从糖尿病的发病机制看中药桑枝总生物碱的多重药理作用

尽管T2DM发病机制和防治研究不断深入,但全球T2DM患病率、发病率仍在攀升。随着T2DM病理生理机制研究更新,提高了对通过多种生物学途径有效控制血糖、保护胰岛β细胞、同时兼具减少心血管和肾脏等并发症风险药物的需求。源于自然界的天然药物常有多重药理作用且副作用小,与单纯化学合成药物相比,对糖尿病多病因治疗、保证治疗的安全性上,更具发展潜力。从中国传统中药材桑枝中提取分离的“有效组分”天然药物桑植总生物碱（SZ-A）,具有独特的多重药理药效特点和更少的副作用。在胃肠道中,SZ-A可精准作用于双糖酶靶点,通过抑制糖苷酶的活性减缓葡萄糖的消化和吸收而快速控制餐后血糖,胃肠副作用比其他糖苷酶抑制剂类药物更小。本文基于充分的循证医学证据,深入阐释不同生物碱成分的协同机制,挖掘SZ-A用于糖尿病治疗的临床综合获益,探讨SZ-A用于MS治疗的发展潜力。     

糖尿病药物治疗的现状

近年来，随着对糖尿病（DM）发病机制的深入研究，众多新型降糖药物获得研发，为DM患者的治疗提供了更多选择。临床医师合理选择降糖药物，能有效控制血糖，减少药物不良反应，降低DM患者并发症的发生。本文系统地综述了DM治疗药物进展，详细介绍了胰岛素分泌促进剂、胰岛素增敏剂、α-葡萄糖苷酶抑制剂、肠促胰岛素及二肽基肽酶Ⅳ抑制剂，以及胰岛素各类药物和新药情况，同时介绍了正在研发的其他降糖药物和治疗糖尿病并发症的药物。     

钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂临床合理应用中国专家建议

正通过控制2型糖尿病(T2DM)患者多种代谢异常和高血压,预防和延缓糖尿病的大血管病变和微血管病变、提高患者生活质量,延长患者寿命是治疗T2DM的目标。当前,T2DM的控制还面临巨大的挑战,在糖尿病患者的血糖控制上仍需更有效的新型降糖药物来满足传统降糖药物未能满足的治疗需求。钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)是一种     

藏族2型糖尿病患者在口服降糖药物基础上加用地特胰岛素或甘精胰岛素的临床研究

目的观察拉萨地区藏族T2DM患者在口服降糖药物基础上加用地特胰岛素(Det)或甘精胰岛素(Gla)治疗对血糖和体重的影响。方法 70例拉萨地区藏族T2DM患者,在1种或2种口服降糖药的基础上加用Det或Gla。结果治疗3个月后,两组血糖均得到有效控制,加用Gla的T2DM患者体重增加1.3kg,加用Det增加0.2kg。结论拉萨地区藏族T2DM患者在口服降糖药物同时加用基础胰岛素治疗降糖效果较好,低血糖发生率低,而且能减少体重的增加。     

降糖速度与T2DM患者心肌酶学变化的关系

目的 探讨降糖速度对2型糖尿病(T2DM)患者心肌酶学水平变化的影响.方法 选取T2 DM患者202例.将降糖速率≤6mmol·L-1.d-1的患者纳入T2DM1组105例,降糖速率＞6 mmol·L-·d-1的患者纳入T2 DM2组97例.监测并记录两组患者降糖前、降糖后、随访期间3个时间段肌酸激酶同工酶(CK-MB)、肌红蛋白、肌钙蛋白(cTnI)的变化情况.结果 T2DM1组降糖后(CK-MB)、肌红蛋白、cTnI水平较降糖前显著下降(P＜0.05).T2DM1组随访期间心肌酶学水平较降糖前亦明显下降(P＜0.05).T2 DM2组降糖后CK-MB、肌红蛋白、cTnI水平较降糖前上升(P＜0.05).而T2 DM2组随访期间心肌酶学水平较降糖前明显下降(P＜0.05).另外,T2 DM2组降糖前后心肌酶学差值明显高于T2 DM1组(P＜0.05).结论 长期良好的控制血糖可以有效降低心肌酶学水平,但当降糖速度过快时反而会加重心肌细胞损伤,导致心肌酶学水平上升,所以应当合理控制降糖速度.     

