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。

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。

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。

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。

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。

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。

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。

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。

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。

BACKGROUND & AIMS: :Increased arterial stiffness, as estimated from aortic pulse wave velocity (Ao-PWV), and albuminuria are independent predictors for cardiovascular disease in type 2 diabetes mellitus (T2DM). Whether angiotensin receptor blockers (ARBs), drugs with cardio-renal protective effects, improve Ao-PWV to a greater extent than other equipotent antihypertensive medications remains unclear. After a 4-week washout phase, we compared the effects of valsartan (n=66), an ARB, with that of amlodipine (n=65), a calcium channel blocker on Ao-PWV in 131 T2DM patients with pulse pressure (PP) >or=60 mm Hg and raised albumin excretion rate (AER) in a 24-week randomized, double-blind, parallel group study. Hydrochlorothiazide (HCTZ) 25 mg/d was added to valsartan 160 mg and amlodipine 5 mg/od uptitrated to 10 mg/od after 4 weeks to ensure equivalent BP control. After 24 weeks brachial and central aortic PP had fallen to a similar extent with attained mean (SD) brachial and central PP of 61.6 (13.6) and 47.3 (14.1) mm Hg in the valsartan/HCTZ group and 61.5 (12.2) and 47.3 (9.9) mm Hg in the amlodipine group, respectively. Ao-PWV showed a significantly greater reduction, mean (95% CI), -0.9 m/s (-1.4 to -0.3) for valsartan/HCTZ compared to amlodipine (P=0.002). AER fell significantly only with Val/HCTZ from 30.8(20.4, 46.5) to 18.2(12.5, 26.3) mcg/min, (P=0.01) with between treatment difference in favor of Val/HCTZ of -15.3mcg/min (P<0.001). Changes in AER and Ao-PWV were not correlated. Valsartan/HCTZ improves arterial stiffness and AER to a significantly greater extent than amlodipine despite similar central and brachial BP control. These 2 effects, which appear independent of each other, may explain the specific cardio-renal protective properties of ARBs.

背景与目标： ：从主动脉脉搏波速度（Ao-PWV）估计的动脉僵硬度增加和白蛋白尿是2型糖尿病（T2DM）心血管疾病的独立预测因子。尚不清楚血管紧张素受体阻滞剂（ARBs）（具有心脏-肾脏保护作用的药物）是否比其他等效的降压药物更大程度地改善Ao-PWV。经过4周的冲洗期后，我们比较了131位T2DM脉压患者（PP）的ARB缬沙坦（n = 66）和钙通道阻滞剂氨氯地平（n = 65）对Ao-PWV的影响）>或= 60 mm Hg，并在24周的随机，双盲，平行小组研究中提高了白蛋白排泄率（AER）。 4周后，将25 mg / d的氢氯噻嗪（HCTZ）加入缬沙坦160 mg，将氨氯地平5 mg / od升至10 mg / od，以确保等效的BP控制。 24周后，缬沙坦/ HCTZ组的臂和中枢主动脉PP下降幅度相似，达到的平均（SD）臂和中枢PP分别为61.6（13.6）和47.3（14.1）mm Hg，分别为61.5（12.2）和47.3（氨氯地平组分别为9.9）mm Hg。与氨氯地平相比，缬沙坦/ HCTZ的Ao-PWV降低幅度明显更大，均值（95％CI）-0.9 m / s（-1.4至-0.3）（P = 0.002）。仅Val / HCTZ的AER显着下降，从30.8（20.4，46.5）降至18.2（12.5，26.3）mcg / min，（P = 0.01），而Val / HCTZ的治疗差异为-15.3mcg / min（P < 0.001）。 AER和Ao-PWV的变化没有相关性。尽管氨氯地平具有相似的中枢和肱动脉血压控制功能，但缬沙坦/ HCTZ的动脉硬化和AER改善程度明显大于氨氯地平。这两种相互独立出现的效应可能解释了ARB的特定心脏-肾脏保护特性。

BACKGROUND & AIMS: OBJECTIVE:To search for a possible association of type 1 diabetes with 10 validated type 2 diabetes loci, i.e., PPARG, KCNJ11, WFS1, HNF1B, IDE/HHEX, SLC30A8, CDKAL1, CDKN2A/B, IGF2BP2, and FTO/RPGRIP1L. RESEARCH DESIGN AND METHODS:Two European population samples were studied: 1) one case-control cohort of 514 type 1 diabetic subjects and 2,027 control subjects and 2) one family cohort of 483 complete type 1 diabetic case-parent trios (total 997 affected). A total of 13 tag single nucleotide polymorphisms (SNPs) from the 10 type 2 diabetes loci were analyzed for type 1 diabetes association. RESULTS:No association of type 1 diabetes was found with any of the 10 type 2 diabetes loci, and no age-at-onset effect was detected. By combined analysis using the Wellcome Trust Case-Control Consortium type 1 diabetes data, SNP rs1412829 in the CDKN2A/B locus bordered on significance (P = 0.039) (odds ratio 0.929 [95% CI 0.867-0.995]), which did not reach the statistical significance threshold adjusted for 13 tests (alpha = 0.00385). CONCLUSIONS:This study suggests that the type 2 diabetes loci do not play any obvious role in type 1 diabetes genetic susceptibility. The distinct molecular mechanisms of the two diseases highlighted the importance of differentiation diagnosis and different treatment principles.

