自体造血干细胞移植治疗1型糖尿病的研究进展

1型糖尿病(T1DM)是一种T细胞介导的自身免疫性疾病,以胰腺B细胞选择性破坏,导致患者体内胰岛素分泌绝对不足为特征[1]。目前,T1DM的治疗主要以外源性胰岛素替代治疗为主,患者需每日注射胰岛素,但胰岛素的使用只是延缓疾病的发展却并不能治愈糖尿病。T1DM的最终治疗需要去除免疫     

以糖尿病酮症发病42例患者临床分析

42例以糖尿病酮症为首发患者临床特点、治疗转归等综合分析,并进行随访6～12个月。结果酮症时病情重,合并酸中毒,酮体消失时间长的患者倾向于T,DM,依赖于胰岛素治疗。酮症时病情轻,无酸中毒,酮体消失时间短的患者倾向于T2DM（胰岛素抵抗为主）,胰岛素促泌剂和／或胰岛素增敏剂治疗就能很好控制病情。结论以糖尿病酮症为首发症状的糖尿病患者可以根据发病时临床表现及短期病情进展划分为两类（即T1DMT、T2DM）。     

从个体化治疗角度出发,理性看待2型糖尿病胰岛素强化治疗

胰岛素的问世对于糖尿病治疗具有划时代的历史意义.随着医学科技发展,在胰岛素制剂不断变革的同时,胰岛素临床应用领域也取得了很大的进展.除1型糖尿病（T1DM）患者的胰岛素治疗是绝对适应证外,2型糖尿病（T2DM）患者是否需要胰岛素治疗以及胰岛素治疗模式的选择是非常个体化的,特别是胰岛素强化治疗,其内涵和临床应用价值在T2DM患者中的体现是非常值得审视和探讨的问题.     

钠葡萄糖协同转运体2抑制剂辅助治疗1型糖尿病患者发生酮症酸中毒的研究进展

终生外源性胰岛素替代治疗是1型糖尿病(T1DM)的主要治疗方法，绝大多数非胰岛素的降糖药物不适用于T1DM。钠葡萄糖协同转运体2抑制剂(SGLT2i)通过阻断肾脏近端小管的钠葡萄糖协同转运体2(SGLT2)来抑制葡萄糖的重吸收，目前广泛应用于2型糖尿病(T2DM)的治疗。临床研究表明SGLT2i能有效控制T1DM患者的血糖，但具有增加酮症酸中毒(DKA)的风险，其中非高血糖性DKA(euDKA)是SGLT2i所致DKA的常见形式。SGLT2i导致DKA的主要机制为大量排出尿糖以降低血糖，从而降低胰岛素、升高胰高血糖素水平，导致胰岛素和胰高血糖素比例失衡，胰高血糖素可促进肝细胞对脂肪的分解及脂肪酸的氧化，从而刺激肝脏生酮。T2DM患者在应用SGLT2i的情况下发生euDKA,需要警惕T1DM的可能。为避免DKA的发生，挑选合适的患者、慎重降低胰岛素用量、降低SGLT2i剂量、定期监测酮体变化、避免诱因及补充液体可能是合理的方法。SGLT2i适当增加酮体可能对心血管、肾脏及大脑有益。     

基础胰岛素治疗的临床研究进展

我国糖尿病患病率已达到9.7%[1].优化血糖控制均可减少1型糖尿病(T1DM)和2型糖尿病(T2DM)远期并发症的发生[2].最近UKPDS的后序随访数据结果提示胰岛素治疗降低了T2DM患者大血管的发病风险[3].目前糖尿病治疗中多建议在确诊后首先采用生活方式干预联合二甲双胍控制血糖,在疗效不佳时可选用磺脲类、格列奈类或基础胰岛素治疗[4].     