小檗碱调节糖脂代谢机制研究进展

<正>2型糖尿病(T2DM)占DM 90%以上。对于T2DM的治疗除饮食和运动之外,还包括口服降糖药物和皮下注射胰岛素。通过降糖治疗可有效减少DM并发症,但临床用药的副作用,如二甲双胍和阿卡波糖的胃肠道反应、噻唑烷二酮类增加心血管疾病的风险等限制其临床应用。传统中药具有多方位、多环节、多靶点的特点,在DM治疗中历史悠久,其中,黄连及其组成小檗碱在糖脂代谢方面有广泛的应用前景。本文就近年国     

非应激状态下2型糖尿病高血酮患者临床特点分析

目的探讨非应激状态下住院2型糖尿病(T2DM)高血酮患者的临床特征。方法以入院随机末梢血酮是否≥0.6 mmol/L将2015-10-01至2016-06-30入住南京大学医学院附属鼓楼医院内分泌科134例非应激状态下入院随机血糖≥13.9 mmol/L的T2DM患者分为高血酮组(25例)和非高血酮组(109例)。比较两组一般情况、糖化血红蛋白(HbA1c)、空腹血糖(FBG)、血清C肽、生化检查、甲状腺功能、骨代谢指标及入院前降糖药物使用情况。结果高血酮组较非高血酮组年龄轻、病程短、HbA1c及FBG高、餐后2 h C肽水平低、合并更多低血清游离T3,入院前应用胰岛素比例低,降糖药物种类少;年轻、短病程、高HbA1c、低血清游离T3为住院T2DM患者高血酮独立危险因素。结论非应激状态下住院T2DM患者酮症不少见,加强T2DM筛查及病程短患者血糖控制,可避免严重高血糖及酮症,血酮检测有助于发现酮症,避免酮症酸中毒(DKA)发生。     

胰高糖素样肽-1(GLP-1)受体激动剂用于治疗2型糖尿病的临床专家共识

胰高糖素样肽-1受体激动剂(GLP-1RA)不仅显著降低2型糖尿病(T2DM)患者的血糖, 还可以改善多种心血管危险因素, 部分GLP-1RA被证实具有明确的心血管保护作用。本共识针对GLP-1RA降糖治疗的应用时机, 与其他降糖药物联用时的注意事项, 对T2DM合并动脉粥样硬化性心血管疾病(ASCVD)、心力衰竭(HF)或慢性肾脏疾病(CKD)患者治疗结局的影响, 在T2DM特殊人群中的应用等临床问题给出了具体的推荐意见。     

2型糖尿病患者口服降糖药治疗的新认识

糖尿病(DM)已成为世界范围内的第五大死因。我国1996年统计资料显示DM患者发病率已从80年代初不足1％发展到3.12％,北京、上海等大城市患病率已达5％以上。如果将糖耐量异常统计在内,则我国现有DM患者约6000万左右,居世界第2位,仅次于印度。我国95％为2型糖尿病(T2DM),其中少部分(约15％)在早期阶段通过饮食、运动和减轻体重等力法,可以控制病情,而大多数需应用口服降糖药物治疗。目前治疗T2DM的口服降糖药物有3类:第一类为促进胰岛素分泌的药物,包括磺脲类和非磺脲类(瑞格列奈、萘格列奈):第二类为加强胰岛素对周围细胞作用     

2型糖尿病患者的安全降糖策略:利格列汀对比格列美脲治疗2型糖尿病的心血管结局研究试验的启示

近年来,随着大量高质量循证医学证据的涌现,各项权威糖尿病诊疗指南的决策理念逐渐转向关注具有明确心血管获益或安全的降糖药物。二肽基肽酶-4抑制剂作为最早开展心血管结局研究(CVOT)的新型降糖药物,已经证实了其心血管安全性。而新近公布的使用利格列汀对比格列美脲治疗2型糖尿病(T2DM)患者的心血管结局研究(CAROLINA)作为目前唯一以活性药物(格列美脲)作为对照开展的CVOT与利格列汀治疗具有心脏和(或)肾脏疾病高风险的成人T2DM患者的心血管与肾脏安全性结局试验(CARMELINA)相互补充,在更广泛的T2DM人群中证实了利格列汀的长期心血管安全性,为T2DM患者选择最优治疗方案提供了更多的循证证据。     

