Relationship between age and autonomic neuropathy in diabetes mellitus

The influence of age on diabetic autonomic neuropathy was studied. In the present study autonomic neuropathy was assessed by cardiac beat-to-beat variation during deep breathing (BBV) and pupil area prior to photic stimulus (A1). In the studies on BBV a total of 440 subjects (11-82 years in age) were divided into three groups: those with a duration of diabetes of less than 5 years and without obvious diabetic complications; those with a duration of diabetes of longer than 5 years and with diabetic complications; and non-diabetic, healthy subjects. The relationship between BBV and age was examined in each group. In the studies on A1 a total of 101 subjects (22-75 years in age) were investigated in the same way. The results were as follows: (1) The autonomic nerve function of young diabetics corresponds to that of old non-diabetics in terms of cardiac beat-to-beat variation and pupil area prior to photic stimulus; (2) in young diabetics duration of diabetes and the complications influence the autonomic nerve function; (3) autonomic nerve function is related to age. Age is more influential than duration of diabetes and diabetic complications, especially in the older subjects.     

2型糖尿病外周感觉神经病变和心自主神经病变关系的研究

目的探讨T2DM外周感觉神经病变和心自主神经病变之间的关系。方法选取T2DM患者148例,采集临床资料,测定FPG、HbA1c及LDL-C等生化指标;进行定量感觉神经检查(以色列TSA-II定量感觉神经测定仪),结合临床症状评价糖尿病外周感觉神经病变;进行心血管反射试验检查,结合临床症状评价糖尿病心自主神经病变。结果外周感觉神经病变的患病率为28%,心自主神经病变的患病率为10%;无外周感觉神经病变的患者中心自主神经病变的患病率为6%,存在外周感觉神经病变的患者中心自主神经病变的患病率为21%;与对照组相比,外周感觉神经病变组和心自主神经病变组的病程较长,FPG、HbA1c及LDL-C水平较高,差异有统计学意义(P<0.05)。结论糖尿病心自主神经病变可发生于无外周感觉神经病变的患者;病程、FPG、HbA1c及LDL-C可能为糖尿病外周感觉神经病变和心自主神经病变的危险因素。     

Gastric myoelectrical activity in patients with type I diabetes mellitus and autonomic neuropathy

In patients with diabetes mellitus and gastroparesis, dysrhythmias of gastric myoelectrical activity, especially tachygastrias, are thought to be involved in the pathogenesis of dyspeptic symptoms. Using surface electrogastrography we studied the prevalence of these abnormalities, and their relationships to dyspeptic symptoms and the extent of cardiac autonomic neuropathy in 30 euglycemic patients with type I diabetes mellitus and 12 controls. Neither in the fasting nor in the postprandial state were differences in mean frequency of gastric electrical control activity and its variability found between patients and controls. In the fasting state, the power content of the 3 cpm component in the power spectrum of the electrogastrogram was even higher in patients than in controls (P=0.049). In the fasting state, second harmonics of the 3 cpm fundamental gastric signal were seen more often in patients than in controls (P=0.03). In patients with symptoms during the study, no second harmonics were found after the meal. The postprandial/fasting power ratio was decreased in patients with symptoms during the study as compared to patients without symptoms and controls (P<0.05). The incidence of dysrhythmias, such as tachygastrias and bradygastrias, was not higher in patients than in controls (17% and 8%, respectively). No correlation was found between electrogastrographic parameters and the severity of autonomic neuropathy or dyspeptic symptoms scored before the study. In conclusion, this study has shown that patients with type I diabetes mellitus and autonomic neuropathy studied under euglycemic conditions do not have grossly disturbed myoelectrical activity, except when symptomatic during the study.Supported by the Dutch Diabetic Foundation.     

Left ventricular diastolic abnormalities in diabetes mellitus I in relation to cardiovascular autonomic neuropathy and retinopathy

In this study the authors evaluated left ventricular performance in two groups of type I diabetes, with or without autonomic neuropathy, using the pulsed Doppler echocardiographic method. They also evaluated the eventual presence of retinopathy in these groups. A significant left ventricular performance alteration was observed only in the first group (with autonomic neuropathy) in particular concerning the diastolic phase. In this group they found a significant correlation with the presence of retinopathy (p<0.01), in contrast to the second group, which had a lower incidence of retinopathy. It is possible to presume that diabetic patients with autonomic neuropathy had, as compared with a similar group without this feature, more nerve damage and also greater vascular damage, which can be expressed by the more significant presence of retinopathy and alteration of the left ventricular diastolic phase.     