经典1型糖尿病患者胰岛素抵抗的高胰岛素正葡萄糖钳夹研究

目的 应用高胰岛素正葡萄糖钳夹技术评价1 型糖尿病(T1DM)患者胰岛素抵抗程度.方法 选择新诊断T1DM患者8例,初诊未治2型糖尿病(T2DM)患者8例,均经2周胰岛素强化治疗后进行高胰岛素正葡萄糖钳夹检测胰岛素敏感性指数(ISI),并与正常糖耐量志愿者10例进行比较.结果 T1DM组的年龄、BMI、空腹胰岛素(FIns)及空腹C-肽等各项参数显著低于正常对照组(P＜0.05),而腰臀比(WHR)、收缩压(SBP)、舒张压(DBP)、TC、TG、LDI-C、HDL-C均与正常对照组差异无统计学意义.T1DM组与T2DM组比较,年龄、BMI、WHR、FIns、空腹C-肽、SBP、TC、TG均显著低于T2DM组(P＜0.05).正常对照组、T1DM组、T2DM组ISI分别为12.83±1.09、9.95±0.50、3.80±0.20,3组间ISI差异有统计学意义(P＜0.05).结论 高胰岛素正葡萄糖钳夹检测结果显示,TIDM患者的ISI显著低于正常人,但高于T2DM患者.     

1型糖尿病患者外周血 CD4＋CD2＋5细胞数量及其对胰岛素治疗效果的影响

目的：探讨1型糖尿病（ T1DM）患者外周血中CD4＋CD2＋5调节性T细胞（以下简称CD4＋CD2＋5）在数量及对其胰岛素治疗效果的影响。方法采用流式细胞仪检测56例1型T1DM 患者（ T1DM 组）、43例2型糖尿病（T2DM）患者（T2DM组）及52例健康对照者（对照组）外周血中的CD4＋CD2＋5细胞比例,分析CD4＋CD2＋5比例与胰岛素治疗效果的关系。结果 T1DM组CD4＋CD2＋5比例显著低于其它两组P＜0．05）,且细胞比例越低,胰岛素治疗效果越差。结论 CD4＋CD2＋5在1型糖尿病患者外周血中呈低表达,可导致胰岛素的治疗效果下降。     

地特胰岛素在控制体重方面的优势

超重和肥胖是糖尿病发生的主要危险因素。胰岛素降糖治疗可能会进一步增加2型糖尿病（T2DM）患者的体重,从而给本已超重或肥胖的T2DM患者的身心健康带来沉重负担。本文就地特胰岛素在控制体重方面的优势进行探讨。     

胰岛移植治疗1型糖尿病的过去、现在和未来

1型糖尿病（T1DM）是一种自身免疫性疾病,在胰岛素问世之前,T1 DM患者从发病到死亡的时间在儿童不足1年、成人不足4年,胰岛素的发现使得T1 DM从致死性疾病转变为慢性疾病.美国糖尿病学会糖尿病控制与并发症研究（DCCT）显示,通过胰岛素强化治疗可显著降低糖尿病视网膜病变、神经病变和肾脏病变进展,但不能避免胰岛功能的持续下降并最终出现血糖剧烈波动的＂脆性糖尿病＂的出现.     

估计葡萄糖处置率在评估1型糖尿病患者胰岛素抵抗中的应用价值

1型糖尿病(T1DM)在临床中以胰岛素绝对缺乏为特征。随着生活方式的改变、外源性胰岛素的强化治疗、血糖控制不佳, 胰岛素抵抗(IR)在T1DM中也引起人们的重视。IR是预测T1DM发生心血管疾病及并发症的一个重要危险因素, 但在临床实践中难以评估。利用估计葡萄糖处置率作为间接评估T1DM是否存在IR的工具, 并可以预测糖尿病并发症风险。因此, 早期识别T1DM中是否合并IR将有助于风险分层, 除了优化降糖之外, 可以早期通过改变生活方式或药物治疗改善IR并预防慢性并发症从而改善该人群的预后和生活质量。     

Role of Glucagon-Like Peptide-1 Analogue Versus Amylin as an Adjuvant Therapy in Type 1 Diabetes in a Closed Loop Setting With ePID Algorithm

