两种胰岛素短期强化方法治疗2型糖尿病的疗效比较

目的:在新住院的糖尿病患者中,比较不同类型的胰岛素类似物以及不同的注射方式的血糖控制和依从性的差异。方法:选择44例糖尿病患者,随机分为两组,每组22例。其中一组应用长效胰岛素类似物甘精胰岛素联合速效胰岛素类似物优泌乐多次皮下注射,另一组应用预混胰岛素类似物优泌乐50皮下注射。结果:患者的8个点血糖(空腹,三餐后2 h,午、晚餐前,24点,3点)均达到目标值。结论:两种注射方法均能获得良好的血糖控制,使用预混胰岛素类似物的患者依从性更好。     

预混胰岛素联合长效胰岛素与三速一长方案治疗初诊2型糖尿病的对比观察

目的观察早晚餐前预混胰岛素联合睡前长效胰岛素的注射方案(两预混一长)与三餐前速效胰岛素联合睡前长效胰岛素的注射方案(三速一长)对伴有明显高血糖的初诊2型糖尿病患者的降糖效果以及安全性。方法将60例初诊伴有明显高血糖的2型糖尿病患者随机分为I、Ⅱ两组,每组30例。I组三餐前皮下注射赖脯胰岛素联合睡前皮下注射甘精胰岛素;Ⅱ组早晚餐前皮下注射精蛋白锌重组赖脯胰岛素混合注射液25联合睡前皮下注射甘精胰岛素。比较空腹血糖、三餐后2小时血糖、胰岛素用量、达标时间以及低血糖发生人次。结果治疗后两组患者血糖、达标时间、低血糖发生率差异无统计学意义(>0.05),每日胰岛素用量Ⅱ组较I组明显减少(<0.05)。结论预混胰岛素联合长效胰岛素与三速一长方案治疗治疗效果、安全性相当,胰岛素用量减少。     

预混人胰岛素类似物的临床应用

预混人胰岛素类似物是指将速效人胰岛素类似物和精蛋白结晶的人胰岛素类似物按一定比例预混的制剂。当2型糖尿病患者口服降糖药治疗血糖仍不能达标时,就需要启动胰岛素治疗,可采用每日1—2次预混人胰岛素类似物的起始治疗方案;当患者需要强化血糖控制时,可采用每日3次预混人胰岛素类似物的强化治疗方案。     

门冬胰岛素30治疗2型糖尿病疗效观察

目的:观察胰岛素类似物门冬胰岛素30治疗血糖控制较差的2型糖尿病患者的临床疗效、安全性及耐受性。方法:将40例2型糖尿病患者随机分为两组,B组于早、晚餐前30 min注射预混人胰岛素30R,A组于早、晚餐时注射门冬胰岛素30,药物剂量根据血糖高低调整,比较治疗后两组空腹血糖、餐后血糖、血糖达标时间、胰岛素用量、发生低血糖时血糖值。结果:门冬胰岛素30和预混人胰岛素30R两组均可有效降低血糖(P<0.01),降糖效果差异无统计学意义(P>0.05),门冬胰岛素30组发生低血糖时血糖值高于预混人胰岛素30R组(P<0.05),尤其是夜间严重低血糖水平的发生。结论:在2型糖尿病患者中应用门冬胰岛素30降糖效果显著,安全性高,患者耐受性和依从性好。     

应用动态血糖监测系统评价2型糖尿病患者使用诺和锐30与诺和灵30R血糖漂移和低血糖发生率对比研究

目的:用动态血糖监测方法评价预混胰岛素类似物和预混胰岛素治疗2型糖尿病(T2DM)时血糖漂移和低血糖发生率的差异.方法:分别使用门冬胰岛素30注射液和预混人胰岛素30R注射液治疗2组T2DM患者,采用动态血糖监测系统检测的方法,评价2组患者血糖漂移和低血糖发生率的差异.结果:2种胰岛素都能有效控制血糖,门冬胰岛素30注射液组血糖漂移度小于预混人胰岛素30R注射液组,差异有统计学意义(P＜0.05),门冬胰岛素30组低血糖事件少于预混人胰岛素30R注射液,差异统计学意义(P＜0.05).结论:门冬胰岛素30注射液和预混人胰岛素30R注射液治疗T2DM,在血糖控制良好时,前者血糖漂移及低血糖发生率低于后者.     

