Plasma catecholamines and renin in diabetes mellitus

Summary Plasma and urinary norepinephrine (PNE, UNE) and epinephrine, plasma renin activity (PRA) and their interrelations with posture, age, the body sodium-volume state and blood pressure were analyzed in 90 normal and 100 non-azotemic diabetic subjects. Ages ranged from 18 to 76 yrs, urinary sodium from 51 to 249 mEq/24h. Fortysix patients had a normal supine blood pressure, 54 had hypertension. Diabetics had an increased (p<0.01) mean exchangeable sodium, while blood volume was normal. Upright posture caused a comparable increase in PNE in normal and diabetic subjects; but the response of PRA was blunted (p<0.001) in diabetics, with subnormal responsiveness in 32% of cases. Epinephrine levels in diabetics were normal and unchanged with posture or age. In both groups supine and upright PNE and PRA correlated (p<0.05) positively with age, but not with urinary sodium. Comparison with dynamic normal ranges relative to age revealed low upright PNE in 14% and low or high PRA in 12 and 6% of diabetics, respectively. The low-norepinephrine subgroup had a higher exchangeable sodium and lower PRA than the normal-norepinephrine patients (p<0.025). Low-renin patients had a higher exchangeable sodium and lower UNE than normal or high-renin patients. Orthostatic decrease in blood pressure was noted in low or normal-renin, but not in high-renin patients. These findings suggest that patients with non-azotemic diabetes mellitus have usually a normal adrenergic response to postural changes; and physiological variations of PNE and PRA with age are largely maintained. However, diminished renin-responsiveness is common. Distinct sodium retention could contribute to norepinephrine or renin suppression in some patients and possibly also to the frequent development of hypertension in diabetes mellitus.This work was supported by the Swiss National Science Foundation     

Effects of exercise training on plasma catecholamines and blood pressure in labile hypertensive subjects

Summary Plasma catecholamine concentrations (norepinephrine, NE; epinephrine, E) were measured along with heart rate (HR) and blood pressure (BP) at rest in supine (20 min) and standing (10 min) positions and in response to cycle ergometer exercise (5 min; 60% estimated maximal aerobic power) in 12 hypertensive patients before and after 20 weeks of aerobic training on cycle ergometer (six males, one female) or by jogging (five males). In a control group of labile hypertensive patients (five males, two females), estimated maximal aerobic power as well as HR and BP at rest in the supine and standing positions and in response to exercise were not modified from the first to the second evaluation (43±4 vs 43±5 ml·kg^–1·min^–1). In comparison estimated maximal aerobic power significantly increased in both training groups (cycle: 38±4 to 43±4; jogging: 38±3 to 46±4 ml·kg^–1·min^–1). However HR and BP were not modified following training, except for small reductions in systolic (18.9 to 18 kPa: 142 to 135 mmHg) and diastolic pressures (13.3 to 12 kPa: 100 to 90 mmHg) (p<0.05) at standing rest in the cycle group. Changes in plasma E and NE concentrations at rest and in response to exercise were small and not consistent: plasma NE was lower at standing rest following cycle training, (559±95 vs 462±108 pg·ml^–1) but a similar reduction was observed in the control group (428±45 vs 321±28 pg·ml^–1); plasma E was lower at rest following cycle training (29±7 vs 12±8 pg·ml^–1), but was higher in response to exercise (137±24 vs 419±113 pg·ml^–1). These results are in accordance with previous reports which do not clearly demonstrate that physical training in hypertensive patients lowers BP and the activity or reactivity of the sympathetic system.     