Postprandial hyperglycemia due to paradoxical hyperglucagonemia is a major challenge of diabetes treatment despite the use of the artificial pancreas. We postulated that adjunctive therapy with pramlintide or exenatide would attenuate hyperglycemia in the postprandial phase through glucagon suppression, thereby optimizing the functioning of the closed-loop (CL) system. Subjects with type 1 diabetes (T1DM) on insulin pump therapy were recruited to participate in a 27-hour hospitalized admission on 3 occasions (2-4 weeks apart) and placed on the insulin delivery via CL system in random order to receive (1) insulin alone (control), (2) exenatide 2.5 µg + insulin, (3) pramlintide 30 µg + insulin. Medications were given prior to lunch and dinner, which was a standardized meal of 60 grams of carbohydrates. Insulin delivery was as per the ePID algorithm via the Medtronic CL system and continuous subcutaneous glucose monitoring via Medtronic Sof-sensors. Ten subjects age 23 ± 1 years with a HbA1c of 7.29 ± 0.3% (56 ± 1 mmol/mol) and duration of T1DM 10.6 ± 2.0 years participated in the 3-part study. Exenatide was found to be significantly better in attenuating postprandial hyperglycemia as compared to insulin monotherapy (P < .03) and pramlintide (P > .05). Glucagon suppression was statistically significant with exenatide (P < .03) as compared to pramlintide. Insulin requirements were lower with adjunctive therapy, but statistically insignificant. Insulin monotherapy results in postprandial hyperglycemia in T1DM in the CL setting and adjunctive therapy with exenatide reduces postprandial hyperglycemia effectively and should be considered as adjunctive therapy in T1DM.     

SGLT-2抑制剂治疗1型糖尿病的心血管保护作用

T1DM与早发性心血管疾病密切相关。有些T1DM患者血糖控制未达标,需辅助疗法以助其实现达标。钠-葡萄糖协同转运蛋白2抑制剂(SGLT-2i)是独立于Ins作用机制的新型降糖药,SGLT-2i辅助治疗T1DM可改善血糖、血脂、血尿酸、尿蛋白异常,降低体重、BP等心血管事件高危因素且减少每日Ins用量。本文对SGLT-2i联合Ins辅助治疗T1DM的作用机制、心血管保护作用及安全性进行综述。     

Lessons in initiating insulin in clinical practice

Insulin therapy in type 2 diabetes (T2DM) can produce greater improvements in fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) than oral antidiabetic drugs (OADs). There is a growing trend to recommend initiation of insulin in T2DM patients sooner in the course of the disease, and good results have been achieved in insulin-na?ve patients during randomised, controlled trials, often using aggressive dose titration algorithms. The Physicians' Routine Evaluation of Safety & Efficacy NovoMix((R)) 30 Therapy (PRESENT) study was a 6-month observational study of the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) as monotherapy or in combination with OADs in inadequately controlled patients with T2DM. This review article compares results from those patients who entered the study insulin-na?ve (either with or without previous OAD treatment), with results from randomised, controlled trials of BIAsp 30 in insulin-na?ve T2DM patients. It aims to provide guidance on the initiation of insulin in patients with T2DM, focusing on the efficacy of BIAsp 30 when used for this purpose, and highlighting both the low risk of hypoglycaemia associated with therapy, and the availability of delivery devices that can minimise injection site discomfort and help to overcome psychological insulin resistance.     

