heart rate variability today. Prog Cardiovasc Dis 55:321–331

    Article  PubMed  Google Scholar 

  30. Yki-Jarvinen H, Koivisto VA (1986) Natural course of insulin resistance in type I diabetes. N Engl J Med 315:224–230

    Article  CAS  PubMed  Google Scholar 

  31. Ziegler D, Laude D, Akila F, Elghozi JL (2001) Time- and frequency-domain estimation of early diabetic cardiovascular autonomic neuropathy. Clin Auton Res 11:369–376

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Our deepest appreciation and thanks to Dr. Robert Rizza for his valuable and constructive suggestions with study design. The authors also wish to thank Drs. Timothy Curry and John Eisenach (Department of Anesthesiology) for placement of brachial artery catheters. The authors further wish to acknowledge the contributions of the nursing and technical staff: Cheryl Shonkwiler, Barbara Norby, Shelly Roberts, Karen Krucker, Sarah Wolhart, Jean Knutson, Brent McConahey, Pamela Reich, Nancy Meyer, Pam Engrav, and Christopher Johnson of the Mayo Clinic. In addition, we thank the Clinical Research Unit staff at Mayo Clinic, the Immunochemical Core Laboratory at Mayo Clinic, in particular Hilary Blair. We are deeply indebted to our research participants. We thank Brandon Bucher and Brenton Nelson at ADinstruments for the development of the Spontaneous Cardiac Baroreflex Analysis Program. Funding sources: NIH DK090541 (MJJ, RB), NIH NS32352 (MJJ), NIH T32 DK07352 (EAW, JKL), NIH F32 DK84624 (EAW), NIH 1 UL1 RR024150 (Mayo Clinic CTSA, MJJ), and NIH DK29953 (RB).

Conflict of interest

The authors have no conflicts of interest and there are no concurrent submissions.

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Authors and Affiliations

  1. Department of Anesthesiology, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA

    Jacqueline K. Limberg, Kathryn E. Farni, Jennifer L. Taylor & Michael J. Joyner

  2. Department of Endocrinology, Mayo Clinic, Rochester, MN, USA

    Simmi Dube, Ananda Basu & Rita Basu

  3. Department of Physiology, Michigan State University, East Lansing, MI, USA

    Erica A. Wehrwein

Authors
  1. Jacqueline K. Limberg
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  2. Kathryn E. Farni
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  3. Jennifer L. Taylor
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  4. Simmi Dube
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  5. Ananda Basu
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  6. Rita Basu
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  7. Erica A. Wehrwein
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  8. Michael J. Joyner
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Corresponding author

Correspondence to Jacqueline K. Limberg.

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Limberg, J.K., Farni, K.E., Taylor, J.L. et al. Autonomic control during acute hypoglycemia in type 1 diabetes mellitus. Clin Auton Res 24, 275–283 (2014). https://doi.org/10.1007/s10286-014-0253-y

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  • DOI: https://doi.org/10.1007/s10286-014-0253-y

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