心率变异性分析对糖尿病合并自主神经病变的诊断价值

采用24小时标准差法（SDNN）和心率变异指数法（HRVI），分析34例Ⅱ型糖尿病患者和42例正常人的心率变异（HRV），结果发现Ⅱ型糖尿病患者的HRV显著低于正常人（P＜0．05）。糖尿病合并自主神经病变（AN）者HRV显著低于不合并AN者。HRV与呼吸差、立卧差、30／15比值和乏氏指数呈正相关（γ分别为：0．86，0．90，0．78，0．81，P＜0．05）。如将SDNN＜30ms作为判定糖尿病合并AN的指标，敏感性是80．0％，特异性是84．2％。提示HRV可作为评价糖尿病合并AN的指标。     

高血压合并糖尿病患者血压变异性与心率变异性的相关性

目的探讨高血压合并糖尿病患者血压变异性与心率变异性的相关性。方法选择90例原发性高血压患者为高血压组,92例高血压合并糖尿病患者为高血压合并糖尿病组,90例同期健康体检者为对照组。测定糖化血红蛋白(HbA1c)、血肌酐(Cr)、空腹血糖(FBG)等生物化学指标。进行24 h动态心电图和动态血压同步测量,计算机自动计算各指标。比较三组一般情况、心率变异性、血压变异性的差异,并采用Pearson分析各指标之间的相关性。结果三组HbA1c、FBG差异有统计学意义,性别、年龄、血脂、血肌酐差异无统计学意义。高血压组、高血压合并糖尿病组心率变异性指标低于对照组(P0.05),高血压合并糖尿病组心率变异性指标低于高血压组(P0.05)。三组SBP、DBP、SSD、dSSD、nSSD、sCV、dCV比较差异有统计学意义(P0.05),其在高血压组、高血压合并糖尿病组高于对照组(P0.05),在高血压合并糖尿病组高于高血压组(P0.05),三组DSD、dDSD、nDSD差异无统计学意义(P0.05)。高血压组、高血压合并糖尿病组24 h平均收缩压标准差SSD与SDNN、SDANN、rMSSD、SDNNIndex、PNN50呈负相关。结论与高血压患者相比,高血压合并糖尿病患者自主神经功能受损更加明显,随访患者的血压变异性和心率变异性有助于评估病情、改善预后。     

糖尿病心血管自主神经病变检查方法的研究进展

目前无创检测糖尿病心血管自主神经病变（DCAN）的方法有标准心血管反射试验、心率变异性（HHV）和压力反射敏感性（BRS）分析等，可用于糖尿病患者心血管自主神经功能的评估以及分析DCAN和血糖控制、肥胖、心源性猝死、颈动脉硬化、胰岛素抵抗及运动治疗等的关系。另外，影像学方法如核素显像检测也可应用于DCAN，并可提供糖尿病患者心脏失去自主神经支配的直接证据。     

Relationship between autonomic function, 24-h blood pressure, and albuminuria in normotensive, normoalbuminuric patients with Type 1 diabetes

We performed a battery of cardiovascular reflex tests, 24-h ambulatory blood pressure (AMBP) and 24-h urinary albumin excretion (UAE) in 116 normoalbuminuric and normotensive patients with Type 1 diabetes. Tests of heart rate variation (HRV) included the coefficient of variation (CV) and the low-frequency (LF), mid-frequency (MF), and high-frequency (HF) bands of spectral analysis at rest, HRV during deep breathing (CV, mean circular resultant — MCR), Valsalva ratio, and maximum/minimum 30:15 ratio. Autonomic neuropathy, characterized as an abnormality of more than two tests, was found in 33 patients. Patients with neuropathy compared to those without neuropathy showed significantly higher mean day and night diastolic blood pressure (dBP), mean systolic night blood pressure (sBP), and mean day and night heart rate (HR). Mean night dBP was inversely related to MF, HF, and HRV during deep breathing; mean day dBP and mean night sBP to HF; mean night HR to CV at rest, MF, HF, HRV during deep breathing, 30:15 ratio; mean day HR to HF, HRV during deep breathing, Valsalva, and 30:15 ratio. Mean 24-h UAE was not significantly different in neuropathic than in nonneuropathic patients. UAE was inversely related to CV at rest and HF. In the stepwise multiple regression analysis, reduced MF, HF, HRV during deep breathing, and high levels of UAE and HbA1c were associated with high night dBP. Autonomic neuropathy is already present in normotensive Type 1 diabetic patients at the normoalbuminuric stage and related to BP and albuminuria.     