Total plasma clearance of infused norepinephrine in non-azotemic diabetes mellitus

Summary The total plasma clearance of norepinephrine (NE) was assessed during steady state NE infusion at two different dose rates in 27 patients with non-azotemic diabetes mellitus as compared with 27 normal subjects. Lower NE dose rates were required in diabetics than in normal subjects (P<0.001) to induce similar increases in blood pressure. However, plasma NE levels during NE infusion correlated closely (r=0.79 and 0.78;P<0.001) with concomitant dose rates, and this relationship was similar in both study groups. Moreover, the plasma NE clearance did not differ between low and high dose rates of NE infusion, and was similar in diabetics and normal subjects (6.0±3.1 and 5.1±2.6 liter/min, respectively). It correlated inversely with the pre-infusion plasma NE (r=–0.38 and –0.53;P<0.05); this relationship was also similar in the two groups. The correlation relating plasma NE to NE infusion rates as well as the plasma NE clearance did not differ between the 13 diabetics without and the 14 with signs of peripheral neuropathy or between the 17 patients with normal and the 10 patients with high blood pressure. These findings suggest that the kinetics of circulating NE are usually unaltered in non-azotemic diabetes mellitus. An increased pressor responsiveness to NE, in the presence of normal plasma NE concentrations and clearance rates, may be a setting predisposing for the development of hypertension in diabetic patients.Supported by the Swiss National Science Foundation     

血压正常的2型糖尿病患者24h动态血压与血清胱抑素C相关性研究

目的:探讨血压正常的2型糖尿病(T2DM)患者24 h动态血压与血清胱抑素C(Cys C)的相关性。方法:入选符合纳入标准的T2DM患者82例,据血清Cys C水平将患者分为对照组(Cys C<1.25 mg/L,共42例)和高Cys C组(Cys C≥1.25 mg/L,共40例),所有患者均进行24 h动态血压监测(ABPM)。结果:高Cys C组患者在24 h收缩压(24hSBP)、白天收缩压(dSBP)、夜间收缩压(nSBP)、24 h平均脉压(24hmPP)、白天平均脉压(dmPP)、夜间平均脉压(nmPP)、夜间收缩压最低均值、起床前2 h收缩压均值及起床后2 h收缩压均值与对照组比较,差异均有统计学意义(P<0.05);而在24hDBP、dDBP、nDBP、夜间舒张压最低均值、起床前2 h舒张压均值及起床后2 h舒张压均值与对照组比较,差异均无统计学意义(P>0.05)。对Cys C作Pearson相关分析显示,Cys C与24hSBP、dSBP、nSBP、24hmPP、dmPP、nmPP、夜间收缩压最低均值、起床前2 h收缩压均值及起床后2 h收缩压均值呈正相关(P<0.05),但与24hDBP、dDBP、nDBP、夜间舒张压最低均值、起床前2 h舒张压均值及起床后2 h舒张压均值无相关(P>0.05)。结论:血压正常的T2DM患者中,其收缩压及平均脉压可能与DN有一定相关性。     

血糖波动与糖尿病大血管病变的相关研究

目的:探讨血糖波动与糖尿病动脉粥样硬化(AS)大血管病变的关系。方法:对3组不同糖耐量者进行连续3d的动态血糖监测,分析平均血糖水平(MBG)、日内平均血糖波动幅度(MAGE)以及日间血糖平均绝对差(MODD);并用B型超声观察双侧颈动脉内膜中层厚度(IMT)、内膜连续性及AS积分等指标。结果:(1)与糖耐量正常(NGT)组比较,糖耐量受损(IGT)组和新诊断2型糖尿病(T2DM)组高血压、冠心病、中风的发生率逐渐增高,且后2组间有显著差异。(2)从NGT组到IGT组再到T2DM组,IMT、AS积分等动脉粥样硬化指标逐渐增加,差异显著。(3)动态血糖监测结果显示:IGT组和T2DM组血糖波动幅度比NGT组明显增大,以T2DM组最明显。(4)多元分析发现平均IMT和AS积分与MAGE正相关。结论:波动性高血糖与AS密切相关,血糖波动幅度大的患者发生糖尿病大血管并发症的危险性高。血糖稳态受损可能是糖尿病大血管并发症的危险因素之一。     

Changes in blood pressure,heart rate and blood constituents during heat exposure in men with elevated blood pressure

