糖基化产物对正常大鼠尿蛋白排泄和肾脏结构的影响

目的为探讨糖基化产物对正常肾脏的特异性损害作用。方法正常大鼠静脉注射体外制备的糖基化血清蛋白（ＧＳＰ），为期２个月，观察ＧＳＰ对大鼠尿蛋白排泄、肾皮质糖基化产物和肾脏形态的影响。结果接受ＧＳＰ的大鼠血清和肾组织中糖基化终产物（ＡＧＥｓ）水平、肾小球硝基四氮唑蓝（ＮＢＴ）染色强度、尿蛋白排泄量和尿量均明显高于对照组。光学和电子显微镜观察显示，给予ＧＳＰ的大鼠肾小球体积明显增大，肾小球系膜区扩大伴有细胞外基质增加，ＰＡＳ阳性物质沉着增多和肾小球基底膜节段性增厚。结论糖基化产物能引起类似糖尿病肾病的肾脏损害。     

Effect of protein intake on glycaemic control and renal function in Type 2 (non-insulin-dependent) diabetes mellitus

Summary Recent clinical investigations have suggested that dietary protein intake may modulate the progression of diabetic nephropathy and influence glycaemic control in Type 2 (non-insulin-dependent) diabetes mellitus. Twelve normotensive Type 2 diabetic patients with microalbuminuria took part in a randomized cross-over trial of a 3-week high protein diet (2.0 g/kg desirable weight per day) and a 3-week moderate protein diet (0.8 g/kg desirable weight per day) to test the simultaneous effect of protein intake modulation on glycaemic control and renal function. Both diets were isoenergetic and the moderate protein diet was supplemented with calcium and phosphate. Renal function and glycaemic control were evaluated at the beginning and at the end of each diet. The moderate protein diet reduced the urinary albumin excretion rate, glomerular filtration rate, creatinine clearance, and proteinuria without adversely affecting glycaemic control; fasting glycaemia and the ratio of fructosamine to proteins were significantly reduced. The high protein diet induced similar improvements in glycaemic control but small changes in renal function.     

Indices of renal structure and function in patients with type 1 diabetes mellitus

The evaluation of renal biopsies from diabetic patients rests upon measurements of many structures in glomeruli, the tubules and the interstitium. These individual values can also be expressed as an index of renal structure. To assess the validity of the individual values versus a published index of renal structure, we evaluated glomerular basement membrane width, mesangial volume fraction, other measures of glomerular structure, and percentage glomerulosclerosis in type 1 diabetic subjects with renal function ranging from normal to marked albuminuria, hypertension, and a falling glomerular filtration rate. For all measured structural parameters and for the index, all groups of diabetic patients, even those who had completely normal renal function, had values different from non-diabetic subjects (P<0.001). Furthermore, there was an excellent correlation between the structural index and a similar functional index (r=0.77).     

Atrial natriuretic peptide in Type 2 diabetes mellitus: response to a physiological mixed meal and relationship to renal function

Relatively few data exist on atrial natriuretic peptide (ANP) characteristics in Type 2 diabetes mellitus (DM). Therefore, plasma immunoreactive ANP concentrations were measured before and for 4 h following the ingestion of a physiological mixed meal in 8 newly diagnosed, normotensive, normoalbuminuric, patients with Type 2 DM and 6 normotensive, non-diabetic controls. In patients with Type 2 DM, basal plasma ANP concentrations were 4.0 ± 2.0 and not significantly changed following ingestion of the meal, with peak levels of 4.9 ± 2.8 pmol l⁻¹. Non-diabetic controls had higher basal plasma ANP concentrations, 8.7 ± 3.4 pmol l⁻¹ (p < 0.05), significantly increasing to a peak of 11.9 ± 6.3 pmol l⁻¹ at 30 min post meal. Extracellular fluid volume (ECV) was not different between diabetic patients and controls (15877 ± 2679 vs 13668 ± 1792 ml³). Glomerular filtration rate (GFR) (isotopic clearance corrected for body surface area) was elevated in diabetic patients (mean ± SD) 130 ± 39 vs 98 ± 10 ml min⁻¹, p < 0.05). For the DM subjects, basal ANP levels were negatively correlated with GFR (r_s − 0.74, p < 0.05) and effective renal plasma flow (ERPF) (r_s − 0.8, p < 0.05). We conclude that patients with Type 2 DM demonstrate reduced basal plasma ANP concentrations which are inversely correlated to renal function. In contrast to non-diabetic controls, ANP in Type 2 DM does not rise in response to feeding. © 1998 John Wiley & Sons, Ltd.     

