2型糖尿病关注的新问题

世界人口中 2型糖尿病平均患病率为 2 %～ 7.2 % ,成人糖尿病中 90 %是 2型糖尿病 ,儿童 2型糖尿病占所有 2型糖尿病的 1%～ 2 % ,而且有急剧增多的趋势。2型糖尿病是一种慢性代谢性疾病 ,成人 2型糖尿病基本病因是胰岛 β细胞功能异常和胰岛素抵抗导致 2型糖尿病病人血糖及脂肪代谢异常 ,两者共同作用于胰岛素的三个主要靶器官———肝脏、骨骼肌及脂肪组织 ,肝脏的胰岛素抵抗表现为肝糖输出增加 ,骨骼肌及脂肪组织的胰岛素抵抗表现为葡萄糖利用率降低。儿童 2型糖尿病发病机制首先是胰岛素作用失常 ,随后造成胰岛素功能衰竭。儿童在 2型糖…     

α-葡萄糖苷酶抑制剂的研究进展

糖尿病是一种多病因引起、以高血糖为特征的内分泌代谢紊乱性疾病。高血糖是由胰岛素分泌不足、胰岛素抵抗,或二者共同存在而引起。世界上,糖尿病患者已超过1．7亿,已成为继心血管疾病和肿瘤之后第三大严重威胁人类健康的非传染性疾病^[1]。临床上,根据糖尿病发病机制不同,主要分为1型糖尿病（胰岛素依赖型）和2型糖尿病（非胰岛素依赖型）,我国以2型居多。治疗2型糖尿病的药物主要分为：（1）胰岛素及类似物：如赖脯胰岛素等;（2）促胰岛素分泌剂：如磺酰脲类;（3）胰岛素增敏剂：如噻唑烷类衍生物;     

抗糖尿病药物研究进展

糖尿病是一种慢性进行性病 ,病人主要表现为高血糖及糖尿。持续的高血糖会导致许多并发症的产生 ,如视网膜、肾脏、神经系统病变及血管并发症。血管并发症是糖尿病患者致死致残的主要原因。因此保持接近正常范围的血糖水平对于预防糖尿病并发症十分重要。　　临床将糖尿病分为两型。 1型糖尿病 (胰岛素依赖型 )是由于胰岛 β细胞损害引起胰岛素分泌水平极低而致高血糖 ,约占糖尿病人的 10 %。其治疗只能依赖于外源性给予胰岛素。另一大类为 2型(非胰岛素依赖型 ) ,是胰岛素分泌的相对不足及胰岛素作用环节不健全而致血糖水平升高[1] 。对 2…     

过氧亚硝基阴离子在糖尿病及其并发症中的作用

据世界卫生组织统计,2002年全球约有1.7亿糖尿病患者,预计到2030年患糖尿病的人数将增加1倍[1].在糖尿病患者中2型糖尿病约占90%,以胰岛素抵抗为特点,并与肥胖和脂质代谢紊乱有关.1型糖尿病人占5%～10%,主要发生于儿童和青年人,以分泌胰岛素的胰腺β细胞损伤导致胰岛素分泌不足为特点.高血糖是这两种类型糖尿病最显著的特征.持续的高血糖刺激可引起氧化应激和硝化应激,导致过量一氧化氮(NO)和超氧阴离子产生,两者通过非酶促化学反应可形成细胞毒性更强的过氧亚硝基阴离子(ONOO-).     

不同时期儿童糖尿病的血糖控制目标

糖尿病是由于胰岛素分泌能力或（和）胰岛素作用缺陷而致的以高血糖为特征的慢性代谢性疾病。在各种糖尿病类型中，1型糖尿病占5％～10％，患病人群以儿童、青少年为主。这些孩子需要每日注射2～4次的胰岛素，且需对身体发育成长提供充足的营养，在使用胰岛素与预防低血糖、防治并发症、维持正常的生长发育中取得平衡，需要家人在照顾孩子方面具有良好的初步训练，     

糖尿病药物治疗及机制研究进展

糖尿病可分为两型:1型--胰岛素依赖性糖尿病(insulin-dependent diabetes meilitus,IDDM),是由于胰岛B细胞破坏,胰岛素分泌缺乏而致高血糖;2型--非胰岛素依赖性糖尿病(non-insulin-dependent diabetes mellitus,NIDDM),是B细胞功能低下,胰岛素相对缺乏及胰岛素作用环节不健全而致血糖水平升高.     