自主神经功能对糖尿病患者24小时动态血压和心率的影响

采用２４小时动态心电图和血压同步监测７５例糖尿病患者和３５例正常对照组。结果显示：随ＳＤＮＮ（２４小时内全部正常Ｒ－Ｒ间期的标准差）的降低，糖尿病患者的２４小时平均血压和心率、白昼收缩压和心率，夜间血压和心率均明显递增，昼夜血压差和心率差递减；２４小时血压波动曲线由类似双峰双谷逐渐变为失去正常节律，且夜间血压高于白昼的血压曲线；视网病变和肾病的发生率也随之增高，结论：糖尿病患者高血压的发生、发展和     

Exercise training and cardiac autonomic function in type 2 diabetes mellitus: A systematic review

Cardiac autonomic neuropathy (CAN) is a common complication of type 2 diabetes mellitus (T2DM). It has been found to independently predict all cause and cardiovascular disease (CVD) mortality. It remains unclear whether exercise training could improve autonomic control in T2DM patients. The purpose of this study was to systematically review the effects of exercise training on cardiac autonomic function in T2DM patients. Electronic databases (MEDLINE, CENTRAL, PEDro, Scopus and Web of science) were systematically searched to retrieve relevant evidence. Clinical trials administering exercise training for at least 4 weeks and examining either heart rate variability (HRV), baroreflex sensitivity (BRS), heart rate recovery (HRR) as outcome measures were eligible. Eighteen articles were found to be relevant and were then assessed for characteristics and quality. Fifteen studies out of 18 found that exercise training leads to positive improvements in autonomic function of T2DM patients. Exercise participation enhances cardiac autonomic function of type 2 diabetics and therefore should be implemented in their management programs.     

Altered cerebral regulation in type 2 diabetic patients with cardiac autonomic neuropathy

Aims/hypothesis Assessment of cerebral regulation in diabetic patients is often problematic because of the presence of cardiac autonomic neuropathy. We evaluated the technique of oscillatory neck suction at 0.1 Hz to quantify cerebral regulation in diabetic patients and healthy control subjects. Subjects and methods In nine type 2 diabetic patients with cardiac autonomic neuropathy and 11 age-matched controls, we measured blood pressure and cerebral blood flow velocity responses to application of 0.1 Hz neck suction. We determined spectral powers and calculated the transfer function gain and phase shift between 0.1 Hz blood pressure and cerebral blood flow velocity oscillations as parameters of cerebral regulation. Results In the patients and control subjects, neck suction did not significantly influence mean values of the RR interval, blood pressure and cerebral blood flow velocity. The powers of 0.1 Hz blood pressure and cerebral blood flow velocity oscillations increased in the control subjects, but remained stable in the patients. Transfer function gain remained stable in both groups. Phase shift decreased in the patients, but remained stable in control subjects. Conclusions/interpretation The absence of an increase in the power of 0.1 Hz blood pressure and cerebral blood flow velocity oscillations confirmed autonomic neuropathy in the diabetic patients. Gain analysis did not show altered cerebral regulation. The decrease in phase shift in the patients indicates a more passive transmission of neck suction-induced blood pressure fluctuations onto the cerebrovascular circulation, i.e. altered cerebral regulation, in the patients, and is therefore suited to identifying subtle impairment of cerebral regulation in these patients.     