三种胰岛素应用方案治疗2型糖尿病疗效观察

目的:比较短效人胰岛素联合中效中性鱼精蛋白锌人胰岛素、预混型精蛋白生物合成人胰岛素和双时相门冬胰岛素三种胰岛素方案的有效性和安全性。方法:将本院2008年1月至2011年5月住院的120例T2DM,根据不同降糖方案分为强化治疗组、预混胰岛素组、胰岛素类似物组。分别检测空腹、三餐后2h末梢毛细血管全血血糖,达标的天数,住院的时间,低血糖事件不良反应发生率。结果:三种胰岛素治疗方案均可使血糖达标,强化治疗组空腹及三餐后血糖在三组中最低,但低血糖发生频率较其余两组高,胰岛素类似物组低血糖发生频率在三组中最低,强化治疗组及胰岛素类似物组住院日均较短。结论:强化治疗适合对血糖控制较严格、要求节省住院日并且能够配合每天多次胰岛素注射的糖尿病患者使用,但要注意低血糖风险;预混型精蛋白生物合成人胰岛素则一种经济简单治疗方案;双时相门冬胰岛素30是本研究资料中较安全的方法。     

胰岛素的起始治疗与调整方案

正胰岛素起始治疗主要有三种方案,分别介绍如下。1基础胰岛素+口服降糖药基础胰岛素(包括中效胰岛素及长效胰岛素类似物)起始剂量为0.2 U/(kg·d),睡前注射,根据空腹血糖水平调整胰岛素用量。可与各类口服降糖药(包括胰岛素促泌剂)联用。2预混胰岛素(或预混胰岛素类似物)预混胰岛素起始剂量一般为0.2～0.4 U/(kg·d),按1︰1的     

速效与长效人胰岛素类似物联合治疗儿童Ⅰ型糖尿病30例分析

目的观察分析速效人胰岛素类似物联合长效人胰岛素类似物治疗儿童1型糖尿病的疗效。方法Ⅰ型糖尿病患儿30例,用速效人胰岛素类似物诺和锐与长效人胰岛素类似物蓝特司联合治疗,并与普通胰岛素加中效胰岛素治疗对比。结果速效与长效人胰岛素类似物联合治疗后4、8、12月,糖化血红蛋白值比治疗开始时明显降低,有统计学意义(P<0.05);严重低血糖和轻中度低血糖出现次数减少,有统计学意义(P<0.05)。结论长效人胰岛素类似物蓝特司和速效人胰岛素类似物诺和锐联合治疗儿童Ⅰ型糖尿病疗效较好。     

双相门冬氨酸胰岛素30对老年2型糖尿病的疗效

老年2型糖尿病患者由于基础疾病较多,病程较长,容易出现血糖控制不佳或发生药物性低血糖。双相门冬氨酸胰岛素30(商品名诺和锐30,丹麦诺和诺德公司生产)是一种预混的人胰岛素类似物,含有30%可溶性门冬胰岛素和70%精蛋白结合的结晶门冬胰岛素,可以在餐前立刻注射,在控制糖尿病患者餐后血糖的同时,能更好地降低低血糖发生率。我院于2006年2月至2007年2月对     

