Vascular reactivity to noradrenaline and neuropeptide Y in the streptozotocin-induced diabetic rat

Abstract. The study aimed to assess vascular reactivity to noradrenaline with and without neuropeptide Y in diabetic rats, and to determine whether any abnormality could be attributed to insulin deficiency or to hyperglycaemia per se . The authors compared non-diabetic rats ( n = 9) and rats with streptozotocin-induced diabetes that were either untreated ( n = 10), or treated with insulin ( n = 9) or food restriction ( n = 8) to restore near-normoglycaemia. After 4 weeks of diabetes, contractile responses to noradrenaline (0.24–48 μmolL^-1), without and with neuropeptide Y (0.1 μmolL^-1), were assessed using an isometric myograph in two mesenteric arteries from each rat. Vessels from untreated diabetic rats were significantly more reactive to noradrenaline than the control vessels when tested without ( P <0.0001) but not with ( P = NS) neuropeptide Y. Diabetic rats rendered nearly normoglycaemic through food restriction showed dose-response curves that were very similar to the untreated diabetic group ( P = NS). By contrast, insulin-treated diabetic vessels showed reduced sensitivity to noradrenaline, with and without neuropeptide Y, compared with both the diet-restricted and untreated vessels (both P μ0.0001). The authors conclude that vascular sensitivity to noradrenaline, without or with neuropeptide Y, is reduced over a wide dose range in vessels taken from rats treated in vivo with insulin; furthermore, vessels taken from diabetic rats not treated with insulin (hypoinsulinaemic) tended to be more reactive than either control vessels or those taken from the insulin-treated rats. The latter group of rats were probably hyperinsulinaemic for much of the time; the results may therefore support the hypothesis that insulin acts as a vasodilator.     

The platelet angiotensin II receptor in type I diabetes: studies in patients with and without nephropathy

Abstract. Experimental studies demonstrate impaired regulation of the mesangial angiotensin II (AII) receptor in diabetes. This could contribute to the disturbance of glomerular blood flow and the development of diabetic nephropathy. The aim of this study was to determine whether a similar receptor abnormality occurs in patients with type I insulin-dependent diabetes mellitus (IDDM) and if so whether this is more prevalent in patients with micro- or macro-albumi-nuria. The platelet AII receptor was chosen because of its availability from the circulation and its comparable regulatory properties to tissue-based receptors. The interaction between plasma All and its platelet receptor was examined in 45 patients with TDDM and 36 age- and sex-matched control subjects. Seven patients had clinical nephropathy and two had persistent micro-albuminuria. The duration of diabetes varied from 1 month to 42 years. There was a significant inverse correlation between plasma AIT and the logarithm of receptor number in the control group (r= -0.555, P <0.001). This relationship was not observed in the diabetic patients irrespective of the duration of disease or the presence of nephropathy. Receptor expression in patients without nephropathy showed no correlation with either duration of disease or the degree of glycaemic control. However, a significant relationship between AII receptor number and duration of diabetes was noted in the group with nephropathy (r = 0.723, P <0.05). Patients without nephropathy had a significantly lower receptor number than control subjects (i.e. 3.9 ± 0.4 and 5.1±0.7 sites per cell respectively; P = 0.02), while comparable values to controls were observed in patients with renal disease (5^.7 ±1.2 sites per cell). Plasma renin and AII levels for both groups of patients were comparable to those observed in the control subjects. If these findings are representative of tissue-based AII receptors, then the loss of ligand/receptor relationship in the presence of higher receptor expression in patients with nephropathy could provide an explanation for the glomerular haemodynamic abnormalities observed in human diabetes.     