Vascular calcification, autonomic neuropathy, and peripheral blood flow in patients with diabetic nephropathy

The possibility that digital gangrene in patients with diabetic nephropathy might be due to abnormalities of peripheral blood flow secondary to vascular calcification has been investigated. Twenty patients with renal failure due to diabetic nephropathy were studied. Peripheral blood flow was measured using venous occlusion plethysmography, together with an assessment of medial arterial calcification on plain radiographs of the hands and feet, and transcutaneous oxygen tension (TcPO2). Hallux blood flow was markedly raised (median 22.5, range 11.5-56.5, ml min-1 100-ml-1) compared with non-diabetic control subjects (4.7, 1.1-10.5, ml min-1 100-ml-1; p less than 0.01) and similar to that in diabetic patients with autonomic neuropathy (29.5, 16.7-49.6, ml min-1 100-ml-1). Although vascular calcification was common and extensive in the patients with diabetic nephropathy, TcPO2 measurements in the supine foot were normal and did not indicate tissue ischaemia. We conclude that despite extensive vascular calcification high peripheral blood flow occurs in the feet of these patients at rest together with normal transcutaneous oxygen tension.     

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.     

Low prevalence of cardiac autonomic neuropathy in Type 1 diabetic patients without nephropathy.

AIM: To assess the prevalence of cardiac autonomic neuropathy (CAN) in Type 1 diabetic patients with and without nephropathy. METHODS: Sixty-six consecutive patients without nephropathy (n = 24), with incipient (n = 26) or overt nephropathy (n = 16) and a diabetes duration between 21 and 31 years were examined. Heart rate variability (HRV) as measure for CAN was investigated with short-term spectral analysis in the low-frequency (LF) band (0.06-0.15 Hz), reflecting sympathetic and vagal activity, and high-frequency (HF) band (0.15-0.50 Hz), reflecting vagal activity. HRV was expressed as spectral power (ms2, log-transformed). Normal, age-corresponding reference values were established in 184 controls. QTc intervals and dispersion were measured. RESULTS: After adjustment for age, there was no significant difference between healthy controls and patients without nephropathy. After further adjustment for diabetes duration, HbA1c, hypertension and treatment with beta-blockers, HRV in both frequency bands decreased with evidence of nephropathy. LF band (supine): patients without nephropathy 5.56 (4.89-6.21) (least squares means and 95% confidence interval (CI)), incipient nephropathy 5.72 (5.15-6.29) and overt nephropathy 4.11 (3.27-4.96). HF band (supine): without nephropathy 5.93 (5.26-6.60), incipient nephropathy 5.99 (5.41-6.57) and overt nephropathy 4.84 (4.00-5.68). Significant differences were found for patients without and with incipient nephropathy compared with those with overt nephropathy in the LF band and between patients with incipient nephropathy compared with those with overt nephropathy in the HF band. QTc intervals and QTc dispersion increased significantly with increasing nephropathy. CONCLUSIONS: Long-term Type 1 diabetes without nephropathy was not associated with impaired cardiac autonomic function in our study. However, in those with nephropathy, a loss of both vagal and sympathetic activity was present, and the severity of CAN correlated positively with more advanced nephropathy.     

Vascular dysfunction and autonomic neuropathy in Type 2 diabetes.

AIMS: To test the hypothesis that arterial dysfunction in Type 2 diabetes is related to autonomic neuropathy. METHODS: Arterial function and autonomic neuropathy were assessed over two consecutive days in 45 Type 2 diabetic and control subjects. Systemic arterial compliance (SAC), arterial stiffness (pulse-wave velocity, PWV) and carotid intima thickness (IMT) were assessed; these markers reflect early vascular disease and predict clinical vascular events. Autonomic neuropathy was assessed using heart rate variability with continuous ECG recording during various breathing and postural manoeuvres and an overall autonomic score was generated. Fasting metabolic parameters including glucose, insulin, HbA(1c) and lipid profile were measured. RESULTS: Autonomic neuropathy tests were all repeatable in diabetic subjects. Compared with controls, diabetic subjects had arterial dysfunction with increased PWV (P = 0.009), IMT (P < 0.001) and reduced SAC (P = 0.053). After adjustment for age, central PWV correlated with fasting insulin (r(2) = 0.45, P < 0.05) and autonomic score (r(2) = 0.44, P < 0.05), peripheral PWV correlated with autonomic score (r(2) = 0.51, P < 0.005) and IMT correlated with fasting insulin (r(2) = 0.5, P < 0.005). The presence of autonomic neuropathy correlated with fasting insulin (P = 0.015), but not age, duration diabetes, lipids or blood pressure. CONCLUSION: Using repeatable measures of autonomic neuropathy and vascular function in Type 2 diabetic subjects, we have demonstrated associations between autonomic neuropathy, vascular dysfunction and hyperinsulinaemia. This may help to explain the excess cardiovascular mortality seen in diabetic subjects with autonomic neuropathy.     

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.     