Effect of mulberry leaf extract with enriched 1‐deoxynojirimycin content on postprandial glycemic control in subjects with impaired glucose metabolism

Aims/Introduction: The glucose analogue, 1‐deoxynojirimycin (DNJ), found in mulberry (Morus alba) leaves, is a promising α‐glucosidase inhibitor. We evaluated the effect of the ingestion of mulberry leaf extract with enriched DNJ content on postprandial hyperglycemia in subjects with impaired glucose metabolism. Materials and Methods: In study 1, we carried out a randomized, double‐blind, crossover trial to assess the effects of single ingestion of mulberry leaf extract (3, 6 or 9 mg DNJ) or placebo on blood glucose and insulin concentrations during 2 h after a carbohydrate (200 g boiled white rice) challenge in 12 subjects with fasting plasma glucose (FPG) in the range of 100–140 mg/dL. Study 2 was a randomized, double‐blind, placebo‐controlled trial to assess the efficacy of 12‐week extract supplementation (6 mg DNJ, t.i.d.) for long‐term glycemic control in 76 subjects with FPG in the range of 110–140 mg/dL. Results: In study 1, ingestion of the mulberry leaf extract led to attenuated postchallenge acute glycemia in a dose‐dependent manner (P = 0.006, group × time interaction, two‐way anova ). In study 2, the serum 1,5‐anhydroglucitol concentration, a sensitive indicator of postprandial glycemic control, in the extract group increased and was higher than that in the placebo group over the 12‐week treatment period (P < 0.001, group × time interaction, two‐way anova ); no differences in FPG, glycated hemoglobin and glycated albumin concentrations were observed between the groups. Conclusions: Long‐term ingestion of mulberry leaf extract with enriched DNJ content could result in improved postprandial glycemic control in individuals with impaired glucose metabolism. These trials were registered with UMIN (no. UMIN000003154 and UMIN000003155). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00101.x, 2011)     

药桑不同提取物对2型糖尿病大鼠的治疗作用

目的 探讨药桑醇提物与水提物对2型糖尿病(T2DM)大鼠的治疗作用.方法 采用高脂高糖饮食同时腹腔注射链脲佐菌素复制T2DM大鼠模型.将动物随机分为模型组、拜糖平阳性对照、药桑醇提物组(20 mg/kg)和水提物组(20 mg/kg),并设置正常对照组.4 w后处死大鼠取血清测定血糖、果糖胺、血脂生化指标[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)];取新鲜肝脏测定肝糖原、超氧化物歧化酶(SOD)、丙二醛(MDA).结果 与正常对照组比较,模型组血糖、果糖胺、MDA、TC、TG、LDL-C水平明显升高(P＜0.01),肝糖窄、HDL-C含量、SOD活性明显降低(P＜0.05).与模型组比较,药桑组各项指标有明显改善(P＜0.05).结论 药桑不同提取物可降低血糖、提高机体抗氧化能力,对T2DM大鼠具有一定的治疗作用.     

Effect of age and Helicobacter pylori infection on gastric acid secretion

BACKGROUND: Whether gastric acid secretion decreases with age is still controversial. With the discovery of Helicobacter pylori, the association of this bacterium with gastric acid secretion has also been discussed. The aim of this study was to investigate the relationship between gastric acid secretion, age and H. pylori infection. METHODS: The presence of H. pylori infection, the grade of fundic atrophic gastritis (FAG), and gastric acid secretion were investigated in 280 subjects without localized lesions in the upper gastrointestinal tract. Helicobacter pylori infection was confirmed by Giemsa and immunohistochemical staining, and FAG of biopsy specimens was graded on a scale of 0-4. RESULTS: Both basal and maximal acid output decreased with age in H. pylori-positive subjects, while they did not change with age in H. pylori-negative subjects. Gastric acid secretion decreased with the progression of FAG. An age-correlated decrease in gastric acid secretion in H. pylori-positive subjects depended on an increasing prevalence of FAG with age. CONCLUSIONS: In the population studied, advancing age had no influence on gastric acid secretion in H. pylori-negative subjects. Gastric acid secretion decreases with age in H. pylori-positive subjects because of the increasing prevalence of FAG with age.     

