甘精胰岛素联合格华止治疗2型糖尿病的疗效和安全性

目的比较每日注射一次长效重组甘精胰岛素注射液与中效低精蛋白锌人胰岛素(NPH)联合口服格华止治疗2型糖尿病的血糖控制情况和发生低血糖的风险。方法35例口服一种或两种降糖药但血糖控制不良的2型糖尿病患者(HbA1 c>7.5%),随机分为甘精胰岛素治疗组(n=17)和NPH组(n=18),分别采用每晚10点注射甘精胰岛素加口服格华止(500mg,tid)和每晚10点注射NPH胰岛素加口服格华止(500mg,tid)治疗。根据空腹血糖(FBG)水平调整胰岛素用量,以两组FBG均达到5.6mmol/L为治疗目标,共治疗12周,观察血糖控制情况和低血糖发生率。结果治疗后甘精胰岛素组和NPH胰岛素组的平均FBG和HbA1 c无明显差异(P>0.05);但甘精胰岛素组低血糖发生率明显少于NPH组(P<0.05)。结论每日注射1次长、中效胰岛素联合格华止的方案可使绝大多数口服降糖药物治疗血糖控制不良的2型糖尿病患者血糖获得理想控制,甘精胰岛素的低血糖发生率明显低于NPH胰岛素。     

格列美脲联用甘精胰岛素或中性鱼精蛋白锌胰岛素治疗2型糖尿病的疗效及安全性

目的探讨格列美脲联用甘精胰岛素治疗磺脲类药物继发性失效的2型糖尿病患者的疗效及安全性。方法50例口服降糖药血糖控制不理想的2型糖尿病患者随机分为甘精胰岛素治疗组（IG组）和鱼精蛋白锌胰岛素治疗组（NPH组），予睡前皮下注射胰岛素联合口服格列美脲治疗12周，比较两组疗效及安全性。结果治疗后两组FBG、2hBG、HbA1c均明显下降，但IG组低血糖事件明显少于NPH组（P〈0．01）。结论格列美脲联用甘精胰岛素治疗2型糖尿病的方案安全有效，能减少低血糖事件的发生。     

两种基础胰岛素类似物——地特胰岛素与甘精胰岛素治疗2型糖尿病临床效果比较

目的比较口服药控制不佳的2型糖尿病患者加用1天1次地特胰岛素或甘精胰岛素治疗的有效性、安全性及体重的变化。方法选取60例口服药控制不佳的2型糖尿病患者,保持原有口服药方案不变,按随机数字表法随机分为两组,每组30例,一组加用1天1次睡前地特胰岛素注射(治疗组),一组加用甘精胰岛素(对照组),治疗期为12周,比较两组治疗前后空腹血糖(FBG)、糖化血红蛋白(HbA1c)、体重的变化及低血糖的发生。结果两组的HbA1c和FBG同治疗前相比均有明显下降(P0.01),但组间比较差异均无统计学意义(P0.05);与对照组相比,治疗组体重增加少,差异有统计学意义(P0.01);两组各发生1例低血糖,发生率均为3.3%。结论口服药治疗不佳的2型糖尿病患者,加用1天1次地特胰岛素治疗同甘精胰岛素相比,有效性、安全性相似,但体重增加少。     

甘精胰岛素联合口服格列美脲(亚莫利)治疗2型糖尿病的疗效观察

目的比较甘精胰岛素联合格列美脲(亚莫利)治疗2型糖尿病血糖控制情况与低血糖发生的风险。方法89例应用口服降糖药血糖控制不佳的2型糖尿病患者[空腹血糖(FBG)≥10 mmol/L)],按治疗方法分为中效鱼精蛋白锌人胰岛素(NPH)组29例,甘精胰岛素治疗组25例和甘精胰岛素联合亚莫利治疗组35例。依照空腹血糖(FBG)水平调整胰岛素用量,治疗目标值FBG<7.0 mmol/L,治疗时间12周。观察治疗后血糖水平、血糖达标时间、低血糖发生情况及体质指数(BM I)等指标。结果治疗后3组患者空腹血糖、餐后2 h血糖均明显低于治疗前各组水平(P<0.05);甘精胰岛素联合亚莫利组低血糖发生率明显低于其他两组(P<0.05);甘精胰岛素联合亚莫利组治疗前后BM I无明显差异(P>0.05)。结论甘精胰岛素联合亚莫利能较好地控制2型糖尿病病人血糖,且低血糖发生率低,对病人体重影响小,具有安全、方便的特点,是2型糖尿病理想的治疗方案。     

