肠抑胃肽与2型糖尿病

肠抑胃肽(GIP)促进胰岛B细胞分泌胰岛素的作用减低或缺失是2型糖尿病发病机制的重要环节，具体可能与GIP受体的异常有关。应用GIP降解酶抑制剂、化学修饰的GIP可改善血糖水平，转染了GIP／胰岛素基因序列的K细胞能以血糖依赖方式分泌人胰岛素，并能在B细胞功能缺失下维持血糖。     

胰岛素或磺脲类药物联合二甲双胍治疗对2型糖尿病患者胰岛β细胞功能的影响

2型糖尿病(T2DM)的发生是在胰岛素抵抗(IR)的基础上，随着病程的进展，胰岛β细胞的功能出现进行性衰变所致。在临床治疗中，采用何种方案对T2DM患者的胰岛β细胞功能有较好的保护作用，尚待解决。本研究对我院的T2DM患者用磺脲类口服降糖药加二甲双胍或胰岛素加二甲双胍强化治疗3年，观察患者治疗前后的胰岛β细胞功能和胰岛素抵抗的差异。     

2型糖尿病流行病学

一、概述2型糖尿病占糖尿病总体人群95%以上,患病率高,起病隐匿,早期症状不明显,流行病学主要调查其患病率。1型糖尿病比较罕见,典型者多见于儿童,流行病学常常调查其儿童人群的年发病率。1型糖尿病流行病学调查往往有专门说明。其实胰岛β细胞自身免疫损伤所致的1型糖尿病可以     

那格列奈和瑞格列奈对2型糖尿病患者胰岛β细胞功能的改善作用

目的探讨那格列奈和瑞格列奈对2型糖尿病患者胰岛β细胞功能的改善作用。方法选择经生活干预治疗6个月以上、血糖控制不理想的2型糖尿病患者200例,采用随机双盲双模拟平行对照的方法分为两组,其中100例给予那格列奈60~90 mg治疗,100例采用瑞格列奈0.5~1.0 mg,两组均治疗12 w,治疗前后分别观察Homa-β、IRG、AUCi/AUCg等胰岛β细胞功能指标,测量空腹血糖(FPG)、餐后2 h血糖(2 h PG)、空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C),量身高和体重,用稳态模式法评估胰岛素抵抗(Homa-IR)。结果两组患者治疗前FPG、2 h PG、HbA1c等指标比较无差异(P0.05);那格列奈组患者治疗后FPG、2 h PG、HbA1c等指标与治疗前比较差异显著(P0.05);瑞格列奈组患者治疗后FPG、2 h PG等指标与治疗前比较差异显著(P0.05);两组患者治疗后FPG、2 h PG、HbA1c等指标比较无差异(P0.05);两组患者治疗前TC、TG、HDL-C、LDL-C等指标比较无差异(P0.05);那格列奈组患者治疗后TC、LDL-C等指标与治疗前比较差异显著(P0.05);瑞格列奈组患者治疗后TC、TG、HDL-C、LDL-C等指标与治疗前比较无差异(P0.05);两组患者治疗后TC、TG、HDL-C、LDL-C等指标比较无差异(P0.05);两组患者治疗前胰岛素抵抗(IR)、FINS、体重指数(BMI)等指标比较无差异(P0.05);那格列奈组患者治疗后IR、BMI与治疗前比较有差异(P0.05);瑞格列奈组患者治疗后IR、FINS、BMI指标与治疗前比较无差异(P0.05);那格列奈组患者治疗后IR水平与瑞格列奈组患者治疗后比较差异显著(P0.05);那格列奈组患者治疗后FINS、BMI与瑞格列奈组患者治疗后比较无差异(P0.05);两组患者治疗前Homa-β、IRG、AUCi/AUCg等胰岛β细胞功能指标比较无差异(P0.05);两组患者治疗后Homa-β、IRG、AUCi/AUCg等胰岛β细胞功能指标与治疗前比较差异显著(P0.05);两组患者治疗后FPG、2 h PG、HbA1c等指标比较无差异(P0.05)。结论那格列奈和瑞格列奈均能有效改善对2型糖尿病患者胰岛β细胞功能和IR。     

糖肾平,D860双盲治疗过程中Ⅱ型糖尿病患者胰岛B细胞功能变化

29例Ⅱ型糖尿病患者,分别接受糖肾平(15例)和D860(14例)双盲治疗4个月。在治疗前、后共作3次馒头餐试验,测定血清胰岛素、C肽和血糖水平,对比观察治疗前后和两组之间胰岛B细胞功能变化,并与正常组(15例)比较。结果表明,治疗前患者胰岛功能明显相对不足,餐后胰岛素分泌延缓,C肽/血糖比值低于正常。治疗后显著改善,空腹C肽/血糖比值正常。糖肾平在4个月疗程中主要通过改善胰岛功能而降血糖。     

2型糖尿病人群线粒体基因突变的研究

目前已知的几种单基因突变糖尿病(DM)中，线粒体tRNA^Leu(UUR)基因3243A→G点突变最为多见，已在不同种族中被发现。本研究对线粒体基因突变热点区域一tR—NA^Leu(UUR)基因及其邻近区域内的4个位点(np3243、np3316、np3394、np3426)进行筛查，旨在探讨线粒体基因突变在我国2型糖尿病(T2DM)患者中的存在情况。     

继发性磺脲类药物失效的2型糖尿病患者胰岛β细胞功能测定

磺脲类药物是２型糖尿病（ＤＭ）治疗的首选药,但磺脲类降糖药物（ＳＵ）继发失效是临床上常见的问题。为探讨继发性ＳＵ失效的２型ＤＭ人胰岛β细胞的释放功能,我们观察了２１例继发性ＳＵ失效的ＤＭ者胰岛β细胞的分泌功能,并与２５例ＳＵ有效的ＤＭ者及正常人比较。１．对象：糖尿病患者４６例（按１９８５年ＷＨＯ制定的诊断标准）,其中ＤＭ磺脲类有效组（ＤＳＥ）２５例,血糖控制采用饮食控制、运动、口服ＳＵ,ＦＢＧ≤８．０ｍｍｏｌ／Ｌ,２ｈＢＧ≤１０ｍｍｏｌ／Ｌ,肝肾功能正常。糖尿病磺脲类药物继发失效组（ＤＳＦ）２１…     

磺脲类药物继发失效2型糖尿病患者2种治疗方案疗效比较

2型糖尿病的主要病理生理改变包括胰岛素抵抗和胰岛素分泌功能障碍,磺脲类药物通过作用于胰岛β细胞钾离子通道直接引起靶向胰岛素分泌以控制血糖。英国糖尿     

细胞因子介导的2型糖尿病β细胞损伤机制

胰岛 β细胞损伤是 2型糖尿病的重要发病机制。近年研究发现细胞因子白介素 (IL) 1β、肿瘤坏死因子 (TNF) α、干扰素 (IFN) γ、IL 6、瘦素等可通过不同途径直接或间接参与 2型糖尿病 β细胞损伤。一氧化氮、核因子κB等在细胞因子介导的β细胞损伤中起重要作用。     

2型糖尿病的抗炎治疗

胰岛素抵抗与胰岛β细胞功能障碍是2型糖尿病发病的主要病理生理基础,而炎性反应因子介导的慢性非特异性低度炎性反应状态与胰岛素抵抗及β细胞功能障碍密切相关.传统意义上的降糖药物如二甲双胍、噻唑烷二酮类药物、胰岛素、胰高血糖素样肽-1以及他汀类降脂药都具有抗炎效应.新型的抗炎药物如白细胞介素1受体拮抗剂、白藜芦醇、姜黄素等可以通过多种途径改善炎性反应状态而降低血糖.因此,针对炎性反应因子的抗炎治疗有望成为一种崭新的糖尿病治疗u方法.     

自然疗法治疗2型糖尿病的研究进展

虽然传统的降糖药物和胰岛素在控制2型糖尿病方面有较明确的疗效,然而,终身接受药物治疗对患者的身心健康危害极大.近年来,物理疗法、情志疗法、运动疗法、食物疗法等自然疗法在2型糖尿病中的应用越来越受到重视,且疗效显著.物理疗法是应用一种或多种物理因素作用于人体,以防治疾病的方法;情志疗法是通过社会、家庭和患者的积极沟通,使患者保持积极乐观的心态和稳定的情绪,树立战胜疾病的信心,有助于疾病的康复;运动疗法是指有治疗意义的运动,通过有计划的、多样性的、合理的重复性运动达到一定的促进健康的目的;饮食疗法即利用食物来影响机体各方面的功能,使其获得健康或疾病防治的一种方法.     

