Evaluation of a new indicator test for sudomotor function (Neuropad) in the diagnosis of peripheral neuropathy in type 2 diabetic patients.

Sudomotor neuropathy is associated with reduction of plantar sweating and contributes to the pathogenesis of diabetic foot ulcers. The aim of the present study was to evaluate the new indicator test for sudomotor function (Neuropad) in the diagnosis of peripheral neuropathy among type 2 diabetic patients. This study included 104 type 2 diabetic patients (51 men) with a mean age of 64.2+/-5.6 years and a mean diabetes duration of 12.8+/-3.7 years. Peripheral neuropathy was diagnosed by means of the Diabetic Neuropathy Index (DNI). Sudomotor neuropathy was assessed by means of colour change in the indicator test. Peripheral neuropathy was diagnosed in 71 patients (68.3 %). Sudomotor neuropathy was diagnosed in 67 patients (94.4 %) with peripheral neuropathy and in 10 patients (30.3 %) without peripheral neuropathy (p=0.0001). Compared with DNI, sensitivity of the indicator test for diagnosing peripheral neuropathy was 94.4 % and specificity was 69.7 %. Overall prevalence of neuropathy was higher using the indicator test (77 patients, 74.0 %) than using the DNI (71 patients, 68.3 %). Time until complete colour change of the indicator test was 23.8+/-6.7 min in patients with peripheral neuropathy and 7.7+/-1.2 min in patients without peripheral neuropathy (p=0.001). Among patients with peripheral neuropathy, time until complete colour change of the indicator test was 14.2+/-1.9 min in those with a DNI value between 2.5 and 4.5, while it was 32.8+/-2.6 min in those with a DNI value between 5 and 8 (p=0.003). CONCLUSIONS: Use of the new indicator test has a very high sensitivity in detection of diabetic peripheral neuropathy. Sudomotor dysfunction can be demonstrated in a considerable part of patients with normal clinical examination. Time until complete colour change of the indicator test is associated with severity of peripheral neuropathy.     

Platelet alpha 2 adrenergic receptors, plasma catecholamines and orthostatic hypotension in insulin-dependent diabetic patients

Plasma catecholamine levels, total platelet alpha 2-adrenoceptor number and affinity state (using [3H]-yohimbine binding) have been investigated in insulin-dependent diabetic patients with (n = 12) or without (n = 10) orthostatic hypotension as well as in normal control subjects (n = 6). Mean resting basal catecholamine values were similar in the three groups. One min standing elicited an increase in norepinephrine plasma level (but not in epinephrine plasma levels) in control group but not in diabetic patients (with or without orthostatic hypotension). The maximal number of platelet alpha 2-adrenoceptors (and Kd) calculated by [3H]-yohimbine saturation experiments was similar in the three groups. The percentage of platelet alpha 2-adrenoceptors in high affinity state determined by inhibition experiments of [3H]-yohimbine binding by UK14,304 (a specific alpha 2-adrenergic full agonist) was significantly lower in diabetic patients with orthostatic hypotension (29.2 +/- 5.3%) than in the other two groups. No significant difference was found between the control group (60.0 +/- 2.0%) and diabetic patients without orthostatic hypotension (64.3 +/- 3.1%). These results indicate that orthostatic hypotension in insulin-dependent diabetic patients is marked by a lack of noradrenaline increase in standing position and by a decrease in platelet alpha 2-adrenoceptors in high affinity state. Thus we suggest that orthostatic hypotension of diabetes mellitus is the result of sympathetic nerves injuries and of abnormalities in alpha 2-adrenoceptors coupling.     

