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.
Similar content being viewed by others
References
(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
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
Bazett HC (1920) An analysis of time-relations of the electrocardiogram. Heart 7:353–370
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
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
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
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
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
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
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
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
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
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
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
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
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
Malpas SC, Maling TJ (1990) Heart-rate variability and cardiac autonomic function in diabetes. Diabetes 39:1177–1181
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
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
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
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
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
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
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
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
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
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
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
Xhyheri B, Manfrini O, Mazzolini M, Pizzi C, Bugiardini R (2012) Heart rate variability today. Prog Cardiovasc Dis 55:321–331
Yki-Jarvinen H, Koivisto VA (1986) Natural course of insulin resistance in type I diabetes. N Engl J Med 315:224–230
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
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10286-014-0253-y