2型糖尿病使用诺和锐30和诺和灵30R治疗的观察

目的:比较预混胰岛素类似物(诺和锐30)和预混人胰岛素(诺和灵30R)治疗2型糖尿病的疗效。方法:将54例2型糖尿病患者随机分为诺和锐30治疗组和诺和灵30R治疗组。治疗12周,观察患者糖化血红蛋白(HbA1C)、空腹血糖、餐后2h血糖、低血糖发生率、胰岛素用量的差异。结果:接受诺和锐30治疗组糖化血红蛋白、餐后2h血糖控制好于诺和灵30R治疗组(P<0.05);空腹血糖、胰岛素用量两组差异无统计学意义(P>0.05);空腹血糖、胰岛素用量两组差异无统计学意义(P>0.05):低血糖发生率诺和锐30组少于诺和灵30R,低血糖发生率低于诺和灵30R。结论:诺和锐30能够在餐前立即注射,极大的提高了方便性、灵活性、安全性、依从性。     

地特胰岛素临床药理研究

地特胰岛素是一种安全、有效的长效基础胰岛素类似物。与中效胰岛素及其他长效胰岛素相比,地特胰岛素具有吸收平稳、不出现峰值的特点。地特胰岛素低血糖事件、尤其是夜间低血糖的发生率最低,每日只需用药1次,即使与甘精胰岛素相比,也存在注射部位不良反应少,体质量增加少的优点,适用于1型及2型糖尿病患者的基础血糖控制。     

重组人胰岛素类似物蛋白在大肠杆菌中克隆、表达与纯化

目的:设计合成编码Des30、B26 H、B28D和B26 H-B28D基因,用大肠杆菌BL21(DE3)表达上述4种速效人胰岛素原蛋白,为探知B26 H-B28D功能和用植物系统表达速效胰岛素原类似物研究做必要的准备。方法:基于人胰岛素氨基酸和小C肽(TYPGDVPK)序列,按植物(油菜)偏爱密码子设计合成了198 bp编码人速效胰岛素原基因Des30。随后以Des30为模板,用PCR突变技术扩增并创造了基因B26 H、B28D和B26 H-B28D,并构建了4个原核表达载体,转化大肠杆菌BL21(DE3)后,经IPTG诱导、用Ni-NTA亲和柱纯化、复性、胰岛素体外成熟(酶解)获得重组人胰岛素突变体蛋白。结果:4种人速效胰岛素原类似物在宿主菌中均以包涵体形式存在,IPTG诱导时间以8 h为佳。Western blot结果表明,带his-tag的速效人胰岛素原蛋白已成功在宿主菌中表达,用Ni-NTA亲和柱纯化获得了较纯的速效人胰岛素原蛋白。纯化的包涵体蛋白通过低温透析复性,然后用胰蛋白酶和羧肽酶B酶切,Western blot结果显示,释放出的单体胰岛素与阳性对照一样具有免疫活性,RP-HPLC和MALDI-TOF质谱检测表明,酶切产物分子量峰值分别与预测的人胰岛素类似物分子量一致。结论:该研究为B26 H-B28D功能研究和用植物系统表达人类胰岛素的研究奠定基础。     

Efficacy of insulin analogues in diabetic patients attending primary care centers

Objectives:

To measure the efficacy of new insulin analogues compared with the conventional types of insulin, and to compare their effects on patient satisfaction regarding their weight changes and the frequency of hypoglycemic episodes.

Methods:

In this retrospective cohort observational study, data was collected from the medical records of 122 eligible diabetics on insulin therapy attending government primary care centers in Jeddah, Kingdom of Saudi Arabia from June 2013 to July 2014. The data collected considered the efficacy, safety, and patient satisfaction of the types of insulin therapy used for their treatment.

Results:

After 12 weeks, there was a reduction in mean glycosylated hemoglobin (HbA1c) of -0.88% for the analogue type versus -0.19% for the conventional type, and at 24 weeks, the mean drop in HbA1c was -2.02% for the analogue type versus -1.12% for the conventional type, but the differences were not statistically significant. More patients (87% versus 38%) on analogue compared with conventional insulin treatment were satisfied with therapy.

