门冬胰岛素治疗2型糖尿病疗效及安全性评价

目的观察门冬胰岛素30治疗2型糖尿病的疗效及安全性。方法60例口服降糖药物效果差的2型糖尿病患者随机分为门冬胰岛素组和Novolin30R组,观察12周,比较2组治疗前后的血糖控制情况、糖化血红蛋白、空腹C肽、餐后2h C肽、体重、胰岛素用量、低血糖发生率的变化。结果两组均能有效的控制血糖的作用（P〈0．05）,在控制空腹血糖方面无明显差异,门冬胰岛素30组的有更好的控制早餐、晚餐后血糖得到明显改善,低血糖的发生率减少。差异有统计学意义（P〈0．05）,所需胰岛素量较少,但差异无统计学意义（P〉0．05）。结论每天2次注射门冬胰岛素30较诺和灵30组能更好的控制餐后血糖,且低血糖发生率低。     

甘精胰岛素治疗2型糖尿病的临床观察

目的：观察胰岛素类似物甘精胰岛素治疗2型糖尿患者的临床疗效、安全性及耐受性。方法：将80例2型糖尿病患者随机分为两组，A组于三餐前注射速效胰岛素联合睡前皮下注射甘精胰岛素．B组于三餐前注射速效胰岛素联合睡前皮下注射中效胰岛素的方法控制高血糖，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、低血糖发生率。结果：甘精胰岛素和中效胰岛素两组均可有效降低血糖（P〈0．01），降糖效果无明显差异（P〉0．05），甘精胰岛素组低血糖发生率明显低于中效胰岛素组（P〈0．05）．尤其是夜间严重低血糖事件的发生。结论：在2型糖尿病患者中应用甘精胰岛素降糖效果显著．安全性高．病人耐受性和依从性好。     

诺和锐30与诺和灵30R治疗2型糖尿病疗效观察

【目的】比较双时相门冬胰岛素（诺和锐30）和预混人胰岛素（诺和灵30R）治疗2型糖尿病的有效性和安全性。【方法】128例患者随机分为诺和锐30组和诺和灵30R组各64例,采用每日早、晚餐前两次皮下注射,治疗时间8周,观察两组患者空腹血糖、餐后2h血糖、低血糖发生率、胰岛素用量的差异。【结果】诺和锐30治疗组餐后2h血糖控制优于诺和灵30R组（P〈0．05）,空腹血糖、胰岛素用量两组差异无显著性（P〉0．05）;低血糖发生率诺和锐30组低于诺和灵30R组。【结论】诺和锐30治疗2型糖尿病降低患者餐后血糖效果明显,且低血糖发生率低。     

两种不同胰岛素强化治疗方法对新诊断2型糖尿病患者胰岛β细胞功能的影响

【目的】比较持续皮下胰岛素输注（CSⅡ）和多次胰岛素皮下注射（MSⅡ）在2型糖尿病强化降糖中的效果。【方法】60例新诊断2型糖尿病病人,分成胰岛素泵治疗组24例（CSⅡ组）和皮下注射胰岛素组36例（MSⅡ组）,治疗2周,观察两组治疗前后空腹及餐后血糖、胰岛素、C肽变化,比较两组血糖达标天数、最大胰岛素用量、平均胰岛素用量及低血糖现象发生情况。【结果】治疗后两组血糖均有明显下降（P〈0．05）,胰岛素及C肽水平较治疗前明显升高（P〈0．05）,两组治疗后上述改变无明显统计学差异（P〉0．05）。但CSⅡ组血糖达标时间较MSⅡ组短,平均胰岛素用量及最大胰岛素用量均较MSⅡ组少,且低血糖发生次数也较MSⅡ组少,差异均有统计学意义（P〈0．05）。【结论】CSⅡ和MSⅡ两种治疗方法均可有效降低2型糖尿病患者血糖,改善胰岛β细胞分泌功能,对初发的2型糖尿病有良好治疗效果,其中胰岛素泵可以缩短血糖达标天数,减少胰岛素用量,降低低血糖发生率,有一定优势。     