Association between eating behaviour and current glycaemic control, body mass or autonomic nervous function in long-term type I and type II diabetic patients

This cross-sectional study was aimed at investigating the association between eating behaviour and current glycaemic control, body mass or autonomic nervous function in patients with type I and type II diabetes mellitus (DM). In 72 patients (31 type I DM, 41 type II DM) we investigated body mass index (BMI), serum cholesterol, serum triglycerides, haemoglobin A1c (HbA1c) and autonomic nervous function (seven standardized tests). The three-factor eating questionnaire was used to investigate cognitive control of eating behaviour (CC) and susceptibility to eating problems (SEP). The mathematical product of CC and SEP provides information about disinhibition of eating control (DEC). In type I DM, there was a correlation between SEP and age ( r =−0.536, P <0.01), SEP and duration (−0.441, P <0.05), SEP and HbA1c (0.438, P <0.05), and between DEC and duration (−0.371, P <0.05) and DEC and HbA1c (0.376, P <0.05). In type II DM, there was a correlation between SEP and BMI (0.401, P <0.01) and between DEC and BMI (0.429, P <0.01). Low CC was associated with autonomic nervous dysfunction in type I DM ( P =0.022). In type II DM, autonomic nervous dysfunction was associated with high SEP ( P =0.044). In conclusion, the correlation between eating behaviour and HbA1c or triglycerides in type I DM indicates that the questionnaire is able to address current parameters of diabetes control. Self-assessment of eating behaviour in type I and type II diabetic patients reveals associations between eating behaviour and autonomic nervous function.     

NGAL、炎症细胞因子在2型糖尿病肾脏疾病患者体内的变化

目的 探讨中性粒细胞明胶酶相关载脂蛋白（NGAL）以及炎症细胞因子在2型糖尿病肾脏疾病（T2DM DKD）患者体内的变化情况。方法 2型糖尿病患者180例,根据尿微量白蛋白排泄量分为单纯糖尿病组、早期肾病组和临床肾病组,每组60例;同时选取健康志愿者60例作为对照组,检测各组NGAL、白细胞介素6（IL 6）和肿瘤坏死因子α（TNF α）的表达水平。 结果 治疗前,糖尿病患者的IL 6、TNF α水平表达明显高于对照组患者,同时糖尿病肾脏疾病越严重,其血清中的IL 6、TNF α水平越高（P＜0.05）。对各组患者空腹血糖、肾功能指标进行检测,发现糖尿病患者的空腹血糖（FPC）、血肌酐（SCr）、尿素氮（BUN）水平表达明显高于对照组患者,同时糖尿病肾病越严重,其血清中的FPC、SCr、BUN水平越高（P＜0.05）。结论 2型糖尿病肝肾疾病患者患病程度越严重,其体内NGAL、炎症细胞因子的表达就越高。     

938例糖尿病足病变严重程度与糖尿病肾病分期研究

目的探讨糖尿病足Wagner分级（1～5级）与糖尿病肾病分期（Ⅰ～Ⅴ）之间的相关性。方法 2001年1月至2008年6月期间在天津医科大学代谢病医院足病科住院的938例2型糖尿病合并糖尿病足病的患者为研究对象,根据Wagner分级分为足病较轻组（Wagner 1～2级组）和足病较重组（Wagner 3～5级组）,入院时留取24小时尿测量微量白蛋白（MAU）。结果糖尿病足病较重组与足病较轻组相比,糖化血红蛋白（HbA1c）和MAU水平明显增高,分别为HbA1c（9.63±2.37）%vs（9.12±2.05）%（P〈0.01）;MAU[43.85（90.40）]mg/d vs[27.50（59.35）]mg/d（P〈0.01）;足病较重组患有严重肾病（Ⅳ～Ⅴ期）的发生率明显高于糖尿病足病较轻组（30.8%vs 23.5%,P〈0.05）。结论糖尿病足病变严重程度较高者严重肾病发生率较高,MAU水平也较高。     

