• 【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。
  • 【德国1型糖尿病患者中UVB照射和维生素D浓度的时间趋势。】 复制标题 收藏 收藏
    DOI:10.1016/j.jsbmb.2012.11.008 复制DOI
    作者列表:Langer J,Penna-Martinez M,Wallasch M,Bon D,Badenhoop K
    BACKGROUND & AIMS: BACKGROUND:Type 1 diabetes (T1D) is an autoimmune disease which is characterised by the destruction of insulin-producing beta cells in human pancreas leading consequently to a hyperglycaemic metabolism. Recent studies have shown that low cholecalciferol (25(OH)D3) concentrations may contribute to the development of T1D. The 25(OH)D3 status depends mostly on human skin production influenced by exposure to UVB radiation. Our intention was to examine whether there was a change in UVB radiation in the past years and if this has an impact on patients' vitamin D status. METHODS:We analysed the 25(OH)D3 concentration of blood samples from 287 T1D patients in the years 2004-2007 at the University Hospital Frankfurt. Moreover, daily UVB irradiation data of this time were received. Wilcoxon-Mann-Whitney test and Spearman correlation test were used for statistical analyses. RESULTS:We observe a strong correlation between UVB irradiation and the 25(OH)D3 concentration of German T1D patients (correlation coefficient=rho=0.56, p=7×10(-3)). Moreover, 25(OH)D3 blood levels obtained in summer (Apr-Oct) were significantly higher than in the winter season (p=8×10(-3)). In the years 2004-2007 there was a significant decline of UVB radiation in the summers (rho=-0.21, p<10(-6)) but no change was found in (rho=-0.07, p=0.12). This corresponds to a significant decrease of 25(OH)D3 levels in T1D patients over the summers (rho=-0.24, p=2×10(-3)) but not in winters (rho=-0.03, p=0.73). CONCLUSION:Our results reveal a significant correlation of UVB irradiation and the vitamin D concentration of German T1D patients. A decrease of UVB irradiation over the summers 2004-2007 is accompanied by a decline of 25(OH)D3 levels observed in those summer months which may indicate a local time trend requiring further investigation into the environmental factors of vitamin D deficiency. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
    背景与目标: 背景:1型糖尿病(T1D)是一种自身免疫性疾病,其特征是破坏人胰腺中产生胰岛素的β细胞,从而导致高血糖代谢。最近的研究表明,低胆钙化固醇(25(OH)D3)浓度可能有助于T1D的发展。 25(OH)D3的状态主要取决于受到UVB辐射影响的人类皮肤生产。我们的目的是检查过去几年中UVB辐射是否发生变化,以及这是否会对患者的维生素D状况产生影响。
    方法:我们分析了法兰克福大学医院2004-2007年间287例T1D患者的血样中25(OH)D3的浓度。此外,接收了该时间的每日UVB照射数据。统计分析采用Wilcoxon-Mann-Whitney检验和Spearman相关检验。
    结果:我们观察到UVB照射与德国T1D患者的25(OH)D3浓度之间有很强的相关性(相关系数= rho = 0.56,p = 7×10(-3))。此外,夏季(Apr-Oct)获得的25(OH)D3血液水平显着高于冬季(p = 8×10(-3))。在2004-2007年,夏季的UVB辐射显着下降(rho = -0.21,p <10(-6)),但未发现变化(rho = -0.07,p = 0.12)。这对应于T1D患者在夏季(rho = -0.24,p = 2×10(-3))的25(OH)D3水平显着降低,而在冬季(rho = -0.03,p = 0.73)则没有显着降低。
    结论:我们的结果显示德国T1D患者的UVB照射与维生素D浓度之间存在显着相关性。在2004-2007年夏季,UVB辐射的减少伴随着在夏季月份观察到的25(OH)D3水平的下降,这可能表明当地时间趋势需要进一步研究维生素D缺乏的环境因素。本文是名为“维生素D车间”的特刊的一部分。
  • 【利拉鲁肽与二肽基肽酶-4抑制剂在日本患者中治疗2型糖尿病的网络荟萃分析。】 复制标题 收藏 收藏
    DOI:10.1080/03007995.2017.1345730 复制DOI
    作者列表:Ayers D,Kanters S,Goldgrub R,Hughes M,Kato R,Kragh N
    BACKGROUND & AIMS: AIMS:To determine the comparative efficacy and safety of liraglutide and dipeptidyl peptidase-4 (DPP-4) inhibitors as antidiabetics for Japanese patients with uncontrolled type 2 diabetes (T2DM). METHODS AND MATERIALS:We searched for randomized controlled trials (RCTs) evaluating outcomes among Japanese adults with uncontrolled T2DM and including liraglutide or DPP-4 inhibitors up to August 2016. We extracted data on trial and patient characteristics, and the following outcomes: HbA1c, weight, patients meeting HbA1c <7%, patients experiencing hypoglycemic events, microalbuminuria, estimated glomerular filtration rate (eGFR) and creatinine. We synthesized data using network meta-analyses (NMA) using a Bayesian framework. Continuous outcomes were modeled using normal likelihoods and an identity link, while dichotomous outcomes were modeled using a binomial likelihood and a logit