BACKGROUND & AIMS: :Relationships between eating and affective disorders remain complex and unclear. Brain glucose metabolism of anorectic patients has been demonstrated to be reduced both globally and regionally, with a particular relative hypometabolism in the parietal cortex. To explore the possible influence of weight loss or depressive symptomatology on brain metabolism, we studied age- and sex-matched low-weight anorectic and depressed patients, normal-weight depressed patients, and healthy volunteers. Absolute global and regional glucose activity levels were reduced in low-weight patients, with the lowest values being found for anorectic patients. In relative values, anorectic patients showed a significant parietal hypometabolism in comparison to control subjects while they had higher metabolism in the caudate nuclei when compared with the other groups. Absolute hypometabolism of glucose seems to be a consequence of low weight as it was found in both low-weight anorectic and low-weight depressive patients. In addition, absolute glucose values were significantly correlated with body mass index in all subjects. Future positron emission tomographic studies in psychiatric patients should control for alimentary parameters.

背景与目标： 饮食和情感障碍之间的关系仍然复杂且不清楚。厌食症患者的脑葡萄糖代谢已被证实在全球和区域均降低，顶叶皮层中存在特定的相对低代谢。为了探索减肥或抑郁症状对脑代谢的可能影响，我们研究了年龄和性别相匹配的低体重厌食症和抑郁症患者，正常体重的抑郁症患者以及健康志愿者。低体重患者的全球和区域绝对葡萄糖活性水平降低，而厌食患者的葡萄糖水平最低。在相对价值方面，与对照组相比，厌食患者的顶叶代谢明显降低，而尾核中的新陈代谢较其他组更高。葡萄糖的绝对低代谢似乎是低体重的结果，因为它在低体重厌食症患者和低体重抑郁症患者中均被发现。另外，在所有受试者中，绝对葡萄糖值与体重指数显着相关。未来精神病患者的正电子发射断层扫描研究应控制饮食参数。

BACKGROUND & AIMS: BACKGROUND:Control of hyperglycemia in adult medical and surgical intensive care units (ICUs) has been shown to dramatically decrease morbidity and mortality. Algorithms to achieve glycemic control in the ICU setting are evolving. We have evaluated the use of a discrete proportional-integral-derivative (PID) algorithm to control hyperglycemia in pediatric ICU (PICU) patients both with and without diabetes. METHODS:Six PICU patients [four with diabetic ketoacidosis (DKA) and two with glucocorticoid-induced hyperglycemia] with glucose values >150 mg/dL were enrolled. Their hyperglycemia was managed with a PID algorithm that provided recommendations for both changes in the intravenous insulin infusion rate and the time to obtain the next discrete glucose value. Glucose targets were adjusted based on clinical circumstances. RESULTS:Patients (mean age 9.2 years; range 1.8-14 years) utilized the algorithm for a total of 454.4 h. Mean time to the initial glucose target was 8.7 h (range 1.3-15.1 h) in five patients. One subject with hyperosmolar DKA did not achieve target before discharge from the PICU, and another was at target when the algorithm was initiated. After the glucose target was achieved, the mean SD was 23.5 mg/dL, and glucose values were >40 mg/dL above target 13% of the time and <40 mg/dL below target 1% of the time. There were no glucose values <55 mg/dL. CONCLUSION:The PID algorithm safely and effectively controlled hyperglycemia in a PICU, despite multiple changes in intravenous fluids, steroid doses (including high-dose pulses), and hemodialysis.

背景与目标： 摘要背景：控制成人医学和外科重症监护病房（ICU）的高血糖症已显着降低发病率和死亡率。在ICU设置中实现血糖控制的算法正在不断发展。我们评估了使用离散比例积分微分（PID）算法来控制有或没有糖尿病的小儿ICU（PICU）患者的高血糖。
方法：招募了6例PICU患者[其中4例患有糖尿病酮症酸中毒（DKA），2例患有糖皮质激素引起的高血糖症]，其血糖值> 150 mg / dL。他们的高血糖症通过PID算法进行管理，该算法为静脉内胰岛素输注速率的变化以及获得下一个离散葡萄糖值的时间提供了建议。根据临床情况调整葡萄糖靶标。
结果：患者（平均年龄9.2岁；范围1.8-14岁）使用该算法的时间总计为454.4小时。五名患者达到初始血糖目标的平均时间为8.7小时（范围1.3-15.1小时）。高渗性DKA的一名受试者在未从PICU出院前未达到目标，另一名受试者在算法启动时就达到了目标。达到葡萄糖目标后，平均SD为23.5 mg / dL，并且葡萄糖值在目标时间的13％之上大于40 mg / dL，在目标时间的1％以下小于40 mg / dL。没有葡萄糖值＜55mg / dL。
结论：尽管静脉输液，类固醇剂量（包括大剂量脉搏）和血液透析发生了多种变化，PID算法仍可安全有效地控制PICU中的高血糖。