Conclusion:

In the primary health care setting, insulin analogues showed greater efficacy improvements than conventional insulin therapy within 6 months. However, conventional insulin therapy can still be used at primary care centers with limited resources, and when patients refuse to be converted.Diabetes mellitus is a major cause of morbidity and mortality, and its global prevalence is rising rapidly.1 The estimated direct annual medical cost of diabetes care in Saudi Arabia is enormous; it constitutes an economic burden on the country.2 Since diabetes mellitus is a chronic illness that requires continuing medical care to reduce the risk of long-term complications,3 currently many diabetic patients attend the governmental primary care centers to receive this care. Studies from the United Kingdom confirmed the benefits of improved glycemic control in patients with types 1 and 2 diabetes mellitus,4,5 and they recommended tight glycemic control to maintain the glycosylated hemoglobin (HBA1c) concentrations of 7% or less. Insulin therapy is indicated to control all patients with type 1 diabetes, uncontrolled type 2 diabetics, and gestational diabetes to achieve the recommended target. There are 2 main types of insulin, the old conventional insulin that include the regular human insulin, and intermediate-acting neutral protamine Hagedorn insulin (NPH); however, these agents could not mimic the physiological pattern of endogenous insulin secretion, so insulin analogues were developed to overcome this limitation.6 Despite this theoretical superiority, the short acting insulin analogues were found to have a minor benefit to HBA1c values compared with the regular insulin in adult patients with type 1 diabetes mellitus, and no benefit in the population with type 2 or gestational diabetes.7 The 2 basal insulin analogues, insulin Glargine and Detemir, which have different chemical structures and modes of actions, were also developed to overcome the limitations of NPH insulin. Hypoglycemia and weight gain were always the main fear for patients on insulin, but studies on the analogues were conflicting, some did not observe a major clinical advantage in terms of hypoglycemia for either the rapid-acting or the long-acting insulin analogues over conventional insulins, others found that both rapid and long-acting analogues had little benefit in terms of glycemic control or reduced hypoglycemia. But insulin analogues were superior over the conventional insulins in terms of quality of life.8,9 The insulin analogues although expensive, adding to the enormous budget of the Ministry of Health in the treatment of diabetes mellitus, were introduced for free dispensing in some governmental primary health care centers in January 2014. The available analogues are the long-acting, Glargine (Sanofi, Bridgewater, NJ, USA), and the short acting Lispro (Eli Lilly & Co, Indianapolis, IN, USA) and Aspart (Novo Nordisk Inc., Plainsboro, NJ, USA), and their biphasic analogues, namely, Humalog in both concentrations 25/75 and 50/50 (Eli Lilly & Co, Indianapolis, IN, USA), and also NovoMix 30/70 (Novo Nordisk Inc., Plainsboro, NJ, USA). Though some patients are satisfied and refused to convert, efforts are in place to replace the current conventional insulin with the new insulin analogues for their proposed superiority of efficacy, safety, and quality of life. This study was carried out to help the general practitioners in choosing among the different insulin types, and in counseling their diabetic patients attending the government primary care health centers regarding their choice of insulin therapy.     

胰岛素强化治疗对新诊断2型糖尿病胰岛功能的影响

目的：评价胰岛素强化治疗对新诊断2型糖尿病患者胰岛功能的影响;方法：96例新诊断2型糖尿病患者给予胰岛素多次皮下注射,应用预混胰岛素每日3次或长效胰岛素注射液与短效胰岛素注射液联合每日4次治疗,根据病情特点可联合口服药物双胍类及糖苷酶类,噻唑酮类药物治疗3月,前后检测血糖及胰岛素水平（行75g葡萄糖耐量试验监测5段血糖及胰岛素水平）,糖化血红蛋白,体重,前后对照研究.结果：96例患者胰岛素强化治疗后血糖明显下降,糖化血红蛋白明显下降,β细胞指数明显改善,胰岛素早相分泌指数I/G明显改善,胰岛素抵抗指数IR无明显统计学意义,体重无明显变化.结论：胰岛素强化治疗新诊断2型糖尿病患者,可积极控制血糖,明显改善β细胞功能及胰岛素早相分泌,而对体重及胰岛素抵抗改善不明显.     

Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review

CONTEXT: Newer insulin therapies, including the concept of physiologic basal-prandial insulin and the availability of insulin analogues, are changing clinical diabetes care. The key to effective insulin therapy is an understanding of principles that, when implemented, can result in improved diabetes control. OBJECTIVE: To systematically review the literature regarding insulin use in patients with type 1 and type 2 diabetes mellitus (DM). DATA SOURCES: A MEDLINE search was performed to identify all English-language articles of randomized controlled trials involving insulin use in adults with type 1 or type 2 DM from January 1, 1980, to January 8, 2003. Bibliographies and experts were used to identify additional studies. STUDY SELECTION AND DATA EXTRACTION: Studies were included (199 for type 1 DM and 144 for type 2 DM, and 38 from other sources) if they involved human insulins or insulin analogues, were at least 4 weeks long with at least 10 patients in each group, and glycemic control and hypoglycemia were reported. Studies of insulin-oral combination were similarly selected. DATA SYNTHESIS: Twenty-eight studies for type 1 DM, 18 for type 2 DM, and 48 for insulin-oral combination met the selection criteria. In patients with type 1 DM, physiologic replacement, with bedtime basal insulin and a mealtime rapid-acting insulin analogue, results in fewer episodes of hypoglycemia than conventional regimens. Rapid-acting insulin analogues are preferred over regular insulin in patients with type 1 DM since they improve HbA1C and reduce episodes of hypoglycemia. In patients with type 2 DM, adding bedtime neutral protamine Hagedorn (isophane) insulin to oral therapy significantly improves glycemic control, especially when started early in the course of disease. Bedtime use of insulin glargine results in fewer episodes of nighttime hypoglycemia than neutral protamine Hagedorn regimens. For patients with more severe insulin deficiency, a physiologic insulin regimen should allow lower glycemic targets in the majority of patients. Adverse events associated with insulin therapy include hypoglycemia, weight gain, and worsening diabetic retinopathy if hemoglobin A1C levels decrease rapidly. CONCLUSIONS: Many options for insulin therapy are now available. Physiologic insulin therapy with insulin analogues is now relatively simple to use and is associated with fewer episodes of hypoglycemia.     

2: Recent advances in therapy of diabetes

As suboptimal blood glucose control has a lasting harmful effect even if control improves later, intensive insulin therapy to minimise hyperglycaemia is now recommended for all patients with type 1 diabetes. The new rapid- and long-acting insulin analogues offer more physiological insulin profiles than traditional insulin preparations. Continuous insulin infusion ("pump therapy") may provide a solution for some patients with frequent hypoglycaemia or hypoglycaemic unawareness. Continuous blood glucose monitoring reveals postprandial hyperglycaemia and asymptomatic nocturnal hypoglycaemia and may be especially useful for programming overnight basal insulin rates for pump therapy. In type 2 diabetes, management should change with disease progression; introduction of insulin should not be delayed if metabolic control becomes suboptimal.     