link. RESULTS:The systematic literature review yielded 39 publications pertaining to 38 trials. A total of 27 trials (5032 patients) reported change in HbA1c at 12 weeks and at 24 weeks 9 trials (2091 patients). All treatments showed statistically significant reductions in HbA1c relative to placebo at 12 and 24 weeks. Liraglutide 0.9 mg was statistically superior to all DPP-4 interventions (vildagliptin, sitagliptin, linagliptin, alogliptin, teneligliptin, trelagliptin and omarigliptin) at 12 weeks and 24 weeks among those reporting. Treatments were not statistically differentiable with respect to weight change and risk of hypoglycemia. Finally, no comparisons of eGFR and microalbuminuria were conducted, as this data was reported in too few trials to conduct analyses. LIMITATIONS:Some important outcomes were limited by poor reporting (eGFR and microalbuminuria) or low event rates (hypoglycemia). The follow-up time was relatively short. Clinically, the 24 week time point is more important as it demonstrates more sustained results. CONCLUSIONS:Our research suggests that liraglutide 0.9 mg offers a more efficacious treatment option for T2DM than the DPP-4 inhibitors among adult Japanese patients and that it is a viable option for this population.
    背景与目标: 目的:确定利拉鲁肽和二肽基肽酶-4(DPP-4)抑制剂作为抗糖尿病药对日本2型糖尿病(T2DM)患者的比较疗效和安全性。
    方法和材料:我们搜寻了截至2016年8月截止的未控制T2DM的日本成年人(包括利拉鲁肽或DPP-4抑制剂)在日本成年人中评估结局的随机对照试验(RCT)。我们提取了有关试验和患者特征的数据,以及以下结果:HbA1c,体重,满足HbA1c <7%的患者,发生降血糖事件,微量白蛋白尿,估计的肾小球滤过率(eGFR)和肌酐的患者。我们使用贝叶斯框架,使用网络荟萃分析(NMA)对数据进行了合成。使用正常可能性和同一性联系对连续结果进行建模,而使用二项式可能性和对数联系对二分结果进行建模。
    结果:系统的文献综述产生了涉及38个试验的39种出版物。共有27项试验(5032例患者)报告了12周和24周时HbA1c的变化9项试验(2091例患者)。在12周和24周时,所有治疗均显示HbA1c相对于安慰剂有统计学意义的降低。在报告的12周和24周中,0.9 mg利拉鲁肽优于所有DPP-4干预措施(维格列汀,西他列汀,利那列汀,阿格列汀,替利格列汀,海拉格汀和奥格列汀)。就体重变化和低血糖风险而言,治疗无统计学差异。最后,没有进行eGFR和微量白蛋白尿的比较,因为该数据报道的试验太少而无法进行分析。
    局限性:一些重要的结果受到报告不佳(eGFR和微量白蛋白尿)或事件发生率低(低血糖)的限制。随访时间相对较短。临床上,24周时间点更为重要,因为它显示了更持久的结果。
    结论:我们的研究表明,在日本成年患者中,0.9mg利拉鲁肽比DPP-4抑制剂对T2DM提供更有效的治疗选择,并且对于这一人群是可行的选择。
  • 【2型糖尿病伴或不伴视网膜病变患者中27种房水细胞因子的研究。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Dong N,Xu B,Wang B,Chu L
    BACKGROUND & AIMS: PURPOSE:To compare the changes in the levels of 27 aqueous humor cytokines between nondiabetic controls and patients with type 2 diabetes and to ascertain the association of these cytokines with diabetic retinopathy (DR). METHODS:Undiluted aqueous humor samples were obtained from 102 nondiabetic patients (102 eyes) and 136 consecutive diabetic patients (136 eyes) who were divided into nine groups according to the Early Treatment of Diabetic Retinopathy Study severity scale. The concentrations of 27 cytokines in the aqueous humor samples were measured using a multiplex bead immunoassay. RESULTS:Compared with the nondiabetic controls, the diabetic patients had significantly higher concentrations of interleukin-1β (IL-1β; p<0.001), IL-6 (p<0.001), IL-8 (p<0.001), monocyte chemoattractant protein-1 (p<0.001), interferon gamma-induced protein-10 (p<0.001), and vascular endothelial growth factor (p<0.001) in the aqueous humor. However, the IL-10 (p=0.002) and IL-12 (p=0.013) concentrations were significantly lower for the diabetic patients. There were no significant differences in the concentrations of other cytokines between the diabetic patients and the controls. The IL-1β, IL-6, IL-8, monocyte chemoattractant protein-1, and interferon gamma-induced protein-10 levels in the aqueous humor increased as the severity of DR increased. The correlation was significant. However, the vascular endothelial growth factor concentration was not correlated with the severity of DR. In addition, the IL-10 and IL-12 levels in the aqueous humor decreased as the severity of DR increased, and this negative correlation was significant. CONCLUSIONS:Various cytokines associated with inflammation and angiogenesis may contribute to the pathogenesis of DR, and chemokines may be more closely related to the development of this disease.