阿托伐他汀对老年2型糖尿病患者颈动脉硬化的影响

目的探讨阿托伐他汀对老年2型糖尿病患者颈动脉硬化的影响。方法选择100例合并颈动脉硬化的老年2型糖尿病患者,随机分为对照组50例(仅控制血糖)和联合组50例(在控制血糖基础上,口服阿托伐他汀20mg/晚),疗程为12个月。测定治疗前后颈动脉硬化相关指标、血脂及高敏C反应蛋白(hs-CRP)。结果两组患者治疗前颈动脉内膜中层厚度(IMT)、斑块检出率、斑块Crouse积分及颈动脉内径无显著差异;与治疗前比较,对照组治疗12个月后颈动脉IMT、斑块检出率及Crouse积分明显增加(P<0.05),颈动脉内径、血脂及hs-CRP水平无明显变化;联合组治疗12个月后颈动脉IMT、斑块检出率、Crouse积分明显降低,颈动脉内径明显增加(P<0.05),治疗6个月、12个月后血清LDL-C、TG、TC、hs-CRP明显降低,HDL-C明显升高(P<0.05)。IMT、Crouse积分均与LDL-C、TG、TC、hs-CRP呈正相关,与HDL-C呈负相关(P<0.05)。结论在控制血糖的同时,联合应用阿托伐他汀,对延缓老年2型糖尿病患者颈动脉硬化进展有一定影响。     

New therapies for type 2 diabetes: what place for incretin-based agents and rimonabant compared to the previous ones?

Treatment of type 2 diabetes (T2DM) is based on lifestyle changes and oral antidiabetic agents or insulin. The UKPDS study has confirmed metformin (Met) as the initial monotherapy. Accordingly, Met is widely regarded as the first drug of choice for most patients with T2DM. Safety and efficacy of sulphonylureas (SU) have been confirmed by several clinical trials. Recently, thiazolidinediones (TZD) have addressed some aspects of insulin-resistance that characterized several T2DM patients. However, SU and TZD are associated with various side effects that limit their use in many patients. New agents have been recently developed which potentiate the activity of the incretin (GLP1). GLP1, a gut hormone secreted in response to meal ingestion, is rapidly degraded by dipeptidylpeptidase-4 (DPP-4). GLP1 enhances insulin secretion and inhibits glucagon secretion in a glucose-dependent manner, delays gastric emptying and, in animal studies, preserves beta-cell mass by reducing apoptosis and stimulates of beta-cell proliferation. GLP1 levels are abnormally low in T2DM patients. Two classes of agents based on GLP1 have been launched: DPP-4 inhibitors and DPP-4 resistant GLP1 analogues. Randomized studies confirmed their efficacy to improve glycemic control in T2DM patients. Orally administered DPP-4 inhibitors reduce HbA1c by 0.5-1.1%, without hypoglycaemic events and no weight gain. The sub-cutaneous injected GLP1 analogues (exenatide and liraglutide) show larger reductions in HbA1c by 0.8-1.7% and weight loss but are associated with gastrointestinal side effects contributing to a significant treatment interruption. Several studies support the use of DPP-4 inhibitors in combination with Met as a promising second line treatment.     

Endogenous opioids, the enteric nervous system and gut motility

Opium alkaloids have been used for centuries as potent antidiarrheals and analgesics, their constipating action in the latter instance taken as an unwanted effect. It was only during the last decade that the physiological role of opioid peptides present in both neurons and endocrine cells of the gastrointestinal (GI) tract has been defined. The recognition of distinct opioid receptor types which may be differentially involved in the control of motility, acid and electrolyte secretion in the GI tract presently focuses the attention of researchers in this field on the identification of receptor-type-selective opioid agonists in order to free these clinically extremely useful drugs from side effects. The present review provides a survey of mostly physiological data on the functional role of intestinal opioids.     