尿L-FABP与2型糖尿病患者肾功能变化的纵向研究

上海市浦东新区卫生系统重点学科群建设基金（PWZxq2014-07）     

Enhanced nonenzymatic glycation of eye lens proteins in experimental diabetes mellitus: an approach for the study of protein alterations as mediators of normal aging phenomena

The levels of advanced nonenzymatic glycation endproducts (ACE) were investigated by spectrofluorimetry in eye lens proteins obtained from rats with experimental diabetes of 3 and 6 months duration and from normal age-matched control rats. Diabetic animals showed higher AGE levels at both times studied. However the older control animals showed protein ACE levels comparable to those of the experimental 3 months diabetic group. These data suggest that a pathological phenomenon such as enhanced nonenzymatic glycation, associated to diabetic hyperglycemia, can be considered as a process leading to an accelerated aging of proteins. Thus experimental diabetes mellitus may be used as a model to investigate physiological protein senescence.     

糖尿病对老年高血压患者心脏结构和功能的影响

目的探讨糖尿病对老年高血压患者心脏结构和功能的影响。方法将351例60岁以上的住院患者分为3组，即单纯高血压（EH）组149例，高血压合并2型糖尿病（T2DM）组129例和对照组73例，依据超声心动图结果评价心脏的结构和功能。结果与单纯EH组比较，EH＋T2DM组的舒张末期左心室内径（LVD）、左室质量（LVM）、左室质量指数（LVW1）、收缩末期左心房内径（LA）、收缩末期升主动脉内径（AO）、射血分数（EF）、平均左室短轴缩短率（FS）、舒张晚期二尖瓣最大血流速度（A值）、左心室舒张早期二尖瓣最大血流速度（E值）／A值明显升高，EH＋T2DM组E／A小于0．8或大于1．6的例数大于EH组和对照组（P=0．03）；EH＋T2DM组的房颤发生率大于对照组（P=0．012）。结论糖尿病对老年高血斥患者心脏结构、收缩和舒张功能均有一定的影响，高血糖可加重老年高血压患者心脏结构和功能的异常。     

C反应蛋白与糖尿病血管内皮功能

随着对糖尿病发病机制的深入研究，血管内皮功能紊乱在糖尿病及其血管并发症中的作用逐渐被认识。C反应蛋白（CRP）是公认的系统性炎症标志物，在糖尿病特别是存在血管并发症的患者中其水平显著升高。CRP通过核因子影响一氧化氮、内皮黏附分子、纤溶系统、血管平滑肌和血管紧张素受体、骨髓衍生的内皮祖细胞等途径作用于血管内皮组织，影响血管内皮功能造成内皮功能紊乱，进而促进糖尿病血管并发症的发生和发展。     

Effect of a low protein diet on the resistance of Churra sheep to Teladorsagia circumcincta