甘精胰岛素联合瑞格列奈治疗预混胰岛素疗效欠佳的2型糖尿病效果观察

目的探讨每日2次预混胰岛素治疗的2型糖尿病患者转为每日注射一次甘精胰岛素联合瑞格列奈治疗的有效性和安全性。方法 46例每日注射2次预混胰岛素（联合或不联合口服降糖药）血糖控制欠佳的2型糖尿病患者换用每日注射一次甘精胰岛素联合瑞格列奈治疗,在治疗第0周及12周分别记录空腹血糖、餐后2小时血糖、糖化血红蛋白（HbA1c）及胰岛素用量。结果治疗12周后空腹血糖、餐后2小时血糖、HbA1c均较基线水平显著下降（P〉0.05）;治疗前后胰岛素剂量无明显差异（P〉0.05）;低血糖事件共发生3人次。结论预混胰岛素治疗血糖控制欠佳的2型糖尿病患者转为每日注射一次甘精胰岛素联合瑞格列奈治疗能有效并安全的控制血糖。     

初诊2型糖尿病两种胰岛素强化治疗方法的比较

【目的】观察诺和锐30R三餐前皮下注射与诺和锐R三餐前皮下注射加睡前注射来得时在初诊的2型糖尿病患者的疗效,胰岛素用量和低血糖风险。【方法】将本科2009年2月至2010年2月期间68例初诊的2型糖尿病住院患者随机分成A、B组,A组使用诺和锐30R三餐前皮下注射;B组使用诺和锐R三餐前皮下注射加睡前注射来得时,出院后继续治疗,为期12周。观察两组患者5个时点（空腹及三餐后2h,睡前）的血糖、糖化血红蛋白（HbAlc）,每天胰岛素平均用量及低血糖事件的差异。【结果】两组患者经过胰岛素治疗后各时点血糖及HbAlC均较治疗前明显下降（P〈0．05）,A和B两组胰岛素强化治疗方法均有效,但A组胰岛素用量、血糖达标时间、住院天数、低血糖发生率均低于B组、有统计学差异（P〈0．05）。【结论】对于初诊2型糖尿病患者,每天3次餐前注射诺和锐30R是一种快速、有效、安全的强化治疗方法。     

甘精胰岛素联合阿卡波糖与预混胰岛素治疗初发2型糖尿病的疗效和安全性比较

【目的】比较甘精胰岛素联合阿卡波糖与预混胰岛素治疗新诊断的2型糖尿病患者的疗效和低血糖的风险。【方法】70例新诊断的2型糖尿病患者随机分为甘精胰岛素组（简称甘精组）和预混胰岛素组（诺和灵30R,简称预混组）,每组各35例。甘精组每晚9时注射甘精胰岛素一次,三餐前口服阿卡波糖（拜糖平）;预混组每日早晚餐前分别注射诺和灵30R预混胰岛素,共治疗16周,观察血糖控制和低血糖发生情况。【结果】治疗后两组的FBG和餐后血糖都明显下降,但甘精组的下降幅度明显大于预混组,差异有显著性（P〈0.01）;到达终点时预混组剂量明显大于甘精组,差异有显著性（P〈0.05）;甘精组低血糖事件明显少于预混组（甘精组5例,预混组16例,χ2=4.285,P〈0.05）。【结论】初发2型糖尿病患者采用每日注射一次甘精胰岛素加口服阿卡波糖或每日2次注射预混胰岛素治疗,均能达到明显降糖效果。甘精胰岛素与预混胰岛素相比降低FBG的效果更好;低血糖的发生率低;胰岛素的用量少;每日一次皮下注射更方便,依从性更好。     

