持续皮下胰岛素注射强化治疗初诊2型糖尿病患者的疗效

目的探讨短期持续皮下胰岛素注射治疗(CSII)对初诊2型糖尿病(T2DM)患者血糖控制的影响。方法采用病例对照研究,对58例空腹血糖10 mmol/L的初诊T2DM患者,分为CSII治疗组和每天多次胰岛素注射治疗组(MSII治疗组),每组29例,比较两组治疗前后血糖控制效果、胰岛素用量等。结果两组血糖均显著下降(P0.01);血糖达标胰岛素日最大用量CSII组〔(0.60±0.15)U/kg〕较MSII组〔(0.89±0.21)U/kg〕明显减少(P0.01);血糖达标平均控制天数CSII组〔(6.3±2.1)d〕与MSII组〔(9.5±4.9)d〕相比明显减少(P0.01)。结论 CSII较MSII能更快速有效控制血糖。     

胰岛素泵与胰岛素多次皮下注射治疗2型糖尿病的疗效对比

目的：对比观察胰岛素泵与传统胰岛素多次皮下注射治疗维吾尔族2型糖尿病的疗效。方法：80例维吾尔族2型糖尿病患者被随机分为两组：胰岛素泵持续皮下输注（CSII）组（40例）,常规多次胰岛素皮下注射（MSII）组（40例）,分别对两组治疗前、治疗后血糖、糖化血红蛋白水平,血糖达到强化治疗目标[空腹血糖（FBG）〈7．0mmol／L,餐后2h血糖（2hBG）〈10．0mmol／L]的时间、每日胰岛素用量及低血糖发生情况进行对比。结果：两组治疗后FBG、2hBG、糖化血红蛋白（HbAlC）浓度均低于治疗前（P均〈0．05）。CSII组治疗后各时段血糖（FBG,2hBG）均明显低于MSII组（P〈0．01,〈0．05）。和MSII组比较,CSII组血糖达到强化治疗目标时间显著减少[（12．9±3．3）d：（8．3±2．1）d],胰岛素用量显著减少[（46．9±5．1）U／d：（30．5±6．7）U／d]。P均〈0．001。结论：胰岛素泵强化治疗控制糖尿病患者血糖优于常规胰岛素治疗方法,值得推广。     

胰岛素持续皮下注射治疗糖尿病合并脑卒中38例疗效观察

目的比较不同胰岛素给药方法治疗糖尿病合并脑卒中的疗效。方法将76例糖尿病患者分为胰岛素泵持续皮下注射(CSII)组及胰岛素多次皮下注射(MSII,4次/d)组。静脉输注5%葡萄糖溶液者,CSII组每4g葡萄糖同步增加基础量胰岛素1U;MSII组用微量注射器同步静脉注射胰岛素1U。结果治疗期间血糖平均值、血糖达标时间、低血糖(血糖2.78mmol/L)发生率两组间比较,差异均有统计学意义[(7.86±1.15)vs(10.05±1.87)mmol/L;(3.53±1.16)vs(6.49±2.75)d;23.7%vs 57.9%,P0.01];治疗后14d,两组间神经功能缺损程度(NIHSS)比较,差异有统计学意义[(21.63±4.73)vs(24.06±5.15)分,P0.05];两组间并发症发生率、死亡率比较,差异无统计学意义(23.7%vs 39.5%,5.3%vs 10.5%,P0.05)。发病后3个月,两组Barthel指数评分比较,差异有统计学意义(P0.05)。结论 CSII治疗糖尿病合并脑卒中,在血糖控制和神经功能恢复方面疗效优于MSII。     

胰岛素泵治疗初诊2型糖尿病疗效观察

对我院52名FPG》11．1mmol/L的初诊T2DM患者，随机分为2组，一组采用CSII，另一组用MSII，结果：CSII组治疗后各时间点血糖显著下降，且平均血糖低于MSII组，血糖达标所需时间短，胰岛素用量少，低血糖发生率低。结论：短期胰岛素泵强化治疗对初诊FPG较高的T2DM患者疗效满意。     

胰岛素泵治疗老年2型糖尿病的疗效观察

目的对比应用胰岛素泵(CSII)与多次皮下注射胰岛素(MSII)对血糖控制不佳的老年2型糖尿病(T2DM)患者的治疗效果及安全性。方法将58例老年T2DM患者随机分为CSII组(30例)和MSII组(28例),进行胰岛素治疗。分别检测2组治疗前后的三餐前后及睡前血糖、血糖控制时间、每日胰岛素用量、低血糖发生的次数以及治疗后的糖化血红蛋白(HbA1c)水平并进行统计分析。结果2组均能达到目标血糖值,但CSII组血糖控制达标时间、胰岛素用量及低血糖发生率均明显少于MSII组(P<0.01),CSII治疗后HbA1c水平显著低于MSII组(P<0.01)。结论CSII有效模拟人体生理胰岛素分泌,用于老年T2DM患者能更快、更有效地控制高血糖,减少低血糖的发生率,并且效果能持续较长时间。     