2型糖尿病及糖尿病肾病患者视黄醇结合蛋白4检测的意义

目的探讨2型糖尿病(T2DM)及其合并肾病(DN)患者血视黄醇结合蛋白4(RBP4)浓度变化及临床意义。方法根据尿清蛋白排泄率(UAER)将118例T2DM患者分为单纯糖尿病(SDM)组47例、早期糖尿病肾病(EDN)组40例和临床糖尿病肾病(CDN)组31例;另选30例健康体检者作为对照(NC)组。采用酶联免疫吸附试验双抗体夹心法检测RBP4。结果 SDM、EDN、CDN组RBP4、超敏C-反应蛋白(hs-CRP)较NC组升高(P<0.05),随病情加重,升高更为明显。RBP4与hs-CRP高度相关(r=0.77,P<0.01)。T2DM患者血浆RBP4水平随着尿清蛋白的增加而升高。结论 T2DM患者血浆RBP4水平明显升高,可作为DN早期的敏感的诊断指标。     

血清铁调素-25水平与2型糖尿病肾病中肾功能不良进展的相关性研究

目的分析血清铁调素-25与2型糖尿病肾病中肾功能不良进展之间是否具有相关性。方法该研究试验设计为巢式病例对照设计,220例患者资料来源于2015年4月至2019年6月在徐州市中心医院住院的2型糖尿病肾病患者。血清铁调素-25水平采用ELISA法检测,以肾功能不良进展(肾替代疗法或血清肌酐加倍)作为结局指标。采用多因素Cox回归分析为主要的分析方法,配合以肾小球滤过率(GFR)为分层因素的分层分析。结果Cox分析显示血清铁调素-25水平与2型糖尿病所致的慢性肾病患者的肾功能不良进展之间不具有相关性(HR=1.18,95%CI:0.97~1.45)。分层分析显示GFR是以上关系的效应修饰因素:GFR低[<51.8 mL/(min·1.73 m 2)]时,血清铁调素-25水平与2型糖尿病肾病不良进展之间呈正相关(HR=2.56,95%CI:1.50~4.40),而GFR高的时候,血清铁调素-25水平与2型糖尿病肾病不良进展之间呈负相关(HR=0.00,95%CI:0.00~0.21)。结论血清铁调素-25水平在部分人群中对2型糖尿病肾病不良进展具有预测作用。     

早期2型糖尿病肾病患者成纤维细胞生长因子水平的变化及意义

目的：研究早期2型糖尿病肾病（T2DN）患者外周血成纤维细胞生长因子（FGF‐23）水平的变化及临床意义。方法2012年3月至2013年11月该院门诊及住院治疗的2型糖尿病（T2DM）患者98例,其中单纯糖尿病（DM）组31例,早期糖尿病肾病（DN）组34例,临床DN组33例,并选健康者30例作为健康对照组。采用酶联免疫吸附试验测定外周血FGF‐23水平,同时测定血胱抑素C（CysC）、血磷（P）、血钙（Ca）,并计算P和Ca乘积,根据年龄、性别和血肌酐估算肾小球滤过率（eGRF）。结果各组T2DM患者FGF‐23、CysC明显高于健康对照组,eGFR明显低于健康对照组（P＜0．05）;与单纯DM组比较,早期DN组FGF‐23、CysC明显升高,eGFR明显降低（P＜0．05）;临床DN组与早期DN组比较,FGF‐23、CysC进一步升高,eGFR进一步降低,差异有统计学意义（P＜0．01）。血P在健康对照组、单纯DM组及早期DN组中差异无统计学意义（P＞0．05）,临床DN组血P及Ca＆#215;P值则较其他组明显升高,差异有统计学意义（P＜0．01）。相关性分析显示,DN患者FGF‐23水平与CysC、P呈正相关（P＜0．01）,与eGFR呈负相关（P＜0．01）,与年龄、体质量指数、Ca等无相关性（P＞0．05）。结论早期T2DN外周血FGF‐23水平的升高早于Ca和P的变化,且随DN进展,FGF‐23水平逐渐升高,FGF‐23可作为早期T2DN诊断的有效指标之一,并可成为T2DN进展的预警指标。     