糖尿病口服药物研究进展

糖尿病是以高血糖为主要特征的代谢性内分泌疾病,系因胰岛素绝对或相对不足,或靶细胞对胰岛素敏感性减低所致。可分为胰岛素依赖型和非胰岛素依赖型。其中1型糖尿病为胰岛素分泌绝对不足,需外源性胰岛素治疗,口服降糖药无效;2型糖尿病为胰岛素相对分泌不足,大多数可使用口服降血糖药治疗。本资料对目前治疗糖尿病各种类型的口服药物的作用机制、临床应用及主要不良反应做一概述。     

糖尿病口服药物的应用

糖尿病是由多种病因引起的慢性高血糖为特征的代谢紊乱,高血糖是由于胰岛素分泌或作用的缺陷,或者两者同时存在而引起。久病可引起多系统损害,导致眼、肾、神经、心脏和血管等组织的慢性进行性病变,引起功能缺陷及衰竭。糖尿病按病因学分为4型,其中2型糖尿病较为多见,目前治疗2型糖尿病的药物主要选用口服降糖药和胰岛素。     

2型糖尿病的口服药物治疗

2型糖尿病（或称非胰岛素依赖型糖尿病,NIDDM）是一种因胰岛素分泌和作用异常所引起的慢性代谢障碍.它是以胰岛素抵抗和高血糖为特征,并常伴有高血压、脂代谢紊乱和肥胖.2型糖尿病是最为常见的糖尿病类型,约占糖尿病总发病率的90%.2型糖尿病的主要病理变化为胰岛β细胞功能低下,而胰岛素抵抗可能是β细胞衰竭的主要原因.     

应用诺和灵30R治疗初诊2型糖尿病临床观察

糖尿病是由多种病因引起的以慢性高血糖为特征的代谢紊乱.久病可引起多系统损害,导致眼、肾、神经、心脏、血管等组织的慢性进行性病变,引起功能缺陷及衰竭[1].2 型糖尿病(T2DM)的发生是胰岛B 细胞分泌的胰岛素不足以代偿胰岛素抵抗的结果[2].早期科学诊断及合理用药非常必要.     

2型糖尿病新一代降糖药的药物基因组学的最新进展

精准医学是综合考虑个人的基因、环境和生活方式的一种新的疾病预防和治疗理念。随着药物遗传学和药物基因组学迅速发展和壮大,对个体遗传变异和药物剂量与治疗反应之间的联系进行研究,成为精准医学治疗的关键。2型糖尿病是一种以高血糖为特征的慢性代谢性疾病,可以导致心血管、肾脏等并发症。最新美国糖尿病协会和欧洲糖尿病协会的2型糖尿病高血糖管理共识中建议,合并动脉粥样硬化性心血管疾病（ASCVD）或慢性肾脏疾病、有低血糖风险或体质量相关问题的2型糖尿病患者,在二甲双胍单药起始治疗后优先使用胰高血糖素样肽-1（GLP-1）受体激动剂、钠-葡萄糖共转运体-2（SGLT2）抑制剂和二肽基肽酶-4（DPP-4）抑制剂。药物基因组学研究已经鉴定出许多与降糖药物反应相关的生物标志物,这些基因的功能变异对血糖控制、不良反应和并发症的风险有显著影响。我们综述了临床实践中新型二线降糖药物的药物遗传学的最新进展,为精准医学预防和治疗T2DM及其并发症提供有效工具。     