Summary Although the vascular volume response of hypertensive men during exercise has been rather well characterized, the effect of resting heat exposure in this patient population has not been examined. This was done in the present report in seven men with high blood pressure (BP) (i. e., diastolic pressure>12 kPa (90 mmHg) upon initial interview) and 5 normotensive control subjects. 50 min after each subject had consumed an amount of water equal to 1% of his body weight, he reclined on a cot. 10 min later the subject was carried into an environmental chamber equilibrated at Tdb=45 C, Twb=28 C. Free-flowing venous blood samples were obtained from a cubital vein, and BP and heart rate were measured, before the heat exposure and at 15 min intervals during the experiment. Within 30 min systolic, diastolic and mean BP of the high BP subjects had decreased to normal levels; no BP changes were detected in normotensive subjects. Accompanying this depressor response was an exaggerated elevation in plasma glucose concentration. No alterations were found with haematocrit, plasma osmolality or electrolytes, or total protein and albumin. The data suggest that heat exposure may have been more stressful for the subjects with high BP than for their controls. This finding implies that phasic depressor responses may be as important as phasic pressor episodes in the aetiology of established essential hypertension.Training Grant HL07050 from the National Institutes of Health supported this project     

Increased protein glycation in diabetes mellitus is associated with decreased aspirin-mediated protein acetylation and reduced sensitivity of blood platelets to aspirin

Reduced effectiveness of the most common antiplatelet drug, acetylsalicylic acid (ASA, aspirin), in diabetes mellitus has been associated with a lowered platelet sensitivity to ASA and related to glycemic control in diabetic patients. Our objectives were (a) to monitor the chemical background of how chronic hyperglycemia affects platelet response to ASA in diabetes and (b) to study a chemical competition between the amount of bound acetyl residues and the extent of protein glycation in blood platelets. Using whole-blood impedance aggregometry and platelet function analyzer (PFA-100) we observed a reduced platelet response to ASA in diabetic patients (14% vs. 79% for PFA-100 collagen-epinephrine occlusion time) and an association between the index of glycemic control and platelet refractoriness to ASA (r_S=–0.378). Impaired platelet response to ASA was related to enhanced platelet protein glycation (3.6±0.4 in diabetes vs. 2.3±0.4 µmol fructosamine/µg protein in control) and reduced incorporation of acetyl residue into proteins of platelets from diabetic patients (47.4±2.0 in control vs. 33.1±0.7 µmol acetyl/µg protein in diabetic subjects). Incubation of blood platelets with increasing concentrations of glucose and ASA under in vitro conditions led to excessive modification in protein amino groups: glucose and ASA competed with each other in the course of nonenzymatic modifications, glycosylation, or acetylation, and their contributions to the occupancy of protein amino groups (R²=0.22 for glucose, R²=0.43 for ASA) were dependent upon the concentrations of glucose and ASA. Overall the effects of high glucose and high ASA on the overall occupancy of protein free amino groups are not additive. While at higher concentrations ASA overcomes the effects of hyperglycemia and retards glycation, high glucose makes acetylation less efficient, and therefore the resultant chemical modification becomes greatly reduced. In conclusion, diminished susceptibility of various platelet proteins and receptors on blood platelet membranes to acetylation and high ambient glucose might underlie the apparently differentiated sensitivity of blood platelets to ASA and determine platelet insensitivity to aspirin in diabetic patients     

长链非编码RNA与糖尿病关系的研究进展*

Long non-coding RNAs (lncRNAs) are a group of RNAs, which are longer than 200 nucleotides without containing functional open reading frame and cannot encode protein. The study of lncRNA will help to understand the multi-level expression regulatory network of the body, and is expected to provide the basis of prediction, diagnosis and treatment of complex diseases. Although the functions and mechanism of lncRNA remain unclear, some studies indicate that lncRNA is involved in the development of diabetes mellitus, and those lncRNAs may be new diagnostic markers and therapeutic targets.     