2型糖尿病患者血浆脂联素浓度改变及其与胰岛素抵抗的关系

目的　了解 2型糖尿病患者血浆脂联素浓度的改变 ,并探讨与胰岛素抵抗的关系。方法　测定 64例 2型糖尿病和 3 0例正常对照组的血浆脂联素、空腹血糖 (FPG)、糖化血红蛋白 (HbA1c)、空腹血浆胰岛素 (FINS)、血脂、体重指数(BMI) ,计算胰岛素抵抗指数 (HOMA IR)及 β 细胞功能指数 (HOMA β)。比较脂联素浓度的改变 ,以及与其它因素的相关性。结果　正常对照组、非肥胖糖尿病组及肥胖糖尿病组 ,脂联素浓度依次降低 ,且均有统计学意义。大中血管并发症糖尿病组血浆脂联素水平较无大中血管并发症糖尿病组明显降低。在糖尿病患者中血浆脂联素与BMI、HOMA IR呈负相关 (P <0 0 5 ) ,与高密度脂蛋白胆固醇 (HDL c)呈正相关 (P <0 0 5 )。与FBG、HbA1c、甘油三酯 (TG)、总胆固醇 (TC)及 β 细胞功能指数 (HOMA β)相关性不明显。结论　 2型糖尿病患者血浆脂联素水平明显下降 ,并且与胰岛素抵抗有一定的相关性     

Prevalence,characteristics and risk factors of diabetic retinopathy in type 2 diabetes mellitus patients in Jordan: a cross-sectional study

ObjectivesTo measure the prevalence of diabetic retinopathy in patients with type 2 diabetes, to define their characteristics, and identify the associated risk factors.MethodsWe performed a cross sectional study of 1316 adult patients with type 2 diabetes mellitus who attended an ophthalmology clinic. Demographic, clinical, and laboratory data were analyzed. Diabetic retinopathy (DR) was diagnosed using a complete ophthalmic evaluation, including a fundic examination. Two regression models were constructed to identify the risk factors associated with DR and the parameters associated with the stage of retinopathy.ResultsMen accounted for 774 (58.8%) of the participants. The prevalence of DR was 28.2% (371 participants). DR was significantly more common in participants who were ≥60 years old, were women, had had diabetes for >10 years, were taking insulin, were not taking metformin, had a body mass index >30 kg/m², were current smokers, or had a history of hypertension. Advanced stages of DR were more common in participants in the later stages of nephropathy and with albuminuria.ConclusionsPoor glycemic control, smoking, and advanced diabetic kidney disease are most closely associated with retinopathy. Further longitudinal studies are necessary to identify the mechanisms underlying these relationships and to guide community-based interventions.     

Angiotensin-converting enzyme gene polymorphism and stroke in type 2 diabetic patients in Taiwan

BACKGROUND: The effect of traditional risk factors on the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and stroke was rarely studied previously. We investigated such effect in Taiwanese type 2 diabetic patients. MATERIALS AND METHODS: A total of 872 (422 men and 450 women) patients aged 63.5 (SD: 11.6) years were recruited. Among them, 92 cases (48 men and 44 women) had stroke. Polymerase chain reaction was used to classify the genotypes as II, ID and DD. Analyses were performed in separate sexes. RESULTS: The adjusted odds ratios for stroke for ID vs. II and DD vs. II were 0.837 (0.413-1.697) and 1.778 (0.596-5.300), respectively, for men; but were 1.700 (0.824-3.505) and 3.706 (1.375-9.985), respectively, for women. In models assuming recessive (DD vs. II + ID), dominant (DD + ID vs. II) and additive (II = 0, ID = 1 and DD = 2) transmission, none of the odds ratios was significant for men; but were all significant for women: 2.784 (1.137-6.818), 1.996 (1.006-3.962) and 1.877 (1.155-3.050), respectively. In models using patients without risk factors (hypertension, obesity, smoking or dyslipidaemia ) as a referent group and comparing them to patients with the risk factor and with ID/II, and with DD genotypes, all models (except for smoking) favoured an increasing trend of risk with patients having the risk factor and DD genotype at the highest risk in women. Similar trends for hypertension and dyslipidaemia were also observed in men. CONCLUSION: Traditional risk factors play an important role in the association between the ACE genotypes and stroke. Patients with DD genotype and having traditional risk factors are at the highest risk.     