Decreased high affinity state in platelet alpha 2-adrenoceptors from diabetic patients with orthostatic hypotension

Plasma catecholamine levels, total platelet alpha 2-adrenoceptor number and affinity state (using [3H]yohimbine binding) were investigated in insulin-dependent diabetic patients with (n = 12) or without (n = 10) orthostatic hypotension due to autonomic neuropathy as well as in normal control subjects (n = 6). Mean resting basal catecholamine values were similar in the three groups. One-minute standing elicited an increase in norepinephrine plasma level (but not in epinephrine plasma levels) in control group but not in diabetic patients (with or without orthostatic hypotension). The maximal number of platelet alpha 2-adrenoceptors (and KD) calculated by [3H]yohimbine saturation experiments was similar in the three groups. The percentage of platelet alpha 2-adrenoceptors in high affinity state (inhibition experiments of [3H]yohimbine by UK14,304, a specific alpha 2-adrenergic full agonist) was significantly lower in diabetic patients with orthostatic hypotension (29.2 +/- 5.3%) than in the other two groups. No significant difference was found between the control group (60.0 +/- 2.0%) and diabetic patients without orthostatic hypotension (64.3 +/- 3.1%). Since platelet alpha 2-adrenoceptors are thought to be a suitable index of vascular alpha-adrenoceptors, the decrease in platelet alpha 2-adrenoceptors in high affinity state could explain the occurrence of orthostatic hypotension in insulin-dependent diabetic patients. Multiple pathophysiological mechanisms underly orthostatic hypotension in insulin-dependent diabetic patients and include anomalies both in the sympathetic nervous system and in alpha 2-adrenoceptor coupling.     

Increase in reflex vasoconstriction with indomethacin in patients with orthostatic hypotension and central nervous system involvement

Since indomethacin may be effective in the treatment of orthostatic hypotension, the ability of this drug to increase reflex vasoconstriction was studied in six patients with orthostatic hypotension and in five normal subjects. Reflex forearm vasoconstriction during lower body negative pressure at 20-40 mm Hg was measured before and after indomethacin 50 mg by mouth. In patients with orthostatic hypotension and central nervous system involvement indomethacin increased recumbent blood pressure, resting forearm vascular resistance, and reflex forearm vasoconstriction during lower body negative pressure. The fall in blood pressure with lower body negative pressure was not significantly inhibited by indomethacin, but mean blood pressure during lower body negative pressure was higher after than before indomethacin. Indomethacin did not alter these responses in normal subjects. The increase in reflex vasoconstriction with indomethacin may contribute to its therapeutic effects in the treatment of orthostatic hypotension.     

Reproducibility of the new indicator test for sudomotor function (Neuropad) in patients with type 2 diabetes mellitus: short communication.

The aim of this study was to examine the reproducibility of the new indicator test for sudomotor function (Neuropad) in type 2 diabetic patients. The study included 142 type 2 diabetic patients (70 men) with a mean age of 67.3 +/- 7.6 years and a mean diabetes duration of 14.2 +/- 6.3 years. Sudomotor function was assessed by means of colour change in the indicator test. Each patient was examined twice. Moreover, inter-observer variability was assessed in 60 patients (35 patients with sudomotor dysfunction, 25 patients without sudomotor dysfunction). In the right foot, a highly significant (r = 0.91, p = 0.001) correlation was observed between time until complete colour change of the test on the first (910.7 +/- 431.6 seconds) and second examination (935.8 +/- 440.1 seconds). In the left foot, a highly significant (r = 0.89, p = 0.001) correlation was observed between time until complete colour change of the test on the first (911.6 +/- 430.3 seconds) and second examination (940.5 +/- 441.2 seconds). Reproducibility was excellent both in patients with sudomotor dysfunction (p = 0.001) and in those without sudomotor dysfunction (p = 0.001). Agreement in diagnosis of sudomotor dysfunction between the two examinations was 98 %. Inter-observer reproducibility was excellent (p = 0.001), both in patients with sudomotor dysfunction and in those without sudomotor dysfunction. Intra- and interobserver Coefficient of Variance ranged between 4.1 % and 5.1 %. CONCLUSIONS: These results indicate that reproducibility of the new indicator test for sudomotor function is excellent in type 2 diabetic patients with or without sudomotor impairment.     

Impairment of cerebral autoregulation in diabetic patients with cardiovascular autonomic neuropathy and orthostatic hypotension.

