岩藻聚糖硫酸酯降血糖作用机制的研究进展

糖尿病是以高血糖和胰岛素抵抗为特征的内分泌和代谢系统疾病,已成为世界范围内一种普遍疾病。岩藻多糖基于其特定的化学结构,如单糖组成和糖苷键,具有良好的降糖作用和理想的糖尿病治疗潜力。岩藻聚糖硫酸酯具有多种生物活性,但其结构复杂、高分子量和高粘性的特性限制了其应用,而低分子量岩藻多糖粘度低、溶解度好,且研究表明低分子量岩藻多糖具有更好的降血糖作用,因此其低分子量产物的研究具有重大意义。本文讨论了岩藻多糖的结构特征,包括主干结构、糖苷键位置、单糖类型、硫酸盐含量,着重介绍了多糖分子量和降血糖活性的关联,继而引申出低分子量降血糖作用及其作用机理,以期为明晰岩藻多糖的构效关系及进一步的应用提供理论基础。     

Rapid Reduction in Use of Antidiabetic Medication after Laparoscopic Sleeve Gastrectomy: The Newfoundland and Labrador Bariatric Surgery Cohort (BaSCo) Study

Background:

Patients who have undergone bariatric surgery generally need fewer medications as they experience improvement in, or even resolution of, various medical conditions, including type 2 diabetes mellitus, hypertension, and dyslipidemia. Published data on changes in medication use after laparoscopic sleeve gastrectomy, a type of bariatric surgery that is growing in popularity, are limited.

Objective:

To determine whether patients took fewer medications for management of type 2 diabetes, hypertension, and dyslipidemia after laparoscopic sleeve gastrectomy, relative to preprocedure medications.

Methods:

In this prospective, single-centre cohort study, a nurse practitioner used standard medication reconciliation and study data-extraction forms to interview adult patients who had undergone laparoscopic sleeve gastrectomy and determine their medication use and pertinent demographic data. The data were analyzed using generalized estimating equations and standard statistical software. Outcome measures included changes in the use of antidiabetic, antihypertensive, and antilipemic medications at 1, 3, and 6 months after the surgery.

Results:

A total of 65 patients who underwent laparoscopic sleeve gastrectomy between May 2011 and January 2014 met the study inclusion criteria. Before surgery, the 30 patients with type 2 diabetes were taking an average of 1.9 antidiabetic medications. One month after the procedure, 15 (50%) had discontinued all antidiabetic medications, with a further decline at 3 and 6 months (p < 0.001 at each time point). Among the patients who were taking antihypertensives (n = 48) and antilipemics (n = 33) before surgery, the decline in use occurred at a more modest rate, with 6 (12%) and 2 (6%), respectively, discontinuing these medication classes within 1 month, and 12 (25%) (p = 0.001) and 8 (24%) (p = 0.015) having discontinued by 6 months.

Conclusions:

These findings suggest that patients with a history of type 2 diabetes mellitus, hypertension, and/or dyslipidemia who undergo laparoscopic sleeve gastrectomy are less likely to require disease-specific medications shortly after surgery.     

地黄化学成分及其药理作用研究进展

地黄Rehmannia glutinosa为玄参科地黄属植物, 其块根为常用中药。该植物块根和叶中含有大量的环烯醚萜类成分, 同时还存在紫罗兰酮、二苯乙烯、三萜、黄酮、酚酸、木脂素、含氮类、糖及其他类化合物;药理研究表明梓醇等多个成分具有抗心脑血管疾病、神经保护、抗糖尿病及其并发症、抗骨质疏松、增强免疫等多种药理作用。由于中药地黄显著的滋补作用, 历来是研究的热点。对最近5年有关地黄的化学成分和药理研究进行综述, 为进一步研究提供参考。     

2种近缘中药翻白草和仙鹤草的化学成分和降血糖活性比较

翻白草Potentilla discolor和仙鹤草Agrimonia pilosa是蔷薇科(Rosaceae)2种近缘的药用植物,具有明确的降血糖活性,作为治疗糖尿病的中药材应用于临床。基于药用植物亲缘学(pharmaphylogeny)的理论,总结二者主要活性成分的生物合成途径,进而比较二者活性成分的共性及差异,并对物质基础与疗效之间的相关性进行总结。结果表明,2种近缘中药共有的生物合成途径占到60%,刺蒺藜苷、槲皮素等共有成分及翻白叶苷A、蔷薇酸等差异性成分同时也是活性成分,而特征成分及其量的差别可能引起功效及作用方式的不同。     