对家兔糖尿病模型胰岛素治疗的实验观察

目的以胰岛细胞的变化和凋亡程度为判断标准,探讨家兔糖尿病模型胰岛素用药治疗的适宜方案。方法利用四氧嘧啶制作家兔糖尿病模型,设计了多次胰岛素治疗组（A组）、50R预混胰岛素治疗组（B组）、30R预混胰岛素治疗组（c组）3种治疗方案,共治疗30d,记录血糖达标时间及达标时Ins剂量,并与未治组、对照组比较血糖、胰岛素抗体及组织病理学变化;用苏木素-红染色（HE染色法）标记观察胰岛组织片及胰岛凋亡细胞。结果B组的达标胰岛素用量为（5．62±0．67）U／kg,较A、C少,C达标时胰岛素用量最多为（8．83±1．17）U／kg,差异有统计学意义（P〈0.01）。A组血糖达标时间最短为（7．00±1．31）d、C组血糖达标时间最长为（19．63±1．41）d,各组间比较差异有统计学意义（P〈0．001）。胰岛素抗体结合率C组最高,与A、B组比较差异有统计学意义（P〈0．01）。C组胰岛损害最轻,胰岛凋亡细胞最少。各治疗组胰岛受损和凋亡严重程度A〉B〉C。结论30R预混胰岛素治疗方案最佳。提供一个较高的基础胰岛素浓度加少量餐时胰岛素峰值量治疗糖尿病,血糖平稳缓降,对糖尿病胰岛细胞有治疗和保护作用。多次胰岛素3短加1中的强化治疗及太短时间达标的方法不可首选。     

Withdrawal after substitution of a short-acting for a long-acting benzodiazepine

A withdrawal syndrome occurred in two patients after substitution of a short-acting benzodiazepine for a long-acting benzodiazepine. Both patients had used long-acting benzodiazepines on a daily basis for many years. In one case, oxazepam was substituted for diazepam, and in the other, temazepam was substituted for flurazepam hydrochloride. In both cases the short-acting benzodiazepine was substituted in a once-daily dosage. Withdrawal symptoms followed and persisted for at least one month. Relative advantages and disadvantages of short-acting and long-acting benzodiazepines are discussed.     

预混胰岛素剂型和剂量量化选择探讨

目的探讨胰岛素治疗糖尿病时预混胰岛素的量化选择。方法研究以我院收治的需要换用胰岛素治疗但无急性并发症的2型糖尿病住院患者为研究对象。随机分为5次皮下胰岛素注射组（Fi组）和4次皮下胰岛素注射组（Fo组）各60例,比较两种治疗方法预混胰岛素选择预混胰岛素剂型和估算剂量的准确性以及5次皮下胰岛素注射餐前普通胰岛素（RI）和中性胰岛素（NPH）用量及其比值（RI/NPH）对预混胰岛素剂型选择和剂量估算的影响。结果 5次胰岛素注射方案控制血糖,选择预混胰岛素剂型时出现错误Fi组为2例（3.3%）明显少于Fo组9例（15%）（=4.90,P〈0.05）。估计预混胰岛素剂量Fi组准确率和较准确率（69.1%）均明显高于Fo组（30.8%）（=33.75,P〈0.01）。选择30%短效预混胰岛素时RI/NPH在0.41~0.51,而选择50%短效预混胰岛素RI/NPH在0.63~0.81（t=5.56,P〈0.01）,预混胰岛素的估计剂量与该餐前RI和NPH用量之和的比值接近1（t=0.16,P〉0.05）。结论五次胰岛素注射方案能够量化选择适合糖尿病患者的预混胰岛素剂量和剂型。     

3种不同方案胰岛素强化治疗对初诊2型糖尿病患者血糖及胰岛功能的影响

目的观察3种不同方案的胰岛素强化治疗对初诊2型糖尿病(T2DM)患者血糖及胰岛功能的影响。方法 60例初诊T2DM患者随机分为3组,分别接受2周的胰岛素泵持续皮下输注(CSII)、三餐前门冬胰岛素+睡前甘精胰岛素的4次皮下注射或门冬胰岛素30三餐前皮下注射治疗,比较其血糖水平及胰岛功能的变化,以及血糖达标时间、胰岛素剂量、低血糖情况等。结果 3组血糖水平均较治疗前明显下降,HOMAβ升高、HOMA IR下降。3组低血糖情况相当,CSII组血糖达标时间最短、胰岛素剂量最少。结论对于初诊T2DM患者,3种胰岛素强化治疗方案均能有效地控制血糖,并使胰岛β细胞功能得到部分恢复,减轻胰岛素抵抗。