AIMS: Impaired cerebrovascular reactivity and autoregulation has been previously reported in patients with diabetes mellitus. However, the contribution of cardiovascular diabetic autonomic neuropathy and orthostatic hypotension to the pathogenesis of such disturbances is not known. The purpose of this study was to evaluate cerebral blood flow velocity in response to standing in patients with diabetes and cardiovascular autonomic neuropathy with or without orthostatic hypotension. METHODS: We studied 27 patients with diabetes--eight had cardiovascular autonomic neuropathy and orthostatic hypotension (age 46.4 +/- 13.5 years, diabetes duration 25.0 +/- 11.0 years), seven had autonomic neuropathy without hypotension (age 47.3 +/- 12.7 years, diabetes duration 26.4 +/- 12.1 years), and 12 had no evidence of autonomic neuropathy (age 44.1 +/- 13.8 years, diabetes duration 17.1 +/- 10.2 years)-and 12 control subjects (age 42.6 +/- 9.7 years). Flow velocity was recorded in the right middle cerebral artery using transcranial Doppler sonography in the supine position and after active standing. RESULTS: Cerebral flow velocity in the supine position was not different between the groups studied. Active standing resulted in a significant drop of mean and diastolic flow velocities in autonomic neuropathy patients with orthostatic hypotension, while there were no such changes in the other groups. The relative changes in mean flow velocity 1 min after standing up were -22.7 +/- 16.25% in patients with neuropathy and orthostatic hypotension, +0.02 +/- 9.8% in those with neuropathy without hypotension, -2.8 +/- 14.05% in patients without neuropathy, and -9.2 +/- 15.1% in controls. CONCLUSIONS: Patients with diabetes and cardiovascular autonomic neuropathy with orthostatic hypotension show instability in cerebral blood flow upon active standing, which suggests impaired cerebral autoregulation.     

胰高血糖素刺激试验在2型糖尿病患者中的应用价值

目的　进一步研究胰高血糖素刺激试验在 2型糖尿病 (DM 2 )患者中的应用价值。方法　应用放射免疫法分别测定正常对照组和年龄组、病程组、BMI组的三对亚组空腹C肽、胰高血糖素刺激后 6minC肽水平。结果　≤ 50岁组的 6minC肽明显低于正常对照组 (P <0 0 5) ;年龄组 :≤ 50岁和 >50岁两个亚组的空腹血浆C肽、6minC肽以及C肽增加率的差异无显著意义 (P >0 0 5) ;病程组 :>10年组的 6minC肽显著小于≤ 10年组 (P <0 0 1) ,两个亚组的空腹C肽、C肽增加率差异无显著意义 (P >0 0 5) ;BMI组 :≥ 2 5kg/m2 组的空腹C肽、刺激后 6minC肽均显著大于 <2 5kg/m2 组 (P均 <0 0 5) ,C肽增加率差异无显著性 (P >0 0 5)。结论　胰高血糖素刺激后C肽的变化对于鉴别DM2患者胰岛B细胞功能的差异性具有重要的临床应用价值     

Decreased alpha 2-adrenergic receptors on platelet membranes from diabetic patients with autonomic neuropathy and orthostatic hypotension

Platelet adrenergic receptors were studied in normal subjects and diabetic patients with autonomic neuropathy to determine the relationship between adrenoreceptor status and orthostatic hypotension. The binding of [3H]clonidine and [3H]yohimbine to platelet membranes was measured in diabetic patients with autonomic neuropathy and orthostatic hypotension (n = 12) and without orthostatic hypotension (n = 11), diabetic patients without autonomic neuropathy (n = 12), and normal subjects (n = 9). Mean basal and standing plasma norepinephrine levels were not different in the four groups, and there was no relationship between orthostasis and norepinephrine responses. The diabetic patients with orthostatic hypotension had a significantly greater fall in mean blood pressure [31 +/- 2.8 (+/- SE) mm Hg] than any of the other three groups. Diabetic patients with diabetic autonomic neuropathy and orthostatic hypotension had a 30-40% decrease in number of platelet alpha 2-adrenergic receptors, as demonstrated by [3H]clonidine and [3H]yohimbine binding. The maximum number of binding sites for clonidine was 34 +/- 2.8 (+/- SE) fmol/mg protein in normal subjects, 27.4 +/- 3.4 in diabetic patients with neuropathy, 26 +/- 2.5 in diabetic patients with autonomic neuropathy without orthostatic hypotension, and 20.4 +/- 3.8 fmol/mg protein in diabetic patients with autonomic neuropathy with orthostatic hypotension (P less than 0.001). The maximum number of binding sites for yohimbine was 112 +/- 12.6 in normal subjects, 127 +/- 10 in diabetic patients without orthostatic hypotension, and 87 +/- 12.4 fmol/mg protein in patients with diabetic autonomic neuropathy with orthostatic hypotension (P less than 0.001). Reduced platelet alpha 2-receptors are associated with postural hypotension in diabetic autonomic neuropathy. If applicable to the postjunctional alpha 2-adrenergic receptor on sympathetic neurons, reduced vascular responses to changes in posture would be expected despite normal or enhanced norepinephrine secretion.     