Relationship between autonomic neuropathy and thermogenesis in non diabetic and diabetic obese patients

Autonomic neuropathy is a well known complication of diabetes. Diabetes is often superimposed on obesity. A reduction in the variability of the heart rate in the resting state has been demonstrated in 16 obese diabetic subjects as well as in 34 obese non-diabetic subjects. The coefficient of variation (CV) of the heart rate during 30 minutes of resting was significantly decreased in both obese groups (3.9 +/- 0.2% for the diabetics; 5.2 +/- 0.2%, p less than 0.01 for the non diabetics) as compared to their own controls (4.5 +/- 0.6% and 6.5 +/- 0.4%, respectively). Age also contributes to decreased heart rate variability. Furthermore, this defect of autonomic function has been correlated with the blunted glucose-induced thermogenesis (GIT) seen in both obese groups (r = 0.52, p. less than 0.001): the increase in energy expenditure over basal values following a 100 g oral glucose load was only 4.8 +/- 0.8% for the diabetic obese group (p less than 0.001), and 8.5 +/- 0.7% for the non-diabetic obese group (p less than 0.001) as opposed to their own controls (12.4 +/- 1.3% and 13.3 +/- 0.6% respectively). Measurement of the variability of heart rate in obese individuals may be of predictive value in assessing blunted glucose-induced thermogenesis in non diabetic and diabetic obese patients.     

2型糖尿病患者高血压与糖尿病性神经病变的关系

目的 探讨2型糖尿病患者高血压与糖尿病性神经病变的关系。方法 利用心自主神经功能检测系统和神经电生理检测仪对107例（高血压组52例,非高血压组55例）2型糖尿病患者的心自主神经功能和肢体的末梢神经传导速度、皮肤痛温觉、振动沉进行测定,以判断心自主神经病变和末梢神经病变。结果 两组间末梢神经功能和心自主神经功能各指标除心的是距频谱分析的高频值外差异均无显著性（P＜0.05）。Logistic回归分析显示高血压与心自主神经病变显著相关（P＜0.01）,而与末梢神经病变无显著相关。结论 2型糖尿病患者高血压是心自主神经病变发病的危险因素,而与末梢神经病变无明显关系。     

血清胆红素与糖尿病周围神经病变相关性研究

目的探讨血清胆红素与糖尿病周围神经病变（DPN）的关系。方法收集110例2型糖尿病（T2DM）并发周围神经病变患者（DPN组）、220例单纯T2DM患者（DM组）和健康体检者278名（Con组）的血清胆红素等临床资料,并进行Logistic回归分析,筛选DPN的危险因素。对间接胆红素（IBIL）进行进一步的分析。结果（1）低血清INL、病程长、LDLC升高是DPN的危险因素。（2）协方差分析表明,控制尿白蛋白（UA1b）等因素后,DPN组的INL水平[（9．7±0．6）μmol／L]仍然明显低于DM组[（12．0±0．6）μmol／L]和Con组[（11．4±0．3）μmol／L]。结论低血清IBIL与DPN密切相关,是DPN发病相关因素之一。     

Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus.

AIMS: Recent studies have indicated that proinsulin C-peptide shows specific binding to cell membrane binding sites and may exert biological effects when administered to patients with Type 1 diabetes mellitus. This study was undertaken to determine if combined treatment with C-peptide and insulin might reduce the level of microalbuminuria in patients with Type 1 diabetes and incipient nephropathy. METHODS: Twenty-one normotensive patients with microalbuminuria were studied for 6 months in a double-blind, randomized, cross-over design. The patients received s.c. injections of either human C-peptide (600 nmol/24 h) or placebo plus their regular insulin regimen for 3 months. RESULTS: Glycaemic control improved slightly during the study and to a similar extent in both treatment groups. Blood pressure was unaltered throughout the study. During the C-peptide treatment period, urinary albumin excretion decreased progressively on average from 58 microg/min (basal) to 34 microg/min (3 months, P < 0.01) and it tended to increase, but not significantly so, during the placebo period. The difference between the two treatment periods was statistically significant (P < 0.01). In the 12 patients with signs of autonomic neuropathy prior to the study, respiratory heart rate variability increased by 21 +/- 9% (P < 0.05) during treatment with C-peptide but was unaltered during placebo. Thermal thresholds were significantly improved during C-peptide treatment in comparison to placebo (n = 6, P < 0.05). CONCLUSION: These results indicate that combined treatment with C-peptide and insulin for 3 months may improve renal function by diminishing urinary albumin excretion and ameliorate autonomic and sensory nerve dysfunction in patients with Type 1 diabetes mellitus.     

2型糖尿病视网膜病变与血清抵抗素水平的关系

目的 探讨血清抵抗素水平与2型糖尿病(T2DM)视网膜病变(DR)的关系. 方法 将T2DM患者分为3组:单纯T2DM未合并DR组(DM组)95例、单纯型DR组(SDR组)62例和增殖型DR组(PDR组)30例.ELISA法检测187例T2DM患者血清抵抗素水平. 结果 PDR组和SDR组血清抵抗素水平显著高于DM组(P<0.01或P<0.05);而且经校正性别、年龄和BMI后,PDR组抵抗素水平仍显著高于DM组(P<0.05).Spearman相关性分析结果显示,DR患者血清抵抗素与BMI、SBP、空腹胰岛素和HOMA-IR呈显著性相关(P<0.05).Logistic回归分析结果显示,血清抵抗素水平与PDR显著相关(OR=1.164,P<0.05). 结论 血清抵抗素水平与DR相关,抵抗素可能参与DR尤其是PDR的发生与发展.