地特胰岛素联合瑞格列奈对初发2型糖尿病疗效的观察

目的：评价地特胰岛素联合瑞格列奈对初发2型糖尿病患者血糖和体重的影响。方法：初发2型糖尿病患者60例,随机分为两组,分别于睡前皮下注射地特胰岛素（n=30）或甘精胰岛素（n=30）。两组均联合口服瑞格列奈（1mg,3次/d）治疗12周,比较两组治疗前后空腹血糖（FPG）、餐后2h血糖（2hPG）、糖化血红蛋白（HbA1c）、体重、低血糖的变化。结果：与治疗前比较,两组FPG、2hPG、HbA1c均明显下降,差异均有统计学意义（P〈0.05）。两组低血糖发生率差异无统计学意义（P〉0.05）,而地特胰岛素组体重增加明显低于甘精胰岛素组（P〈0.05）。结论：对初发2型糖尿病,与甘精胰岛素相比,地特胰岛素联合瑞格列奈可有效控制血糖,在减少体重增加方面更有优势。     

Insulin glargine in the treatment of type 1 and type 2 diabetes

Insulin glargine is an analogue of human insulin that is modified to provide a consistent level of plasma insulin over a long duration. Pharmacokinetic and pharmacodynamic studies show that a single injection of insulin glargine leads to a smooth 24-hour time-action profile with no undesirable pronounced peaks of activity. In clinical trials, this profile has been associated with at least equivalent, if not better, glycemic control than other traditional basal insulins and a significantly lower rate of overall and nocturnal hypoglycemia. The convenience of a once-daily injection, a lack of need for resuspension (insulin glargine is a clear solution when injected), and lower rates of hypoglycemia should translate into improvements in patient treatment satisfaction. This review appraises the evidence for the view that insulin glargine represents an advance in basal insulin therapy for both type 1 and type 2 diabetes patients.     

New methods in insulin treatment

The primary aim of insulin therapy is to replace endogenous insulin secretion in patients with type 1 or type 2 diabetes between meals and overnight as well as postprandially. The most frequently used insulin for basal therapy is the intermediate-acting neutral protamin Hagedorn (NPH) insulin, although it does not correspond to a physiological profile. Insulin glargine is a new extended-action recombinant insulin analog, which is absorbed slowly into the bloodstream, reaching peak action in about 4 h and maintaining this concentration profil for 24-30 h. Some studies demonstrated that insulin glargine reduces the incidence of hypoglycemia and is at least as effective as NPH insulin given once or twice daily. It is equally effective administered before breakfast, dinner or at bedtime. Similar absorption rates were recorded after subcutaneous injection in differents part of body. The continuous subcutaneous insulin infusion utilizing an external insulin infusion pump (CSII) is one approach to intensive insulin therapy. Some studies indicate that pump therapy is associated with improved glycemic control compared with traditional insulin therapies and with significant decreases in frequency of both mild and severe hypoglycemic episodes. The author summarizes the indication, the effect and side effects of pump therapy.     

门冬胰岛素应用于胰岛素泵对餐后血糖和血糖波动的影响

目的 探讨门冬胰岛素与可溶性人胰岛素在持续皮下胰岛素输注(CSII)中对餐后血糖和血糖波动的影响.方法 选择345例2型糖尿病患者,随机以门冬胰岛素(门冬胰岛素组173例)和可溶性人胰岛素(人胰岛素组172例)作为泵用胰岛素进行CSII强化治疗,监测1d 9次末梢血糖(三餐前后、22:00、0:00和3:00),比较两组餐后血糖和血糖波动情况.结果 门冬胰岛素组较人胰岛素组对空腹和早、晚餐后血糖控制更好,餐后血糖波动更小,达标时间较短[分别为(4.40±2.16)、(5.68±2.29)d](P<0.05),且低血糖的发生率明显较低(P<0.05).结论 在CSII强化治疗中,门冬胰岛素可更快、更有效降低血糖,尤其有利于餐后血糖控制和减少整体的血糖波动.     