BACKGROUND & AIMS: AIM:This study assessed whether the poor correlation between HbA1c and oral glucose tolerance test (OGTT) for dysglycaemia diagnosis may be explained by haemoglobin glycation (HbG). METHODS:A total of 1033 consecutive overweight or obese patients with no known diabetes underwent OGTT and measurement of HbA1c to diagnose diabetes and dysglycaemia (American Diabetes Association criteria). For each OGTT result category, low, medium and high HbG was defined according to the mean HbA1c/fructosamine ratio and mean fructosamine. High HbG was defined as values greater than mean values in each OGTT category for both HbA1c/fructosamine ratio and fructosamine levels, and low HbG was defined as lower values of both. The remaining patients were considered medium HbG. RESULTS:Based on OGTT and HbA1c values, 267 (25.8%) and 443 (42.8%) patients had intermediate hyperglycaemia, and 66 (6.4%) and 95 (9.2%) patients had diabetes, respectively. The results were discordant for intermediate hyperglycaemia or diabetes diagnosis in 41.7% and for diabetes diagnosis in 10.0% of the patients. The proportion of patients with HbA1c≥6.5%, but without OGTT-diagnosed diabetes, was 0%, 3.8% and 32.8% in the low-HbG, medium-HbG and high-HbG groups, respectively. In contrast, the proportion of patients with HbA1c<5.7%, but with an abnormal OGTT, was 30.4%, 11.1% and 0%, respectively. The AUROC of HbA1c to detect OGTT-diagnosed diabetes was better in the medium-HbG group [0.874 (0.816-0.931)] than in those with low or high HbG [0.628 (0.489-0.768); P<0.01]. Only age was independently associated with high-HbG status [10-year OR: 1.3 (1.1-1.5); P<0.0001]. CONCLUSION:Haemoglobin glycation may explain many of the discordant results between HbA1c and OGTT when used for dysglycaemia diagnosis.

背景与目标： 目的：该研究评估了HbA1c与口服葡萄糖耐量试验（OGTT）诊断血糖异常之间的不良关联是否可以通过血红蛋白糖化（HbG）来解释。
方法：总共1033例不明糖尿病的连续超重或肥胖患者接受OGTT并测量HbA1c以诊断糖尿病和血糖异常（美国糖尿病协会标准）。对于每个OGTT结果类别，根据平均HbA1c /果糖胺比率和平均果糖胺定义低，中和高HbG。高HbG定义为HbA1c /果糖胺比率和果糖胺水平在每个OGTT类别中均大于平均值，而低HbG定义为两者均较低。其余患者被认为是中等HbG。
结果：基于OGTT和HbA1c值，分别有267例（25.8％）和443例（42.8％）的患者出现中度高血糖，分别为66例（6.4％）和95例（9.2％）的糖尿病。结果与41.7％的中度高血糖或糖尿病诊断和10.0％的患者的糖尿病诊断不一致。低HbG，中HbG和高HbG组中HbA1c≥6.5％但无OGTT诊断的糖尿病的患者比例分别为0％，3.8％和32.8％。相反，HbA1c <5.7％但OGTT异常的患者比例分别为30.4％，11.1％和0％。在中等HbG组[0.874（0.816-0.931）]中，HbA1c的AUROC检测OGTT诊断的糖尿病要好于HbG较低或较高[0.628（0.489-0.768）]。 P ＜0.01]。只有年龄与高HbG状况独立相关[10年OR：1.3（1.1-1.5）； P <0.0001]。
结论：血红蛋白糖基化可解释HbA1c和OGTT在诊断血糖异常中的许多不一致结果。

BACKGROUND & AIMS: :Chronic exposure to high glucose leads to diabetic nephropathy characterized by increased mesangial matrix protein (e.g., collagen) accumulation. Altered cell signaling and gene expression accompanied by oxidative stress have been documented. The contribution of the tyrosine kinase, c-Src (Src), which is sensitive to oxidative stress, was examined. Cultured rat mesangial cells were exposed to high glucose (25 mmol/L) in the presence and absence of Src inhibitors (PP2, SU6656), Src small interfering RNA (siRNA), and the tumor necrosis factor-α-converting enzyme (TACE) inhibitor, TAPI-2. Src was investigated in vivo by administration of PP2 to streptozotocin (STZ)-induced diabetic DBA2/J mice. High glucose stimulated Src, TACE, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK1/2, p38), and collagen IV accumulation in mesangial cells. PP2 and SU6656 blocked high glucose-stimulated phosphorylation of Src Tyr-416, EGFR, and MAPKs. These inhibitors and Src knockdown by siRNA, as well as TAPI-2, also abrogated high glucose-induced phosphorylation of these targets and collagen IV accumulation. In STZ-diabetic mice, albuminuria, increased Src pTyr-416, TACE activation, ERK and EGFR phosphorylation, glomerular collagen accumulation, and podocyte loss were inhibited by PP2. These data indicate a role for Src in a high glucose-Src-TACE-heparin-binding epidermal growth factor-EGFR-MAPK-signaling pathway to collagen accumulation. Thus, Src may provide a novel therapeutic target for diabetic nephropathy.

