Pieter Simons

10%). Hemodynamic parameters Pulse rate, blood pressure (diastolic, mean, systolic), and stroke volume were continuously monitored with the FloTrac system (HemoSphere, Edwards Lifesciences, Irvine, CA, U.S.) connected to the arterial cannula.. Heart Rate Variability The electrocardiogram was sampled at 200 Hz (IntelliVue MX850, Philips, Eindhoven, the Netherlands), and interbeat interval data were extracted. With specific software (Kubios HRV v3.1, Kuopio, Finland) cardiac autonomic activity was analyzed.25 The parasympathetic (PNS) index was computed using the following parameters: mean RR interval, root mean square of successive RR interval differences (RMSSD), and Poincar´e plot index SD1 in normalized units. The sympathetic (SNS) index was computed using the following parameters: mean RR interval, Baevsky’s stress index, and Poincar´e plot index SD2 in normalized units. An association between a low heart rate variability and autonomic imbalance, whether symptomatic or asymptomatic, has been described in patients with T2DM compared to HC.26,27 Statistical analysis Based on prior studies assessing changes in hypoxic sensitivity, a sample size calculation was performed targeting a statistical power of 90%. It was determined that a sample size of n = 28 would be sufficient to detect significant changes in HVR. We planned to enroll fifteen individuals with T2DM with a balanced gender distribution. Additionally, fifteen age, sex, and weight-matched HC were enrolled. Data were compared between T2DM and HC using linear mixed-effects models using packages lme4 and lmerTest in R (version 4.2.2, R Foundation for Statistical Computing, Vienna, Austria). Data are represented as means ± 95% CI, unless otherwise stated. 104

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