地特胰岛素联合伏格列波糖对门诊初诊老年2型糖尿病的疗效及安全性

目的探讨地特胰岛素联合伏格列波糖对门诊初诊老年2型糖尿病患者的疗效及安全性。方法 60例患者随机分两组,治疗组采用地特胰岛素联合伏格列波糖,对照组采用精蛋白锌重组赖脯胰岛素50R;16周后,比较两组空腹血糖、餐后2h血糖、血糖波动程度、糖化血红蛋白（HbA1c）、低血糖发生率、体重、血脂变化。结果两组均可有效地控制血糖、HbA1c（P〈0.01）,组间降低幅度比较,差异无统计学意义（P〉0.05）;但治疗组在血糖波动程度、低血糖发生率、体重增加方面均优于对照组（P〈0.05）。两组治疗后的血脂均较治疗前改善,但差异无统计学意义（P〉0.05）。结论地特胰岛素联合伏格列波糖可安全、有效、平稳地控制老年2型糖尿病患者的血糖,低血糖发生率及体重增加较少,患者满意度高。     

Combining insulins for optimal blood glucose control in type I and 2 diabetes: focus on insulin glulisine

Normalization of blood glucose is essential for the prevention of diabetes mellitus (DM)-related microvascular and macrovascular complications. Despite substantial literature to support the benefits of glucose lowering and clear treatment targets, glycemic control remains suboptimal for most people with DM in the United States. Pharmacokinetic limitations of conventional insulins have been a barrier to achieving treatment targets secondary to adverse effects such as hypoglycemia and weight gain. Recombinant DNA technology has allowed modification of the insulin molecule to produce insulin analogues that overcome these pharmacokinetic limitations. With time action profiles that more closely mimic physiologic insulin secretion, rapid acting insulin analogues (RAAs) reduce post-prandial glucose excursions and hypoglycemia when compared to regular human insulin (RHI). Insulin glulisine (Apidra) is a rapid-acting insulin analogue created by substituting lysine for asparagine at position B3 and glutamic acid for lysine at position B29 on the B chain of human insulin. The quick absorption of insulin glulisine more closely reproduces physiologic first-phase insulin secretion and its rapid acting profile is maintained across patient subtypes. Clinical trials have demonstrated comparable or greater efficacy of insulin glulisine versus insulin lispro or RHI, respectively. Efficacy is maintained even when insulin glulisine is administered post-meal. In addition, glulisine appears to have a more rapid time action profile compared with insulin lispro across various body mass indexes (BMIs). The safety and tolerability profile of insulin glulisine is also comparable to that of insulin lispro or RHI in type 1 or 2 DM and it has been shown to be as safe and effective when used in a continuous subcutaneous insulin infusion (CSII). In summary, insulin glulisine is a safe, effective, and well tolerated rapid-acting insulin analogue across all BMIs and a worthy option for prandial glucose control in type 1 or 2 DM.     

Optimizing insulin use in type 2 diabetes: role of basal and prandial insulin in long-term care facilities

Approximately 25% of patients in nursing homes have diabetes, and it is the primary reason for 12% of nursing home admissions among residents 45 to 75 years of age. Glycemic control is important to reduce the risk of diabetic complications in this patient population. Management of diabetes in the long-term care setting is complicated, because many residents already have diabetic complications and other comorbidities. Data from several studies suggest that a significant number of nursing home residents receive suboptimal diabetes care. This review is intended to provide guidance for optimizing glycemic control in patients with type 2 diabetes in long-term care facilities. Oral antidiabetic drugs (OADs) represent first-line pharmacotherapy for diabetes. However, because of the progressive nature of type 2 diabetes, most patients will eventually require insulin. Adding a basal insulin analog, such as insulin glargine or insulin detemir, to an OAD is a simple, safe, and effective strategy for introducing insulin therapy. These long-acting insulin analogs provide effective glycemic control with a lower risk of hypoglycemia, a particular concern in the elderly, compared with NPH insulin. In patients whose insulin requirements have increased as a result of increases in post-prandial glucose excursions, prandial insulin should be added following a stepwise approach to therapy. Overall patient care and optimizing treatment of type 2 diabetes and its associated complications are vital services provided by the nursing staff at long-term care facilities.     