Heart failure and diabetes: Clinical significance and epidemiology of this two-way association

People with type 2 diabetes (T2DM) and those with prediabetes have an increased risk of heart failure (HF). Longer duration of T2DM correlates with a greater risk of HF, but HF is also seen in patients with recent-onset diabetes. Insulin resistance is more likely to be present in patients with HF. The risk of HF persists even in the face of standard-of-care preventive treatments for atherosclerotic cardiovascular (CV) disease. HF is commonly the presenting symptom of CV disease in people with diabetes and is the most expensive complication of diabetes because of the high cost of hospitalizations. Recently hospitalization for HF has been included in CV outcome trials (CVOTs), including for medications that are used to treat T2DM, which has led to new therapies for all HF patients. In addition, these CVOTs have shown that many drugs used in the therapy of diabetes are either neutral or detrimental in the HF patient and should be used with caution in patients with existing HF or those at high risk of HF. Most recently, sodium-glucose cotransporter-2 receptor blockers have shown efficacy in both HF with reduced ejection fraction (EF) and HF with preserved EF. The only other oral or injectable diabetes agent shown to improve outcomes in both is metformin.     

Managing diabetes and liver disease association

There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening.Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival.Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemiaStatins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficialGiven the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention.The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients.In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted.This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.     

Undeniable need for ultrafast-acting insulin: the pediatric perspective

Insulin therapy in youth with type 1 diabetes mellitus (T1DM) poses a special challenge because childhood is an unsteady state with increasing weight, height, and caloric needs, leading to varying insulin requirements. The current rapid-acting insulin analogs are not as fast and short-acting as needed to meet these challenges. This review describes the unique characteristics of insulin action in youth with T1DM based on previously published euglycemic clamp studies. It also explains the rationale behind the need for ultrafast-acting insulins to advance open- and closed-loop insulin therapy for the pediatric population with diabetes. Lastly, it briefly summarizes ongoing and future projects to accelerate insulin action in youth with T1DM.     

Clinical utility of insulin and insulin analogs

Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes.     

GLP-1 receptor agonists today

Type 2 diabetes mellitus (T2DM) is a complex, progressive disease affecting an estimated 257 million people worldwide. A number of unmet needs exist with traditional T2DM therapies, which can lead to insufficient glycaemic control and increased risk of diabetes-associated complications. An emerging class of diabetes therapeutics, the glucagon-like peptide-1 (GLP-1) receptor agonists, appear to address many of the unmet needs of patients with T2DM. This review summarises the recent findings and current clinical guidelines of the currently approved GLP-1 receptor agonists and explores the new GLP-1 receptor agonists in development. It also concentrates on the physiological basis for early use of GLP-1 receptor agonists, their use as an alternative to insulin therapy, the rationale for combining them with insulin and their cost-effectiveness.     

Empagliflozin, a novel potent and selective SGLT-2 inhibitor, improves glycaemic control alone and in combination with insulin in streptozotocin-induced diabetic rats, a model of type 1 diabetes mellitus

Aim: Sodium glucose cotransporter‐2 (SGLT‐2) is key to reabsorption of glucose in the kidney. SGLT‐2 inhibitors are in clinical development for treatment of type 2 diabetes mellitus (T2DM). The mechanism may be of value also in the treatment of type 1 diabetes mellitus (T1DM). This study investigated effects of the SGLT‐2 inhibitor, empagliflozin, alone and in combination with insulin, on glucose homeostasis in an animal model of T1DM. Methods: Sprague–Dawley rats were administered a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Acutely, STZ rats received two doses of insulin glargine with or without empagliflozin, and blood glucose was measured. In a subchronic study, STZ rats received empagliflozin alone, one or two insulin‐releasing implants or a combination of one implant and empagliflozin over 28 days; blood glucose and HbA_1c were measured. Results: In the acute setting, empagliflozin in combination with 1.5 IU insulin induced a similar glucose‐lowering effect as 6 IU insulin. Both interventions were more efficacious than monotherapy with 1.5 IU insulin. In the subchronic study, 12‐h blood glucose profile on day 28 in the combination group was lower than with one implant, and similar to two implants. Plasma HbA_1c was improved in the combination group and in animals with two implants. Conclusions: Empagliflozin reduced blood glucose levels in a T1DM animal model. Empagliflozin combined with low‐dose insulin showed comparable glucose‐lowering efficacy to treatment with high‐dose insulin. Our data suggest that empagliflozin is an efficacious adjunctive‐to‐insulin therapy with the clinical potential for the treatment of T1DM.