鹰嘴豆中3种异黄酮及其乙氧基化衍生物体外协同降糖活性研究＊

目的：通过对鹰嘴豆中3种异黄酮类化合物染料木素、鹰嘴豆芽素A、刺芒柄花素进行乙氧基化结构修饰,研究其降糖活性及协同降糖活性。方法：对上述3种异黄酮类化合物进行乙氧基化结构修饰,并研究该3种异黄酮类化合物及其衍生物降糖活性,并对化合物进行组合给药,研究其之间存在的协同降糖活性,选择胰岛素抵抗HepG2细胞作为降糖活性筛选模型。结果：获得4个乙氧基化产物,3个母体异黄酮衍生物中染料木素的降糖活性优于鹰嘴豆芽素A和刺芒柄花素,差异具有统计学意义（P<0.05）,3个母体异黄酮衍生物最大给药剂量与阳性药盐酸二甲双胍相比,效果不如盐酸二甲双胍,差异均具有统计学意义（P<0.05或P<0.01）。衍生物中化合物a和d之间差异无统计学意义（P>0.05）,化合物b和c降糖效果均不如化合物a和d,差异具有统计学意义（P<0.05）,其中化合物d较修饰前降糖活性有明显提高（P<0.05）。组合5的降糖活性与盐酸二甲双胍相当,差异无统计学意义（P>0.05）。结论：本研究发现,通过化合物组合,化合物之间可以起到协同作用,发挥更好的降糖效果,为开发具有自主知识产权的降糖药物提供一定的基础。     

Time-dependent effect of an oral hypoglycemic agent upon serum glucose levels

Summary A constant dosage of glibenclamide (50 μg/kg i.p.) was administered to normal mice at 4-h intervals during the day. Blood samples were collected up to 360 min after the injection, for glucose determination. It was found that neither the depth nor the duration of the glibenclamide-induced hypoglycemia was constant throughout the day. These results demonstrate the existence of a circadian rhythm of the glibenclamide effect on serum glucose levels. They also suggest that a day-time schedule of therapy with this drug should result in improved control of serum glucose. Traduzione a cura di G.U.     

Drug price,dosage and safety: Real-world evidence of oral hypoglycemic agents

ObjectivesDrug price reduction is one of the major policies to restrain pharmaceutical expenses worldwide. This study explores whether there is a relationship between drug price and clinical quality using real-world data.MethodsPatients with newly-diagnosed type 2 diabetes receiving metformin or sulfonylureas during 2001 and 2010 were identified using the claim database of the Taiwan universal health insurance system. Propensity score matching was performed to obtain comparable subjects for analysis. Pharmaceutical products were categorized as brand-name agents (BD), highpriced generics (HP) or low-priced generics (LP). Indicators of clinical quality were defined as the dosage of cumulative oral hypoglycemic agents (OHA), exposure to other pharmacological classes of OHA, hospitalization or urgent visit for hypoglycemia or hyperglycemia, insulin utilization and diagnosis of diabetic complications within 1 year after diagnosis.ResultsA total of 40,152 study subjects were identified. A generalized linear mix model showed that HP and BD users received similar OHA dosages with comparable clinical outcomes. By contrast, LP users had similar outcomes to BD users but received a 39% greater OHA dosage. A marginally higher risk of poor glycemic control in LP users was also observed.ConclusionsDrug price is related to indicators of clinical quality. Clinicians and health authorities should monitor the utilization, effectiveness and clinical safety indicators of generic drugs, especially those with remarkably low prices.     

燮理糖肾颗粒降糖作用的实验研究

目的 观察以肾主藏精泻浊为理论基础,采用补肾泻浊化瘀法配制燮理糖肾颗粒的降糖效果.方法 分别选用自发性糖尿病KKAy小鼠、四氧嘧啶致高血糖大鼠、四氧嘧啶致高血糖小鼠及正常大鼠,4种模型随机分为模型组,燮理糖肾颗粒4、8、16 g生药/kg剂量组,西药组,并设正常对照组,观察给药前、后血糖变化.结果 与正常组比较,模型组动物血糖明显升高,并稳定到实验结束,糖尿病模型成立.与模型组比较,燮理糖肾颗粒8、16 g生药/ks剂量组,动物血糖明显降低,燮理糖肾颗粒各剂量组对正常大鼠血糖无明显影响.结论 以肾主藏精泻浊为理论基础,采用补肾泻浊化瘀法配制燮理糖肾颗粒有降糖效果.     

Review of empagliflozin monotherapy for previously untreated patients with type 2 diabetes mellitus: Comparison with sitagliptin

This Practice Pearl provides a review and brief commentary of the 24-week, double-blind, parallel-group, randomized, Phase III study by Roden et al., which assessed the efficacy and safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin, 10 mg or 25 mg as monotherapy, versus placebo and the dipeptidyl peptidase-4 inhibitor sitagliptin, in previously untreated patients with type 2 diabetes mellitus (T2DM). Compared to placebo, empagliflozin improved glycemic control, with additional benefits on bodyweight and systolic blood pressure, versus placebo and sitagliptin. Treatment was well tolerated. The authors concluded that empagliflozin is a potential new approach to treat patients with T2DM who are inadequately controlled with diet and exercise alone. This paper advances our understanding of empagliflozin, which so far, appears to be a promising therapeutic option for the management of patients with T2DM.