Day and night variation in ambulatory blood pressure in type 1 diabetes mellitus with nephropathy and autonomic neuropathy

Abstract. The objective was to study ambulatory blood pressure and heart rate variability between day and night in patients with type 1 (insulin-dependent) diabetes mellitus with different degrees of diabetic nephropathy, and to evaluate the influence of autonomic neuropathy and type of antihypertensive treatment. Twenty type 1 diabetic patients with diabetic nephropathy and antihypertensive treatment were studied with 24-h ambulatory blood pressure monitoring using an oscillometric method. They were compared with eight insulin-treated diabetic patients with short duration of diabetes (1–5 years) and with 10 apparently healthy subjects. The degree of autonomic neuropathy was evaluated by measuring the RR-interval during deep breathing and uprising. The 24-h blood pressure was generally higher in patients with diabetic nephropathy compared to those other two groups. These patients also had a lower ratio between day and night in diastolic blood pressure compared to the control subjects (1.15 ± 0.12 vs. 1.25 ± 0.76, P < 0.05) and heart rate compared to the diabetic patients without nephropathy, as well as the control subjects (1.15 ± 0.08 vs. 1.26 ± 0.09 vs. 1.27 ± 0.08, P < 0.01, respectively). All patients with diabetic nephropathy had clinical signs of autonomic neuropathy as judged by RR-interval measurements during deep breathing and uprising.     

Altered hand skin blood flow in type 1 (insulin-dependent) diabetes mellitus

Disturbed upper limb skin blood flow has been described in insulin-dependent (Type 1) diabetes mellitus, but the pathophysiological mechanism remains unclear. Hand skin blood flow was therefore measured at room temperature and following immersion of hands in cold and warm water in 13 healthy control subjects, in 10 patients with Type 1 diabetes mellitus and cardiovascular autonomic neuropathy, and a further 10 Type 1 diabetic patients with normal cardiovascular autonomic tone. Following cold challenge there was failure of digital artery clampdown in all diabetic patients in comparison with healthy control subjects (p less than 0.005), and the index finger temperature fell less (p less than 0.05). Laser Doppler flow was reduced at the palms at room temperature or following the warm challenge (p less than 0.008), as well as on the dorsum at room temperature (p less than 0.05), in all diabetic patients. In addition laser Doppler flow in the diabetic patients was reduced at the palms and dorsum immediately following cold water challenge (p less than 0.004) and this reduction persisted 15 min (p less than 0.05) and 30 min (p less than 0.01) into the recovery phase. In comparison to those diabetic patients with normal cardiovascular tone, those with cardiovascular autonomic neuropathy had reduced laser Doppler flow at the pulp 15 min after cold water immersion (p less than 0.05), at the nailbed immediately after cold water immersion (p less than 0.01), and at the palms immediately after warm water challenge (p less than 0.01).     

Dysfunction of pre- and post-operative cardiac autonomic nervous system in elderly patients with diabetes mellitus

The pre- and post-operative cardiac autonomic nervous functions were compared in elderly, non-cardiac surgery patients with diabetes mellitus (DM) and without diabetes mellitus (NDM). A group of 30 unpremedicated elderly patients scheduled to undergo elective non-cardiac surgery were studied, including 15 DM patients and 15 NDM patients. Each component of heart rate variability (HRV) analysis in the frequency domain was monitored with Holter during the nights of the day before and on 1st and 2nd day after operation. After surgery, total power (TP), high frequency (HF), low frequency (LF) and very low frequency (VLF) significantly decreased as compared to the baseline values before operation in both groups (p < 0.05). The LF/HF ratio was significantly changed in DM group but did not change in NDM group. On the 2nd postoperative day, TP, HF, LF and VLF in DM group were further decreased as compared to those on the 1st postoperative day and were significantly lower than those in NDM group (p < 0.01 or 0.05), but these indices in NDM group did not show significant decreases. Surgery induced the cardiac autonomic nervous dysfunction in elderly patients not only with DM but also without diabetes. On the 2nd postoperative day, the disturbances of cardiac autonomic nervous activity were more sever in DM patients, compared to the 1st postoperative day, but was not significantly more sever than in the NDM patients.     