背景与目标： ：长期暴露于高葡萄糖会导致糖尿病肾病，其特征是肾小球系膜基质蛋白（例如胶原蛋白）蓄积增加。已经记录了改变的细胞信号传导和基因表达并伴有氧化应激。检查了对氧化应激敏感的酪氨酸激酶c-Src（Src）的贡献。在存在和不存在Src抑制剂（PP2，SU6656），Src小干扰RNA（siRNA）和肿瘤坏死因子-α转化酶（TACE）的情况下，将培养的大鼠肾小球系膜细胞暴露于高葡萄糖（25 mmol / L）抑制剂，TAPI-2。通过对链脲佐菌素（STZ）诱导的糖尿病DBA2 / J小鼠施用PP2在体内研究了Src。高葡萄糖刺激的Src，TACE，表皮生长因子受体（EGFR），有丝分裂原激活的蛋白激酶（MAPK），细胞外信号调节激酶（ERK1 / 2，p38）和胶原IV在肾小球膜细胞中的蓄积。 PP2和SU6656阻止了Src Tyr-416，EGFR和MAPK的高葡萄糖刺激磷酸化。这些抑制剂和siRNA以及SAPI敲除的Src敲除也废除了高葡萄糖诱导的这些靶标的磷酸化和胶原IV的积累。在STZ糖尿病小鼠中，白蛋白尿，Src pTyr-416升高，TACE活化，ERK和EGFR磷酸化，肾小球胶原蛋白积聚和足细胞丢失均被PP2抑制。这些数据表明Src在高葡萄糖-Src-TACE-肝素结合表皮生长因子-EGFR-MAPK信号通路中积累胶原蛋白的作用。因此，Src可以为糖尿病性肾病提供新的治疗靶标。

BACKGROUND & AIMS: :Abstract Glucose has been found to impair the inhibition of platelets with aspirin and alter the basal activity of nitric oxide synthase (NOS) in platelets. The aim of this work was to study the effects of glucose on the inhibitory pathways in activated platelets. A short-term incubation of glucose impaired the inhibition of platelet aggregation induced by agents activating an NOS-dependent pathway, such as l-arginine, adenosine and α-tocopherol. However, glucose had no effect on the inhibition induced by iloprost and BW245C, agents that activate the cyclic adenosine monophosphate (cAMP) signaling pathway. Potassium lactate attenuated the effects of the same inhibitors as glucose did. The inhibitors of glucose transport prevented the effect of glucose. Dichloroacetate, known to prevent the conversion of pyruvate to lactate and to decrease lactate in platelets, significantly attenuated the effect of glucose in platelets. The data support the suggestion that the effect of glucose on the inhibition of platelets by agents activating an NOS-dependent pathway is mediated by glucose metabolite lactate.

背景与目标： 摘要：已发现葡萄糖会削弱阿司匹林对血小板的抑制作用，并改变血小板中一氧化氮合酶（NOS）的基础活性。这项工作的目的是研究葡萄糖对活化血小板抑制途径的影响。葡萄糖的短期温育削弱了由激活NOS依赖性途径的药物（如L-精氨酸，腺苷和α-生育酚）诱导的血小板凝集抑制作用。但是，葡萄糖对伊洛前列素和BW245C所诱导的抑制作用没有影响，伊洛前列素和BW245C可以激活环磷酸腺苷（cAMP）信号通路。乳酸钾减弱了与葡萄糖相同的抑制剂的作用。葡萄糖转运的抑制剂阻止了葡萄糖的作用。众所周知，二氯乙酸盐可防止丙酮酸转化为乳酸盐并减少血小板中的乳酸盐，从而大大减弱了葡萄糖在血小板中的作用。数据支持这样的建议，即葡萄糖对乳酸的影响是通过激活NOS依赖性途径的药物对血小板的抑制作用。

BACKGROUND & AIMS: AIMS/HYPOTHESIS:Impaired regulation of lipolysis and accumulation of lipid intermediates may contribute to obesity-related insulin resistance and type 2 diabetes mellitus. We investigated insulin-mediated suppression of lipolysis in abdominal subcutaneous adipose tissue (AT) and skeletal muscle (SM) of obese men with normal glucose tolerance (NGT) and obese type 2 diabetic men. METHODS:Eleven NGT men and nine long-term diagnosed type 2 diabetic men (7 ± 1 years), matched for age (58 ± 2 vs 62 ± 2 years), BMI (31.4 ± 0.6 vs 30.5 ± 0.6 kg/m(2)) and [Formula: see text] (28.9 ± 1.5 vs 29.5 ± 2.4 ml kg(-1) min(-1)) participated in this study. Interstitial glycerol concentrations in AT and SM were assessed using microdialysis during a 1 h basal period and a 6 h stepwise hyperinsulinaemic-euglycaemic clamp (8, 20 and 40 mU m(-2) min(-1)). AT and SM biopsies were collected to investigate underlying mechanisms. RESULTS:Hyperinsulinaemia suppressed interstitial SM glycerol concentrations less in men with type 2 diabetes (-7 ± 6%, -13 ± 9% and -27 ± 9%) compared with men with NGT (-21 ± 7%, -38 ± 8% and -53 ± 8%) (p = 0.014). This was accompanied by increased circulating fatty acid and glycerol concentrations, a lower glucose infusion rate (21.8 ± 3.1 vs 30.5 ± 2.0 μmol kg body weight(-1) min(-1); p < 0.05), higher hormone-sensitive lipase (HSL) serine 660 phosphorylation, increased saturated diacylglycerol (DAG) lipid species in the muscle membrane and increased protein kinase C (PKC) activation in type 2 diabetic men vs men with NGT. No significant differences in insulin-mediated reduction in AT interstitial glycerol were observed between groups. CONCLUSIONS/INTERPRETATION:Our results suggest that a blunted insulin-mediated suppression of SM lipolysis may promote the accumulation of membrane saturated DAG, aggravating insulin resistance, at least partly mediated by PKC. This may represent an important mechanism involved in the progression of insulin resistance towards type 2 diabetes. TRIAL REGISTRATION:ClinicalTrials.gov NCT01680133.

背景与目标： 目的/假设：脂解作用的调节受损和脂质中间体的积累可能会导致肥胖相关的胰岛素抵抗和2型糖尿病。我们调查了胰岛素抵抗正常的肥胖男性和2型糖尿病男性肥胖者的腹部皮下脂肪组织（AT）和骨骼肌（SM）的胰岛素介导的脂解抑制作用。
方法：11名NGT男性和9名经长期诊断的2型糖尿病男性（7±1岁），年龄相匹配（58±2 vs 62±2岁），BMI（31.4±0.6 vs 30.5±0.6 kg / m（2） ）和[公式：参见文字]（28.9±1.5 vs 29.5±2.4 ml kg（-1）min（-1））参与了这项研究。在1 h的基础期和6 h的逐步高胰岛素血症-正常血糖钳制（8、20和40 mU m（-2）min（-1））中使用微透析法评估AT和SM中的间质甘油浓度。收集AT和SM活组织检查以研究潜在的机制。
结果：与NGT男性（-21±7％，-38±8）相比，高胰岛素血症抑制的2型糖尿病男性的间质SM甘油浓度更低（-7±6％，-13±9％和-27±9％） ％和-53±8％）（p = 0.014）。这伴随着循环脂肪酸和甘油浓度的增加，葡萄糖输注速率的降低（21.8±3.1 vs 30.5±2.0μmolkg体重（-1）min（-1）; p <0.05），激素敏感性脂肪酶更高（ HSL）丝氨酸660磷酸化，2型糖尿病男性患者与NGT男性相比，肌肉膜中饱和二酰基甘油（DAG）脂质种类增加，蛋白激酶C（PKC）活化增加。两组之间在胰岛素介导的AT间质甘油减少方面没有观察到显着差异。
结论/解释：我们的结果表明，胰岛素介导的SM脂解抑制作用减弱可能会促进膜饱和DAG的积累，加重胰岛素抵抗，至少部分是由PKC介导的。这可能代表了胰岛素抵抗向2型糖尿病发展的重要机制。
试用注册：ClinicalTrials.gov NCT01680133。

BACKGROUND & AIMS: :Protein tyrosine phosphatase 1B (PTP1B) is a key element in the negative regulation of the insulin signaling pathway and may play an important role in diabetes and obesity. We identified ursolic acid, a natural pentacyclic triterpenoid that occurs widely in traditional Chinese medicinal herbs, as an inhibitor of PTP1B by screening an extract library of the traditional Chinese medicinal herbs used a diabetes clinic. By modifying urosolic acid, we designed and synthesized a derivative with a K(i) of 283 nM. As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase alpha and epsilon, which are all possibly involved in the insulin pathway. The ursolic acid derivative enhanced insulin receptor phosphorylation in CHO/hIR cells and stimulate glucose uptake in L6 myotubes.

背景与目标： ：蛋白酪氨酸磷酸酶1B（PTP1B）是胰岛素信号通路负调节的关键因素，可能在糖尿病和肥胖症中起重要作用。通过筛选用于糖尿病门诊的传统中草药提取物库，我们确定了熊果酸（一种普遍存在于传统中草药中的天然五环三萜类化合物）作为PTP1B抑制剂。通过修饰熊果酸，我们设计并合成了K（i）为283 nM的衍生物。作为PTP1B的竞争性抑制剂，熊果酸及其衍生物还抑制T细胞蛋白酪氨酸磷酸酶和src同源性磷酸酶2，但不抑制白细胞抗原相关的磷酸酶或蛋白酪氨酸磷酸酶α和epsilon，这些都可能与胰岛素途径有关。熊果酸衍生物增强CHO / hIR细胞中胰岛素受体的磷酸化，并刺激L6肌管中的葡萄糖摄取。

BACKGROUND & AIMS: INTRODUCTION:Basal leptin level has been demonstrated to correlate positively with many indices of obesity, as well as insulin resistance. However, to date, little is known about regulation of leptin in obese children with incipient glucose metabolic disorders. OBJECTIVE:The aim of this study was to define the precise influence of the glucose tolerance status on plasma leptin in obese boys and girls separately. MATERIAL AND METHODS:70 obese children with impaired glucose tolerance (IGT) and well-matched 70 normal glucose-tolerant (NGT) subjects were examined. Fasting and 2-h post glucose load plasma glucose and insulin levels as well as fasting leptin levels were determined, apart from anthropometric measurements. RESULTS:Leptin levels were significantly lower in girls with IGT compared to NGT girl (17.7+/-6.5 microg/L vs. 23.1+/-7.7 microg/L; p<.001). No such difference was observed in boys. In a multiple regression analysis adjusting for age and adiposity, in the female group plasma glucose and insulin levels 2-h after glucose load were the best predictors of fasting plasma leptin (r=-0.49, p<.005 and r=0.34, p<.05; respectively). In boys, plasma insulin level 2-h after glucose load was the independent determinant of leptin (r=0.36, p<.05). CONCLUSION:The differences between regulation of leptin synthesis in girls and boys with simple obesity were found. The stimulatory effect of insulin on leptin synthesis was greater in girls with normoglycemia than in girls with impaired glucose tolerance.

背景与目标： 简介：基础瘦素水平已被证明与许多肥胖指数以及胰岛素抵抗呈正相关。然而，迄今为止，关于肥胖儿童早期糖代谢紊乱中瘦素的调控知之甚少。
目的：本研究的目的是明确定义葡萄糖耐量状态对肥胖男孩和女孩血浆瘦素的精确影响。
材料与方法：检查了70名糖耐量受损（IGT）肥胖儿童和70名正常糖耐量（NGT）受试者的匹配性。除了人体测量之外，还测定了空腹和葡萄糖负荷后2小时的血浆葡萄糖，胰岛素水平以及空腹瘦素水平。
结果：IGT女孩的瘦素水平明显低于NGT女孩（17.7 /-6.5 microg / L vs. 23.1 /-7.7 microg / L； p <.001）。在男孩中没有观察到这种差异。在校正年龄和肥胖的多元回归分析中，在女性组中，葡萄糖负荷后2小时的血浆葡萄糖和胰岛素水平是空腹血浆瘦素的最佳预测指标（r = -0.49，p <.005，r = 0.34，p <.05;分别）。在男孩中，葡萄糖负荷后2小时的血浆胰岛素水平是瘦素的独立决定因素（r = 0.36，p <.05）。
结论：发现单纯性肥胖的男孩和女孩的瘦素合成调控存在差异。血糖正常的女孩胰岛素对瘦素合成的刺激作用大于葡萄糖耐量受损的女孩。

BACKGROUND & AIMS: OBJECTIVE:We determined the longitudinal association of glucose metabolism with retinopathy in a sample of the Australian population. RESEARCH DESIGN AND METHODS:The Australian Diabetes Obesity and Lifestyle (AusDiab) study is a national, longitudinal study of adults aged > or =25 years from 42 randomly selected areas of Australia. Retinopathy was assessed at baseline in 1999-2000 and 5 years later in 2004-2005 in participants identified as having diabetes (based on self-report and oral glucose tolerance test) and impaired glucose metabolism and in a random sample with normal glucose tolerance. Complete retinal data were available for 1,192 participants. Photographs were graded at two time points according to a simplified version of the Wisconsin grading system. RESULTS:The 5-year incidences of retinopathy were 13.9 and 3.0% among those with known and newly diagnosed diabetes at baseline, respectively. Of those who developed incident newly diagnosed diabetes at follow-up, 11.9% had retinopathy at baseline compared with 5.6% of those who did not progress to incident newly diagnosed diabetes (P = 0.037). After adjustment for factors identified as risk factors for diabetes, individuals with retinopathy signs at baseline were twice as likely to develop incident newly diagnosed diabetes compared with those who did not have retinopathy signs at baseline. CONCLUSIONS:The 5-year incidence of retinopathy was 13.9% among individuals with known diabetes. Nondiabetic individuals with retinopathy signs at baseline had a twofold higher risk of developing incident newly diagnosed diabetes 5 years later. This result provides further evidence that mild retinopathy signs may be a preclinical marker of underlying microvascular disease and future diabetes risk.

背景与目标： 目的：我们确定了澳大利亚人群样本中葡萄糖代谢与视网膜病变的纵向相关性。
研究设计与方法：澳大利亚糖尿病肥胖与生活方式研究（AusDiab）是一项全国纵向研究，研究对象是来自澳大利亚42个随机选择地区的25岁或以上的成年人。在1999-2000年和5年后的2004-2005年的基线时，对被鉴定为患有糖尿病（根据自我报告和口服葡萄糖耐量试验）和葡萄糖代谢受损的参与者以及随机抽取的葡萄糖耐量正常的参与者进行了视网膜病变评估。完整的视网膜数据可供1,192名参与者使用。根据简化版的威斯康星州评分系统，在两个时间点对照片进行了评分。
结果：在基线时已知和新诊断的糖尿病患者中，视网膜病变的5年发生率分别为13.9％和3.0％。在随访中发展为新诊断为糖尿病的人中，基线时有11.9％的视网膜病变，而未进展为新诊断为糖尿病的人为5.6％（P = 0.037）。在对确定为糖尿病危险因素的因素进行校正后，基线时视网膜病变征象的个体发生新近诊断出的糖尿病的可能性是基线时没有视网膜病变征象的个体的两倍。
结论：已知糖尿病患者的5年视网膜病变发生率为13.9％。基线时具有视网膜病变征象的非糖尿病患者在5年后患新诊断出的糖尿病的风险要高两倍。该结果提供了进一步的证据，表明轻度的视网膜病变征象可能是潜在的微血管疾病和未来糖尿病风险的临床前标志物。

BACKGROUND & AIMS: :Thirteen positron emission tomographic studies of cerebral glucose utilization were carried out in 12 patients with postanoxic syndrome due to cardiac arrest. Seven subjects were in a persistent vegetative state. The 5 other subjects were normally conscious, but disclosed focal neurological signs. When compared with normal values, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative subjects, and to a lesser degree (+/- 25%) in conscious patients. The most consistent regional alterations were found in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories, followed by the frontomesial junction (5 cases), the striatum (3 cases with dystonia), thalamus (2 cases), and visual cortex (2 cases with cortical blindness). These data suggest that brain anoxia can result in global brain hypometabolism, which appears related to the vigilance state, as well as in regional alterations preferentially located in arterial border zones.

背景与目标： ：对12名因心脏骤停而导致的缺氧后综合征的患者进行了13次正电子发射断层扫描术，研究了脑葡萄糖利用情况。七名受试者处于持续的植物生长状态。其他5名受试者通常是有意识的，但有局灶性神经系统体征。当与正常值比较时，营养受试者的平均脑葡萄糖代谢急剧下降（+/- 50％），而意识清醒的患者的平均脑葡萄糖代谢降低程度较小（+/- 25％）。最一致的区域性改变是在顶枕皮层（9例），椎骨和颈动脉领土之间的边界，其次是额骨交界处（5例），纹状体（肌张力障碍3例），丘脑（2例）。 ）和视觉皮层（2例皮质失明）。这些数据表明，脑缺氧可导致整体脑代谢不足，这与警惕状态以及优先位于动脉边界区域的区域改变有关。

BACKGROUND & AIMS: :Medicinal plants constitute an important source of potential therapeutic agents for diabetes. In the present study, we investigated the effects of Moringa oleifera (MO) Lam, Moringacea, on glucose tolerance in Wistar rats and Goto-Kakizaki (GK) rats, modeled type 2 diabetes. Major polyphenols in MO powder were quercetin glucosides, rutin, kaempferol glycosides and chlorogenic acids by HPLC analysis. As the results of glucose tolerance test, MO significantly decreased the blood glucose at 20, 30, 45and 60 min for GK rats and at 10, 30 and 45 min for Wistar rats (p<0.05) compared to the both controls after glucose administration. The area under the curve of changes in the blood glucose was significantly higher in the GK control group than in the GK plus MO group (p<0.05) in the periods 30-60 min and 60-120 min. Furthermore, MO significantly decreased stomach emptying in GK rats (p<0.05). The results indicated that MO has an ameliorating effect for glucose intolerance, and the effect might be mediated by quercetin-3-glucoside and fiber contents in MO leaf powder. The action of MO was greater in GK rats than in Wistar rats.

背景与目标： ：药用植物构成了糖尿病潜在治疗剂的重要来源。在本研究中，我们调查了辣木（MO）林，辣木对Wistar大鼠和Goto-Kakizaki（GK）大鼠（模型2型糖尿病）的葡萄糖耐量的影响。通过HPLC分析，MO粉末中的主要多酚是槲皮素葡糖苷，芦丁，山emp酚糖苷和绿原酸。作为葡萄糖耐量试验的结果，与给予葡萄糖后的两个对照组相比，MO显着降低了GK大鼠在20、30、45和60分钟时的血糖，而Wistar大鼠在10、30和45分钟时降低了血糖（p <0.05）。在30-60分钟和60-120分钟期间，GK对照组的血糖变化曲线下面积显着高于GK + MO组（p <0.05）。此外，MO显着降低了GK大鼠的胃排空（p <0.05）。结果表明，MO对葡萄糖不耐症具有改善作用，其作用可能是由槲皮素-3-葡萄糖苷和MO叶粉中的纤维含量介导的。 MO的作用在GK大鼠中比在Wistar大鼠中更大。

BACKGROUND & AIMS: :Inhibition of repair of sublethal and potentially lethal damage was observed in respiratory-deficient mutants of yeast during fractionated X-irradiation in the presence of equimolar concentrations of 2-deoxy-D-glucose and glucose in the growth medium. In the wild-type cells, on the other hand, an enhancement of repair of the potentially lethal damage was obtained under similar conditions. These results suggest, by analogy, that in higher organisms also, 2-deoxy-D-glucose may differentially inhibit the repair of radiation damage in hypoxic tumor cells while enhancement of repair processes could be expected in normal tissues.

背景与目标： ：在生长培养基中存在等摩尔浓度的2-脱氧-D-葡萄糖和葡萄糖的情况下，在分级X射线辐照期间，在酵母的呼吸不足突变体中观察到了对亚致死和潜在致死性损伤的修复的抑制作用。另一方面，在野生型细胞中，在类似条件下获得了对潜在致死性损伤的修复增强作用。类似地，这些结果表明，在高等生物中，2-脱氧-D-葡萄糖也可以差异地抑制缺氧肿瘤细胞中辐射损伤的修复，而在正常组织中有望增强修复过程。

BACKGROUND & AIMS: :During continuous ambulatory peritoneal dialysis, the peritoneum is directly and continuously exposed to unphysiologic peritoneal dialysis fluid; the resulting mesothelial damage has been suggested to cause loss of ultrafiltration and dialysis efficacy. The present study investigated the effect of a high glucose concentration on cultured human peritoneal mesothelial cells to clarify the cause of decreased dialysis efficacy during prolonged peritoneal dialysis. High glucose caused a concentration-dependent decrease in cell proliferation, damage to the intercellular junctions, and excess production of transforming growth factor-beta (TGF-beta). The levels of intercellular junctional proteins (ZO-1, E-cadherin, and beta-catenin) were decreased, and immuno-staining by anti-ZO-1 and anti- beta-catenin antibodies became weaker and often discontinuous along the cell contour. Mannitol had similar but weaker effects at the same osmolality, and an anti-TGF-beta neutralizing antibody reduced the effects of high glucose. Therefore, these effects were induced not only by glucose itself but also by hyperosmolality and by a glucose-induced increase of TGF-beta. These findings suggest that the peritoneal mesothelium is damaged by prolonged peritoneal dialysis using high glucose dialysate and that impairment of the intercellular junctions of peritoneal mesothelial cells by high glucose dialysate induces peritoneal hyperpermeability and a progressive reduction in dialysis efficacy.

背景与目标： ：在连续非卧床腹膜透析过程中，腹膜直接和连续暴露于非生理性腹膜透析液中；已经表明，由此引起的间皮损害会导致超滤和透析功效的丧失。本研究调查了高浓度葡萄糖对培养的人腹膜间皮细胞的影响，以阐明长时间腹膜透析过程中透析功效降低的原因。高葡萄糖会引起细胞增殖的浓度依赖性下降，对细胞间连接的破坏以及转化生长因子-β（TGF-β）的过量产生。细胞间连接蛋白（ZO-1，E-cadherin和β-catenin）的水平降低，并且抗ZO-1和抗β-catenin抗体的免疫染色变得更弱，并且通常沿细胞轮廓不连续。甘露醇在相同的重量克分子渗透压浓度下具有相似但较弱的作用，抗TGF-β中和抗体可降低高葡萄糖的作用。因此，这些作用不仅由葡萄糖本身引起，而且由高渗性和由葡萄糖引起的TGF-β增加引起。这些发现表明，使用高葡萄糖透析液的长期腹膜透析会损害腹膜间皮，而高葡萄糖透析液对腹膜间皮细胞的细胞间连接的损伤会诱导腹膜高通透性并逐渐降低透析功效。

BACKGROUND & AIMS: BACKGROUND:This follow-up study aimed to assess the frequency of late effects on glucose and lipid metabolism after bone-marrow transplantation in childhood. METHODS:23 long-term survivors (median age 20 years) were studied 3-18 years after bone-marrow transplantation and compared with 23 healthy controls matched for age and sex and with 13 patients in remission from leukaemia. FINDINGS:12 (52%) of the 23 bone-marrow transplantation patients had insulin resistance, including impaired glucose tolerance in six and type 2 diabetes in four. The core signs of the metabolic syndrome (hyperinsulinaemia and hypertriglyceridaemia combined), were found in nine (39%) of the bone-marrow transplantation patients compared with one (8%) of the 13 leukaemia patients and none of the healthy controls (p=0.0015). The frequency of insulin resistance increased with the time since bone-marrow transplantation. Abdominal obesity, but not overweight, was common among the patients with insulin resistance. INTERPRETATION:Long-term survivors of bone-marrow transplantation are at substantial risk of insulin resistance, impaired glucose tolerance, and type 2 diabetes even at normal weight and young age. They also develop typical signs of the metabolic syndrome. We advocate measurement of serum lipids, fasting blood glucose, and serum insulin for the follow-up of all patients who undergo transplants in childhood, to be continued regularly and possibly life-long.

背景与目标： 背景：这项后续研究旨在评估儿童骨髓移植后对葡萄糖和脂质代谢的后期影响频率。
方法：对23名长期存活者（中位年龄为20岁）进行了骨髓移植后3-18年的研究，并与年龄和性别相匹配的23名健康对照者以及13名白血病缓解的患者进行了比较。
结果：23例骨髓移植患者中有12例（52％）具有胰岛素抵抗，其中6例患者的糖耐量降低，而4例患者的2型糖尿病。在9名（39％）骨髓移植患者中发现了代谢综合征的核心症状（合并高胰岛素血症和高甘油三酯血症），而13名白血病患者中有1名（8％）却没有健康对照（p = 0.0015）。自骨髓移植以来，胰岛素抵抗的频率随时间增加。胰岛素抵抗患者常见腹部肥胖，但不超重。
解释：即使在正常体重和年轻年龄下，长期接受骨髓移植的幸存者仍存在胰岛素抵抗，糖耐量受损和2型糖尿病的重大风险。他们还发展出代谢综合症的典型体征。我们提倡测量所有儿童时期接受移植手术的患者的血脂，空腹血糖和血清胰岛素水平，并定期且可能终生持续进行。

BACKGROUND & AIMS: OBJECTIVE:We have recently reported that the initial distribution volume of glucose (IDVG) reliably measures the central extracellular fluid (ECF) volume in the presence of fluid gain or loss. However, it is not clear if IDVG consistently reflects central-ECF volume when redistribution of fluid occurs in the absence of fluid gain or loss. This study was designed to investigate changes in fluid volumes during phentolamine infusion in dogs. DESIGN:Prospective animal study. SETTING:Institutional animal research laboratory. SUBJECTS:Fourteen anesthetized and ventilated mongrel dogs. INTERVENTIONS:Anesthetized animals were mechanically ventilated and received infusions of normal saline (n = 7) or phentolamine (10 microg kg min) (n = 7). Plasma volume was estimated using the indocyanine green (ICG) dilution method (PV-ICG) and IDVG was calculated using a one-compartment model by simultaneous administration of ICG 0.5 mg/kg and glucose 100 mg/kg before, during, and after infusion of either drug. MEASUREMENTS AND RESULTS:PV-ICG during infusion was not different between groups. However, IDVG significantly decreased (P < 0.05) following phentolamine infusion when compared with normal saline infusion. CONCLUSION:Our results suggest that IDVG rather than PV-ICG consistently measures central extracellular fluid volume, even when redistribution of fluid occurs.

背景与目标： 目的：我们最近报道说，在存在体液增减的情况下，葡萄糖的初始分布体积（IDVG）可以可靠地测量中心细胞外液（ECF）的体积。但是，尚不清楚在没有流体增减的情况下发生流体的重新分配时，IDVG是否能始终如一地反映中心ECF量。这项研究旨在调查在狗的酚妥拉明输注过程中体液量的变化。
设计：前瞻性动物研究。
地点：机构动物研究实验室。
主题：十四只麻醉和通风的杂种狗。
干预措施：对麻醉过的动物进行机械通气，并输注生理盐水（n = 7）或苯妥拉明（10 microg kg min）（n = 7）。使用吲哚菁绿（ICG）稀释方法（PV-ICG）估算血浆体积，并使用一室模型通过在输注之前，之中和之后同时施用0.5 mg / kg的ICG和100 mg / kg的葡萄糖来计算IDVG任何一种药物。
测量和结果：输注期间的PV-ICG在两组之间没有差异。然而，与生理盐水输注相比，酚妥拉明输注后IDVG显着降低（P <0.05）。
结论：我们的结果表明，IDVG而不是PV-ICG始终能测量中央细胞外液量，即使在发生液体重新分配时也是如此。