SUMMARY The aim of this study was to understand the influence of a low protein diet on the resistance of the Churra breed sheep to infection with Teladorsagia circumcincta. A previous experiment in our department demonstrated significant differences between resistant and susceptible sheep infected with T. circumcincta, in eggs per gram of faeces, serum pepsinogen, serum IgA and peripheral eosinophilia (unpublished). The sheep were fed with a balanced protein diet. In the current assay there were significant differences between the resistant and susceptible groups in egg output, serum pepsinogen and worm burden. The optical densities (OD) of the IgA in blood samples, nasal secretions and saliva were tested throughout the study and the differences between groups were not significant. At necropsy adult worm length, the number of eggs in utero in adult females, the number of fourth stage larvae and the OD of gastric mucus IgA did not differ between groups either. Moreover, due to diet there was a loss of weight in both groups but this was not significant. Our results support the view that low protein diets could influence immune function and as a result resistant genotypes do not show any superiority in comparison with susceptible ones.     

1型糖尿病对主动脉缩窄大鼠结构和功能的影响

目的探讨糖尿病是否能加重左心室超负荷引起的心力衰竭。方法 3周龄雄性Wistar大鼠54只,随机分为4组:假手术组14只,胸主动脉缩窄(TAC)组12只,假手术+链脲佐菌素(STZ)组15只(STZ组),TAC+STZ组(联合组)13只。记录大鼠的体质量演变,并分别于TAC术后15、50d对所有大鼠行超声心动图检查。在TAC术后66d处死大鼠,分离左心房、右心房、心室等,进行称重,天狼星红染色分析心肌纤维化。结果与假手术组比较,STZ组50d舒张末室间隔厚度(IVST)、左心室后壁舒张末厚度(PWT)、左心室质量、心率明显降低(P<0.01);TAC组15dIVST、PWT、LVM明显升高(P<0.01)。与15d比较,TAC组和联合组50d左心室肥厚百分比明显增高(P<0.01)。与假手术组比较,STZ组大鼠体质量、左心室质量、左心房质量、肺脏质量、左心室质量/胫骨长度明显降低,左心室质量/体质量明显升高;而TAC组大鼠左心室质量、左心房质量、肺脏质量、左心室质量/胫骨长度、左心室质量/体质量明显升高(P<0.05,P<0.01)。结论糖尿病明显增加了TAC诱导的左心室肥厚,但并没有加重TAC大鼠模型的心力衰竭指征,可能是因为糖基化终产物的聚集所致。     

联合低血糖生成指数及低血糖生成负荷饮食干预对2型糖尿病患者糖脂代谢的影响

目的：评价联合低血糖生成指数（ LGI ）及低血糖生成负荷（ LGL ）的饮食干预对社区2型糖尿病（T2DM）患者血糖血脂代谢指标的影响。方法整群随机抽取湖南省长沙市金盆岭三真社区内三个不同小区,分别在各小区内随机抽取已确诊的T2DM且符合本研究纳入标准的35例患者为研究对象,将三个小区以抽签的形式随机分为全天饮食干预组（A组）、早餐饮食干预组（B组）及对照组（C组）。通过3个月分组干预,即保持患者原治疗方案不变的情况下,指导A组患者一日三餐采用LGI及LGL的食物,B组仅早餐采用LGI及LGL的食物,而C组饮食不作要求,比较干预前后三组患者空腹血糖（FBG）、餐后2 h血糖（2 hPG）、糖化血红蛋白（HbA1c）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）指标的变化。符合正态分布的计量资料比较采用单因素的方差分析。结果多个独立样本比较Kruskal-Wallis H检验显示,干预前后三组的 HbA1c 均有改善（均 P ＜0.05）,其中 A 组 HbA1c 改善优于 B、C 组（H ＝26.749,P ＜0.0167）;干预前后三组的HDL-C均有所下降（均P＜0.05）,其中A组患者的HDL-C下降幅度大于B组及C组（H＝12.671,P＜0.0167）;干预前后三组的TG均有改善（均P＜0.05）,其中A组、B组的TG改善优于C组（H＝14.921,P＜0.0167）。结论联合LGI及LGL饮食干预能有效改善T2DM患者HbA1c、HDL-C及TG,其中全天饮食干预较早餐饮食干预更有效。     