短期胰岛素泵治疗对不同病程2型糖尿病患者胰岛β细胞功能的影响

目的观察胰岛素泵强化治疗2周对不同病程2型糖尿病患者胰岛β细胞功能及胰岛素抵抗改善的差异。方法选择不同病程的2型糖尿病患者共90例,根据病程长短分为新诊断糖尿病组（A组）、病程1～5年糖尿病组（B组）、病程5年以上糖尿病组（C组）,各组30例。对3组患者进行2周胰岛素泵强化治疗,以空腹血糖〈6.1 mmol·L-1,餐后2 h血糖〈8.0 mmol·L-1为治疗目标,治疗前后行标准馒头餐试验,检测3组患者空腹及餐后2 h的血糖、胰岛素、C肽,用稳态模型计算治疗前后的胰岛β细胞功能指数（Homa-β）,胰岛素抵抗指数（Homa-IR）。结果 A组和B组治疗后Homaβ-、空腹C肽均较治疗前升高,差异有统计学意义（P〈0.05）,而C组治疗后Homaβ-、空腹C肽较治疗前亦升高,但差异无统计学意义（P〉0.05）;A组的Homaβ-治疗前后的差值与B组比较,差异有统计学意义（P〈0.05）;强化治疗前后各组Homa-IR差异均有统计学意义（P〈0.05）。结论胰岛素强化治疗能改善病程较短的2型糖尿病患者的胰岛β细胞功能,新诊断的2型糖尿病患者获益更大。理想的血糖控制都能使胰岛素抵抗得到改善。     

胰岛素类似物治疗初诊腹型肥胖的2型糖尿病临床观察及随访

目的观察使用胰岛素类似物治疗初诊腹型肥胖2型糖尿病患者的疗效及安全性,并在出院后改用"一针一药"方案,直至停用胰岛素,随访治疗方案的变化。方法选取2007年3月至2010年11月符合纳入标准的40例糖尿病住院男性患者,随机分为2组,A组20例采用门冬胰岛素每日三餐前联合睡前1次甘精胰岛素注射;B组20例门冬胰岛素每日三餐前注射。2组均采用胰岛素强化治疗直至血糖控制达标,观察治疗前后空腹血糖(FBG)、餐后2小时血糖(2hPPG)、C肽、血糖达标时间和达标时胰岛素使用量,以及低血糖发生情况。出院后改为口服药配合晚间注射1次甘精胰岛素,每日胰岛素总量<20U时停用胰岛素,仅用口服药(非促泌剂)配合运动饮食治疗,观察至复用胰岛素时的持续时间。结果全部患者治疗后血糖水平显著下降,C肽水平显著增加,2组间比较差异无统计学意义(P均>0.05);A组血糖达标时间短,胰岛素用量少,低血糖发生率高。出院随访显示仅使用口服药物仍可在一定时间内良好控制血糖。结论初诊腹型肥胖的2型糖尿病患者使用胰岛素类似物强化治疗安全、有效。     

中药汤剂联合胰岛素治疗2型糖尿病的临床疗效观察及对胰岛β细胞功能的影响

目的：观察中药汤剂（六味地黄汤加减）联合胰岛素治疗2型糖尿病的疗效及对胰岛β细胞功能的影响。方法将80例2型糖尿病患者随机分为治疗组和对照组各40例。对照组给予胰岛素治疗,治疗组在对照组治疗基础上加用自拟中药组方治疗。观察治疗前后的血糖、糖化血红蛋白、血脂、C肽和低血糖发生情况,比较2组疗效及安全性。结果2组治疗前后空腹血糖、餐后2 h血糖、糖化血红蛋白、空腹C肽、空腹血脂和低血糖发生率比较差异均有统计学意义（P＜0.05）。结论六味地黄汤加减方联合胰岛素优化治疗方案在控制2型糖尿病临床症状,改善高糖、高脂、高凝状态,改善胰岛β细胞功能的同时,可降低患者低血糖发生率,提高安全性和依从性,改善患者的生活质量。     