达格列净联合用药治疗糖尿病的临床研究进展

糖尿病是一种以高血糖为特征的慢性代谢性疾病,给人类生命健康带来严重危害。当单一降糖药疗效不佳时,常采用2种及2种以上降糖药进行治疗。达格列净是近年新上市的一种钠-葡萄糖共转运蛋白2（sodium-glucose contransporter 2,SGLT2）抑制剂,用于糖尿病疗效显著,不良反应少,应用广泛。临床上糖尿病及其并发症治疗效果不佳时,常将达格列净与胰岛素、二甲双胍、利拉鲁肽、沙格列汀、吡格列酮、阿卡波糖、中药等联用,以增强疗效,降低不良反应发生率。本文通过对达格列净与上述降糖药物联用治疗糖尿病的疗效和安全性进行总结和评价,以期为SGLT2抑制剂联合用药、降糖药合理应用和糖尿病治疗提供参考。     

Type 1 diabetes mellitus: primary, secondary, and tertiary prevention

We have entered the era of clinical trials to prevent type 1 diabetes mellitus (T1DM). Before 1922, when insulin was first given to a patient with diabetes, a diagnosis of T1DM was considered a death sentence. Advances in treatment for subjects with diabetes are not yet sufficient to prevent the deleterious impact of diabetes on both day-to-day activities and the early morbidity and mortality still associated with the disease. We now understand a great deal about blood glucose regulation and potential health complications associated with long-term T1DM, but the mystery of why, or the pathogenesis of this devastating disease, remains elusive. Great strides toward unraveling this mystery have been made over the past several decades. Even without definitive answers, we are moving from the period of discovery and animal research to the era of clinical trials. In this review, we wish to convey the palpable excitement in the field. It is time to determine if we can safely change the course of T1DM.     

Defining the Role of Repaglinide in the Management of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia due to a combination of insulin resistance and impaired insulin secretion. The hyperglycemia is associated with an increased risk for micro- and macrovascular complications, and lowering fasting and postprandial hyperglycemia may be protective against these complications. Repaglinide is an insulin secretagogue that lowers blood glucose levels in patients with T2DM. We review the effects of repaglinide in patients with T2DM, its impact on glycemia and its non-glycemic effects, and its effects when used in special situations or patient populations. Results from randomized controlled trials, observational studies, and safety reports involving humans and published in the English-language through 1 May 2007 identified by a search in PubMed/MEDLINE were evaluated. Present knowledge indicates that repaglinide reduces fasting and postprandial hyperglycemia and the level of glycosylated hemoglobin (HbA1c) in patients with T2DM. It is at least as effective in reducing HbA1c and fasting plasma glucose as sulphonylureas, metformin, or the glitazones and in combination therapy with other drugs, repaglinide is as effective as any other combination. Some studies show a better effect of repaglinide on postprandial glycemia than the comparators. Its propensity to induce hypoglycemia is similar to or a little less than that of sulphonylureas. Repaglinide is associated with less weight gain than sulphonylureas and the glitazones. Repaglinide has primarily a role in the treatment of T2DM when metformin cannot be used due to adverse effects, when metformin fails to adequately control blood glucose levels, when there is a need for flexible dosing (i.e. the elderly or during Ramadan fasting), or when there is a specific wish to lower postprandial glucose. Repaglinide may also have an advantage when an oral agent is needed in diabetic patients with renal impairment. Because of its short duration of action, repaglinide should be taken before each meal, usually at least three times a day. Although no study has investigated whether repaglinide lowers total mortality or cardiovascular endpoints, several studies indicate beneficial effects on cardiovascular surrogate endpoints, such as carotid intima-media thickening, markers of inflammation, platelet activation, lipid parameters, endothelial function, adiponectin, and oxidative stress. In conclusion, repaglinide is a compound that can be used in both mono- and combination therapy for the treatment of both fasting and postprandial hyperglycemia in patients with T2DM. It can be used in patients at different stages of the disease, from uncomplicated to severe renal impairment. Although the drug has been tested in a large number of clinical trials and observational studies, its world-wide use is far less than, for example, sulphonylureas. Repaglinide may offer an additional potential for lowering blood glucose levels in T2DM that until now has not been fully realized by many clinicians.     