长效胰岛素联合口服降糖药治疗2型糖尿病的疗效与安全性

目的比较每日注射一次长效重组甘精胰岛素注射液与中效低糖蛋白锌人胰岛素(NPH)联合口服格列吡嗪控释片治疗2型糖尿病的血糖控制情况和低血糖的风险. 方法 56例口服降糖药血糖控制不理想的2型糖尿病患者按31随机分为甘精胰岛素治疗组(n=42)和NPH组(n=14).分别采用每日晨起口服格列吡嗪控释片5 mg,每晚10点注射重组甘精胰岛素和每日晨起口服格列吡嗪控释片5mg,每晚10点注射中效NPH胰岛素.根据空腹血糖(FBG)水平调整胰岛素用量,以两组FBG均达到＜6.7 mmol/L为治疗目标,共治疗12周,观察血糖控制和低血糖事件发生情况,分析FBG达标时所用甘精胰岛素日剂量与治疗前FBG、BMI和病程的关系. 结果治疗后两组Alc及全天血糖谱均较基线水平明显下降,两组下降幅度比较无统计学意义,但甘精胰岛素注射组低血糖事件明显少于NPH组(甘精胰岛素组3例,7.1% ; NPH组5例,35.7%.χ2＝7.0,P＝0.008).危险因素相关分析结果显示,血糖达标时甘精胰岛素使用量与治疗前FBG和BMI显著相关. 结论每日注射一次中、长效胰岛素联合一次口服降糖药的方案可使更多2型糖尿病患者血糖达标,长效甘精胰岛素的应用能减少低血糖事件的发生,这种简便的治疗方案可使患者依从性大大提高.理想的基础胰岛素的补充有利于全天血糖控制.     

两种胰岛素方案治疗2型糖尿病的疗效与安全性比较

目的:比较赖脯胰岛素联合中效胰岛素(中性鱼精蛋白锌胰岛素,neutral protamine hagedorn, NPH)与常规猪胰岛素(regular insulin, RI)联合甘精胰岛素2种方案治疗2型糖尿病的疗效和低血糖发生情况.方法:将32例2型糖尿病患者设为A组,30例2型糖尿病患者设为B组.A组采用餐前皮下注射赖脯胰岛素加睡前皮下注射NPH治疗,B组采用餐前皮下注射RI加睡前皮下注射甘精胰岛素治疗,治疗12周后分析2种方案的胰岛素剂量、降低血糖效果以及低血糖发生率.结果:2种方案降低血糖的疗效相当.B组睡前用的甘精胰岛素剂量明显多于A组所用的NPH剂量,B组餐前所用RI剂量明显少于A组赖脯胰岛素剂量,同时B组的低血糖发生率明显低于A组.结论:2种治疗方案均能够有效控制血糖,与餐前皮下注射赖脯胰岛素加睡前皮下注射NPH方案相比,餐前皮下注射RI加睡前皮下注射甘精胰岛素方案不易发生低血糖.     

地特胰岛素联合门冬胰岛素30注射液治疗妊娠期糖尿病的临床效果

目的探究地特胰岛素联合门冬胰岛素30注射液治疗妊娠期糖尿病的临床效果。方法选取妊娠期糖尿病患者96例,按随机数字表法分为2组。对照组48例,予以门冬胰岛素30注射液治疗;研究组48例,在对照组治疗基础上给予地特胰岛素治疗。比较2组治疗效果、血糖达标时间、治疗前后空腹血糖(FBG)、餐后2 h血糖(2 hPG)、血红蛋白(HAb1c)水平及低血糖发生率。结果与对照组比较,研究组治疗总有效率显著升高,血糖达标时间明显缩短,治疗后研究组FBG、2 hPG、HAb1c水平均明显降低,差异有统计学意义(P<0.05);研究组低血糖发生率与对照组比较,差异无统计学意义(P>0.05)。结论地特胰岛素联合门冬胰岛素30注射液治疗妊娠期糖尿病疗效确切,可有效控制FBG、2 hPG、HAb1c水平,缩短血糖达标时间,且不增加低血糖风险,安全性高。     