Low-carbohydrate diet by staple change attenuates postprandial GIP and CPR levels in type 2 diabetes patients

AimsThe aim of this study is to investigate the effects of a low-carbohydrate staple food (i.e., low-carbohydrate bread) on glucose and lipid metabolism and pancreatic and enteroendocrine hormone secretion in comparison with meals containing normal-carbohydrate bread, without consideration of the carbohydrate content of the side dishes.MethodsT2DM patients (n = 41) were provided meals containing low-carbohydrate bread (LB) together with side dishes or normal-carbohydrate bread (NB) together with side dishes every other day as a breakfast. Blood glucose levels were evaluated by using a continuous glucose monitoring system; blood samples were collected before and 1 and 2 h after the breakfast.ResultsPostprandial blood glucose levels, plasma insulin, plasma glucose-dependent insulinotropic polypeptide (GIP) and plasma triglyceride were significantly lower and plasma glucagon levels were significantly higher in LB compared with those in NB. Plasma glucagon-like peptide-1 (GLP-1) levels did not differ in the LB and NB groups.ConclusionsThese results indicate that changing only the carbohydrate content of the staple food has benefits on glucose and lipid metabolism in T2DM patients concomitant with the decrease of insulin and GIP secretion, which ameliorate body weight gain and insulin resistance.     

1型糖尿病的非胰岛素辅助降糖治疗

1型糖尿病（T1DM）是一种自身免疫介导的以胰岛素分泌减少或胰岛素绝对缺乏为特征的疾病,胰岛素治疗是 其主要的治疗方式。胰岛素治疗存在着增加体重和低血糖风险的缺点。与此同时,胰岛素治疗不能延缓或阻止胰岛 功能的进行性破坏,因此T1DM患者病程中晚期多出现脆性糖尿病。文章总结了近些年有关T1DM非胰岛素辅助治 疗的最新研究进展,详细阐述了口服降糖药、注射类药物、免疫治疗等作为胰岛素的辅助治疗带来的新作用,为改善 T1DM患者生活质量带来新思路与新展望。     

The Effects of Naloxone and Morphine on Postprandial Gastrointestinal Hormone Secretion

Postprandial gastrointestinal hormone secretion was not affected by the intravenous administration of naloxone. However, after the administration of morphine, multiple effects were observed. Postprandial pancreatic polypeptide, motilin, and enteroglucagon secretion were abolished and there was a reduction in the secretion of insulin, gastric inhibitory polypeptide, and neurotensin. There was prolonged secretion of gastrin. Levels of vasoactive intestinal polypeptide, somatostatin, and pancreatic glucagon were not affected. Many of these changes can be accounted for by the ability of morphine to delay gastric emptying. The prolonged secretion of gastrin could result from a combination of impaired gastric emptying and reduced postprandial gastric acid secretion. Inhibition of vagal acetylcholine release is the most likely explanation for the abolition of pancreatic polypeptide secretion. With the exception of the effects on motilin, pancreatic polypeptide, and enteroglucagon secretion this study provides no evidence that opiate substances directly affect the secretion of gastrointestinal hormones.     

血糖控制对2型糖尿病病人骨转换的影响

目的 探讨血糖控制对２型糖尿病（ＤＭ）骨转换的影响。方法 测定４３例２型ＤＭ患者血骨特异性碱性磷酸酶（ＢＡＰ）、尿脱氧吡啶酚（ＤＰＤ）和血尿钙、磷、镁水平，并与正常组比较。结果 ２型ＤＭ患者血ＢＡＰ、尿ＤＰＤ以及钙、磷高于正常对照；治疗后ＢＡＰ、ＤＰＤ降低。ＢＡＰ和ＤＰＤ变化水平与糖化血红蛋白、尿糖和尿钙、磷变化水平正相关。结论 控制血糖能使２型ＤＭ患者骨转换降低。