Do glucagon-like peptide-1 receptor (GLP-1R) agonists have potential as adjuncts in the treatment of type 1 diabetes?

ABSTRACT

Introduction: Glucagon-like peptide-1 (GLP-1) is produced by the gut, stimulates insulin secretion from the pancreatic β-cells, and inhibits glucagon secretion from the α-cells. The GLP-1 receptor (GLP-1R) agonists are used in the treatment of type 2 diabetes (T2DM).

Area covered: This review covers the clinical trials of the GLP-1R agonists (exenatide and liraglutide) and their potential as adjunct treatment in type 1 diabetes mellitus (T1DM).

Expert opinion: GLP-1R agonists are unable to increase insulin secretion, in subjects with T1DM, who are C-peptide negative. Also, the GLP-1R agonists either have no effect or cause a small inhibition of glucagon secretion in subjects with T1DM. There is no evidence that the GLP-1R agonists cause a major reduction in HbA1c, or have a major effect on hypo- or hyperglycemia in subjects with TD1M. The main beneficial effect of the GLP-1R agonists is probably the modest weight loss, which may underlie the reduction in dose of insulin used. Given that the GLP-1R agonists cause gastrointestinal adverse effects, and with reduced insulin doses, increase the risk of ketosis, it seems to me that the risk with these agents may outweigh any benefit in T1DM, and that they have little potential as adjuncts in the treatment of T1DM.     

Type 1 diabetes in children and adolescents--new strategies in management and treatment

Type 1 diabetes (T1D) is the most common metabolic disease in childhood with an increasing incidence of about 3 to 5% per year, particularly in preschool children. Despite substantial progresses in diabetes research concerning its pathogenesis and etiology in the last decades, there is no strategy for primary prevention in subjects with subclinical signs of diabetes. Nowadays, it is well-known that T1D is caused by partial or total destruction of pancreatic islet cells, resulting in progressive incapacity to produce insulin. This inflammation is of an autoimmune nature, resulting both from environmental and genetic influences. Children with T1D usually have a several day history of typical symptoms such as frequent urination, excessive thirst and weight loss, which appear when about 80% of the pancreatic beta cells are already destroyed. If those symptoms are misinterpreted, the continuing hyperglycaemic metabolism leads to a potential life-threatening condition the diabetic ketoacidosis. Patients with T1D require daily subcutaneous injections of insulin, with the overall aim to mimic the physiological release of insulin during meal-associated and fasting periods (intensive insulin therapy). The most important parameters to evaluate the effectiveness of insulin treatment are blood glucose monitoring and HbA1c. The increased availability of systems for continuous glucose monitoring may help patients to have a better insight into their metabolic conditions. Sensor-based insulin treatment is likely to have a significant impact on paediatric diabetes therapy and education in the future.     

余甘子治疗糖尿病及其并发症的研究进展

糖尿病是一种严重威胁人类健康的常见疾病,糖尿病并发症则是导致糖尿病致死率增高的主要原因。研究表明余甘子具有调节免疫、抗氧化等多种生物活性,能够降低血糖,促进胰岛素的分泌,对糖尿病及糖尿病神经病变、糖尿病心血管并发症、糖尿病视网膜病变、糖尿病肾病、降低糖尿病引起的消耗等都有肯定的治疗作用。本文就余甘子在治疗糖尿病及其并发症方面的研究进展进行综述。     

