Advanced Cross-Correlation Function Application to Identify Arterial Baroreflex Sensitivity Variations From Healthy to Diabetes Mellitus

Shoou Jeng Yeh, Chi Wen Lung, Yih Kuen Jan, Ben Yi Liau

Research output: Contribution to journalArticlepeer-review


Diabetes mellitus (DM) is a chronic disease characterized by elevated blood glucose levels, which leads over time to serious damage to the heart, blood vessels, eyes, kidneys, and nerves. DM is of two types–types 1 or 2. In type 1, there is a problem with insulin secretion, and in type 2–insulin resistance. About 463 million people worldwide have diabetes, and 80% of the majority live in low- and middle-income countries, and 1.5 million deaths are directly attributed to diabetes each year. Autonomic neuropathy (AN) is one of the common diabetic complications, leading to failure in blood pressure (BP) control and causing cardiovascular disease. Therefore, early detection of AN becomes crucial to optimize treatment. We propose an advanced cross-correlation function (ACCF) between BP and heart rate with suitable threshold parameters to analyze and detect early changes in baroreflex sensitivity (BRS) in DM with AN (DM+). We studied heart rate (HR) and systolic BP responses during tilt in 16 patients with diabetes mellitus only (DM−), 19 diabetes mellitus with autonomic dysfunction (DM+), and 10 healthy subjects. The ACCF analysis revealed that the healthy and DM groups had different filtered percentages of significant maximum cross-correlation function (CCF) value (p < 0.05), and the maximum CCF value after thresholds was significantly reduced during tilt in the DM+ group (p < 0.05). The maximum CCF index, a parameter for the phase between HR and BP, separated the healthy group from the DM groups (p < 0.05). Due to the maximum CCF index in DM groups being located in the positive range and significantly different from healthy ones, it could be speculated that BRS dysfunction in DM and AN could cause a phase change from lead to lag. ACCF could detect and separate DM+ from DM groups. This fact could represent an advantage of the ACCF algorithm. A common cross-correlation analysis was not easy to distinguish between DM− and DM+. This pilot study demonstrates that ACCF analysis with suitable threshold parameters could explore hidden changes in baroreflex control in DM+ and DM−. Furthermore, the superiority of this ACCF algorithm is useful in distinguishing whether AN is present or not in DM.

Original languageEnglish (US)
Article number812302
JournalFrontiers in Neuroscience
StatePublished - Jun 10 2022


  • advanced cross-correlation function
  • autonomic neuropathy
  • baroreflex sensitivity
  • blood pressure
  • diabetes mellitus
  • heart rate

ASJC Scopus subject areas

  • General Neuroscience


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