Insuline et prise de poids

Insulin therapy is a key for type 1 and of type 2 diabetic patients management. As demonstrated by the DCCT and the UKPDS studies, insulin therapy promotes a good metabolic control and reduces microvascular complications in both populations. Body weight increase after insulin therapy initiation may be a barrier to initiation or to intensification of insulin therapy. The body weight increase (around 2.5 kg in type 1 diabetic patient and around 6 kg in type 2 diabetic patient) reach its maximal level during the first 12 months following insulin therapy initiation. The analysis of body composition modifications showed that insulin increases fat mass and lean mass in both type 1 and type 2 diabetic patients to a level similar at what observed before the clinical onset of diabetes. In type 2 diabetic population, the body weight increase after insulin therapy initiation is correlated with the maximal body weight observed in the life. These results suggested that weight gain during insulin therapy is a “catch-up” weight regain. Insulin increases body weight by reducing glycosuria and by reducing neoglucogenesis and various cost expensive metabolic cycles usually observed in hyperglycemic patients. Positive nitrogen balance following insulin therapy promotes lean mass increase. No deleterious effect of weight gain during insulin therapy has been reported in the literature on cardiovascular events in both type 1 (DCCT/EDIC study) and in type 2 diabetic patients (UKPDS study). The association with metformin is recommended to reduce weight gain following insulin therapy. The development of a new basal analogue insulin with preferential hepatic action than peripheral action will favour weight stability resulting in immediate and long-term benefits for patients.     

Decreased first-phase secretion of insulin may play a role in the development of insulin resistance

Decreased first-phase secretion of insulin may play a role in the development of insulin resistance. In the development of type 2 diabetes an abnormal function of the beta-cells and insulin resistance of liver, fat cells and muscle play the main role. An early sign of beta-cell damage can be the loss of first-phase insulin response. This is supposed to precede the development of insulin resistance. Decrease of first-phase secretion of insulin can induce early postprandial hyperglycaemia and hypertriglyceridaemia damaging endothelium of precapillary arterioles of the nutritive capillaries. Insulin-induced endothelium-dependent dilation of these arterioles is inhibited by high glucose and triglyceride levels preventing metabolic effect of insulin on the parenchymal cells surrounded by nutritive capillaries and leading this way to insulin resistance. Second-phase hyperinsulinaemia develops in the impaired glucose tolerance. With the progression of the disease into the type 2 diabetes, insulin secretion decreases in the second-phase, as well. Because of decrease of first-phase insulin secretion in type 2 diabetic patients, early insulin therapy could be a choice of treatment in type 2 diabetes. Results of the UKPDS suggest that insulin-treated type 2 diabetic patients are longer in the near-euglycaemic state compared to those treated by oral hypoglycaemic agents. Recent data support that early insulin therapy of type 2 diabetic patients retains their own insulin secretion capacity and results in lower haemoglobin A1c. A comparison of before-meal rapid-acting insulin analogue and bedtime NPH insulin regimens verified that rapid-acting insulin analogue decreased haemoglobin A1c compared to NPH insulin treatment in type 2 diabetes. On the basis of these data arises the possibility of the change of the attitude "Oh no, not insulin in type 2 diabetes" to the "early rapid-acting insulin analogue treatment" of these patients.     

地特胰岛素在2型糖尿病胰岛素起始治疗中的疗效分析

目的：对HbA1c＆gt;9%的新诊断的T2DM患者进行地特胰岛素（Det）联合二甲双胍的短期强化治疗,探讨Det作为基础胰岛素在T2DM起始治疗中的疗效与安全性。方法：156例新诊断的T2DM患者随机数字表法分为治疗组与对照组,每组78例,两组在口服二甲双胍的基础上,治疗组给予Det联合二甲双胍治疗,对照组给予门冬胰岛素30联合二甲双胍治疗,治疗12周。对其治疗前后血糖控制、低血糖情况和HOMA-β功能进行自身及组间比较。结果：12周治疗后,两组中FBG、2 h PBG、HBA1c较治疗前均明显下降,FC-P、2 h C-P和HOMA-β较治疗前明显升高（P〈0.01）。治疗组低血糖发生率3.85%（3/78）、症状性低血糖1例,对照组24.36%（19/78）、症状性低血糖5例,Det明显优于门冬胰岛素30,比较差异有统计学意义（P〈0.01）。结论：Det作为基础胰岛素联合二甲双胍治疗新诊断时HbA1c＆gt;9%的T2DM患者可以良好控制高血糖且低血糖发生率低,是一种简单、有效、安全的门诊强化治疗方案,适合初诊2型糖尿病的起始治疗。     