Serum homocysteine is weakly associated with von Willebrand factor and soluble vascular cell adhesion molecule 1, but not with C-reactive protein in type 2 diabetic and non-diabetic subjects - The Hoorn Study

BACKGROUND: Hyperhomocysteinaemia may constitute an independent risk factor for cardiovascular disease, but it is still unclear by which pathophysiological mechanisms homocysteine (tHcy) may promote atherothrombosis. The aim of this study was firstly to examine whether tHcy is associated with endothelial dysfunction, increased adherence of leukocytes, and/or chronic low-grade inflammation, as estimated from plasma levels of von Willebrand factor (vWf), soluble vascular cell adhesion molecule 1 (sVCAM-1) and C-reactive protein (CRP), respectively. Secondly we investigated whether the presence of type 2 diabetes modifies these associations. MATERIALS AND METHODS: Six hundred and ten subjects of a general population of middle-aged and elderly subjects, 170 of whom had type 2 diabetes, participated in this cross-sectional study. Linear regression analyses were used to study whether tHcy was associated with vWf, sVCAM-1 and CRP, and whether the presence of diabetes modified these associations. RESULTS: After adjustment for confounders, tHcy was significantly but weakly associated with vWf (beta = 0.15, P = 0.05) and sVCAM-1 (beta = 0.082, P = 0.04). tHcy was not significantly associated with CRP (beta = 0.02, P = 0.91). The presence of diabetes did not significantly modify these associations. CONCLUSIONS: This study provides evidence that tHcy is, at most, weakly associated with endothelial dysfunction as estimated from plasma vWf, and with leukocyte adhesion as estimated from plasma sVCAM-1. tHcy was not significantly associated with chronic low-grade inflammation as estimated from plasma CRP. Our data thus suggest that the link between tHcy and atherothrombosis cannot be explained by associations of tHcy with vWf, sVCAM-1 or CRP.     

胰岛素联合瑞易宁与单用胰岛素治疗继发性口服降糖药物失效的2型糖尿病的对比研究

目的 探讨胰岛素联合瑞易宁治疗与单用胰岛素控制稳定的继发性口服降糖药物失效的2型糖尿病的疗效及可能益处。方法 42例继发性药物失效的2型糖尿病患者用胰岛素控制糖代谢稳定至少2个月后 ,加用瑞易宁治疗 ,剂量从5mg/d开始 ,最大剂量20mg/d ,同时调整胰岛素用量 ,观察3个月。采用前后对比研究的方法 ,观察患者治疗前后的疗效和相关指标的变化。结果 胰岛素联合瑞易宁和单用胰岛素对继发性药物失效的2型糖尿病患者比较 ,空腹血糖(FBG)、糖基化血红蛋白(HbAlc)均能有效控制 ,餐后2h血糖(2hPG)的控制优于单用胰岛素治疗[(10.5±3.2)～(8.2±2.6)mmol/L,p<0.05],联合用药能明显减少胰岛素的用量[(45.2±10.6)u/d～(18.3±3.2)u/d,p<0.001] ,其中2例患者可以停用胰岛素治疗。(空腹C肽/空腹血糖)×100从(0.11±0.03)增加到(0.21±0.05)(p<0.05)。结论 胰岛素联合瑞易宁能控制继发口服降糖药物失效的2型糖尿病的糖代谢水平 ,可能避免对2型糖尿病大血管病变有关的高胰岛素血症。     

Increased minimal vascular resistance and arteriolar hyalinosis in skin on the leg in insulin-dependent diabetic patients