    背景与目标: 目的:比较非糖尿病对照和2型糖尿病患者27种房水细胞因子水平的变化,并确定这些细胞因子与糖尿病性视网膜病(DR)的关系。
    方法:从102例非糖尿病患者(102眼)和136例连续糖尿病患者(136眼)中获得未稀释的房水样本,根据糖尿病视网膜病变的早期治疗研究严重程度量表将其分为9组。使用多重磁珠免疫测定法测量房水样品中27种细胞因子的浓度。
    结果:与非糖尿病对照组相比,糖尿病患者的白细胞介素1β(IL-1β; p <0.001),IL-6(p <0.001),IL-8(p <0.001),单核细胞趋化蛋白的浓度明显升高。房水中的-1(p <0.001),γ干扰素诱导的蛋白10(p <0.001)和血管内皮生长因子(p <0.001)。但是,糖尿病患者的IL-10(p = 0.002)和IL-12(p = 0.013)浓度显着降低。糖尿病患者和对照组之间其他细胞因子的浓度没有显着差异。随着DR的严重性增加,房水中的IL-1β,IL-6,IL-8,单核细胞趋化蛋白-1和干扰素γ诱导的蛋白10水平增加。相关性是显着的。但是,血管内皮生长因子的浓度与DR的严重程度无关。另外,随着DR的严重性增加,房水中的IL-10和IL-12水平降低,并且这种负相关性是显着的。
    结论:与炎症和血管生成有关的多种细胞因子可能是DR的发病机制,而趋化因子可能与该病的发展更密切相关。
  • 【初始主动参与远程监控设备进行自我监控对2型糖尿病患者血糖控制的影响。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-03842-2 复制DOI
    作者列表:Lee MK,Lee KH,Yoo SH,Park CY
    BACKGROUND & AIMS: :This study aimed to investigate the effect of patient engagement in self-monitoring with a telemonitoring device on glycemic control among patients with type 2 diabetes. We conducted a subanalysis of the telemonitoring device study in Kaiser Permanente Northern California members. We divided the telemonitoring group into 53 frequent and 54 infrequent users based on self-monitoring of blood glucose (SMBG) frequency of the first 6 weeks. The frequency of SMBG transmitted from the telemonitoring device was examined over 24 weeks. Clinic and laboratory tests were collected at baseline, 6 weeks and 6 months. There was no significant difference in baseline HbA1c level between the two groups. After 6 months, change in HbA1c was -2.4 ± 1.6% among frequent users and -1.5 ± 1.5% among infrequent users (p = 0.003). The proportion of patients achieving target HbA1C level at 6 months was significantly higher among frequent users than among infrequent users. An increased frequency of SMBG was significantly correlated with a reduction in HbA1c at 6 months. In conclusion, initial active engagement in self-monitoring with a telemonitoring device could provide incremental improvement of glycemic control over 6 months.
    背景与目标: :这项研究的目的是调查患者参与远程监控设备自我监控对2型糖尿病患者血糖控制的影响。我们对北加州Kaiser Permanente成员的远程监控设备研究进行了子分析。根据前6周的血糖自我监测(SMBG)频率,我们将远程监测小组分为53个经常使用的用户和54个不经常使用的用户。在24周内检查了从远程监控设备发送的SMBG的频率。在基线,6周和6个月时收集临床和实验室测试。两组之间的基线HbA1c水平无显着差异。 6个月后,频繁使用者的HbA1c变化为-2.4%±1.6%,不经常使用者的HbA1c变化为-1.5%±1.5%(p = 0.003)。经常使用者在6个月时达到HbA1C目标水平的患者比例显着高于不经常使用者。 SMBG频率增加与6个月时HbA1c减少显着相关。总之,在最初的远程监控设备中积极参与自我监控可以在6个月内逐步改善血糖控制。

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