Role of heating in non-invasive blood pressure measurements in rats

The “tail-cuff technique for indirect blood pressure measurements was standardized, with respect to heating, in experiments on 47 adult Sprague-Dawley rats. The direct, intra-arterial, and the indirect blood pressures were simultaneously obtained. Pulse volume was recorded from the tail by a non-invasive technique, and was controlled by gradual application of heat. It was found that pulse volume and body temperature were poorly related. A stable relation existed, however, between the error in the indirect blood pressure recordings and the pulse volume. The error was minimized, provided that the heating was adjusted to induce a pulse volume of at least 25% of the maximum obtainable value. It was suggested that the validity of the indirect blood pressure recording could be improved, if heat application was regulated on the basis of observations of pulse volume in the tail instead of ambient temperature or body temperature. Errors due to excessive vasoconstriction, or discomfort due to overheating could thereby be minimized.     

糖尿病患者个性EPQ评定

目的 探讨糖尿病患者个性特征。方法 以艾森克个性问卷为工具，对７２例患者和７例正常健康志愿进行对照研究。结果 糖尿病患者Ｎ量表和Ｐ量表分显著高于对照组，性格呈不稳定型也显著多于对照组。结论 糖尿病患者具有性格不稳定和精神质的个性特征。     

山医群体中国地鼠自发的遗传性糖尿病模型

经过五年的工作,我们在一般实验室条件下,对野生地鼠进行驯养和近亲交配,繁育成目前国内较大的中国地鼠山医群体,并建成自发的遗传性糖尿病模型。模型的特点是:动物为非肥胖型,血糖呈中、轻度增高,血清胰岛素浓度表现多样,胰岛病变程度不一,糖尿病发病率受饮食因素影响,且具有多基因遗传特点。相似于人类非胰岛素依赖型糖尿病(NIDDM)。     

糖尿病对精液质量的影响及其机制

糖尿病是由多种病因引起的代谢性疾病,不仅影响男性性功能而且影响男性精液质量。本文综述了糖尿病对男性精液的影响如精子活动力、精子密度、精子DNA损伤等及其发生机制。     

A new model of individual differences in hemodynamic profile and blood pressure reactivity

A quantitative, theory-driven model of hemodynamics was developed, relating reactivity in blood pressure to orthogonal dimensions of "hemodynamic profile" and "compensation deficit," which were derived from the (multiplicative) interaction of cardiac output and total peripheral resistance. A Finapres 2300e was used to estimate blood pressure, cardiac output, and total peripheral resistance in 100 healthy men and women during mental arithmetic and cold pressor tasks on two occasions. Results were consistent with model predictions. As predicted, cardiac output and peripheral resistance reactions were curvilinearly related, and blood pressure reactivity was strongly related to compensation deficit (r = .76-.89). Conversely, the orthogonally defined hemodynamic profile remained independent of blood pressure reactivity (r = .11 or less). The data show that the present model overcomes several difficulties and inconsistencies in previous attempts to obtain an independent measure of hemodynamic profile. The new model could help to elucidate sources of cardiovascular pathogenesis not suggested from the study of blood pressure reactivity alone.     