Quality of life in type 2 diabetes mellitus after a very low calorie diet and exercise

ObjectiveTo evaluate whether the addition of exercise to a very low calorie diet (VLCD) has beneficial short- and long-term effects on health-related quality of life (QoL) in obese patients with type 2 diabetes mellitus (T2DM).MethodsWe included 27 obese, insulin-dependent T2DM patients in a 16-week VLCD study, of whom 13 participated simultaneously in an exercise program (VLCD + E). Before, immediately after and 18 months after the intervention anthropometric measurements, glucoregulation and QoL (SF-36, HADS, NHP and MFI-20) were assessed. Patients were compared to healthy lean and obese (matched for body mass index) controls matched for gender and age.ResultsAt baseline, T2DM patients had significantly worse QoL scores in 18 and 14 of the 22 subscales of the QoL questionnaires, compared to lean and obese controls, resp. The 16-week VLCD (n = 27) decreased bodyweight (? 25.4 ± 1.3 kg, p < 0.0001, p = 0.179 between groups), and improved glucoregulation (HbA1c ? 1.3 ± 0.3%, p < 0.0001, p = 0.488 between groups) and 9 (VLCD-only) and 11 (VLCD + E) of the 22 subscales of QoL.After 18 months, in the VLCD + E group the QoL subscales did not differ from those in obese controls and only 4 of the 22 subscales were significantly worse compared to lean controls. However, in the VLCD-only group 17 and 13 of the 22 QoL subscales were significantly worse compared to the lean and obese controls, resp.ConclusionA 16-week VLCD induces considerable weight loss, metabolic amelioration, and major improvements in QoL in obese T2DM patients. The addition of exercise is of paramount importance for the maintenance of better QoL.     

阿魏酸钠对糖尿病大鼠主动脉胶原非酶糖基化的影响

将链脲佐菌素诱发的糖尿病大鼠，以阿魏酸钠处理8周，可使糖尿病大鼠主动脉的胶原和胶原中糖基化终末产物的含量降低，其机制可能与阿魏酸钠保护抗氧化酶有关。     

Maps of protein structure space reveal a fundamental relationship between protein structure and function

To study the protein structure–function relationship, we propose a method to efficiently create three-dimensional maps of structure space using a very large dataset of > 30,000 Structural Classification of Proteins (SCOP) domains. In our maps, each domain is represented by a point, and the distance between any two points approximates the structural distance between their corresponding domains. We use these maps to study the spatial distributions of properties of proteins, and in particular those of local vicinities in structure space such as structural density and functional diversity. These maps provide a unique broad view of protein space and thus reveal previously undescribed fundamental properties thereof. At the same time, the maps are consistent with previous knowledge (e.g., domains cluster by their SCOP class) and organize in a unified, coherent representation previous observation concerning specific protein folds. To investigate the function–structure relationship, we measure the functional diversity (using the Gene Ontology controlled vocabulary) in local structural vicinities. Our most striking finding is that functional diversity varies considerably across structure space: The space has a highly diverse region, and diversity abates when moving away from it. Interestingly, the domains in this region are mostly alpha/beta structures, which are known to be the most ancient proteins. We believe that our unique perspective of structure space will open previously undescribed ways of studying proteins, their evolution, and the relationship between their structure and function.     

Effect of ischemia on peripheral nerve function in diabetes mellitus

In Japan, diabetic patients are known to be able to sit on the floor for a prolonged time because of mildness or absence of ischemic paresthesia. In order to investigate this resistance to ischemia quantitatively, the mixed nerve function of the median nerve was studied during 30 min of ischemia using surface electrodes in 60 diabetic patients and 15 normal subjects. In studies of 33 unequivocal diabetics, potential amplitudes decreased during ischemia more slowly than in the controls, and at 15 min of ischemia, potential amplitudes were greater in all 33 diabetics than in the 15 normal subjects. The relationship between the resistance to ischemia and various aspects of diabetes was studied further in the 60 diabetics including the 33 aforementioned patients. Resistance to ischemia was found in almost all diabetics and no significant correlation was shown with values for fasting blood glucose and HbA1c, other diabetic complications or duration of diabetes. However, values for potential amplitudes declined to the normal range in seven of 18 patients after strict glucose control. These results suggest that resistance to ischemia is the earliest manifestation of peripheral nerve dysfunction and is different from classical diabetic neuropathy. Furthermore, the method employed in this study is simple, noninvasive and clinically very useful.     