不同阶段糖尿病肾病患者自主神经功能和昼夜血压、心率的变化

探讨自主神经功能和昼夜血压、心率在不同阶段糖尿病肾病患者中的变化。采用 2 4h动态心电图和血压同步监测 38例正常对照组和 84例糖尿病患者 ,包括A组 (正常蛋白尿 ) 4 8例、B组 (微量蛋白尿 ) 2 0例、C组 (大量蛋白尿组 ) 16例。结果 :A组糖尿病患者已有夜间血压和心率增高 ,昼夜血压、心率下降幅度及部分心率变异指标的降低 ;随蛋白尿增多 ,上述指标异常加重 ,并出现白昼血压和心率增高。A、B、C组分别有 5 4 .17%、75 .0 0 %和 87.5 0 %的患者出现昼夜血压节律消失 ,而对照组仅有 2 1.0 5 %。结论 :糖尿病患者普遍存在自主神经病变 ,夜间血压和心率增高可能就是糖尿病肾病早期的临床征象     

Ewing试验及心率变异性对初诊2型糖尿病患者心血管自主神经病变诊断的比较

目的了解初诊2型糖尿病患者的心血管自主神经病变（CAN）患病情况及其特点,比较Ewing试验及心率变异性（HRV）两种常用评价方法对诊断CAN的差异。方法以2009年5月至2010年12月广东省4家医院（中山大学附属第三医院、汕头大学医学院第一附属医院、广东省人民医院、南方医科大学珠江医院）内分泌科收治的90例初诊2型糖尿病患者为糖尿病组,其中男58例,女32例,平均年龄（47±1）岁。以同期40名健康体检者为对照组,其中男21名,女19名,平均年龄为（45±2）岁。所有受试者均接受Ewing试验和24h动态心电图检查并分析HRV指标以诊断CAN,对比两种方法的结果差异。计量资料间比较采用t检验或单因素方差分析,等级资料采用秩和检验。结果（1）Ewing试验显示糖尿病组CAN阳性率[22．2％（20／90）]高于对照组[7．5％（3／40）,X2=4．12,P〈0．05];糖尿病组Ewing试验总评分（92．5分）高于对照组（7．0分,Z=-3．72,P〈0．01）,Ewing试验各指标（Valsalva指数、深呼吸心率差、立卧位心率变化及血压差）评分均较对照组升高,差异均有统计学意义（z值分别为-2．99、-2．23、-1．99、-2．36,均P〈0．05）。（2）HRV分析显示糖尿病组CAN阳性率[34．4％（31／90）]高于对照组[12．5％（5／40）,X2=6．66,P〈0．05];糖尿病组HRV中反映副交感神经功能的指标[全部正常窦性心搏问期（N—N）的标准差、连续5min正常R—R间期均值的标准差及低频功率]均降低,与对照组相比差异均有统计学意义（t值分别为2．06、2．24、6．48,均P〈0．05）,而代表交感神经功能的指标（全程相邻N．N间期之差的均方根值、相邻R—R间期差异≥50ms的百分数、高频功率）差异均无统计学意义（t值分别为0．27、0．15、1．40,均P〉0．05）。结论Ewing试验和HRV检测均显示初诊2型糖尿病患者中CAN阳性率较高,且以副交感神经损害为主;HRV检测较Ewing试验的CAN阳性率高。     

不同血压分级的原发性高血压患者心率变异性分析

目的 探讨不同高血压分级患者的心率变异性（HRV）特征,了解高血压对自主神经功能的影响.方法 纳入2011年6月-2012年6月我院心内科高血压患者（n=167）及健康对照组（n=50）,进一步根据〈中国高血压防治指南〉血压分级标准将高血压组分为：高血压1级组[140 mmHg≤收缩压（SBP）＜160 mmHg和/或90 mmHg≤舒张压（DBP）≤100 mmHg,n=45]、高血压2级组（160≤SBP＜180 mmHg和/或100 mmHg≤DBP≤110 mmHg,n=57）、高血压3级组（SBP≥180 mmHg和/或DBP≥110 mmHg,n=65）,采用24小时动态心电图记录的各组研究对象的HRV资料,分析和比较各组间HRV的5项时域指标SDNN、SDANN、HRV三角指数、RMSSD、PNN50之间的差异.结果 3组高血压组的5项HRV时域指标均低于健康对照组（P＜0.05）;高血压1级组、高血压2级组、高血压3级组三组之间的5项时域指标依次降低,其中SDNN、SDANN、HRV三角指数在对照组、高血压1级组、高血压2级组、高血压3级组任意两组之间比较,差异均具有统计学意义（P均＜0.05）.结论 高血压患者存在自主神经功能受损,并且随着血压分级水平的升高,自主神经受损逐渐加重.     

