Chen Yu-Chen, Liu Wei-Min, Liu Hsin-Ru, Chang Huai-Ren, Chen Po-Wei, Liu An-Bang
Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan.
Department of Medical Informatics, Tzu Chi University, Hualien 970374, Taiwan.
Diagnostics (Basel). 2025 Jun 10;15(12):1474. doi: 10.3390/diagnostics15121474.
Cardiac autonomic neuropathy (CAN) is a common yet frequently underdiagnosed complication of diabetes. While our previous study demonstrated the utility of multiscale cross-approximate entropy (MS-CXApEn) in detecting early CAN, the present study further investigates the use of frequency-domain coherence analysis between systolic blood pressure (SBP) and R-R intervals (RRI) and evaluates the effects of insulin treatment on autonomic function in diabetic rats. At the onset of diabetes induced by streptozotocin (STZ), rats were assessed for cardiovascular autonomic function both before and after insulin treatment. Spectral and coherence analyses were performed to evaluate baroreflex function and autonomic regulation. Parameters assessed included low-frequency power (LFP) and high-frequency power (HFP) of heart rate variability, coherence between SBP and RRI at low and high-frequency bands (LF and HF), spontaneous and phenylephrine-induced baroreflex sensitivity (BRS and BRS), HRV components derived from fast Fourier transform, and MS-CXApEn at multiple scales. Compared to normal controls (LF: 0.14 ± 0.07, HF: 0.19 ± 0.06), early diabetic rats exhibited a significant reduction in both LF (0.08 ± 0.04, < 0.05) and HF (0.16 ± 0.10, > 0.05), indicating impaired autonomic modulation. Insulin treatment led to a recovery of LF (0.11 ± 0.04) and HF (0.24 ± 0.12), though differences remained statistically insignificant ( > 0.05 vs. normal). Additionally, low-frequency LFP increased at the onset of diabetes and decreased after insulin therapy in most rats significantly, while MS-CXApEn at all scale levels increased in the early diabetic rats, and MS-CXApEn declined following hyperglycemia correction. The BRS and BRS showed no consistent trend. Coherence analysis provides valuable insights into autonomic dysfunction in early diabetes. The significant reduction in LF in early diabetes supports its role as a potential marker for CAN. Although insulin treatment partially improved coherence, the lack of full recovery suggests persistent autonomic impairment despite glycemic correction. These findings underscore the importance of early detection and long-term management strategies for diabetic CAN.
心脏自主神经病变（CAN）是糖尿病常见但常被漏诊的并发症。虽然我们之前的研究证明了多尺度交叉近似熵（MS-CXApEn）在检测早期CAN方面的效用，但本研究进一步探讨了收缩压（SBP）与R-R间期（RRI）之间频域相干分析的应用，并评估胰岛素治疗对糖尿病大鼠自主神经功能的影响。在链脲佐菌素（STZ）诱导糖尿病发病时，对大鼠在胰岛素治疗前后的心血管自主神经功能进行评估。进行频谱和相干分析以评估压力反射功能和自主神经调节。评估的参数包括心率变异性的低频功率（LFP）和高频功率（HFP）、SBP与RRI在低频和高频频段（LF和HF）的相干性、自发和去氧肾上腺素诱导的压力反射敏感性（BRS和BRS）、通过快速傅里叶变换得出的HRV成分以及多尺度的MS-CXApEn。与正常对照组（LF：0.14±0.07，HF：0.19±0.06）相比，早期糖尿病大鼠的LF（0.08±0.04，<0.05）和HF（0.16±0.10，>0.05）均显著降低，表明自主神经调节受损。胰岛素治疗使LF（0.11±0.04）和HF（0.24±0.12）有所恢复，尽管差异仍无统计学意义（与正常相比>0.05）。此外，大多数大鼠在糖尿病发病时低频LFP升高，胰岛素治疗后显著降低，而早期糖尿病大鼠所有尺度水平的MS-CXApEn均升高，高血糖纠正后MS-CXApEn下降。BRS和BRS未显示出一致趋势。相干分析为早期糖尿病自主神经功能障碍提供了有价值的见解。早期糖尿病中LF的显著降低支持其作为CAN潜在标志物的作用。虽然胰岛素治疗部分改善了相干性，但缺乏完全恢复表明尽管血糖得到纠正，自主神经损伤仍然持续。这些发现强调了早期检测和糖尿病CAN长期管理策略的重要性。
