Effects of Sustained Insulin-Induced Hypoglycemia on Cardiovascular Autonomic Regulation in Type 1 Diabetes

Effects of Sustained Insulin-Induced Hypoglycemia on Cardiovascular Autonomic Regulation in Type 1 Diabetes Minna L. Koivikko 1 , Pasi I. Salmela 1 , K.E. Juhani Airaksinen 2 , Juha S. Tapanainen 3 , Aimo Ruokonen 4 , Timo H. Mäkikallio 1 and Heikki V. Huikuri 1 1 Department of Internal Medicine, University of Oulu, Oulu, Finland 2 Department of Internal Medicine, University of Turku, Turku, Finland 3 Department of Gynecology and Obstetrics, University of Oulu, Oulu, Finland 4 Department of Clinical Chemistry, University of Oulu, Oulu, Finland Address correspondence and reprint requests to Heikki Huikuri, MD, Department of Internal Medicine, University of Oulu, P.O. Box 5000 (Kajaanintie 50), FIN-90014 University of Oulu, Finland. E-mail: heikki.huikuri{at}oulu.fi Abstract Effects of hypoglycemia on cardiac autonomic regulation may contribute to the occurrence of adverse cardiac events. This study assessed the effects of sustained hyperinsulinemic hypoglycemia on cardiovascular autonomic regulation in type 1 diabetic patients and their nondiabetic counterparts. The study consisted of 16 type 1 diabetic patients and 8 age-matched healthy control subjects who underwent euglycemic and hypoglycemic clamp procedures in a random order. Heart rate variability was measured from continuous electrocardiogram recordings by time and frequency domain methods, along with Poincaré plot analysis during both a hyperinsulinemic-euglycemic and hypoglycemic clamp at three different glucose levels (4.5–5.5, 3.0–3.5, and 2.0–2.5 mmol/l). Controlled hypoglycemia resulted in an increase of supine heart rate in both the diabetic patients (from 72 ± 9 to 80 ± 11 bpm, P < 0.01) and the control subjects (from 59 ± 5 to 65 ± 5 bpm, P < 0.05) and progressive reductions of the high-frequency spectral component and beat-to-beat heart rate variability (SD1; P < 0.05 in the diabetic patients and P < 0.01 in control subjects). No significant changes in heart rate variability occurred during the euglycemic clamp. We conclude that hypoglycemia results in a reduction of cardiac vagal outflow in both diabetic and nondiabetic subjects. Altered autonomic regulation may contribute to the occurrence of cardiac events during hypoglycemia. BP, blood pressure GH, growth hormone Footnotes Accepted November 15, 2004. Received September 9, 2004. DIABETES