短期持续胰岛素输注治疗酮症起病的2型糖尿病疗效观察

目的 比较持续皮下胰岛素输注(CSII,胰岛素泵治疗)与多次皮下注射胰岛素(MSII)治疗酮症起病的2型糖尿病患者,观察其降糖效果和对胰岛β细胞功能的影响.方法 对新发的空腹血糖≥11.1 mmol/L,酮体阳性的60例初诊糖尿病患者随机分组.胰岛素泵持续注射胰岛素组(CSII组)30例,多次皮下注射胰岛素组(MSII组)30例.比较两种方法治疗前后血糖、胰岛素用量、血糖达标时间、低血糖发病率;标准馒头餐胰岛素释放试验的胰岛素及C肽、空腹血浆胰岛素及Homaβ等.结果 CSII组在血糖达标时间、胰岛素用量及低血糖发病率上均优于MSII组(P＜0.05).胰岛β细胞功能在治疗后获得显著改善(P＜0.05).结论 对酮症起病的2型糖尿病患者,短期CSII强化治疗具有快速稳定纠正代谢紊乱、控制血糖和显著改善胰岛β细胞功能的作用.     

用胰岛素泵控制老年人2型糖尿病血糖水平的观察

目的比较胰岛素泵(CSII)和多次皮下注射胰岛素(MSII)治疗老年2型糖尿病患者高血糖的疗效.方法CSII组与MSII组患者各30例,均进行胰岛素强化治疗.治疗前CSII组空腹血糖显著高于MSII组.结果治疗后CSII组空腹血糖、3餐后2h平均血糖(APBG)和睡前血糖[(6.6±1.2)、(8.5±1.5)和(7.0±1.9)mmol/L]均较MSII组[(8.8±2.1)、(9.6±2.2)和(8.6±2.2)mmol/L]下降显著(P<0.05或P＜0.01),达到了预期强化控制水平.CSII组空腹血糖达标率(86.7%)显著高于MSII组(23.3%,P<0.01),两组餐后血糖达标率以及低血糖发生率差异无显著性.CSII组比MSII组少用胰岛素约15%.结论控制餐后高血糖2种方法同样有效,但CSII控制血糖,尤其是对空腹高血糖更迅速有效.     

胰岛素持续皮下注射治疗新诊断2型糖尿病1年随访疗效的观察

目的观察不同胰岛素给药途径对新诊断T2DM的疗效。方法将84例新诊断T2DM患者随机分为胰岛素持续皮下注射治疗(CSII)组和胰岛素多次皮下注射(MSII)组,每组各42例。观察治疗及出院1年后相关指标。结果两组治疗后血糖均下降。与MSII组比较,CSII组血糖达标时间短[(11.2±3.4)vs(7.3±2.1)d,P0.05];胰岛素用量偏少[(0.90±0.21)vs(0.65±0.16)IU/(kg·d),P0.05]。出院1年后,在未采用药物治疗情况下,血糖控制达标者CSII组多于MSII组(36例vs 16例)。结论胰岛素持续皮下注射治疗新诊断T2DM患者,在住院期间及出院1年后疗效和安全性优于胰岛素多次皮下注射治疗。     

胰岛素泵和多次胰岛素皮下注射治疗对糖尿病酮症酸中毒和高渗昏迷的疗效比较

目的比较不同胰岛素给药方法对糖尿病酮症酸中毒（DKA）和糖尿病高渗性昏迷（DHC）的疗效。方法对DKA和DHC患者首先用静脉泵小剂量胰岛素持续输注,在生命体征平稳并能进半流食后分别用不同的胰岛素给药方式进行治疗：（1）持续皮下胰岛素输注（CSII）组;（2）常规4次皮下注射胰岛素（MSII）组。治疗目标为FBG≤7.0mmol/L、2hBG≤10mmol/L。结果两组每日胰岛素用量无统计学差异（P〉0.05）,但平均达标天数CSII组较MSII组明显缩短（P〈0.01）,CSII组血糖波动小,发生低血糖次数明显减少,且FBG及晚餐后2hBG控制亦明显优于MSII组（P〈0.01）。结论在治疗DKA和DHC时采用静脉泵连续小剂量胰岛素输注急救后,使用CSII较MSII能更快、更平稳、更有效地控制高血糖。     

甘精胰岛素在2型糖尿病治疗中的应用

目的 观察甘精胰岛素治疗2型糖尿病(T2DM)的临床疗效.方法 将72例血糖控制不良的T2DM患者随机分为观察组和对照组各36例,两组均口服降糖药,观察组加用甘精胰岛素,对照组加用诺和灵N,观察两组血糖达标时间、空腹血糖、日间血糖漂移、低血糖发生率.结果 观察组血糖达标时间、空腹血糖、日间血糖漂移、低血糖发生率分别为(8.2±2.5)d、(5.0±1.3)mmol/L、(7.1±1.5)mmol/L、5.6%,对照组分别为(11.1±1.8)d、(5.9±1.4)mmol/L、(7.3±1.3)mmol/L、13.9%,两组比较P均＜0.01.结论 应用口服降糖药基础上加用甘精胰岛素可有效控制血糖,且低血糖发生率低.     