Can targeting SIRT-1 to treat type 2 diabetes be a good strategy? A review

INTRODUCTION: Dysregulation of metabolic pathways, caused by imbalances in energy homeostasis, leads to type 2 diabetes characterized by high glucose concentration in the blood due to insulin resistance which is a major disorder in developed countries. AREAS COVERED: One of the recent treatment strategies is using activators of SIRT1, which has been in clinical trials. Many of the cellular processes including insulin secretion, cell cycle, and apoptosis are imperatively regulated by a family of mediators called sirtuins. First known mammalian sirtuin, SIRT1 is a positive regulator of insulin secretion, which triggers glucose uptake and utilization. Since the past decade, a major outstanding question is whether SIRT1 activation is a safe therapy for human diseases such as type 2 diabetes? This review summarizes and discusses the advances of the past decade and the challenges that will brazen out perplexity about homeostasis and metabolic pathways linked to SIRT1 and type 2 diabetes. Furthermore, we described the interlink between SIRT1 metabolic pathways of various tissues such as pancreas, skeletal muscle, adipose tissue and liver. EXPERT OPINION: However be the complexity of the pathways involved, T2DM regulated by SIRT1 affected metabolism is dropping down progressively due to profound research. In the context of interlinking all the SIRT1 pathways in T2DM we found various crucial intermediaries in metabolic tissues, which can also be targeted for future prospects.     

Pharmacotherapy of diabetes in cystic fibrosis patients

Importance of the field: Cystic fibrosis-related diabetes (CFRD) is a unique type of diabetes. In this article I review the pathophysiology of CFRD to gain insight as to why these patients have clinical features of both type 1 and 2 diabetes (DM). The reader will also learn that, although CFRD is different from type 1 and 2 DM, the development of diabetes-induced complications is similar to other types of DM. These complications can include retinopathy, nephropathy and neuropathy resulting from uncontrolled hyperglycemia; however, hyperglycemia and/or insulin deficiency in people with CFRD may exacerbate underlying CF problems, such as decreased pulmonary function and weight loss.

Areas covered in this review: Review medical therapy of CFRD including the over-riding goal of maintaining blood glucose levels in a range as close to normal as possible. The other important goal for diabetes management is to prevent diabetes complications and to encourage psychological wellbeing of the patient. However, as reviewed in this article, the underlying medical condition of people with CF and the basic metabolic differences caused by the disease often provide challenges in maintaining optimal diabetes control.

What the reader will gain: The reader will gain an understanding of how CFRD physically affects the patient with CF and the various pharmacologic therapies available for treatment of this type of diabetes. Furthermore they will gain insight into areas where more research is needed.

Take home message: Cystic fibrosis-related diabetes is unique to CF and thus deserves disease specific medical therapy.     

Replacing SUs with incretin-based therapies for type 2 diabetes mellitus: challenges and feasibility

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by insulin resistance, a steady decline in glucose-induced insulin secretion (most likely caused by a progressive decrease in functional beta-cell mass), and inappropriately regulated glucagon secretion; in combination, these effects result in hyperglycemia. In 1958, sulfonylurea (SU) was introduced to the market as one of the first oral treatments for T2DM. Since then, the ability of SU to stimulate the release of insulin from pancreatic beta-cells by the closure of ATP-sensitive K+-channels has been employed as one of the most widespread treatment options for T2DM. However, SUs are associated with weight gain and a risk of hypoglycemia, and the one-track antidiabetic mechanism of SUs often results in patients being treated with additional antidiabetic drugs. In recent studies, SU has proven to be associated with increased beta-cell apoptosis, suggesting that SU may actually accelerate the progressive decrease in beta-cell mass, thereby promoting the need for insulin replacement. In contrast, the newly developed incretin-based therapies for T2DM employ the beta-cell-preserving properties of incretin hormones - glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). More importantly, incretin-based therapies potentiate glucose-stimulated insulin secretion and may restore reduced glucose-induced insulin secretion in T2DM. Furthermore, the insulinotropic effects of GLP-1 and GIP are glucose-dependent, reducing the risk of hypoglycemia. GLP-1 inhibits glucagon secretion and decreases gastrointestinal motility, in turn reducing food intake and body weight. This feature review focuses on the challenges and feasibilities of replacing SU with incretin-based therapy in patients with T2DM.