心率变异评价Ⅱ型糖尿病患者自主神经功能

目的 研究Ⅱ型糖尿病患者心率变异（ＨＲＶ）与自主神经病及心、肾脏器受损的关系。方法 ５７例Ⅱ型糖尿病患者,分３组：单纯糖尿病组２９例,糖尿病合并冠心病组（糖冠组）１７例,糖尿病肾病组（糖肾组）１１例,正常对照组１５例,全部进行心血管反射试验及ＨＲＶ分析。结果 糖尿病患者合并自主神经病变为４５．６％,各组在ＨＲＶ时域指标及非线性定量分析指标上均较对照组降低,以糖肾组最为显著。比较Ｒ－Ｒ间期散点图,对     

Mechanism of hypotensive transients associated with abrupt bradycardias in conscious rabbits

BACKGROUND: Transient bradycardic hypotensive events occur in resting rabbits. If the hypotension is due to vasodepression, these events may be a model for vasovagal syncope. OBJECTIVES: To determine whether these events are responses to brief stimuli and whether the hypotensive episodes are solely due to rapid-onset bradycardia. METHODS: Rabbits were instrumented with subcutaneous electrocardiogram leads, and cannulae were acutely inserted into an ear artery to obtain continuous arterial pressure measurements. Exposure to brief, low-level auditory stimuli at 5 kHz transiently increased the RR interval by approximately 70 ms and decreased mean arterial pressure by approximately 5 mmHg. RESULTS: These evoked bradycardic hypotensive events were almost identical to previously reported spontaneous bradycardic hypotensive events. Intra-aortic telemetric blood pressure monitoring was used to demonstrate that the evoked hypotension reflected prolonged diastole, rather than local ear arterial vasoconstriction. Furthermore, administration of the muscarinic blocker glycopyrrolate abolished not only bradycardia (RR interval 64+/-14 ms to 1+/-1 ms; P<0.0001), but also hypotension (--4.1+/-0.8 mmHg to --0.4+/-0.3 mmHg; P=0.0055). Finally, cardiac pacing abolished the inducible bradycardia (RR interval 51+/-10 ms to 2+/-1 ms; P=0.0006) and its associated hypotension (--4.1+/-0.7 mmHg to --1.2+/-0.3 mmHg; P=0.003). CONCLUSIONS: Brief auditory stimuli evoked a transient bradycardia mediated by cardiac muscarinic receptors and consequent hypotension. This is not a model for vasovagal syncope.     

Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses at various stages of diabetic neuropathy.

To establish a test battery for the detection and characterization of cardiovascular autonomic neuropathy (CADN) and to evaluate its prevalence, a number of autonomic function tests based on spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses were performed in 261 diabetic patients aged 11-76 years with various stages of peripheral neuropathy. The percentages of abnormal results in the individual tests based on heart rate variation were 6-31% in 115 patients without peripheral neuropathy, 16-45% in 61 patients with subclinical neuropathy, 22-59% in 73 patients with symptomatic peripheral neuropathy, and 67-100% in 12 patients with the latter in conjunction with autonomic symptoms (p < 0.05). The most frequently abnormal indices, each representing a different physiological basis, were the coefficient of variation, low-frequency and mid-frequency power spectrum at rest, mean circular resultant, postural change in systolic blood pressure, and, in particular, the max/min 30:15 ratio and Valsalva ratio. CADN, defined as the presence of > or = 3 abnormalities among these seven parameters was detected in none of 120 control subjects, 13.0% of the patients without peripheral neuropathy, 34.4% of those with subclinical neuropathy, 49.3% of those with symptomatic peripheral neuropathy, and in 100% of the subjects with the latter and concomitant autonomic symptoms (p < 0.05). The overall prevalence of CADN in 103 patients completing all parameters was 46.6%. The corresponding rate of CADN defined as > or = 2 abnormalities among the five tests included in an optimized version of the battery proposed by Ewing and Clarke was 38.8%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma epinephrine and norepinephrine response to stimuli in autonomic neuropathy of type 2 diabetes mellitus