Adherence to a Mediterranean diet and glycaemic control in Type 2 diabetes mellitus

Aims Mediterranean‐type diets reduce the risk of Type 2 diabetes. Whether a Mediterranean‐type diet improves glycaemic control in diabetes remains unknown. Methods We conducted a cross‐sectional analysis in 901 outpatients with Type 2 diabetes attending diabetes clinics located in Campania County, South Italy. We explored the relation between glycated haemoglobin (HbA_1c), measured centrally, self‐measured pre‐ and postprandial glucose levels and consumption of a Mediterranean‐type diet. Adherence to a Mediterranean‐type diet was assessed by a 9‐point scale that incorporated the salient characteristics of this diet (range of scores, 0–9, with higher scores indicating greater adherence). The study was conducted from 2001 to 2007. Results Diabetic patients with the highest scores (6–9) had lower body mass index and waist circumferences, a lower prevalence of the metabolic syndrome and lower HbA_1c and post‐meal glucose levels than diabetic patients with the lowest scores (0–3). In multivariate analysis, mean HbA_1c and 2‐h post‐meal glucose concentrations were significantly lower in diabetic patients with high adherence to a Mediterranean‐type diet than those with low adherence [difference: HbA_1c 0.9%, 95% confidence intervals (CI) 0.5–1.2%, P < 0.001; 2‐h glucose 2.2 mmol/l, 95% CI 0.8–2.9 mmol/l, P < 0.001]. Conclusions In Type 2 diabetes, greater adherence to a Mediterranean‐type diet is associated with lower HbA_1c and postprandial glucose levels.     

The effects of medicinal plants on renal function and blood pressure in diabetes mellitus

Abstract

Diabetes mellitus is one of the most common chronic global diseases affecting children and adolescents in both the developed and developing nations. The major types of diabetes mellitus are type 1 and type 2, the former arising from inadequate production of insulin due to pancreatic β-cell dysfunction, and the latter from reduced sensitivity to insulin in the target tissues and/or inadequate insulin secretion. Sustained hyperglycaemia is a common result of uncontrolled diabetes and, over time, can damage the heart, eyes, kidneys and nerves, mainly through deteriorating blood vessels supplying the organs. Microvascular (retinopathy and nephropathy) and macrovascular (atherosclerotic) disorders are the leading causes of morbidity and mortality in diabetic patients. Therefore, emphasis on diabetes care and management is on optimal blood glucose control to avert these adverse outcomes.Studies have demonstrated that diabetic nephropathy is associated with increased cardiovascular mortality. In general, about one in three patients with diabetes develops end-stage renal disease (ESRD) which proceeds to diabetic nephropathy (DN), the principal cause of significant morbidity and mortality in diabetes. Hypertension, a well-established major risk factor for cardiovascular disease contributes to ESRD in diabetes. Clinical evidence suggests that there is no effective treatment for diabetic nephropathy and prevention of the progression of diabetic nephropathy. However, biomedical evidence indicates that some plant extracts have beneficial effects on certain processes associated with reduced renal function in diabetes mellitus. On the other hand, other plant extracts may be hazardous in diabetes, as reports indicate impairment of renal function. This article outlines therapeutic and pharmacological evidence supporting the potential of some medicinal plants to control or compensate for diabetes-associated complications, with particular emphasis on kidney function and hypertension.