胰岛素泵治疗重症高龄2型糖尿病患者临床分析

目的 比较胰岛素泵持续皮下输注胰岛素与多次皮下注射胰岛素对重症高龄2型糖尿病患者的疗效与安全性.方法 将37例在重症监护室（ICU）住院的重症高龄2型糖尿病患者按随机数字表法分为观察组（19例）和对照组（18例）,观察组用胰岛素泵持续皮下输注赖脯胰岛素,对照组用赖脯胰岛素三餐前及甘精胰岛素晚上睡前常规皮下注射,两组患者及家属均给予糖尿病教育、根据病情合适的糖尿病饮食,比较治疗前后两组患者的血糖变化、胰岛素用量、血糖控制达标时间、低血糖发生率及住院时间.结果 治疗后观察组空腹血糖为（7.2±1.2）mmo1/L,餐后2h血糖为（9.4±1.2） mmol/L,睡前血糖为（9.4±1.3） mmol/L,对照组分别为（8.5±3.0）、（10.0±2.4）、（10.2±2.4）mmol/L,治疗后两组患者空腹血糖、餐后2h血糖及睡前血糖均较治疗前显著下降,且两组治疗后比较差异有统计学意义（P＜0.05）.观察组患者血糖控制达标时间为（5.4±2.5）d,胰岛素用量为（43±9）U/d,而对照组分别为（12.8±3.8）d、（55±10）U/d,两组比较差异有统计学意义（P＜0.05）.观察组未见低血糖发生.结论 胰岛素泵持续皮下输注胰岛素与多次皮下注射胰岛素对重症高龄2型糖尿病均具有较好的疗效与安全性,且胰岛素泵持续皮下输注胰岛素更利于此类患者血糖控制及改善病情.     

Long-acting insulin analogs: progressing slowly

In the last few years short-acting insulin analogs have become increasingly popular. Their introduction has unmasked serious deficiencies in the capacity of isophane insulin to provide a stable basal insulinaemia. The long-acting insulin analogs, insulin glargine and insulin detemir, have been developed as alternatives to isophane insulin. Insulin glargine has a long duration of action and has demonstrated its usefulness in diabetes type 2, specifically a lower incidence of (nocturnal) hypoglycaemia compared to isophane insulin, in clinical practice. Insulin detemir has a very low variability in absorption and also seems to reduce the risk of nocturnal hypoglycaemia in diabetes type 1. More studies are, however, needed. Because of the higher costs of these novel insulins, the decision to switch a patient from isophane insulin to an insulin analog has to be made on an individual basis.     

Review of biphasic insulin aspart in the treatment of type 1 and 2 diabetes

Background

Insulin is an effective treatment for achieving glycemic control and preventing complications in patients with diabetes. In order to make insulin therapy more acceptable to patients, newer formulations of insulin have been developed, such as biphasic insulins. Biphasic insulins conveniently provide both prandial and basal insulin in a single injection. One of the most well-studied biphasic insulins is biphasic insulin aspart 70/30.

Objective

Our goal was to review the current literature on the safety and efficacy of biphasic insulin aspart in type 1 and type 2 diabetes.

Methods

A MEDLINE search was conducted using the terms “biphasic insulin aspart” to identify clinical studies and reviews.

Results

Biphasic insulin aspart more effectively reduces post-prandial glucose compared to other biphasic insulins and basal insulins. Compared to biphasic insulin aspart, fasting glucose levels are lower with NPH, similar with glargine, and similar or lower with biphasic human insulin. Treat-to-target trials have shown that a goal HbA1c below 6.5 or 7% can be achieved with biphasic insulin aspart. The risk of hypoglycemia is similar to or less than that seen with other biphasic insulins or NPH insulin.

Conclusion

Biphasic insulin aspart 70/30 is a safe and effective treatment option for patients with diabetes.     

地特胰岛素与门冬胰岛素强化治疗2型糖尿病疗效观察

目的观察地特胰岛素联合门冬胰岛素强化治疗2型糖尿病患者的疗效。方法将118例口服降糖药物欠佳的2型糖尿病患者随机分为地特胰岛素联合门冬胰岛素组（N-D组）,诺和灵R联合诺和灵N组（N-N组）,连续治疗2周,分别于治疗前后测空腹血糖（FPG）、餐后2h血糖（2hPG）和空腹胰岛素（FINS）,并分别计算HOMA-IR和HOMA-β,记录血糖达标时间、达标日胰岛素类似物用量和低血糖发生频率。结果 N-G组与N-N组FBG、2hPG、Homa-β和Homa-IR比较均无显著性差异,P〉0.05;两组强化治疗前后组内比较FPG、2hPG、Homa-β和Homa-IR比较均为P〈0.01;而N-G组的糖达标时间、胰岛素用量和低血糖发生率均较N-N组低,P〈0.01。结论地特胰岛素联合诺和锐强化治疗可以明显改善胰岛B细胞功能,降低胰岛素抵抗,使多数口服降糖药物控制血糖欠佳的2型糖尿病患者血糖更加快速、安全达标。     

