心率变异评价新疆维吾尔族2型糖尿病患者的自主神经功能

目的　探讨新疆维吾尔族2型糖尿病(T2DM)患者自主神经病变与心率变异(HRV)及其他脏器受损的关系。　方法　选择确诊为 T2DM的 150 例维吾尔族住院患者,其中单纯糖尿病(SDM)组72例,合并心血管疾病的糖尿病(DC)组78例,病程 <5年组54例,5~10年组51例,>10年组45例。正常对照(NC)组为健康的维吾尔族人 60 名,全部进行 24 h动态心电图及 HRV分析。　结果　T2DM患者HRV均小于NC组(t'= 6.5366~9.5677, P<0.05 ),DC组的 HRV较 SDM组低(t=4.0791~8.9233,P<0.05 ),病程>5 年的两组患者所有正常 R R间期的标准差值均低于病程<5年组(t=7.5935~10.631,P<0.05 )。　结论　HRV是早期判断维吾尔族 T2DM患者自主神经病变最准确而又最敏感的方法,可能对是否合并心脏缺血性病变有提示作用。     

2型糖尿病患者心血管自主神经功能与QT离散离及室性心律失常关系的研究

为探讨2型糖尿病患者心血管自主神经功能与QT离散度（QTd)及室性心律失常的关系。随机选取2型糖尿病患者60例,按标准心血管自主神经功能试验（下简称神功试验）结果分为阳性（异常）组35例和阴性组25例,另取35例健康人作为对照组。分别测定QTd和经心率校正的QTd(QTcd),同时记录24小时室性心律失常的发生率,进行对比分析。结果 60例糖尿病患者心血管神功试验的阳性率为58.3%,阳性组的QTd、QTcd较阴性组明显延长,室性心律失常及复杂性室性心律失常的发生率明显增高（P均＜0.01)。认为糖尿病患者的心血管自主神经功能与QTd与QTcd明显增加,其可能是导致室性心律失常和心源性猝死的重要原因之一。     

The connection between QT dispersion and autonomic neuropathy in patients with type 2 diabetes.

It is controversial whether an increase in the QT dispersion (QTd) on the electrocardiogram (ECG) reflects cardiac autonomic neuropathy in diabetic patients. In the current study, the QTd was compared in 60 type 2 diabetic patients and in 30 healthy subjects, and its association with autonomic neuropathy in diabetic patients was investigated. An increased QTd was found in diabetic patients, compared to healthy subjects. The QTd had significant negative associations with the log of the low and high frequency power (log LF and HF, respectively) of the power spectral analyses (PSA) of heart rate variations and the systolic blood response during standing (Delta BP). There was no significant difference in the QTd between patients with and without sympathetic skin response (SSR), reflecting peripheral sympathetic function. A significant positive correlation was also found between QTd and the systolic blood pressure (SBP). On the other hand, there was no correlation between QTd and serum total cholesterol (TC), triglycerides (TG), fasting plasma glucose (FPG), hemoglobin (Hb) A (1C) concentrations or body mass index (BMI). By multiple regression analysis, the log HF, which reflects cardiac parasympathetic function, and the SBP alone were significantly associated with QTd as the dependent variable. The Delta BP and log LF, which partially reflect sympathetic nerve function, had no significant associations with QTd. These findings suggest that QTd reflects cardiac autonomic neuropathy (relative parasympathetic neuropathy) and that the QTd is also influenced by SBP, independent of autonomic neuro-function.     

2型糖尿病患者心血管自主神经功能与QT离散度

目的 :探讨非胰岛素依赖型糖尿病 (2型糖尿病 )患者心血管自主神经功能与 QT离散度 (Q Td)、JT离散度 (JTd)和室性心律失常发生的关系。方法 :2型糖尿病患者 31例 ,按照标准心血管自主神经功能试验的结果分成阳性者及阴性组 ,16例健康人为正常对照组。所有入选人员均测 QTd、JTd及 2 4h Holter心电监测 ,并进行心律失常分析和比较。结果 :2型糖尿病患者心血管自主神经功能异常的发生率为 5 4.8% ,其发生率与病程呈正相关 ,QTd与 JTd显著延长 ,室性心律失常的发生率较高。结论 :QTd和 JTd可作为一项 2型糖尿病自主神经功能异常者发生室性心律失常重要的预测指标     