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.     

Treatment of insulin lipoatrophy with monocomponent insulin

Summary A female diabetic with severe insulininduced lipoatrophy was successfully treated with a monocomponent (MC) Lente preparation. This patient was studied for over 6 years and, during periods of treatment with various insulins of different purity, a variety of reactions was observed in the adipose tissue. Evidence is presented that lipoatrophy may be caused by insulin impurities. Lipoatrophy occurring after treatment with recrystallized, mixed species Lente insulin was substantially reduced after treatment with 10 times recrystallized porcine Lente, but recurred on 4 times recrystallized beef Lente, also in areas where beef Lente was not injected. Beef insulin impurities seem more prone to produce lipoatrophy than pork insulin impurities. It is suggested that MC-insulin is the treatment of choice for this condition.     

Mechanism of action of insulin and insulin analogues

Summary A [¹⁴C]-glucose tracer infusion method was used to compare the effects of insulin infusion on glucose metabolism with the effects of infusion of three semisynthetic modified insulins and of proinsulin. Insulin produced hypoglycaemia in the anaesthetised dog by decreasing hepatic glucose production and increasing peripheral glucose utilisation. Compensatory antihypoglycaemic mechanisms eventually modified these responses. A₁ B₂₉-Diacetyl insulin exerted an hypoglycaemic effect entirely by stimulation of peripheral glucose uptake. A₁-B₂₉ crosslinked insulins and proinsulin produced hypoglycaemia almost entirely by decreasing hepatic glucose production and had little effect on tissue uptake. These observations suggest that insulin analogues may have actions in vivo that are qualitatively different from those of native insulin and suggest that certain analogues have a predominant action on the liver. This has important therapeutic implications concerning the development of semisynthetic insulins for clinical use.     

Measurement of insulin absorption and insulin action

For the practical implementation of every type of insulin therapy it is necessary to know both the time course of action of therapeutically used short- and long-acting insulin preparations and the factors influencing such time-action profiles. The only reliable way to obtain the required quantitative information about the pharmacokinetic and glucodynamic properties of insulin preparations has been the use of the euglycemic glucose clamp technique. The first studies with each new insulin formulation or insulin application technique should be performed with healthy subjects in order to have the most comparable study conditions. Thereafter, results from such clinical-experimental studies should be verified in similar studies with patients with diabetes. Earlier investigational approaches, which either had been limited to the determination of the pharmacokinetic properties of insulin preparations or had used the quantitative decrease of the blood glucose level as a measure of the pharmacodynamic properties, do not provide valid quantitative results. The proposed glucose clamp technique makes possible the quantitative study of the pharmacokinetic and pharmacodynamic properties of insulin preparations under comparative and reproducible conditions.     

Variability of insulin absorption and insulin action

Subcutaneous (s.c.) injections of identical insulin doses may lead to considerable intra- and inter-individual differences in the current metabolic control of patients with diabetes mellitus. This well-known variability of the metabolic effect of insulin hampers practical insulin therapy considerably. The aim of this review is to summarize the knowledge about this topic, with a special focus on the variability of insulin action after pulmonary administration of insulin. A number of studies have been published describing the variability of insulin absorption from the s.c. depot. Only in a few published studies has the variability of insulin action after s.c. administration been quantified. Under controlled experimental conditions s.c. injections of regular insulins result in an intra-individual coefficient of variation (CV) of 15-25% of certain pharmacodynamic summary measures--which characterize the metabolic effect of the applied insulin--in healthy subjects. The inter-individual variability was approximately 10% higher than the intra-individual variability. Subcutaneously injected intermediate- and long-acting insulin preparations were described to have an even greater variability (> 50%) than subcutaneously injected regular insulin. However, in a glucose clamp study s.c. application of NPH insulin led to an intra-individual CV in the range of 12-45% in healthy subjects. The reason for this discrepancy might be that the NPH insulin suspension was sufficiently shaken prior to drawing up the dose. Compared with conventional insulin formulations, rapid- and long-acting insulin analogues appear to have a similar variability, which means that, unfortunately, no considerable advantages in terms of variability were achieved by the invention of these novel insulin preparations. There are no appropriate studies available investigating the variability of the metabolic effect after s.c. insulin administration in patients with diabetes. The inhalation of insulin is a novel form of insulin administration that is currently under clinical development. The variability of the metabolic effect induced by the inhalation of insulin has up to now only been investigated in a small number of (published) studies. In a glucose-clamp study with healthy subjects the inhalation of an identical insulin dose on three study days led to an intra-individual variability that was comparable to that after s.c. injection of regular insulin. In a dose-response study with patients with type 1 diabetes the intra-individual CV was 34% for the area under the curve of the glucose infusion rate for 0-10 h. Studies with patients with type 2 diabetes have shown that the intra-individual CVs were within the range seen after s.c. insulin administration or even lower. In summary, the intra-individual variability of the metabolic effect observed after insulin application, be it subcutaneously injected or be it inhaled, is considerable and, therefore, hampers practical diabetes therapy. To date no means have been found that could lead to a clinically relevant reduction in the variable metabolic effect.