背景与目标： 目的：寻找1型糖尿病与10个经过验证的2型糖尿病基因座的可能关联，即PPARG，KCNJ11，WFS1，HNF1B，IDE / HHEX，SLC30A8，CDKAL1，CDKN2A / B，IGF2BP2和FTO / RPGRIP1L。
研究设计和方法：研究了两个欧洲人口样本：1）一组514名1型糖尿病受试者和2027名对照受试者的病例对照队列，以及2）一组483名1型糖尿病病例-父母三项完整的家庭队列（共997名患者）。 。分析了来自10个2型糖尿病基因座的总共13个标签单核苷酸多态性（SNP），用于1型糖尿病关联。
结果：没有发现1型糖尿病与10个2型糖尿病基因座的任何关联，也没有发现发病年龄的影响。通过使用Wellcome Trust病例对照协会1型糖尿病数据进行的综合分析，CDKN2A / B基因座中的SNP rs1412829具有显着性（P = 0.039）（几率0.929 [95％CI 0.867-0.995]），但未达到调整了13个测试的统计显着性阈值（alpha = 0.00385）。
结论：这项研究表明2型糖尿病基因座在1型糖尿病遗传易感性中没有任何明显的作用。两种疾病的独特分子机制突显了鉴别诊断和不同治疗原则的重要性。

BACKGROUND & AIMS: :Mutations in the gene encoding hepatocyte nuclear factor (HNF)1beta result in maturity-onset diabetes of the young-(MODY)5, by impairing insulin secretory responses and, possibly, by reducing beta-cell mass. The functional role of HNF1beta in normal beta-cells is poorly understood; therefore, in the present study, wild-type (WT) HNF1beta, or one of two naturally occurring MODY5 mutations (an activating mutation, P328L329del, or a dominant-negative form, A263insGG) were conditionally expressed in the pancreatic beta-cell line, insulin-1 (INS-1), and the functional consequences examined. Surprisingly, overexpression of the dominant-negative mutant did not modify any of the functional properties of the cells studied (including insulin secretion, cell growth and viability). By contrast, expression of WT HNF1beta was associated with a time- and dose-dependent inhibition of INS-1 cell proliferation and a marked increase in apoptosis. Induction of WT HNF1beta also inhibited the insulin secretory response to nutrient stimuli, membrane depolarisation or activation of protein kinases A and C and this correlated with a significant decrease in pancrease-duodenum homeobox-1 protein levels. The attenuation of insulin secretion was, however, dissociated from the inhibition of proliferation and loss of viability, since expression of the P328L329del mutant led to a reduced rate of cell proliferation, but failed to induce apoptosis or to alter insulin secretion. Taken together, the present results suggest that mature rodent beta-cells are sensitive to increased expression of WT HNF1beta and they imply that the levels of this protein are tightly regulated to maintain secretory competence and cell viability.

背景与目标： ：编码肝细胞核因子（HNF）1beta的基因突变会削弱胰岛素分泌反应，并可能减少β细胞的数量，从而导致年轻的（MODY）5发病。 HNF1beta在正常的β细胞中的功能作用了解甚少。因此，在本研究中，野生型（WT）HNF1beta或两个自然发生的MODY5突变之一（激活突变P328L329del或显性负性形式A263insGG）在胰腺β细胞系中有条件表达，胰岛素-1（INS-1），并检查其功能后果。出人意料的是，显性负突变体的过表达并未改变所研究细胞的任何功能特性（包括胰岛素分泌，细胞生长和生存力）。相比之下，WT HNF1beta的表达与INS-1细胞增殖的时间和剂量依赖性抑制以及凋亡的显着增加有关。 WT HNF1beta的诱导也抑制了胰岛素对营养物刺激，膜去极化或蛋白激酶A和C活化的分泌反应，这与胰十二指肠同源盒1蛋白水平的显着降低有关。然而，由于P328L329del突变体的表达导致细胞增殖率降低，但是胰岛素分泌的减弱与增殖抑制和生存力丧失分离，但不能诱导细胞凋亡或改变胰岛素分泌。综上所述，本发明结果表明成熟的啮齿动物β细胞对WTHNF1β表达的增加敏感，并且暗示该蛋白的水平被严格调节以维持分泌能力和细胞生存力。