Clinical usefulness of corrected QT intervals in diabetic autonomic neuropathy in patients with type 2 diabetes

BACKGROUND: It is recognized that QTc intervals reflect autonomic nerve function. To investigate the clinical usefulness of corrected QT intervals (QTc) in assessing autonomic nerve function in type 2 diabetes, we measured QTc intervals using Bazett's formula in 58 type 2 diabetic patients and 20 age-matched healthy subjects. METHODS: We examined relationships between QTc intervals and the coefficient of variation of RR intervals (CV(RR)), systolic blood pressure response to standing, and sympathetic skin response (SSR) whose tests reflect autonomic nerve function. We also studied the correlation between QTc and blood pressure or serum lipid concentrations. RESULTS: QTc intervals in diabetic patients were significantly longer than those in healthy subjects and showed a significant but weak negative correlation with CV(RR), as well as systolic blood pressure response to standing. No significant difference in QTc intervals was observed between patients with and without a detectable SSR. QTc intervals showed a significant positive correlation with systolic and diastolic blood pressure although it did not correlate with serum lipid concentrations. QTc also tended to be long in obese diabetic subjects (body mass index > 25). CONCLUSION: QTc intervals might also be affected by other factors such as arteriosclerotic macroangiopathy and obesity, and not only autonomic nerve function. Therefore it might be considered as an overall index for complications, and not for pure autonomic impairment.     

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     

Dapagliflozin and measures of cardiovascular autonomic function in patients with type 2 diabetes (T2D)

AimsSodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce blood pressure without compensatory heart rate elevation, possibly by modulating sympathetic/parasympathetic activity. This may contribute to their cardiovascular benefits in type 2 diabetes (T2D). We evaluated the effects of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN), cardiac function, and glucose variability (GV) in T2D.MethodsPilot, randomized, two-period crossover trial comparing 12-week DAPA versus 12-week glimepiride treatment on CAN measures (cardiovascular autonomic reflex tests and heart rate variability), B-type natriuretic peptide (BNP), and GV (Abbott's Libre Pro devices) using signed rank tests and mixed models from baseline to 12 weeks within and between each period.ResultsForty-five T2D participants on metformin monotherapy (mean age 57 ± 8 years, duration 7 ± 6 years, HbA1c 7.8 ± 1.3%) were enrolled with 41 completing the trial. There were no differences in CAN indices or BNP with each drug compared to baseline and each other. Participants on DAPA demonstrated greater weight loss, reduced time in hypoglycemia, and improved GV compared to glimepiride.ConclusionsShort term treatment with DAPA did not affect CAN measures or BNP in uncomplicated and relatively healthy T2D participants. Longer prospective studies in patients with advanced disease are needed to better understand relationships between SGLT-2 inhibitors and CAN.Clinical trial registration: NCT02973477     

Autoantibodies against autonomic nervous tissues in type 2 diabetes mellitus: no association with cardiac autonomic dysfunction.

There is evidence that autoimmune factors contribute to the pathogenesis of cardiac autonomic dysfunction in Type 1 Diabetes mellitus (DM). To evaluate the presence of autoantibodies against autonomic nervous tissues in Type 2 DM, 127 patients were studied for complement-fixing sympathetic and parasympathetic ganglia (CF-SG and CF-PSG) autoantibodies with an indirect immunofluorescence technique. Five cardiac reflex tests were performed to investigate cardiac autonomic neuropathy. QTc interval was assessed in all patients. As a control group, 60 healthy non-diabetic subjects were also tested for CF-SG and CF-PSG autoantibodies. CF-SG autoantibodies were detected in 11 (9%) and CF-PSG autoantibodies were observed in 7 (6%) Type 2 DM patients, whereas in control subjects, the frequency was 1 (2%) and 0 (0%) respectively (ns vs. Type 2 DM patients). In Type 2 DM patients with cardiac autonomic neuropathy (n=31, 24%), CF-SG autoantibodies and CF-PSG autoantibodies were detected in 3 (10%) patients, respectively, compared to 8 (8%) and 4 (4%) in Type 2 DM patients without cardiac autonomic neuropathy (n=96, 76%, ns v. Type 2 DM with cardiac autonomic neuropathy). Both CF-SG autoantibodies and CF-PSG autoantibodies were observed in 2 (7%) Type 2 DM patients with cardiac autonomic neuropathy and 3 (3%) Type 2 DM patients without cardiac autonomic neuropathy. Type 2 DM patients with cardiac autonomic neuropathy demonstrated a longer QTc-interval (446+/-42 ms) than Type 2 DM patients without cardiac autonomic neuropathy (413+/-45 ms, p=0.0001). In Type 2 DM patients with a prolonged QTc-interval (>440 ms: n=29, 23%), 2 (7%) patients presented with CF-SG and 3 (10%) had CF-PSG autoantibodies. In Type 2 DM, CF-SG and CF-PSG autoantibodies are not frequently observed. The results do not give evidence, that immunological factors--like in Type 1 DM--play a role in the pathogenesis of cardiac autonomic dysfunction in Type 2 DM.     