诺和锐30与诺和灵30R治疗老年2型糖尿病的临床观察

目的：观察诺和锐30和诺和灵30R治疗老年2型糖尿病的临床效果。方法：将2009年1月—2011年1月期间住院的年龄≥60岁的2型糖尿病患者120例随机分为诺和锐30组（60例）、诺和灵30R组（60例）,均为每日早晚2次皮下注射。治疗12周,观察两组血糖控制等临床效果,并分析比较。结果：两组的7点血糖、糖化血红蛋白（HbA 1c）较治疗前明显下降,差异有统计学意义（P〈0.05）。治疗后诺和锐30组早餐后2 h、晚餐后2 h、睡前22：00血糖较诺和灵30R组低,差异有统计学意义（P〈0.05）;两组空腹、午餐前、晚餐前血糖、午餐后2 h及HbA 1c变化差异无统计学意义（P〉0.05）。诺和锐30组低血糖发生率低于诺和灵30R组（P〈0.05）。诺和锐30组日胰岛素用量少于诺和灵30R组（P〈0.05）。两组患者体重的增加值差异无统计学意义（P〉0.05）。结论：治疗后诺和锐30组的早、晚餐后及睡前22：00血糖有明显降低,低血糖发生率较低,更适宜以餐后血糖高为主的老年2型糖尿病患者。     

Twice-daily biphasic insulin aspart 30 versus biphasic human insulin 30: a double-blind crossover study in adults with type 2 diabetes mellitus

OBJECTIVE: The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart (BIAsp 30) with the equivalent premixed biphasic human insulin (BHI 30), administered twice daily, in patients with type 2 diabetes mellitus. METHODS: In this randomized, double-blind, crossover trial, 13 patients (mean age, 64 years; baseline mean glycosylated hemoglobin, 7.7%; mean body mass index, 28.1 kg/m2) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast. At the end of each 2-week treatment period, 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzyme-linked immunosorbent assays. All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance. RESULTS: Total daily insulin exposure was similar between treatment periods. Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17% greater than that of BHI 30 after dinner and 44% greater after breakfast; both differences were statistically significant. The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner (18%) and breakfast (35%). Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group; differences were significant only after breakfast. The mean daily prandial glucose excursion was significantly lower for BIAsp 30 (16.2 mmol x h x L(-1)) than BHI 30 (17.9 mmol x h x L(-1)). Postprandial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast, but were significantly greater after lunch. Mean 24-hour and nocturnal serum glucose concentrations were similar, and both insulins were associated with < or = 7 minor and no major hypoglycemic events. CONCLUSIONS: Premeal injection of BIAsp 30 in a twice-daily regimen significantly reduced overall postprandial glucose excursions. This effect may be of importance when improvement in postprandial glucose control is desired.     

门冬胰岛素30强化治疗对初诊2型糖尿病患者胰岛功能的影响

目的：探讨短期门冬胰岛素30强化治疗对初诊2型糖尿病患者胰岛β细胞功能的影响。方法：对30例初诊2型糖尿病患者每日注射2次门冬胰岛素30,强化治疗2周,治疗前后分别进行口服葡萄糖耐量试验（OGTT）及胰岛素释放试验,测定0,30,120 min的血糖和胰岛素值,分别以稳态模型法β细胞功能指数（HOMA-β）评估β细胞功能,以稳态模型法胰岛素抵抗指数（HOMA-IR）评估胰岛素抵抗状况,以早相胰岛β细胞分泌指数（△I30/△G30,糖负荷30min净增胰岛素与净增葡萄糖的比值）评估早期胰岛素分泌能力。结果：经过短期门冬胰岛素30强化治疗后,患者空腹血糖（FPG）、餐后2 h血糖（2 hPG）、HOMA-IR均明显下降（P〈0.05）;而HOMA-β、△I30/△G30显著升高（P〈0.001）。结论：短期门冬胰岛素30强化治疗能够明显改善初诊2型糖尿病患者胰岛分泌功能,减轻胰岛素抵抗,改善糖代谢。     

两种胰岛素类似物治疗2型糖尿病的比较

目的探讨预混胰岛素类似物门冬胰岛素30注射液（诺和锐30）和长效胰岛素类似物甘精胰岛素注射液（来得时）治疗2型糖尿病的疗效和安全性。方法 83例初诊2型糖尿病随机分成2组,分别给予诺和锐30每天2次及来得时每天1次治疗12周,观察治疗前后空腹血糖（FPG）、餐后2小时血糖（PPG）、糖化血红蛋白（HbA1c）的变化,比较两组血糖达标率、低血糖的发生率。结果诺和锐30组HbA1c较来得时治疗组明显下降,HbA1c（7.42±1.38）%vs（8.31±1.82）%（P〈0.05）。诺和锐30组PPG显著低于来得时组,（7.82±4.18）mmol/L vs（8.21±3.90）mmol/L（P〈0.05）。诺和锐30组PPG达标率更高,83.0%vs 56.1%（P〈0.05）,达标时间更短,（7.85±1.48）天vs（8.25±2.46）天,但低血糖事件较来得时组略高,26.2%vs 12.2%（P〈0.05）。诺和锐30组胰岛素用量高于来得时组,（0.61±0.24）U/kg vs（0.50±0.27）U/kg（P〈0.05）,体质量增加也较明显,（5.6±4.6）kg vs（3.0±4.3）kg（P〈0.05）。结论诺和锐30每天2次治疗比来得时每天1次治疗能更有效地降低血糖,血糖达标时间更短,但低血糖发生率略高。     

Biphasic Insulin Aspart 30/70: Pharmacokinetics and Pharmacodynamics Compared With Once-Daily Biphasic Human Insulin and Basal-Bolus Therapy

OBJECTIVE

Pharmacological profiles of biphasic insulin aspart 30/70 (BIAsp 30) once daily (OD), twice daily (b.i.d.), and three times daily (t.i.d.) were compared with other insulin regimens in two crossover glucose clamp studies of insulin-treated type 2 diabetic patients.

RESEARCH DESIGNS AND METHODS

Study 1 consisted of BIAsp 30 OD, b.i.d., and t.i.d. versus biphasic human insulin 30/70 (BHI 30), OD (n = 24). Study 2 examined BIAsp 30 t.i.d. versus basal-bolus therapy (insulin glargine OD plus insulin glulisine t.i.d.) (n = 24). Pharmacokinetics/pharmacodynamics (PK/PD) were investigated over 24 h.

RESULTS

Study 1: PK and PD were markedly different between BIAsp 30 OD and BHI 30 OD: the maximum insulin concentration and glucose infusion rate (GIR) were higher for BIAsp 30; time to maximum metabolism was 1.7 h sooner for BIAsp 30. Study 2: both regimens showed three distinct prandial-related GIR peaks. GIR 24-h area under the curve for BIAsp t.i.d. was higher than for basal-bolus therapy: 2,585.2 vs. 2,289.2 mg/kg.

CONCLUSIONS

BIAsp had pharmacological advantages over BHI. BIAsp t.i.d. had a similar PD profile to basal-bolus therapy.Premixed insulin analogs are a commonly prescribed first insulin therapy for type 2 diabetic patients and may be a simpler alternative to basal-bolus therapy (1,2). Compared with biphasic human insulin 30/70 (BHI 30), the modern premixed insulin analog, biphasic insulin aspart 30/70 (BIAsp 30) has pharmacokinetics (PK) that more closely match endogenous insulin secretion (3,4). Therefore, an initial once-daily (OD) BIAsp 30 regimen can be safely intensified to twice-daily (b.i.d.) or three-times-daily (t.i.d.) injections (5). To compare the PK and pharmacodynamic (PD) profiles of these different regimens, two crossover glucose clamp studies were carried out in insulin-treated patients with type 2 diabetes.     

预混门冬胰岛素强化治疗对2型糖尿病患者血浆中成纤维细胞生长因子-21水平的影响

目的 探讨预混门冬胰岛素对2型糖尿病(type 2 diabetes mellitus,T2DM)患者血浆成纤维细胞生长因子-21(fibroblast growth factor-21,FGF-21)水平的影响.方法 2008年2-12月采用酶联免疫吸附试验测定44例正常人及37例采用预混门冬胰岛素治疗前后的T2DM...     