Plasma adiponectin and insulin resistance in Korean type 2 diabetes mellitus

Insulin resistance, which implies impairment of insulin signaling in the target tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important role in insulin resistance through the dysregulated production and secretion of adipose-derived proteins, including tumor necrosis factor-alpha, plasminogen activator inhibitor-1, leptin, resistin, angiotensinogen, and adiponectin. Adiponectin was estimated to be a protective adipocytokine against atherosclerosis, and also to have an anti-inflammatory effect. In this study, the relationship between fasting plasma adiponectin concentration and adiposity, body composition, insulin sensitivity (ITT, HOMAIR, QUICK), lipid profile, fasting insulin concentration were examined in Korean type 2 diabetes. The difference in the adiponectin concentrations was also examined in diabetic and non-diabetic subjects, with adjustment for gender, age and body mass index. 102 type 2 diabetics and 50 controls were examined. After a 12-h overnight fast, all subjects underwent a 75 gram oral glucose tolerance test. Baseline blood samples were drawn for the determinations of fasting plasma glucose, insulin, adiponectin, total cholesterol, triglyceride, LDL-cholesterol, and HDL-cholesterol. The body composition was estimated using a bioelectric impedance analyzer (Inbody 2.0). The insulin sensitivity was estimated using the insulin tolerance test (ITT), HOMAIR and QUICK methods. In the diabetic group, the fasting adiponectin concentrations were significantly lower in men than in women. They were negatively correlated with BMI (r=-0.453), hip circumference (r=-0.341), fasting glucose concentrations (r=-0.277) and HOMAIR (r= -0.233). In addition, they were positively correlated with systolic blood pressure (r=0.321) and HDL-cholesterol (r= 0.291). The systolic blood pressure and HDL-cholesterol were found to be independent variables, from a multiple logistic regression analysis, which influenced the adiponectin concentration. Compared with the non-diabetic group, the adiponectin concentrations were significantly lower in the diabetic group, with the exception of obese males. In conclusion, the plasma adiponectin concentrations were closely related to the insulin resistance parameters in Korean type 2 diabetic patients.     

Nodular fibrosis of the lung in diabetes mellitus

The target organs in diabetes mellitus include the kidneys, the eyes and the small vessels. In these organs some specific histopathological changes have been described but there are few reports of histopathoogical changes in the lung in diabetic patients. Several reports describe abnormal pulmonary function in diabetic patients and consider these abnormalities to be due to histopahtological changes found in the pulmonary vessels. We have studied the histopathological changes in the diabetic lung comparing the findings in the autopsies of 61 diabetic and 50 non-diabetic patients. Statistically significant differences in the incidence of chronic obstructive lung disease and pulmonary haemorrhage exist. There are no differences in the incidence of fibrosis of the alveolar walls or intimal and medial thickening of small vessels, changes associated with diabetes according to the literature. We have found a specific type of nodular fibrosis not previously reported which we believe to be typical of diabetes.     

The cutaneous silent period in diabetes mellitus

The cutaneous silent period (CSP) may be useful as a method for the evaluation of smaller and unmyelinated fiber dysfunctions. CSP refers to the brief interruption in voluntary contraction that follows strong electrical stimulation of a cutaneous nerve. The aim the present study is to establish whether CSP can be instrumental in the determination of diabetic neuropathy. The nerve conduction studies and CSP evaluations were both used in patients with Diabetes Mellitus and control group. All patients were given clinical neurological examinations for the determination of small-fiber neuropathy (SFN). The CSP values for patients with SFN were compared with values of those without SFN. The nerve conduction velocities had changed unfavorably in diabetic patients. No median nerve CSP reponse could be obtained in two of the diabetic patients. CSP latency (84.6+/-14.0) in diabetics was longer than controls (76.2+/-13.1) (p=0.018). The duration of CSP was similar for the two groups (p=0.46). The CSP latency showed a correlation with routine nerve conduction studies. While the CSP latencies (86.7+/-15.8) of patients who were clinically diagnosed with SFN were similar to the latencies (81.3+/-10.4) of patients without SFN (p=0.606), the duration of CSP (44.6+/-13.7) in patients with SFN was shorter than the duration (55.3+/-12.2) in patients without SFN (p=0.012). These results indicate that even though the CSP does not provide any advantage over routine electrodiagnostic studies in determining diabetic neuropathy, still it may be a useful method for the early detection of diabetic SFN.     