甘精胰岛素联用格列齐特缓释片治疗2型糖尿病28例

目的:探讨甘精胰岛素联用格列齐特缓释片治疗磺脲类药物继发性失效的2型糖尿病患者的疗效及安全性。方法:56例口服降糖药血糖控制不理想的2型糖尿病患者随机分为甘精胰岛素治疗组(IG组)和中性鱼精蛋白锌胰岛素(NPH)组,予睡前皮下注射胰岛素联合口服格列齐特缓释片治疗12周,比较两组疗效及安全性。结果:治疗后两组空腹血糖(FPG)、餐后2h血浆血糖(2hPG)、糖化血红蛋白(HbAlc)均明显下降,但IG组低血糖事件明显少于NPH组(P<0.01)。结论:甘精胰岛素联用格列齐特缓释片治疗2型糖尿病的方案安全有效,简便易行,能减少低血糖事件的发生。     

格列美脲联合甘精胰岛素治疗2型糖尿病

目的：比较甘精胰岛素（IG）、中性鱼精蛋白锌胰岛素（NPH）分别与格列美脲联用治疗2型糖尿病患者的疗效。方法：39例口服降糖药而血糖控制不佳[糖化血红蛋白（HbA1C）〉7.0%]的2型糖尿病患者睡前注射1次IG;44例口服降糖药而血糖控制不佳（HbA1C〉7.0%）的2型糖尿病患者睡前注射1次NPH。两组均联用格列美脲早晨1次口服治疗16周,比较IG组和NPH组治疗前后空腹血糖（FPG）和HbA1C的变化。结果：治疗16周时,IG组和NPH组的HbA1C值分别下降（4.1±0.7）%和（3.3±0.6）%,FPG水平分别下降3.5±1.6mmol.L-1和4.4±1.6mmol.L-1,两组疗效间的差异均无统计学意义（P〉0.05）。IG组较NPH组发生低血糖事件次数显著减少（P〈0.05）。结论：睡前注射1次IG或NPH联用口服格列美脲的治疗方法可使单纯口服降糖药控制不佳的2型糖尿病患者的血糖得到良好控制。两种方法的疗效大致相同,但IG治疗低血糖事件发生率低,故更具选择优势。     

甘精胰岛素与门冬胰岛素治疗2型糖尿病疗效对比

目的探讨甘精胰岛素与门冬胰岛素对应用口服降糖药血糖不能达标的2型糖尿病(T2DM)患者血糖水平的影响。方法选择血糖控制较差的糖尿病患者60例,随机分为两组:一组以甘精胰岛素治疗;一组以门冬胰岛素三餐前注射,两组均与二甲双胍联用,观察治疗前空腹血糖(FBG)、餐后两小时血糖(2 h BG)、胰岛素用量、二甲双胍用量、低血糖发生率血糖达标时间。结果甘精胰岛素组降糖快速稳定,血糖达标时间短,治疗后FBG、2 h BG更理想,日间血糖波动幅度小,低血糖发生率低,优于门冬胰岛素组(P均0.05)。结论对血糖控制较差的2型糖尿病患者,睡前应用甘精胰岛素治疗,降糖效果显著,且安全平稳。     

New strategies in insulin treatment: analogues and noninvasive routes of administration

Abstract Recent years have seen the development of alternatives to human insulin for the treatment of diabetes. Both rapid-acting and long-acting analogues are available. Alternative routes of insulin administration are emerging. The present review briefly summarizes the present knowledge on insulin analogues and alternative administration routes.     