Minimal vascular resistance (MVR) was determined in a paralysed cutaneous vascular bed at the dorsum of the foot in diabetic patients. Twelve long-term insulin-dependent diabetic (IDDM) patients with and nine short-term IDDM patients without nephropathy and retinopathy and eight control subjects were investigated. The vascular bed was paralysed by local injection of histamine. Skin perfusion pressure was varied by applying graded external counter pressure over the investigated area. Skin blood flow was measured by the local ^99mTc wash-out technique before, during and after three to five step-wise increases of external counter pressure. The MVR was calculated from the reciprocal of the slope of the relationship between blood flow and applied pressure. The MVR was significantly increased in diabetic patients with (mean: 9.3 mmHg ml^-1 ·100 g·min) and without nephropathy and retinopathy (8.5 mmHg ml^-1·100 g·min) compared with non-diabetic subjects (5.2 mmHg ml^-1·100 g·min) (p<0.001 and p<0.005, respectively). Diabetic microangiopathy (increased hyalinusis of the basement membranes in the terminal arterioles) was found in skin biopsies in nine of the 12 long-term IDDM patients and in four of the nine short-term IDDM patients, but not in the control subjects. Multiple regression analysis demonstrated a highly significant direct association between MVR and degree of diabetic microangiopathy in the same skin area (p<0.0002). A less significant direct association between MVR and arm diastolic blood pressure (p<0.05) and blood glucose concentration (p<0.05) was also found. Our results indicate, that terminal arteriolar hyalinosis is the main determinant of the increased minimal vascular resistance in skin in short- and long-term IDDM patients.     

ACE基因插入缺失多态性与糖尿病肾病病情发展的关系

目的：探讨非胰岛素依赖型糖尿病（ＮＩＤＤＭ）肾病（ＤＮ）病情进展与血管紧张素转换酶（ＡＣＥ）基因插入缺失（ＩＤ）多态性的关系。方法：用ＰＣＲ方法分别检测了９２例不同程度蛋白尿的ＮＩＤＤＭ患者的ＡＣＥ基因型。结果：随着ＤＮ蛋白尿程度加重,ＤＤ型频率逐渐增高（微白蛋白尿期１７％,显性蛋白尿期２５％,肾功能不全期４６％）,而ＩＩ型频率逐渐下降（在３组分别为３３％、２９％和８％）,ＤＩ型在３组分布无显著性差异;在肾功能不全期组,ＤＤ型频率（４６％）显著高于肾功能正常期组（２０％）,Ｉ型频率（８％）显著低于肾功能正常期组（３２％）,ＤＩ型频率在２组无显著性差异。结论：ＤＤ型ＮＩＤＤＭ患者发生ＤＮ后,病情进展较快,ＤＤ型是ＤＮ恶化的促进因素;ＩＩ型为保护性因素。     

GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients

BACKGROUND: Progressive beta-cell failure is a characteristic feature of type 2 diabetes; consequently, beta-cell secretagogues are useful for achieving sufficient glycaemic control. The European GUIDE study is the first large-scale head-to-head comparison of two sulphonylureas designed for once-daily administration used under conditions of everyday clinical practice. DESIGN: Eight hundred and forty-five type 2 diabetic patients were randomized to either gliclazide modified release (MR) 30-120 mg daily or glimepiride 1-6 mg daily as monotherapy or in combination with their current treatment (metformin or an alpha-glucosidase inhibitor) according to a double-blind, 27-week, parallel-group design. Efficacy was evaluated by HbA1c and safety by hypoglycaemic episodes using the European Agency definition. RESULTS: HbA1c decreased similarly in both groups from 8.4% to 7.2% on gliclazide MR and from 8.2% to 7.2% on glimepiride. Approximately 50% of the patients achieved HbA1c levels less than 7%, and 25% less than 6.5%. The mean difference between groups of the final HbA1c was -0.06% (noninferiority test P < 0.0001). No hypoglycaemia requiring external assistance occurred. Hypoglycaemia with blood glucose level < 3 mmol L(-1) occurred significantly less frequently (P = 0.003) with gliclazide MR (3.7% of patients) compared with glimepiride (8.9% of patients). The distribution of the sulphonylurea doses was similar in both groups. CONCLUSIONS: This study provides new insights into therapeutic strategies using sulphonylureas. It shows that gliclazide MR is at least as effective as glimepiride, either as monotherapy or in combination. The safety of gliclazide MR was significantly better, demonstrating approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride.