• 【糖尿病患者的高血压治疗不足。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【肥胖和糖尿病突变小鼠胰腺和垂体中神经肽的含量:品系和性别差异。】 复制标题 收藏 收藏
    DOI:10.1016/0026-0495(90)90252-8 复制DOI
    作者列表:Timmers K,Coleman DL,Voyles NR,Powell AM,Rökaeus A,Recant L
    BACKGROUND & AIMS: :The nature of the primary genetic defects in ob/ob and db/db mice are unknown. Both the obese (ob) and diabetes (db) mutations produce similar, multicomponent obese-hyperinsulinemic syndromes when maintained in the same strain of mouse. In an attempt to find differences between these mutations in neuroendocrine function affecting the islets of Langerhans or the pituitary, tissue content of four neuropeptides that are known to be capable of influencing the rate of insulin secretion was examined in obese (ob/ob) and diabetes (db/db) mice. In the first study, C57BL/6Job/ob and control males were studied at 3, 4, and 11 weeks of age. In the second study, db/db mice of both sexes and two inbred strains (C57BL/6J and C57BL/KsJ), which differ markedly in the severity of expression of the diabetes phenotype, were studied at 3 weeks of age, before the development of hyperglycemia and secondary consequences thereof. Immunoreactive peptides were measured in acetic acid extracts of pancreas and pituitary. No differences between male ob/ob and db/db mice of the C57BL/6J strain were found. Marked sex differences in lean control mice were found at 3 weeks of age in pancreatic Met-enkephalin-LI and galanin-LI (with two- to threefold higher content in males). Low pancreatic content (50% to 70% lower than in control mice) of galanin-LI, Met-enkephalin-LI and Leu-enkephalin-LI was associated with hyperinsulinemia in male B6 ob/ob and db/db mice at 3 weeks of age, though not in B6 db/db females and not in BKs db/db mice of either sex.(ABSTRACT TRUNCATED AT 250 WORDS)
    背景与目标: :ob / ob和db / db小鼠的主要遗传缺陷的性质尚不清楚。肥胖(ob)和糖尿病(db)突变在同一小鼠品系中均会产生相似的多成分肥胖-高胰岛素血症综合征。为了发现影响兰格罕氏岛或垂体的胰岛的神经内分泌功能的这些突变之间的差异,在肥胖(ob / ob)和糖尿病患者中检查了四种已知能够影响胰岛素分泌速率的神经肽的组织含量(db / db)小鼠。在第一个研究中,研究了C57BL / 6Job / ob和对照男性在3、4和11周的年龄。在第二项研究中,在发育前的3周龄研究了具有性别和两种近交系(C57BL / 6J和C57BL / KsJ)的db / db小鼠,它们在糖尿病表型的表达严重程度上有显着差异。高血糖及其继发后果。在胰腺和垂体的乙酸提取物中测量了免疫反应性肽。在C57BL / 6J株的雄性ob / ob和db / db小鼠之间未发现差异。在瘦瘦对照小鼠中,在三周龄的胰腺Met-脑啡肽-LI和甘丙肽-LI中发现明显的性别差异(雄性含量高2至3倍)。在3周龄的雄性B6 ob / ob和db / db小鼠中,甘丙肽-LI,Met-脑啡肽-LI和亮-脑啡肽-LI的胰腺含量低(比对照小鼠低50%至70%)与高胰岛素血症相关。年龄,但不是在B6 db / db雌性中,也不是在BK s db / db两种性别的小鼠中。(摘要以250字截断)
  • 【I型糖尿病易感性候选基因的分析:2q31-35号染色体上基因的病例对照和家庭关联研究。】 复制标题 收藏 收藏
    DOI:10.2337/diab.46.6.1069 复制DOI
    作者列表:Owerbach D,Naya FJ,Tsai MJ,Allander SV,Powell DR,Gabbay KH
    BACKGROUND & AIMS: Recent genome searches suggest a putative linkage of many loci to susceptibility to type I diabetes. The chromosome 2q31-35 region is reported to be linked to susceptibility to type I diabetes and is thought to contain several diabetes susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2, CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families are required to confirm and/or identify the actual susceptibility loci. We hereby report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5, which we have used along with previously known polymorphisms of HOXD8 and CTLA4 to test whether these candidate loci are the susceptibility genes on chromosome 2q31-35. Using a case-control design with a subsequent family-association approach to confirm associations, we find no evidence that these candidate genes are associated with susceptibility to type I diabetes.

    背景与目标: 最近的基因组搜索表明,许多基因位点与I型糖尿病易感性的推测联系。据报道,染色体2q31-35与I型糖尿病易感性相关,并被认为含有几个糖尿病易感性基因座。这些候选基因包括HOXD基因簇,BETA2,CTLA4,CD28,IGFBP2和IGFBP5。需要在人群和家庭中进行协会研究,以确认和/或识别实际的易感基因座。我们在此报告了HOXD8,BETA2和IGFBP5的几种先前未知的DNA多态性,并将其与HOXD8和CTLA4的先前已知多态性一起用于测试这些候选基因座是否为2q31-35染色体上的易感性基因。使用病例对照设计和随后的家庭关联方法来确认关联,我们没有发现这些候选基因与I型糖尿病易感性相关的证据。

  • 【社交,运动,饮食和年龄对食蟹猴发展中和未治疗的糖尿病的作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.exger.2017.06.010 复制DOI
    作者列表:Yue F,Zhang G,Quintero JE,Gash DM,Zhang Z
    BACKGROUND & AIMS: :Type 2 diabetes mellitus is the most common form of diabetes that occurs in both human and nonhuman primates. Although spontaneously diabetic nonhuman primates are used extensively in diabetic related research and are a proven valuable tool for the study of the natural history of diabetes, little is known about the key factors that can cause this metabolic disorder and the preventative measures that could be employed to minimize the consequences of diabetes. Using a model of developing and untreated diabetes, this study describes the effects of housing arrangement (socially group- versus individually single-housed), exercise, diet, age, and sex on fasting plasma glucose, key lipids associated with diabetes, and bodyweight in two large cohorts of nonhuman primates. Key findings include exercise/housing arrangement's contribution to significant differences in bodyweight, levels of fasting plasma glucose, total cholesterol, and high- and low-density lipoproteins. Age also had profound effects on glucose, triglyceride and high-density lipoproteins, particularly in single-caged animals. Moreover, females had higher fasting glucose, total cholesterol and triglyceride levels than male counterparts within the same housing situations. These factors may be critical to identifying preventive measures that could eventually be used to minimize obesity and diabetes in humans.
    背景与目标: 2型糖尿病是人类和非人类灵长类动物中最常见的糖尿病形式。尽管自发性糖尿病非人类灵长类动物在糖尿病相关研究中被广泛使用,并且是研究糖尿病自然史的一种有价值的工具,但对引起这种代谢紊乱的关键因素以及可以用于预防该疾病的预防措施知之甚少最大限度地减少糖尿病的后果。本研究使用发展中的糖尿病和未经治疗的糖尿病模型,描述了住房安排(集体居住与个人独居),运动,饮食,年龄和性别对空腹血糖,糖尿病相关的主要脂质和体重的影响。两个大型的非人类灵长类动物。主要发现包括运动/住房安排对体重,空腹血糖水平,总胆固醇以及高密度和低密度脂蛋白的显着差异的贡献。年龄对葡萄糖,甘油三酸酯和高密度脂蛋白也有深远的影响,特别是在单笼动物中。此外,在相同的居住环境下,女性的空腹血糖,总胆固醇和甘油三酸酯水平高于男性。这些因素对于确定预防措施至关重要,这些预防措施最终可用于最大程度地减少人类的肥胖和糖尿病。
  • 【花生对患有高2型糖尿病风险的肥胖女性的血糖反应和食欲的急性和第二餐作用:一项随机交叉临床试验。】 复制标题 收藏 收藏
    DOI:10.1017/S0007114512004217 复制DOI
    作者列表:Reis CE,Ribeiro DN,Costa NM,Bressan J,Alfenas RC,Mattes RD
    BACKGROUND & AIMS: :Nut consumption is associated with a reduced risk of type 2 diabetes mellitus (T2DM). The aim of the present study was to assess the effects of adding peanuts (whole or peanut butter) on first (0-240 min)- and second (240-490 min)-meal glucose metabolism and selected gut satiety hormone responses, appetite ratings and food intake in obese women with high T2DM risk. A group of fifteen women participated in a randomised cross-over clinical trial in which 42·5 g of whole peanuts without skins (WP), peanut butter (PB) or no peanuts (control) were added to a 75 g available carbohydrate-matched breakfast meal. Postprandial concentrations (0-490 min) of glucose, insulin, NEFA, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), appetitive sensations and food intake were assessed after breakfast treatments and a standard lunch. Postprandial NEFA incremental AUC (IAUC) (0-240 min) and glucose IAUC (240-490 min) responses were lower for the PB breakfast compared with the control breakfast. Insulin concentrations were higher at 120 and 370 min after the PB consumption than after the control consumption. Desire-to-eat ratings were lower, while PYY, GLP-1 and CCK concentrations were higher after the PB intake compared with the control intake. WP led to similar but non-significant effects. The addition of PB to breakfast moderated postprandial glucose and NEFA concentrations, enhanced gut satiety hormone secretion and reduced the desire to eat. The greater bioaccessibility of the lipid component in PB is probably responsible for the observed incremental post-ingestive responses between the nut forms. Inclusion of PB, and probably WP, to breakfast may help to moderate glucose concentrations and appetite in obese women.
    背景与目标: :食用坚果与降低2型糖尿病(T2DM)的风险有关。本研究的目的是评估添加花生(全脂或花生酱)对第一次(0-240分钟)和第二次(240-490分钟)膳食葡萄糖代谢的影响,以及选择的肠饱腹感激素反应,食欲等级患有T2DM风险较高的肥胖女性的饮食和食物摄入量。一组15名妇女参加了一项随机交叉临床试验,在该试验中,将75.g可用碳水化合物匹配的42·5克无皮的全花生(WP),花生酱(PB)或无花生(对照)添加早餐餐。早餐后评估餐后血糖,胰岛素,NEFA,胰高血糖素样肽1(GLP-1),肽YY(PYY),胆囊收缩素(CCK),食欲感觉和食物摄入的浓度(0-490分钟)。标准午餐。与对照早餐相比,PB早餐的餐后NEFA增量AUC(IAUC)(0-240分钟)和葡萄糖IAUC(240-490分钟)响应较低。 PB摄入后120和370分钟时的胰岛素浓度高于对照组摄入后的胰岛素浓度。与对照组相比,PB摄入后的按需饮食评分较低,而PYY,GLP-1和CCK浓度较高。 WP产生了相似但不重要的影响。早餐中添加PB可减轻餐后血糖和NEFA的浓度,增强肠饱腹感激素的分泌并减少进食的欲望。 PB中脂质成分的更大生物可及性可能是观察到的坚果形式之间渐增的消味后反应的原因。在早餐中加入PB和可能的WP可能有助于减轻肥胖女性的葡萄糖浓度和食欲。
  • 【糖尿病和胰腺癌的风险:来自胰腺癌队列财团的汇总分析。】 复制标题 收藏 收藏
    DOI:10.1007/s10552-012-0078-8 复制DOI
    作者列表:
    BACKGROUND & AIMS: PURPOSE:Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). METHODS:The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. RESULTS:Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). CONCLUSIONS:These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.
    背景与目标: 目的:糖尿病是怀疑为胰腺癌的危险因素,但有关它是该疾病的危险因素还是结果仍存在疑问。这项研究从NCI胰腺癌队列联合会(PanScan)收集的数据中前瞻性地检查了糖尿病与胰腺腺癌风险之间的关联。
    方法:汇集的数据包括使用嵌套病例对照研究设计的来自十二个队列的1,621例胰腺腺癌病例和1,719例匹配的对照。所有分析均排除在胰腺癌诊断时间(<2年)内被诊断出患有糖尿病的受试者。所有分析均根据年龄,种族,性别,研究,饮酒,吸烟,BMI和胰腺癌家族史进行了调整。
    结果:自我报告的糖尿病与胰腺癌风险增加40%相关(OR = 1.40,95%CI:1.07,1.84)。该关联因糖尿病持续时间而异;持续时间为2-8年的患者风险最高(OR = 1.79,95%CI:1.25,2.55);糖尿病9年没有相关性(OR = 1.02,95%CI:0.68,1.52)。
    结论:这些发现为糖尿病与胰腺癌风险之间的关系提供了支持。糖尿病持续时间最长的患者缺乏相关性可能反映了低胰岛素血症,需要进一步研究。
  • 【HMGA2基因的常见变异会增加2型糖尿病患者对肾病的易感性。】 复制标题 收藏 收藏
    DOI:10.1007/s00125-012-2760-5 复制DOI
    作者列表:Alkayyali S,Lajer M,Deshmukh H,Ahlqvist E,Colhoun H,Isomaa B,Rossing P,Groop L,Lyssenko V
    BACKGROUND & AIMS: AIMS/HYPOTHESIS:Type 2 diabetes is a chronic metabolic disorder associated with devastating microvascular complications. Genome-wide association studies have identified more than 60 genetic variants associated with type 2 diabetes and/or glucose and insulin traits, but their role in the progression of diabetes is not established. The aim of this study was to explore whether these variants were also associated with the development of nephropathy in patients with type 2 diabetes. METHODS:We studied 28 genetic variants in 2,229 patients with type 2 diabetes from the local Malmö Scania Diabetes Registry (SDR) published during 2007-2010. Diabetic nephropathy (DN) was defined as micro- or macroalbuminuria and/or end-stage renal disease. Estimated glomerular filtration rate (eGFR) was assessed using the MDRD-4 formula. Replication genotyping of rs1531343 was performed in diabetic (Steno type 2 diabetes [n = 345], Genetics of Diabetes Audit and Research in Tayside Scotland [Go-DARTS] [n = 784]) and non-diabetic (Malmö Preventive Project [n = 2,523], Botnia study [n = 2,247]) cohorts. RESULTS:In the SDR, HMGA2 single-nucleotide polymorphism rs1531343 was associated with DN (OR 1.50, 95% CI 1.20, 1.87, p = 0.00035). In the combined analysis totalling 3,358 patients with type 2 diabetes (n = 1,233 cases, n = 2,125 controls), carriers of the C-allele had a 1.45-fold increased risk of developing nephropathy (95% CI 1.20, 1.75, p = 0.00010). Furthermore, the risk C-allele was associated with lower eGFR in patients with type 2 diabetes (n = 2,499, β ± SEM, -3.7 ± 1.2 ml/min, p = 0.002) and also in non-diabetic individuals (n = 17,602, β ± SEM, -0.008 ± 0.003 ml/min (log( e )), p = 0.006). CONCLUSIONS/INTERPRETATION:These data demonstrate that the HMGA2 variant seems to be associated with increased risk of developing nephropathy in patients with type 2 diabetes and lower eGFR in both diabetic and non-diabetic individuals and could thus be a common denominator in the pathogenesis of type 2 diabetes and kidney complications.
    背景与目标: 目的/假设:2型糖尿病是与破坏性微血管并发症相关的慢性代谢性疾病。全基因组关联研究已鉴定出与2型糖尿病和/或葡萄糖和胰岛素性状相关的60多种遗传变异,但尚未确定它们在糖尿病进展中的作用。这项研究的目的是探讨这些变异是否也与2型糖尿病患者的肾病发展有关。
    方法:我们研究了2007年至2010年间发表的2 229例2型糖尿病患者的28种遗传变异,这些变异来自当地的马尔默斯堪尼亚糖尿病登记处(SDR)。糖尿病性肾病(DN)被定义为微蛋白尿或巨蛋白尿和/或晚期肾病。使用MDRD-4公式评估估计的肾小球滤过率(eGFR)。 rs1531343的复制基因分型是在糖尿病(Steno 2型糖尿病[n = 345],Tayside Scotland糖尿病的遗传学研究和研究[Go-DARTS] [n = 784])和非糖尿病(Malmö预防项目[n == 2,523],Botnia研究[n = 2,247]队列。
    结果:在SDR中,HMGA2单核苷酸多态性rs1531343与DN相关(OR 1.50,95%CI 1.20,1.87,p = 0.00035)。在总共3358名2型糖尿病患者的综合分析中(n = 1,233例,n = 2,125对照),C-等位基因携带者患肾病的风险增加了1.45倍(95%CI 1.20,1.75,p = 0.00010 )。此外,高风险C等位基因与2型糖尿病患者的eGFR较低有关(n = 2,499,β±SEM,-3.7±1.2 ml / min,p = 0.002),在非糖尿病患者中(n = 17,602) ,β±SEM,-0.008±0.003 ml / min(log(e)),p = 0.006)。
    结论/解释:这些数据表明,HMGA2变异似乎与2型糖尿病患者发生肾病的风险增加以及糖尿病和非糖尿病患者的eGFR降低有关,因此可能是2型糖尿病发病机制的共同指标2糖尿病和肾脏并发症。
  • 【回复:Bayomi等人的“ Plasminogen Activator Inhibitor-1和2型糖尿病患者的心包脂肪”。 (Metab Syndr Relat Disord 2017; 15:269-275)。】 复制标题 收藏 收藏
    DOI:10.1089/met.2017.0070 复制DOI
    作者列表:Avogaro A
    BACKGROUND & AIMS: :Plasminogen activator inhibitor-1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily, which inactivates tissue plasminogen activator (tPA); therefore, increased level of PAI-1 antigen counteracts the anticoagulant effect of tPA and facilitates the fibrin clot formation. Plasma PAI-1 antigen and activity levels are associated with increased body mass index and with features of the insulin resistance syndrome like obesity and diabetes. Visceral adipose tissue produces more PAI-1 than subcutaneous adipose tissue: This increased production of PAI-1 from the visceral adipose tissue is one important link between visceral obesity and cardiovascular disease. Besides visceral adipose tissue, there is mounting evidence that epicardial adipose tissue may be an important source of PAI-1, especially in patients with type 2 diabetes.
    背景与目标: :Plasminogen activator inhibitor-1(PAI-1)是丝氨酸蛋白酶抑制剂(serpin)超家族的一员,它可以使组织纤溶酶原激活物(tPA)失活。因此,PAI-1抗原水平的增加抵消了tPA的抗凝作用,并促进了纤维蛋白凝块的形成。血浆PAI-1抗原和活性水平与体重指数增加以及胰岛素抵抗综合征(如肥胖症和糖尿病)的特征有关。内脏脂肪组织比皮下脂肪组织产生更多的PAI-1:内脏脂肪组织增加的PAI-1产生是内脏肥胖与心血管疾病之间的重要联系。除内脏脂肪组织外,越来越多的证据表明心外膜脂肪组织可能是PAI-1的重要来源,尤其是在2型糖尿病患者中。
  • 【加纳人口的一般和中枢肥胖和2型糖尿病风险的度量。】 复制标题 收藏 收藏
    DOI:10.1111/tmi.12024 复制DOI
    作者列表:Frank LK,Heraclides A,Danquah I,Bedu-Addo G,Mockenhaupt FP,Schulze MB
    BACKGROUND & AIMS: OBJECTIVE:The epidemic of obesity and type 2 diabetes is evident in sub-Saharan Africa (SSA). However, their associations have hardly been examined in this region. METHODS:A hospital-based case-control study in urban Ghana consisting of 1221 adults (542 cases and 679 controls) investigated the role of anthropometric parameters for diabetes. Logistic regression was used for analysis. The discriminative power and population-specific cut-off points for diabetes were identified by receiver operating characteristic curves. RESULTS:The strongest association with diabetes was observed for waist-to-hip ratio: age-adjusted odds ratios per 1 standard deviation difference were 1.95 (95% confidence interval [CI]: 1.64-2.31) in women and 1.40 [1.01-1.94] in men. Also, among women, the odds of diabetes increased with higher waist circumference (1.35 [1.17-1.57]) and waist-to-height ratio (1.29 [1.12-1.50]). Among men, this was not discernible. Rather, hip circumference was inversely related (0.69 [0.50-0.95]). Body mass index was neither associated with diabetes in women (1.01 [0.88-1.15]) nor in men (0.74 [0.52-1.04]). Among both genders, waist-to-hip ratio showed the best discriminative ability for diabetes in this population and the optimal cut-off points were ≥ 0.88 in women and ≥ 0.90 in men. Recommended cut-off points for body mass index and waist circumference had a poor predictive ability. CONCLUSION:Our findings suggest that measures of central rather than general obesity relate to type 2 diabetes in SSA. It remains to be verified from larger population-based epidemiological studies whether anthropometric targets of obesity prevention in SSA differ from those in developed countries.
    背景与目标: 目的:肥胖症和2型糖尿病的流行在撒哈拉以南非洲(SSA)中很明显。但是,在该地区几乎没有检查过它们的关联。
    方法:一项基于医院病例对照研究,由加纳市区的1221名成年人(542例和679名对照)组成,研究了人体测量学参数在糖尿病中的作用。 Logistic回归用于分析。糖尿病的鉴别力和特定人群的临界点通过接受者的操作特征曲线来确定。
    结果:腰臀比与糖尿病的关系最大:女性每1个标准差的年龄校正比值比为1.95(95%置信区间[CI]:1.64-2.31),而女性为1.40 [1.01-1.94] ]的男人。另外,在女性中,糖尿病的几率随着腰围(1.35 [1.17-1.57])和腰高比(1.29 [1.12-1.50])的增加而增加。在男人中,这是不明显的。相反,髋围呈负相关(0.69 [0.50-0.95])。体重指数与女性(1.01 [0.88-1.15])和男性(0.74 [0.52-1.04])均与糖尿病无关。在这两个性别中,腰臀比在该人群中表现出对糖尿病的最佳判别能力,并且最佳的临界点是女性≥0.88,男性≥0.90。推荐的体重指数和腰围临界点的预测能力较差。
    结论:我们的研究结果表明,中枢性肥胖而非一般性肥胖与SSA中的2型糖尿病有关。 SSA中预防肥胖症的人体测量指标是否与发达国家不同,尚需从更大的基于人群的流行病学研究中得到验证。
  • 【链脲佐菌素诱发的糖尿病易感性的菌株差异:对高甘油三酯血症和心肌病的影响。】 复制标题 收藏 收藏
    DOI:10.1016/s0008-6363(97)00045-x 复制DOI
    作者列表:Rodrigues B,Cam MC,Kong J,Goyal RK,McNeill JH
    BACKGROUND & AIMS: OBJECTIVE:Streptozotocin (STZ)-induced diabetes in Wistar rats results in severe hyperlipidemia and a characteristic cardiomyopathy. However, Wistar-Kyoto (WKY) rats made diabetic with a similar dose of STZ did not develop heart dysfunction or hypertriglyceridemia at 12 weeks post-STZ. We investigated whether an apparent resistance of the WKY strain to develop diabetic cardiomyopathy and hypertriglyceridemia following chronic diabetes could be due to a reduced susceptibility to the diabetogenic effects of STZ.

    METHODS:Adult male WKY and Wistar rats were made diabetic with a moderate (55 mg/kg) or high (75 mg/kg) dose of STZ. At 6 weeks of diabetes, glucose tolerance, cardiac function, pancreatic insulin content and basal and post-heparin plasma lipolytic activity were determined.

    RESULTS:Administration of a moderate dose of STZ produced cardiac dysfunction in Wistar but not WKY rats at 6 weeks after diabetes induction. The same dose of STZ in WKY rats also resulted in a lesser degree of hyperglycemia and glucose intolerance, and significantly higher pancreatic insulin content relative to Wistar rats. Following a high dose of STZ, the apparent resistance to developing cardiomyopathy was lost in the WKY rats. As well, the WKY rats demonstrated an equal degree of hyperglycemia and glucose intolerance as Wistar rats. However, unlike the Wistar strain, WKY rats did not demonstrate either hypertriglyceridemia or a reduced heparin-releasable plasma lipoprotein lipase (LPL) activity following a high dose of STZ.

    CONCLUSIONS:These results suggest that the incidence of diabetes-related cardiomyopathy and hypertriglyceridemia in rats may be independently influenced by strain-dependent susceptibilities to the beta-cytotoxic effects of STZ. The absence of hypertriglyceridemia in severely diabetic WKY rats may be linked to the maintenance of a critical level of plasma LPL activity.

    背景与目标: 目标:链脲佐菌素(STZ)诱导的Wistar大鼠糖尿病会导致严重的高脂血症和典型的心肌病。但是,在STZ后12周,使用相似剂量的STZ患糖尿病的Wistar-Kyoto(WKY)大鼠并未出现心脏功能障碍或高甘油三酯血症。我们调查了WKY菌株对慢性糖尿病后糖尿病性心肌病和高甘油三酯血症的明显抵抗是否可能是由于对STZ的致糖尿病作用的敏感性降低所致。

    方法:成年男性用中度(55 mg / kg)或高(75 mg / kg)剂量的STZ使WKY和Wistar大鼠患糖尿病。在糖尿病的6周时,测定了葡萄糖耐量,心脏功能,胰腺胰岛素含量以及肝素基础和血浆中的脂解活性。

    结果:服用中等剂量的STZ诱导糖尿病后6周,Wistar大鼠出现心脏功能障碍,但WKY大鼠没有。与Wistar大鼠相比,WKY大鼠中相同剂量的STZ还导致较低的高血糖和葡萄糖耐受不良,以及显着较高的胰腺胰岛素含量。服用高剂量的STZ后,WKY大鼠失去了明显的对发展性心肌病的抵抗力。同样,WKY大鼠表现出与Wistar大鼠相同程度的高血糖和葡萄糖耐受不良。但是,与Wistar菌株不同,WKY大鼠在高剂量的STZ后既未表现出高甘油三酸酯血症或肝素释放性血浆脂蛋白脂肪酶(LPL)活性降低。

    结论:这些结果表明,大鼠与糖尿病有关的心肌病和高甘油三酯血症的发生可能受到STZ的β细胞毒性作用的应变依赖性敏感性的独立影响。严重糖尿病WKY大鼠缺乏高甘油三酸酯血症可能与维持血浆LPL活性临界水平有关。

  • 【艾塞那肽:治疗2型糖尿病的新选择。】 复制标题 收藏 收藏
    DOI:10.1345/aph.1H060 复制DOI
    作者列表:Yoo BK,Triller DM,Yoo DJ
    BACKGROUND & AIMS: OBJECTIVE:To evaluate available literature characterizing the pharmacology, pharmacokinetics, drug interactions, efficacy, and safety of exenatide in patients with type 2 diabetes. DATA SOURCES:A PubMed database search (1966-May 2006) was conducted, using exenatide as the search term. The manufacturer's prescribing information was also used. STUDY SELECTION AND DATA EXTRACTION:English-language articles were selected and data were extracted with a focus on clinical outcomes associated with the treatment of patients with type 2 diabetes. DATA SYNTHESIS:Exenatide exerts a glucoregulatory effect by various mechanisms including secretion of glucose-dependent insulin, suppression of inappropriately high glucagon levels in patients with type 2 diabetes, delayed gastric emptying, and reduction of food intake. In placebo-controlled clinical studies, plasma exenatide concentrations appeared to exhibit dose-proportional kinetics, reaching peak plasma levels between 2 and 3 hours after a single subcutaneous injection. Exenatide's elimination half-life ranged from 3.3 to 4.0 hours, and the time to reach maximum concentration was about 2 hours. Interactions between exenatide and agents such as digoxin and lisinopril were not considered significant. In Phase III trials, exenatide demonstrated significant reduction of hemoglobin A1c levels from baseline and compared with placebo after 30 weeks of treatment in patients unable to achieve optimal glycemic control with metformin, a sulfonylurea, or oral combination therapy (0.4-0.9%). Patients' weight decreased with exenatide (0.9-2.8 kg), but adverse gastrointestinal (GI) events were common. Exenatide combined with thiazolidonediones, D-phenylalanine derivatives, meglitinides, or alpha glucosidase inhibitors has not been studied. CONCLUSIONS:Clinical trials have demonstrated that exenatide improves glycemic control when added to sulfonylureas and metformin, and it may be an alternative to insulin glargine in patients requiring additional therapy. Hypoglycemia has been encountered in clinical trials of exenatide, especially upon initiation of therapy with sulfonylureas (not with metformin); close patient monitoring is therefore recommended. Further studies should assess the impact of exenatide on clinical outcomes such as micro- and macrovascular disease.
    背景与目标: 目的:评估现有文献中艾塞那肽在2型糖尿病患者中的药理学,药代动力学,药物相互作用,疗效和安全性。
    数据来源:使用艾塞那肽作为搜索词,进行了PubMed数据库搜索(1966年-2006年5月)。还使用了制造商的处方信息。
    研究选择和数据提取:选择英语文章并提取数据,重点是与2型糖尿病患者治疗相关的临床结局。
    数据合成:艾塞那肽通过多种机制发挥糖调节作用,包括分泌葡萄糖依赖性胰岛素,抑制2型糖尿病患者中不适当的高胰高血糖素水平,延迟胃排空和减少食物摄入。在安慰剂对照的临床研究中,血浆艾塞那肽的浓度似乎呈剂量比例动力学,在单次皮下注射后2至3小时内达到峰值血浆水平。艾塞那肽的消除半衰期为3.3到4.0小时,达到最大浓度的时间约为2小时。艾塞那肽与地高辛和赖诺普利等药物之间的相互作用不被认为是重要的。在III期试验中,对于无法用二甲双胍,磺酰脲或口服联合疗法实现最佳血糖控制的患者,艾塞那肽在治疗30周后显示出血红蛋白A1c水平较基线显着降低,并且与安慰剂相比有所降低(0.4-0.9%)。艾塞那肽(0.9-2.8 kg)使患者体重减轻,但胃肠道不良(GI)事件很常见。尚未研究将艾塞那肽与噻唑烷二酮,D-苯丙氨酸衍生物,美格替尼或α葡萄糖苷酶抑制剂合用。
    结论:临床试验表明,艾塞那肽加到磺酰脲类和二甲双胍中可以改善血糖控制,在需要额外治疗的患者中,艾塞那肽可以代替甘精胰岛素。在艾塞那肽的临床试验中遇到了低血糖症,尤其是在开始使用磺酰脲类药物(非二甲双胍)治疗时;因此,建议对患者进行密切监测。进一步的研究应评估艾塞那肽对临床结果如微血管和大血管疾病的影响。
  • 【糖尿病引起的脑血管功能障碍:聚(ADP-核糖)聚合酶的作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.mvr.2006.08.001 复制DOI
    作者列表:Arrick DM,Sharpe GM,Sun H,Mayhan WG
    BACKGROUND & AIMS: :Our goal was to identify the role of poly(ADP-ribose) polymerase (PARP) in cerebrovascular dysfunction in Type 1 diabetes mellitus (T1D). In a first series of studies, rats were assigned to nondiabetic and diabetic (streptozotocin; 50 mg/kg IP) groups. Two to three months after injection of streptozotocin, we examine in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (adenosine diphosphate (ADP), acetylcholine and histamine) and -independent (nitroglycerin) agonists. After the initial examination of reactivity to the agonists, we treated pial arterioles acutely with an inhibitor of PARP (PJ-34; 1 microM), and then we again examined responses to the agonists. In a second series of studies, we examine superoxide production (lucigenin chemiluminescence) by parietal cortex tissue in nondiabetic and diabetic rats. We found that dilation of pial arterioles in response to ADP, acetylcholine and histamine, but not to nitroglycerin, was impaired in diabetic compared to nondiabetic rats. In addition, although PJ-34 did not alter responses in nondiabetic rats, PJ-34 alleviated T1D-induced impairment of NOS-dependent vasodilation. We also found that basal production of superoxide was increased in diabetic compared to nondiabetic rats and that PJ-34 decreased this basal production of superoxide. Our findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism that appears to be related to the formation of superoxide via activation of PARP.
    背景与目标: :我们的目标是确定聚(ADP-核糖)聚合酶(PARP)在1型糖尿病(T1D)的脑血管功能障碍中的作用。在第一个系列研究中,将大鼠分为非糖尿病和糖尿病(链脲佐菌素; 50 mg / kg IP)组。注射链脲佐菌素后两到三个月,我们检查了小动脉对一氧化氮合酶(NOS)依赖性(二磷酸腺苷(ADP),乙酰胆碱和组胺)和非依赖性(硝酸甘油)激动剂的体内反应。初步检查与激动剂的反应性后,我们用PARP抑制剂(PJ-34; 1 microM)急性治疗了小动脉,然后再次检查了对激动剂的反应。在第二系列研究中,我们检查了非糖尿病和糖尿病大鼠顶叶皮质组织的超氧化物生成(荧光素化学发光)。我们发现,与非糖尿病大鼠相比,糖尿病患者对ADP,乙酰胆碱和组胺(而非对硝酸甘油)响应的小动脉小动脉扩张受到损害。此外,尽管PJ-34不会改变非糖尿病大鼠的反应,但PJ-34减轻了T1D诱导的NOS依赖性血管舒张功能受损。我们还发现,与非糖尿病大鼠相比,糖尿病患者的基础过氧化物含量增加,而PJ-34降低了基础过氧化物含量。我们的发现表明,T1D通过一种机制似乎削弱了NOS依赖性的脑小动脉反应性,该机制似乎与通过激活PARP形成超氧化物有关。
  • 【血清视黄醇结合蛋白:肥胖,胰岛素抵抗和2型糖尿病之间的联系。】 复制标题 收藏 收藏
    DOI:10.1111/j.1753-4887.2007.tb00302.x 复制DOI
    作者列表:Wolf G
    BACKGROUND & AIMS: :Insulin resistance occurs under conditions of obesity, metabolic syndrome, and type 2 diabetes. It was found to be accompanied by down-regulation of the insulin-responsive glucose transporter GLUT4. Decreased adipocyte GLUT4 caused secretion by adipocytes of the serum retinol-binding protein RBP4. Enhanced levels of serum RBP4 appeared to be the signal for the development of systemic insulin resistance both in experimental animals and in humans. In mice, increased levels of serum RBP4 led to impaired glucose uptake into skeletal muscle and increased glucose production by liver, whereas lowered serum RBP4 levels greatly enhanced insulin sensitivity. Thus, a link has been established between obesity and insulin resistance: RBP4, the vitamin A-transport protein secreted into the circulation by adipocytes.
    背景与目标: 胰岛素抵抗在肥胖,代谢综合症和2型糖尿病的情况下发生。发现伴随着胰岛素反应性葡萄糖转运蛋白GLUT4的下调。脂肪细胞GLUT4减少导致脂肪细胞分泌视黄醇结合蛋白RBP4。血清RBP4水平升高似乎是实验动物和人类体内系统性胰岛素抵抗发展的信号。在小鼠中,血清RBP4水平升高会导致葡萄糖吸收到骨骼肌中,并增加肝脏产生的葡萄糖,而降低血清RBP4水平会大大增强胰岛素敏感性。因此,在肥胖与胰岛素抵抗之间建立了联系:RBP4,脂肪细胞分泌到循环中的维生素A转运蛋白。
  • 【年轻女性的肥胖,骨密度和微结构之间的关系得以维持,而与糖尿病的状况无关。】 复制标题 收藏 收藏
    DOI:10.1111/cen.13410 复制DOI
    作者列表:Abdalrahaman N,McComb C,Foster JE,Lindsay RS,Drummond R,McKay GA,Perry CG,Ahmed SF
    BACKGROUND & AIMS: BACKGROUND:The relationship between bone health and adiposity and how it may be affected in people with chronic metabolic conditions is complex. METHODS:Seventeen women with type 1 diabetes mellitus (T1DM) and nine age-matched healthy women with a median age of 22.6 years (range, 17.4, 23.8) were studied by 3T MRI and MR spectroscopy to assess abdominal adiposity, tibial bone microarchitecture and vertebral bone marrow adiposity (BMA). Additional measures included DXA-based assessments of total body (TB), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) and fat mass (FM). RESULTS:Although women with T1DM had similar BMI and BMA to the controls, they had higher visceral and subcutaneous adiposity on MRI (P<.05) and total body FM by DXA (P=.03). Overall, in the whole cohort, a clear inverse association was evident between BMA and BMD at all sites (P<.05). These associations remained significant after adjusting for age, BMI, FM and abdominal adiposity. In addition, visceral adiposity, but not subcutaneous adiposity, showed a positive association with BMA (r, .4, P=.03), and a negative association with total body BMD (r, .5, P=.02). Apparent trabecular separation as assessed by MRI showed an inverse association to total body BMD by DXA (r, -.4, P=.04). CONCLUSION:Irrespective of the presence of an underlying metabolic condition, young women display a negative relationship between MRI-measured BMA and DXA-based assessment of BMD. Furthermore, an association between BMA and visceral adiposity supports the notion of a common origin of these two fat depots.
    背景与目标: 背景:在慢性代谢疾病患者中,骨骼健康与肥胖之间的关系及其可能受到的影响是复杂的。
    方法:通过3T MRI和MR光谱法研究了17位1型糖尿病(T1DM)妇女和9位年龄相匹配的健康女性(中位年龄为22.6岁,范围分别为17.4、23.8),以评估腹部肥胖,胫骨微结构和椎骨肥胖症(BMA)。其他措施包括基于DXA的全身(TB),股骨颈(FN)和腰椎(LS)骨矿物质密度(BMD)和脂肪量(FM)评估。
    结果:尽管患有T1DM的女性的BMI和BMA与对照组相似,但其MRI的内脏和皮下脂肪率较高(P <.05),而DXA显示的全身FM较高(P = .03)。总体而言,在整个队列中,BMA和BMD在所有位点之间均存在明显的逆相关性(P <.05)。在调整了年龄,BMI,FM和腹部肥胖后,这些关联仍然很显着。此外,内脏脂肪而不是皮下脂肪与BMA呈正相关(r,.4,P = .03),与全身BMD呈负相关(r,.5,P = .02)。 MRI评估的表观小梁分离显示,DXA与全身BMD呈负相关(r,-。4,P = .04)。
    结论:无论是否存在潜在的代谢状况,年轻女性在MRI测量的BMA与基于DXA的BMD评估之间均显示负相关。此外,BMA和内脏肥胖之间的联系支持了这两个脂肪库的共同起源这一概念。
  • 【减少镁和膳食纤维的摄入量会增加台湾人2型糖尿病的发病率。】 复制标题 收藏 收藏
    DOI:10.1016/j.jfma.2012.07.038 复制DOI
    作者列表:Weng LC,Lee NJ,Yeh WT,Ho LT,Pan WH
    BACKGROUND & AIMS: BACKGROUND/PURPOSE:Several studies have indicated an inverse association between the incidence of diabetes mellitus and magnesium and dietary fiber intake. Few studies have examined both of these associations together, not to mention in Asian populations with prospective study design. We therefore aimed to study how dietary magnesium and fiber intake levels affect diabetes incidence separately or in combination, in a prospective study in Taiwan. METHODS:The study subjects were recruited for a longitudinal study, CardioVascular Disease risk FACtor Two-township Study cycle 2 from November 1990. Data from complete baseline information on dietary and biochemical profile and at least one additional follow-up visit were gathered on a total of 1604 healthy subjects aged 30 years and over. Cox proportional hazard model was used to study the association between diabetes incidence and dietary magnesium and fiber intake level estimated from a food frequency questionnaire. RESULTS:A total of 141 diabetes mellitus events were identified and confirmed during the 4.6 years of follow-up (7365.1 person-years). A significantly higher diabetes risk was observed for people in the lowest quintile of total dietary fiber intake (hazard ratio = 2.04; 95% CI = 1.17-3.53) and magnesium intake (hazard ratio = 2.61; 95% CI = 1.42-4.79) compared with the highest quintile after adjusting for traditional cardiovascular disease risk factors. Similar inverse associations for total dietary fiber were also shown for vegetable fiber and fruit fiber. CONCLUSION:Lower magnesium, lower total dietary fiber intake, or lower intake of both was associated with higher risk of diabetes in the Taiwanese population. Clinical trials are required to confirm the protective effects of the adequate intake of fiber, magnesium, and/or their combination.
    背景与目标: 背景/目的:多项研究表明,糖尿病和镁的发病率与膳食纤维的摄入量成反比。很少有研究同时检查了这两个关联,更不用说在前瞻性研究设计的亚洲人群中了。因此,在台湾的一项前瞻性研究中,我们旨在研究饮食中镁和纤维摄入量水平如何单独或组合影响糖尿病的发生。
    方法:招募研究对象进行纵向研究,从1990年11月开始,进行心血管疾病风险FACtor两镇研究第2周期。从饮食和生化特征的完整基线信息中收集数据,并至少再收集一次随访30岁及以上的1604名健康受试者。使用Cox比例风险模型研究了根据食物频率问卷估计的糖尿病发病率与膳食镁和纤维摄入水平之间的关联。
    结果:在4.6年的随访中(7365.1人年),共确定并确认了141个糖尿病事件。与总膳食纤维摄入量最低的五分之一人群(危险比= 2.04; 95%CI = 1.17-3.53)和镁的摄入量(危险比= 2.61; 95%CI = 1.42-4.79)相比,糖尿病风险显着升高在调整了传统的心血管疾病危险因素后,五分位数最高。对于植物纤维和水果纤维,总膳食纤维的相似逆相关性也显示出来。
    结论:台湾人群中镁含量降低,膳食纤维总摄入量减少或两者摄入量减少均与糖尿病风险较高有关。需要进行临床试验以确认适当摄入纤维,镁和/或它们的组合的保护作用。

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