Biosimilar insulins

Until now most insulin used in developed countries is manufactured and distributed by a small number of multinational companies. Other pharmaceutical companies – many of these are located in countries such as India or China – are also able to manufacture insulin with modern biotechnological methods. Additionally, the patents for many insulin formulations have expired or are going to expire soon. This enables such companies to produce insulins and to apply for market approval of these as biosimilar insulins (BIs) in highly regulated markets such as the EU or the US. To understand the complexity of BIs' approval and usage, scientific and regulatory aspects have to be discussed. Differences in the manufacturing process (none of the insulin-manufacturing procedures are identical) result in the fact that all insulin that might become BIs differ from the originator insulin to some extent. The question is, have such differences in the structure of the insulin molecule and or the purity and so on clinically relevant consequences for the biological effects induced or not. The guidelines already in place in the EU for market approval require that the manufacturer demonstrates that his insulin has a safety and efficacy profile that is similar to that of the ‘original’ insulin formulation. Recently guidelines for biosimilars were issued in the US; however, these do not cover insulin. Although a challenging approval process for insulins to become BI might be regarded as a hurdle to keep companies out of certain markets, it is fair to say that the potential safety and efficacy issues surrounding BI are substantial and relevant, and do warrant a careful and evidence-driven approval process. Nevertheless, it is very likely that in the next years, BIs will come to the market also in highly regulated markets.     

Expanded Basal Insulin Options for Type 2 Diabetes Mellitus

Basal insulin is a component of therapy for many patients with diabetes mellitus. Several concentrated basal insulins are newly available. Nurse practitioners should be aware and informed of the various concentration options as they manage their patients. This article reviews the available concentrated products with a focus on degludec insulin. Nurse practitioners should be knowledgeable of the resulting safety considerations, particularly during transitions of care, or conversions between products.     

芦沙坦对改善大鼠胰岛素抵抗的实验研究

目的 研究芦沙坦（科素亚）对大鼠胰岛素抵抗的影响。方法 用高脂饲料喂养大鼠１个月,造成胰岛素抵抗大鼠动物模型。应用芦沙坦灌服４周,并设立二甲双胍组为对照组,分别于实验后检测大鼠空腹血糖,空腹胰岛素浓度以计算胰岛素抵抗指数（ＩＲＩ）胰岛素敏感性指数（ＩＳＩ）。结果造模各组ＩＲＩ明显高于正常组,Ｐ＜０．０５,其ＩＳＩ低于正常组Ｐ＜０．０５。科素亚组实验前后ＩＲＩ、ＩＳＩ差异性显著,Ｐ＜０．０５。二甲双胍组ＩＲＩ、ＩＳＩ异显著,Ｐ＜０．０５。结论　科素亚与二甲双胍均可以改善胰岛素抵抗（ＩＲ）大鼠的胰岛素抵抗现象,提高胰岛素敏感性。     

Effects of burn injury on insulin secretion and on sensitivity to insulin in the rat in vivo.

Both insulin resistance and impairment of insulin secretion are know to occur in man after injury. The relative importance of these effects was studied in rats 2 h after a non-lethal 20 percent dorsal scald. No impairment of insulin secretion was found after this injury. Concentrations of both blood glucose and plasma insulin were elevated in scalded rats. Scalded rats responded to intravenous glucose injection (1-0 g/kg) with a further rise in plasma insulin concentration, which remained normal for the prevailing blood glucose concentration. However, marked impairment of glucose tolerance was observed, indicating the presence of insulin resistance. After intravenous insulin injection (1-0 U/kg) the initial rate coefficient for fall of blood glucose concentration was significantly lower (p less than 0-02) in scalded (mean 3-9 percent min.(-1) than in control rats (mean 6-3 percent min.(-1). The minimum in blood glucose concentration after insulin injection was reached at 10 min. in control rats, but not until 60 min. after injection in scalded rats. This difference was due to a delay in compensation for the hypoglycaemia in the scalded rats, since the rate of disappearance of insulin measured by injection of a tracer of 125I-labelled bovine insulin was not decreased after this injury. It was concluded that the impairment of glucose utilization in scalded rats (Heath and Corney, 1973) is due to decreased sensitivity to insulin rather than to suppression of insulin release.     