Increase in reflex vasoconstriction with indomethacin in patients with orthostatic hypotension and central nervous system involvement.

Since indomethacin may be effective in the treatment of orthostatic hypotension, the ability of this drug to increase reflex vasoconstriction was studied in six patients with orthostatic hypotension and in five normal subjects. Reflex forearm vasoconstriction during lower body negative pressure at 20-40 mm Hg was measured before and after indomethacin 50 mg by mouth. In patients with orthostatic hypotension and central nervous system involvement indomethacin increased recumbent blood pressure, resting forearm vascular resistance, and reflex forearm vasoconstriction during lower body negative pressure. The fall in blood pressure with lower body negative pressure was not significantly inhibited by indomethacin, but mean blood pressure during lower body negative pressure was higher after than before indomethacin. Indomethacin did not alter these responses in normal subjects. The increase in reflex vasoconstriction with indomethacin may contribute to its therapeutic effects in the treatment of orthostatic hypotension.     

对伴微量白蛋白尿2型糖尿病患者动脉粥样硬化的早期干预

160例2型糖尿病患者分为微量白蛋白尿组(MAU组)42例和正常白蛋白尿组(NAU组)118例.多元逐步回归提示微量白蛋白尿与臂踝脉搏波传播速度(baPWV)和颈动脉内中膜厚度(IMT)独立相关(均P＜0.01).西洛他唑干预后,MAU组baPWV显著下降(P＜0.01).     

Ⅱ型糖尿病患者的定量超声骨密度含量的研究

对１０５例Ⅱ型糖尿病患者的定量超声骨量（ＱＵＳ）进行了研究。结果表明，Ⅱ型糖尿病患者的超声导速度（ＳＯＳ）及其标准差（ｓ）均显著低于健康对照组，且Ⅱ型糖尿病患者的ＳＯＳ峰值比正常组ＳＯＳ峰值推迟一个年龄组，表明Ⅱ型糖尿病患者伴有不同程度骨钙、磷代谢异常，最终导致骨质疏松症。本结果还显示，女性患者显著低于男性患者ＳＯＳ，ｓ，表明女性Ⅱ型糖尿病患者更易受多种因素的影响，导致骨矿含量明显降低。因此，对Ⅱ     

The responses of norepinephrine, renin and aldosterone to standing in diabetic patients with orthostatic hypotension