The objective of this study was to examine epinephrine and norepinephrine plasma levels in patients with clinical type 2 diabetes mellitus, at different stages of autonomic neuropathy. Eighteen patients were classified in groups without (n = 6) and with early (n = 6), definite (n = 3) and severe (n = 3) neuropathy. Blood catecholamine levels were measured after the Valsalva maneuver, cold exposure and orthostatic tests. The norepinephrine basal levels were lower in patients with severe neuropathy (0.4 ± 0.2 nmol/l), compared with the group with no neuropathy (1.3 ± 0.5 nm/l, p = 0.034), or with early neuropathy (1.3 ± 0.7 nm/l, p = 0.035). After the Valsalva maneuver, no increase was found in the group with severe alteration. In patients without neuropathy, cold exposure induced a peak of norepinephrine at 5 min (Δ = 1.9 ± 1.6 nmol/l). The increase was lower in groups with definite and severe damage. In patients with definite or moderate neuropathy, the orthostatic test induced minimal or no response. The epinephrine response to the maneuvers was not significant, and no differences were found among the groups. Norepinephrine basal levels and cold responses are diminished in patients with definite and severe autonomic neuropathy. This provides further evidence on their impaired response to stress. The comparable epinephrine levels in patients with or without autonomic neuropathy indicates that adrenal medullar function is not significantly altered. Received: 28 May 1999 / Accepted in revised form: 28 August 2000     

2型糖尿病下肢神经病变心率变异性时域指标的昼夜节律

目的 了解糖尿病合并周围神经病变患者的自主神经功能.方法 2008年1月至2009年3月按随机数字表法抽取天津医科大学代谢病医院的117例2型糖尿病患者,分为2型糖尿病不伴下肢神经病变组(糖1组)59例和2型糖尿病伴下肢神经病变组(糖2组)58例.无糖尿病的对照组50例来源于我院健康体检者.受试对象均接受体重指数、收缩压、舒张压、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、空腹血糖、餐后2 h血糖、糖化血红蛋白、空腹胰岛素、稳态模型胰岛素抵抗指数、24 h动态心电图心率变异性(HRV)、乏式动作反应指数、30/15比值、呼吸差的检测.统计学处理采用卡方检验、方差分析、配对秩和检验.结果 (1)糖1组、糖2组患者心动周期标准差(SDNN)、每5 min R-R均值的标准差(SDANN)、每5 min R-R均值的标准差指数(SDNNIDX)、相邻R-R差值的均方根(rMSSD)、24 h内相邻R-R间期相差＞50 ms的个数占总心跳次数的百分比(pNN50),与对照组比较差异有统计学意义(F值分别为94.702、77.786、55.422、56.175、49.110,均P＜0.01);(2)对照组SDNN、rMSSD、pNN50日间节律分别为(113±20)ms、(31±15)ms、4%(0～45%),夜间节律分别为(104±25)ms、(38±18)ms、11%(0～45%),日夜间比较差异有统计学意义(t=2.472、4.629、5.007,均P＜0.05);糖1组SDNN Et间节律为(81±16)ms,夜间节律为(77±19)ms,日夜间节律比较差异无统计学意义(t=1.952,P＞0.05),糖2组SDNN、rMSSD、pNN50日间节律分别为(64±15)ms、(21±19)ms、1%(0～30%),夜间节律分别为(64±20)ms、18(7～97)ms、1%(0～28%),日夜间节律比较差异无统计学意义(t值分别为0.155、1.103、1.328,均P＞0.05).结论 2型糖尿病不伴及伴下肢神经病变组均存在自主神经功能受损,但后者的自主神经功能更明显受损.心率变异性时域指标的昼夜节律可有效判断自主神经损害.