Insulins NPH,glargine, and detemir,and risk of severe hypoglycemia among working-age adults*

Introduction: The longer acting basal insulin analogs glargine and detemir have shown a lower incidence of hypoglycemia compared to insulin NPH in clinical studies. We evaluated the real-life risk of severe hypoglycemia among new users of insulins in the working-age population in Finland.

Methods: All persons aged 18–65 years with diabetes mellitus who were newly prescribed with insulins NPH, glargine, or detemir during 2006–2009, were identified from national registers. Risk of severe hypoglycemia requiring hospital care was compared between insulin types.

Results: A total of 16,985 persons initiated basal insulin treatment (5586, 7499, and 3900 patients started NPH, glargine, and detemir, respectively) during follow-up. Five hundred and thirty-six persons were hospitalized because of severe hypoglycemia. Absolute rate (per 1000 patient-years) was 20.6 (95% CI 17.9, 23.8), 17.8 (15.6, 20.3), and 12.4 (9.9, 15.5) for NPH, glargine, and detemir initiators, respectively. With NPH as reference, the adjusted hazard ratio (HR) was 0.92 (95% CI 0.74, 1.15, p?=?0.47) for glargine, and 0.70 (0.51, 0.94, p=?0.018) for detemir. The HR for detemir compared to glargine was 0.76 (0.58, 0.99, p?=?0.040).

Conclusions: Initiating insulin treatment with detemir, but not with glargine, was associated with a significantly lower risk of severe hypoglycemia compared to NPH, among working-age adults.

• KEY MESSAGES

• The comparative safety of modern basal insulins regarding hypoglycemia among the working-age population is unclear.

• Large reductions in the incidence of severe hypoglycemia were seen among real-life patients who started insulin detemir, as compared to patients who initiated glargine or especially NPH insulin.

• Given the large amount of patients using insulin, these findings may have considerable clinical consequences at the population level.

     

Therapy conversion to insulin detemir among patients with type 2 diabetes treated with oral agents: A modeling study of cost-effectiveness in the United States

The aim of this study was to gain a preliminary indication of the long-term clinical and economic implications of converting treatment for patients with type 2 diabetes to insulin detemir±oral hypoglycemic agents (OHAs) in a routine clinical practice setting in the United States. With the use of outcome data and patient characteristics reported from an ongoing prospective observational trial, a validated computer simulation model of diabetes was used to project the clinical and cost outcomes associated with therapy conversion to insulin detemir over a 35-y period from (1) OHA only, (2) neutral protamine Hagedorn insulin (NPH)±OHA, and (3) insulin glargine±OHA. Cost-effectiveness was assessed from a third-party healthcare payer perspective for the year 2005. Costs and clinical outcomes were discounted at a rate of 3%. Treatment with insulin detemir±OHA was associated with increases in quality-adjusted life expectancy of 0.309, 0.350, and 0.333 quality-adjusted life-years (QALYs) versus treatment with OHA alone, NPH±OHA, and insulin glargine±OHA, respectively. Increases in pharmacy costs were partially offset by reduced complications, particularly renal complications and neuropathy. Projected incremental cost-effectiveness ratios were well within the range considered to represent good value in the United States, at $7412, $6269, and $3951 per QALY gained for treatment with Idet+-OHA versus OHA alone, NPH±OHA, and Iglarg±OHA, respectively. On the basis of preliminary evidence of short-term improvements in glycemic control and reduced hypoglycemia, therapy conversion to insulin detemir±OHA from OHA alone, NPH±OHA, or insulin glargine±OHA was projected to increase quality-adjusted life expectancy and to represent a cost-effective treatment option in the United States.     