Pharmacogenetics of type 2 diabetes mellitus,the route toward tailored medicine

Type 2 diabetes mellitus (T2DM) is a chronic disease that has reached the levels of a global epidemic. In order to achieve optimal glucose control, it is often necessary to rely on combination therapy of multiple drugs or insulin because uncontrolled glucose levels result in T2DM progression and enhanced risk of complications and mortality. Several antihyperglycemic agents have been developed over time, and T2DM pharmacotherapy should be prescribed based on suitability for the individual patient's characteristics. Pharmacogenetics is the branch of genetics that investigates how our genome influences individual responses to drugs, therapeutic outcomes, and incidence of adverse effects. In this review, we evaluated the pharmacogenetic evidences currently available in the literature, and we identified the top informative genetic variants associated with response to the most common anti‐diabetic drugs: metformin, DPP‐4 inhibitors/GLP1R agonists, thiazolidinediones, and sulfonylureas/meglitinides. Overall, we found 40 polymorphisms for each drug class in a total of 71 loci, and we examined the possibility of encouraging genetic screening of these variants/loci in order to critically implement decision‐making about the therapeutic approach through precision medicine strategies. It is possible then to anticipate that when the clinical practice will take advantage of the genetic information of the diabetic patients, this will provide a useful resource for the prevention of T2DM progression, enabling the identification of the precise drug that is most likely to be effective and safe for each patient and the reduction of the economic impact on a global scale.     

New therapeutic strategies for the treatment of type 2 diabetes mellitus based on incretins

Orally ingested glucose leads to a greater insulin response compared to intravenously administered glucose leading to identical postprandial plasma glucose excursions, a phenomenon referred to as the "incretin effect". The incretin effect comprises up to 60% of the postprandial insulin secretion and is diminished in type 2 diabetes. One of the very important gastrointestinal hormones promoting this effect is glucagon-like peptide 1 (GLP-1). It only stimulates insulin secretion and normalizes blood glucose in humans under hyperglycemic conditions, therefore it does not cause hypoglycemia. Other important physiological actions of GLP-1 are the inhibition of glucagon secretion and gastric emptying. It further acts as a neurotransmitter in the hypothalamus stimulating satiety. In vitro and animal data demonstrated that GLP-1 increases beta-cell mass by stimulating islet cell neogenesis and by inhibiting apoptosis of islets. In humans, the improvement of beta-cell function can be indirectly observed from the increased insulin secretory capacity after GLP-1 infusions. GLP-1 represents an attractive therapeutic principle for type 2 diabetes. However, native GLP-1 is degraded rapidly upon exogenous administration and is therefore not feasible for routine therapy. The first long-acting GLP-1 analog ("incretin mimetic") Exenatide (Byetta) has just been approved for type 2 diabetes therapy. Other compounds are being investigated in clinical trials (e.g. liraglutide, CJC1131). Dipeptidyl-peptidase IV inhibitors (DPP-IV inhibitors; e.g. Vildagliptin, Sitagliptin) that inhibit the enzyme responsible for incretin degradation are also under study.     

Pharmacologic therapy for type 2 diabetes mellitus.

Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. An elevated rate of basal hepatic glucose production in the presence of hyperinsulinemia is the primary cause of fasting hyperglycemia; after a meal, impaired suppression of hepatic glucose production by insulin and decreased insulin-mediated glucose uptake by muscle contribute almost equally to postprandial hyperglycemia. In the United States, five classes of oral agents, each of which works through a different mechanism of action, are currently available to improve glycemic control in patients with type 2 diabetes. The recently completed United Kingdom Prospective Diabetes Study (UKPDS) has shown that type 2 diabetes mellitus is a progressive disorder that can be treated initially with oral agent monotherapy but will eventually require the addition of other oral agents, and that in many patients, insulin therapy will be needed to achieve targeted glycemic levels. In the UKPDS, improved glycemic control, irrespective of the agent used (sulfonylureas, metformin, or insulin), decreased the incidence of microvascular complications (retinopathy, neuropathy, and nephropathy). This review examines the goals of antihyperglycemic therapy and reviews the mechanism of action, efficacy, nonglycemic benefits, cost, and safety profile of each of the five approved classes of oral agents. A rationale for the use of these oral agents as monotherapy, in combination with each other, and in combination with insulin is provided.     

高尿酸血症与2型糖尿病

大量研究已证实高尿酸血症(HUA)与2型糖尿病(T2DM)密切相关,HUA患者中T2DM发生率显著高于尿酸正常者,而T2DM患者相对于非糖尿病者更容易发展为HUA.HUA可能通过引起慢性炎性反应和胰岛素抵抗参与T2DM的发生、发展,而T2DM中HUA发生率高可能与氧化应激和高胰岛素血症有关.另外,HUA与糖尿病并发症之间也存在紧密联系.