Cost-effectiveness of switching to biphasic insulin aspart in poorly-controlled type 2 diabetes patients in China

INTRODUCTION: Type 2 diabetes is an increasing problem in China, yet there is a paucity of data regarding the cost-effectiveness of pharmacological interventions in the Chinese setting. METHODS: Previous data were obtained from PRESENT (Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy), a multicountry, single-arm, observational study where type 2 diabetes patients poorly controlled with biphasic human insulin (BHI) were converted to biphasic insulin aspart 30 (BIAsp30); the Chinese subgroup experienced an improvement in HbA(1c) and a reduction in hypoglycaemic events. A published and validated computer simulation model of diabetes (the CORE Diabetes Model) was used to estimate the long-term clinical and cost consequences of switching to BIAsp30 from BHI in the Chinese setting. Treatment effects and patient characteristics were derived from PRESENT and countryspecific published sources. Primary research was performed to ascertain patient management practices and diabetes-related complication costs. Risks of modelled complications were derived from landmark clinical trials and epidemiological studies. Costs and clinical projections were made over patient lifetimes from a third-party payer perspective and discounted at 3% annually. Extensive sensitivity analyses were performed. RESULTS: Conversion to BIAsp30 from BHI was projected to improve discounted life expectancy by 0.38 years per patient (9.91 vs 9.53 years) and quality-adjusted life expectancy by 0.91 quality-adjusted life years (QALYs) per patient (6.32 vs 5.41 QALYs). Conversion to BIAsp30 was associated with increased direct medical costs of Chinese Yuan (CNY) 1751 per patient, due to higher pharmacy and management costs (CNY +19,007), offset by reduced diabetes-related complication costs (CNY -17,254) over patient lifetimes. BIAsp30 was associated with an incremental cost-effectiveness ratio of CNY 1926 per QALY gained. CONCLUSION: BIAsp30 was projected to substantially improve clinical outcomes but was associated with increased lifetime medical costs. BIAsp30 would be considered cost-effective in China given a willingness-to-pay threshold of CNY 100,000 per QALY gained in type 2 diabetes patients poorly controlled on BHI.     

Improved postprandial glycemic control with biphasic insulin aspart relative to biphasic insulin lispro and biphasic human insulin in patients with type 2 diabetes

OBJECTIVE: The rapid-acting insulin analogs aspart and lispro have now been developed in biphasic formulations. This trial compared the postprandial serum glucose control of biphasic insulin aspart 30 (BIAsp 30: 30% aspart, 70% protaminated aspart) with that of biphasic insulin lispro 25 (Mix25: 25% lispro, 75% protaminated lispro) and biphasic human insulin 30 (BHI 30: 30% regular insulin, 70% NPH insulin) in insulin-treated subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was an open-labeled, randomized, single-dose, three-way crossover trial of 61 insulin-treated subjects with type 2 diabetes who had no significant late diabetic complications. BIAsp 30 and Mix25 were injected subcutaneously immediately before a test meal, and BHI 30 was injected 15 min before a test meal. The primary target of analysis was serum glucose excursion 0-5 h after a meal. RESULTS: The postprandial glycemic control with BIAsp 30, as assessed by the 5-h postmeal serum glucose excursion, was superior to that with both BHI 30 and Mix25 (16.6 +/- 4.5 vs. 20.1 +/- 4.9 and 18.9 +/- 6.1 mmol/l per hour, respectively; P < 0.001 and P < 0.05). For BIAsp 30 versus BHI 30, this was supported by a reduced maximum glucose concentration [C(max(SG))] (-5%; P < 0.05) occurring earlier (-13 min; P < 0.01). Furthermore, BIAsp 30 displayed a higher maximum serum insulin concentration (+101%; P < 0.001) occurring earlier (-55 min; P < 0.001) compared with BHI 30. Compared with Mix25, there was a shorter time to C(max(SG)) (-11 min; P < 0.05) after treatment with BIAsp 30. CONCLUSIONS: This trial demonstrates that BIAsp 30 improves postprandial glycemic control compared with both Mix25 and BHI 30 in subjects with type 2 diabetes.