糖负荷后血尿酸与胰岛素分泌及胰岛素敏感性/抵抗的相关性分析

目的研究不同糖负荷人群血尿酸(SUA)水平与胰岛素分泌及胰岛素抵抗的关系。方法 389例符合要求的研究对象行口服糖耐量试验(OGTT),测量空腹SUA,OGTT 0、30、60、120min血糖(GLU)和胰岛素(INS)水平,按照OGTT结果将研究对象分为糖耐量正常组(NGT组,n=88)、糖尿病前期组(preDM,n=119)、糖尿病组(DM,n=182),计算研究对象的胰岛素分泌指数(IGI)、120min胰岛素分泌指数(AUC INS_(120)/AUC GLU_(120))、胰岛素抵抗指数(HOMA-IR)、及Matsuda指数;将SUA按四分位水平分组,比较各糖负荷组不同SUA水平胰岛素分泌及胰岛素抵抗差异;计算SUA与胰岛素分泌及HOMA-IR的直线回归方程。结果 DM组SUA水平低于PreDM组[(346.66±90.60)mmol/Lvs.(367.36±92.34)mmol/L],但是略高于NGT组(339.34±89.51)mmol/L,差异有统计学意义(P0.01);DM组IGI指数、AUC INS_(120)/AUC GLU_(120)指数随着SUA升高有降低趋势(P0.01),Matsuda指数随着SUA水平升高有降低趋势(P0.05)。SUA与IGI、AUC INS_(120)/AUC GLU_(120)、HOMAIR、Matsuda指数的二元一次方程分别是Y=4.050+0.144 X,Y=2.343+0.206 X,Y=1.288+0.176 X,Y=129.373-0.202 X。结论 SUA与胰岛素分泌及胰岛素敏感性显著相关,DM组胰岛素分泌随着SUA水平升高而升高,胰岛素敏感性随着SUA水平升高而降低。SUA与胰岛素分泌及胰岛素敏感性的二元一次方程可大概评估胰岛素功能。     

Effects of Burn Injury on Insulin Secretion and on Sensitivity to Insulin in the Rat in vivo

Abstract. Both insulin resistance and impairment of insulin secretion are know to occur in man after injury. The relative importance of these effects was studied in rats 2 h after a non-lethal 20 % dorsal scald. No impairment of insulin secretion was found after this injury. Concentrations of both blood glucose and plasma insulin were elevated in scalded rats. Scalded rats responded to intravenous glucose injection (1. 0 g/kg) with a further rise in plasma insulin concentration, which remained normal for the prevailing blood glucose concentration. However, marked impairment of glucose tolerance was observed, indicating the presence of insulin resistance. After intravenous insulin injection (1. 0 U/kg) the initial rate coefficient for fall of blood glucose concentration was significantly lower (p < 0–02) in scalded (mean 3. 9 % min. ^-1) than in control rats (mean 6–3 % min. ^-1). The minimum in blood glucose concentration after insulin injection was reached at 10 min. in control rats, but not until 60 min. after injection in scalded rats. This difference was due to a delay in compensation for the hypoglycaemia in the scalded rats, since the rate of disappearance of insulin measured by injection of a tracer of 25i-labelled bovine insulin was not decreased after this injury. It was concluded that the impairment of glucose utilization in scalded rats (Heath and Corney, 1973) is due to decreased sensitivity to insulin rather than to suppression of insulin release.     

强化胰岛素治疗对重症监护患者病死率影响的Meta分析

目的 系统评价强化胰岛素治疗(IIT)对重症监护病房(ICU)患者病死率的影响.方法 计算机全面检索收集1966-2009年发表的关于IIT对ICU患者病死率影响的随机对照临床试验文献,并严格评价符合纳入文献的质量,用RevMan 5.0软件进行数据分析.结果 最终纳入23个研究,共11 216例患者.Meta分析结果 显示:IIT方案可有效降低重症监护患者的病死率(包括内科ICU、外科ICU及综合ICU中的病死率),降低患者在ICU期间的感染率和并发症发生率,也可以使目标血糖达到最佳范围,但IIT组低血糖发生率略高于传统胰岛素治疗(CIT)组.结论 IIT治疗方案比CIT治疗方案能明显降低ICU患者的病死率、感染率及并发症发生率,使目标血糖阈值达到期望的范围内,从而提高了患者生存质量;然而在低血糖的控制方面IIT方案不及CIT方案.