Autonomic neuropathy is one of the complications of diabetes, and several lines of evidence, supporting that sympathetic neural dysfunction may play the major role in the orthostatic hypotension (OH) of diabetic patients have been presented. In this paper the responses of plasma norepinephrine (PNE), plasma renin activity (PRA) and plasma aldosterone (PAC) to upright standing were studied in 17 diabetic patients without OH, 25 diabetics with OH and 17 age-matched, non-diabetic normotensives (controls). All were kept on a 200mEq sodium diet. Assay procedure for PNE was high-performance liquid chromatography with trihydroxyindol method and fluorimetric detection using dihydroxybenzylamine as internal standard. Intra- and inter-assay coefficient variations by this method were 3.4 and 5.8% respectively. PRA and PAC were determined by radioimmunoassay. Total blood volume was examined by the plasma tracer method using 131I-HSA and expressed in percent normal. Mean PNE level in the non-diabetic controls was 217 pg/ml in recumbency and increased to a level of 551 at 15 minutes on standing. The PNE responses to standing in the diabetic subjects without OH (defined as group I) were not significantly different from those in the controls. In the diabetics with OH, 14 cases, with the PNE increments less than 1SD below the mean in the controls, were defined as group III, and discriminated from other 11 subjects with OH (group II). PNE levels in group III were significantly lower than in the controls at both recumbency and upright posture. PRA was significantly elevated by standing in the controls and the diabetics except for group II. PRA in all the diabetic groups was significantly lower than in the controls, at both recumbent and upright. The mean values of PAC in the diabetics but group II at supine were significantly lower than those of the control group. PAC levels increased after standing contemporaneously with PRA, though significant rise in group II was shown without PRA response. Total blood volume was significantly (p less than 0.025) decreased in only group II. The results suggest: 1) PNE was normal in the diabetic patients without OH, 2) there are at least two types of OH in diabetes mellitus: one is hypoadrenergic and the other hypovolemic, 3) adrenergic neuropathy may be a cause of low PRA in diabetics with OH but another factor may also be involved in both with and without OH, 4) low PRA is a main factor of low PAC in diabetics (group I and III), but the dissociation between PRA and PAC responses to orthostasis is present in some cases (group II), which reflects disturbances in other regulatory mechanisms of aldosterone secretion.     

实时定量PCR法分析2型糖尿病患者肠道乳酸杆菌菌种数量的改变

目的:明确2型糖尿病患者与正常对照人群比较是否存在总乳酸杆菌及其具体菌种嗜酸乳杆菌、保加利亚乳杆菌、干酪乳杆菌、植物乳杆菌、鼠李糖乳杆菌数目的差异,以及探索乳酸杆菌与血糖、血脂等代谢指标是否相关.方法:选取2型糖尿病患者50人、正常对照者30人作为研究对象,两组性别、年龄、BMI相匹配.检测糖尿病患者空腹血糖、餐后2h血糖、血脂、C反应蛋白等指标,并收集糖尿病患者及对照者粪便提取细菌总DNA,通过实时荧光定量PCR方法测定目标细菌的拷贝数.结果:2型糖尿病组肠道乳酸杆菌(P<0.001)及嗜酸乳杆菌(P<0.001)、保加利亚乳杆菌(P<0.001)、干酪乳杆菌(P=0.008)、鼠李糖乳杆菌(P<0.001)显著高于对照组,且乳酸杆菌与低密度脂蛋白胆固醇显著负相关(P=0.04).结论:2型糖尿病患者肠道总乳酸杆菌及其某些具体菌种数量增多,乳酸杆菌数量的改变对血脂也存在影响.通过饮食调节肠道乳酸杆菌含量可能有助于改善糖尿病、高脂血症等代谢性疾病.     

The change points of HbA(1C) for detection of retinopathy in Chinese type 2 diabetic patients

Aims

To investigate the change points of HbA_1C for detection of retinopathy in Chinese type 2 diabetic patients.

Methods

This cross-sectional investigation included 992 diagnosed type 2 diabetic patients, who received non-mydriatic digital fundus photography examination. Joinpoint regression software was adopted to identify the change points of HbA_1C in association with retinopathy prevalence.

Results

The mean age of all patients was 59.1 ± 8.4 years and the duration of diabetes was 5.5 (95% CI: 5.2-5.9) years. The prevalence of retinopathy was 10.3% in total, and 4.1%, 7.4% and 19.6% in patients with different diabetes duration of ≤5 years, 5-10 years and >10 years, respectively. The change point of HbA_1C was 6.5% (95%CI 5.8-7.5%), at which retinopathy prevalence began to rise sharply. Furthermore, in subjects with diabetes duration ≤5 years, 5-10 years and >10 years, the change points of HbA_1C were 8.1% (95%CI 7.9-8.3%), 6.1% (95%CI 5.7-6.8%), 5.6% (95%CI 5.1-8.1%) for detection of retinopathy, respectively.

Conclusion

The steepest increase in retinopathy prevalence occurred when HbA_1C reached 6.5%. However, the duration of diabetes should be taken into concern, when using the change points of HbA_1C for detection of retinopathy in diabetic patients.