Basic autonomic nervous function in patients with neurocardiogenic syncope

Basic autonomic nervous function was evaluated in patients with neurocardiogenic syncope (NCS). Atropine, isoproterenol, propranolol, phenylephrine, and phentolamine were administered successively, and parasympathetic nerve activity and beta- (and alpha-) activity, sensitivity, and secretion of the sympathetic nerve were determined in patients with NCS and control subjects. In patients with NCS, beta- and alpha- sensitivity were higher and beta-activity and beta- and alpha-secretion lower than in control subjects. In patients with NCS, the increased basic beta-sensitivity may contribute to induce strong cardiac contractions and augment ventricular mechanoreceptor response, and a compensatory state against diminished neuronal sympathetic activity is suggested by the increased alpha-sensitivity.     

Impact of body mass on autonomic function in persons with type 2 diabetes

The aim of this study was to investigate the influence of body mass on autonomic nerve function in persons with type 2 diabetes. Towards this aim we studied two groups of diabetic persons. Group 1: n = 30 lean (mean age 57.2+/-12.5 years, body mass index (BMI) 22.5+/-1.8 kg/m2]. Group 2: n = 35 overweight and obese (age 52.3+/-10.3 years, BMI 28.8 + 3.2 kg/m2). Autonomic neuropathy (DAN) was assessed using the battery of the five classical tests. DAN was diagnosed when at least two of the five tests were abnormal. Abnormalities of the heart rate based tests were considered as indication of parasympathetic and of blood pressure changes as indication of sympathetic dysfunction. The prevalence rates of DAN were not different between group 2 and group 1 (54.2 and 53.3%, respectively, P = 0.54). The same was valid for the rates of parasympathetic and sympathetic dysfunction in the studied groups (51.4 and 53.3% (P = 0.87) in group 2 and 34.2 and 33.3% (P = 0.93) in group 1, respectively). When the values of the arithmetic expression of each single autonomic function test were compared, no significant difference could be shown between the studied groups. In addition, no significant correlation was found between BMI and indices of DAN. These data indicate that moderate increase of body mass does not affect autonomic function in persons with type 2 diabetes.     

Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus

OBJECTIVES: To study effects of insulin-induced hypoglycaemia on the cardiac repolarization, using QT interval measurements, in patients with type 2 diabetes. DESIGN: Hypoglycaemia was induced by an i.v. insulin-infusion and blood glucose was clamped at 2.7 mmol L-1 for 60 min (T = 90-150 min) in two experiments, with (+GLIB) and without (-GLIB) glibenclamide. In a third experiment, with similar hyperinsulinaemia, glucose was clamped at a euglycaemic level (;5 mmol L-1). ECG was continuously recorded for arrhythmia-monitoring, and 12-lead ECGs were recorded at T = 0 and 150 min. QT intervals were measured, and we determined QT dispersion (difference between the maximum and the minimum QT interval) reflecting interlead variability of repolarization. SUBJECTS: Thirteen patients with type 2 diabetes, on combined insulin and glibenclamide treatment, were studied during hypoglycaemia, and eight of them participated in the euglycaemic experiment. RESULTS: No significant arrhythmias were seen during hypoglycaemia but the mean QT intervals and QT dispersion increased significantly (P < 0.001), with no differences between -GLIB and +GLIB. During the euglycaemic clamp all QT measurements remained unchanged. Serum potassium decreased significantly (P < 0.001) during all three clamps, but the decrease was more pronounced during hypoglycaemia. The change in potassium was not correlated to the degree of QT prolongation or QT dispersion. CONCLUSIONS: Significant changes in the repolarization of the heart can be seen during hypoglycaemia in patients with type 2 diabetes, indicating an increased risk of arrhythmia at low blood glucose levels.     

Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study

Aims/hypothesis

The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes.

Methods

We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR >?3.4 mg/mmol) or an estimated (eGFR) <?60 ml min^?1 1.73 m^?2. CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability.

Results

Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (?9.0?±?17.8% vs ?3.3?±?10.3%, p?=?0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (β?=??3.5, p?=?0.03). Spectral analysis variables were also independent predictors of eGFR decline.

Conclusions/interpretation

CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.     

QT interval prolongation in type 2 (non-insulin-dependent) diabetic patients with cardiac autonomic neuropathy

Summary QT interval alterations were measured in 41 non-insulin-dependent (type 2) diabetic patients and 14 age- and sex-matched control subjects. Cardiac autonomic neuropathy (CAN) was assessed by noninvasive tests (deep breathing, Valsalva maneuver and lying-to-standing) and diabetics were divided into three groups according to the results of these tests: diabetics with definitive (n=14), early (n=13) and without (n=14) CAN. The corrected values of QT intervals (QT_c) at rest were significantly longer in diabetics with definitive (447±5 ms; p<0.001), early (426±5 ms; p<0.05) and without (424±5 ms; p<0.05) CAN than in controls (407±5 ms). Moreover, QT_c intervals at rest were significantly (p<0.01) longer in diabetics with definitive CAN than in diabetics with early and without CAN. QT_c intervals at maximum tachycardia, induced by Valsalva maneuver, were considerably longer in diabetics with definitive CAN (451±6 ms) than in controls (407±6 ms; p<0.001) and in diabetics with early (434±6 ms; p<0.05) or without (422±6 ms; p<0.01) CAN. Furthermore, QT_c intervals at maximum tachycardia were significantly (p<0.01) longer in diabetics with early CAN than in controls. QT_c intervals at maximum bradycardia after Valsalva maneuver were significantly longer in diabetics with definitive (446±5 ms; p<0.001), early (434±5 ms; p<0.001) and without (424±5 ms; p<0.01) CAN than in controls (403±5 ms). Moreover, QT_c intervals at maximum bradycardia were considerably (p<0.01) longer in diabetics with definitive than without CAN. At least one abnormal (>440 ms) QT_c period was found in 19 out of 27 patients with early or definitive CAN, but 4 of 14 diabetics without any signs of CAN and none of the controls exibited abnormal QT_c period. It was concluded that QT_c interval prolongation due to imbalance of autonomic nervous tone could be observed in type 2 diabetic patients with CAN, suggesting a possible role in sudden cardiac death.     

Cardiovascular autonomic function and vibration perception threshold in type 2 diabetes mellitus

ObjectiveThe aim of this study was to compare cardiovascular autonomic function tests (AFT) and vibration perception threshold (VPT) of patients with type 2 diabetes mellitus (T2DM) with controls.Research Design/MethodsThe study was conducted on 60 diabetic patients comparing with 30 controls. The cardiovascular AFT and VPT were assessed in both groups.ResultsAmong cardiovascular AFT, E:I ratio [1.24 (1.2–1.32) vs 1.3 (1.24–1.4), p = 0.001], and Valsalva ratio [1.28 (1.22–1.4) vs 1.6 (1.5–1.73), p = 0.001], the indicators of parasympathetic reactivity were reduced in T2DM. Rise in DBP during handgrip, an indicator of sympathetic reactivity was lower in T2DM [12 (10–14) vs 16 (14–18) mmHg, p = 0.001] whereas, fall in SBP during head up tilt [4 (4–8) vs 5 (4–8) mmHg] was comparable. VPT (somatic sensation) was comparable between T2DM and control.ConclusionAutonomic involvement is more marked than somatic, and parasympathetic involvement is more marked than the sympathetic, possibly reflecting severity and chronological pattern of their involvement.     

Left ventricular function in patients with type 2 diabetes mellitus

This study showed that the mean left ventricular ejection fraction, end-diastolic volume, end-systolic volume, and muscle mass are comparable in patients with type 2 diabetes mellitus to gender-matched patients who do not have diabetes mellitus, but abnormal ejection fraction is more common in men, although not in women, with diabetes mellitus than without. The ejection fraction was higher and the volumes and muscle mass were lower in women than men in the presence or absence of diabetes mellitus.