Ultrastructural studies of the rat submandibular gland in streptozotocin induced diabetes mellitus

Summary Increased fluid intake (polydipsia) is one of the classic symptoms of diabetes mellitus. Xerostomia (dry mouth) and resultant thirst are other symptoms of the disease and bear a close relationship to polydipsia. The xerostomia in individuals with diabetes is primarily due to decreased saliva flow which appears to be associated with degenerative changes in the salivary glands. This study examines the response of the rat submandibular gland to streptozotocin induced diabetes mellitus. Adult male rats were given a single I.V. dose of streptozotocin (65 mg/kg body weight) in citrate buffer (pH 4.5). Salivary glands were examined by light and electron microscopy at 4, 8 and 24 h and 3, 7, 14 and 21 days posttreatment. The changes in the acinar cells were characterized by an accumulation of secretory material within the cytoplasm. This secretory protein accumulation was followed by degenerative changes in the acinar cells which frequently resulted in cell death and replacement of secretory cells by connective tissue elements. The loss of secretory volume and potential changes in secretory kinetics are discussed with regard to the xerostomia, thirst and polydipsia exhibited by individuals with diabetes mellitus.This work was supported in part by N.I.H. grant DE-03933. We would like to thank Mrs. Valerie Every for her secretarial assistance.     

32例糖尿病患者交感神经皮肤反应的探讨

目的 :应用交感神经皮肤反应 (SSR)探讨与糖尿病 (DM)相关的植物神经功能状况。方法 :对 32例DM患者及正常组采用电刺激法进行SSR检测。结果 :正常组SSR波形可分为三种类型 :P型、N型、M型 ,其中M型易产生适应性 ,受皮温、刺激强度、深呼吸等影响。 32例DM患者SSR潜伏期异常 17例 ,异常率为 5 3%。DM组与正常组的SSR相比 ,潜伏期和波幅的差异均有非常显著性意义 (P <0 0 1)。病程≤ 5年DM组与正常组的SSR相比 ,潜伏期和波幅的差异均有显著性意义 (P <0 0 5 ) ;而与病程 >5年DM组相比 ,仅潜伏期差异显示显著性意义 (P <0 0 5 ) ,波幅虽有降低 ,但无统计学差异。结论 :SSR可以评价DM患者的植物神经功能状况 ,尤其是潜伏期更有价值 ,可以作为一项动态观察指标。     

2型糖尿病患者的肺弥散功能检测分析(英)

目的：检测2型糖尿病患者的肺通气和弥散功能，探讨肺脏是否为糖尿病慢性病变的靶器官。方法： 对107名2型糖尿病患者行肺通气及弥散功能检测，并与61名年龄、性别匹配的健康者比较。糖尿病患者需行糖化血红蛋白（HbA1c）、尿白蛋白排泄率（AER）检测、眼底检查以及神经传导速度检查，以评价血糖控制水平以及糖尿病微血管病变状况。结果： 2型糖尿病组肺通气功能与正常对照组相比，无显著差异。2型糖尿病组一氧化碳弥散量（DLCO）及单位肺泡容积的一氧化碳弥散量（DLCO/VA）较对照组明显降低（P<0.05）。DLCO、DLCO/VA与微血管病变积分呈负相关（r分别为-0.291、 -0.324，P<0.01）。此外，DLCO/VA还与年龄、病程呈负相关（r分别为-0.269、-0.236，P<0.05）。结论： 2型糖尿病患者虽然肺通气功能基本正常，但有弥散功能受损，提示肺脏可能也是糖尿病慢性病变的靶器官之一。     

Localized insulin-derived amyloidosis in patients with diabetes mellitus: a case report

Three patients with insulin dependent type 1 diabetes mellitus and one with insulin dependent type 2 diabetes mellitus developed localized amyloid tumors at their general insulin injection sites. All 4 patients (two women and two men) were treated with modern recombinant human insulin or insulin analogues. In addition, 1 patient had used both recombinant and animal insulin. The amyloid tumors were resected and examined histologically using Congo red staining and immunohistochemistry. Insulin was found to be the major component of the amyloid tumors in all four patients. These 4 cases were diagnosed recently within a relatively short period of time, which leads to the conjecture that local insulin-derived amyloid tumors remain principally a differential diagnosis of skin tumors in insulin-dependent diabetic patients.