胰岛素强化治疗儿童初发2型糖尿病临床观察

目的 采用胰岛素强化治疗儿童2型糖尿病,观察胰岛功能及其他指标变化情况.方法 将42例儿童初发2型糖尿病患者随机分为2组,门冬胰岛素30治疗(甲)组、地特胰岛素联合速效门冬胰岛素皮下注射(乙)组,治疗3个月.比较2组治疗前后的空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1C)、胆固醇(TC)、甘油三酯(TG)、体重指数(BMU、空腹胰岛素(Fins)、空腹C肽(F-CP)及HOMA-3、HOMA-IR.结果 治疗后乙组比甲组胰岛功能有较大改善,差异有统计学意义,两组其他各值均有改善,两组相比较差异无统计学意义.结论 胰岛素强化治疗有助于儿童糖尿病患者胰岛功能恢复.     

甘精胰岛素联合瑞格列奈对2型糖尿病患者血糖控制及低血糖发生率的影响

目的 探讨甘精胰岛素联合瑞格列奈对0型糖尿病患者血糖控制以及低血糖发生率的影响.方法 选取0型糖尿病患者70例,随机分为两组各35例.对照组予以甘精胰岛素治疗,实验组予以甘精胰岛素联合瑞格列奈治疗,两组均治疗3个月.比较两组的血糖控制及低血糖发生率.结果 治疗后,两组的FPG、0hPG与HbA1c水平均显著低于治疗前,...     

Basal insulin therapy in type 2 diabetes

Patients with type 2 diabetes mellitus are usually treated initially with oral antidiabetic agents, but as the disease progresses, most patients eventually require insulin to maintain glucose control. Optimal insulin therapy should mimic the normal physiologic secretion of insulin and minimize the risk of hypoglycemia. This article discusses the role of insulin therapy in patients with type 2 diabetes, emphasizing long-acting insulin agents designed to approximate physiologic basal insulin secretion and provide control over fasting plasma glucose. Clinical trials of recently developed long-acting insulins are reviewed herein, with emphasis on studies that combined basal insulin with oral agents or with short-acting insulins in a basal-bolus approach. The normal physiologic pattern of insulin secretion by pancreatic beta cells consists of a sustained basal insulin level throughout the day, superimposed after meals by relatively large bursts of insulin that slowly decay over 2 to 3 hours (bolus insulin). Basal support with long-acting insulin is a key component of basal-bolus therapy for patients with diabetes who require insulin with or without the addition of oral agents. Newer long-acting agents such as insulin glargine provide a steadier and more reliable level of basal insulin coverage and may have significant advantages over traditional long-acting insulins as part of a basal-bolus treatment strategy.     

胰岛素诺合灵30R对老年2型糖尿病患者的疗效及安全性分析

目的探究胰岛素诺和灵30R在老年2型糖尿病患者治疗中的效果及安全性。方法选取某院内分泌科2010～2011年间治疗的140例老年糖尿病患者为研究对象,随即将他们分为两组,诺和灵组70例患者给予诺和灵30R治疗;对照组70例患者给予口服降糖药治疗。观察两组患者在空腹血糖(FPG)、餐后2h血糖(2hPBG)、糖化血红蛋白(HbA1c)和低血糖事件发生的情况。结果治疗后诺和灵组患者的控制情况明显好于对照组(P﹤0.05);诺和灵组发生低血糖率1.43%,对照组发生率12.86%,提示使用诺和灵30R安全性明显高于对照组(P﹤0.01)。结论使用胰岛素诺和灵30R治疗老年2型糖尿病安全可靠,可以有效的控制患者的血糖并减少低血糖事件的发生,应广泛推举临床使用。     

Management of Diabetes Mellitus

Abstract

Diabetes mellitus is a common metabolic disorder characterized by high blood glucose levels resulting from an insulin deficiency (type 1 diabetes mellitus) or a combination of insulin deficiency and insulin resistance (type 2 diabetes mellitus). The chronic hyperglycemia associated with diabetes mellitus can cause damage to the eyes, kidneys, heart and peripheral circulation, resulting in substantial morbidity, premature mortality and considerable healthcare costs.In both type 1 and type 2 diabetes mellitus, quality of glycemic control has been shown to be a major factor in the prevention of microvascular complications, and tight blood glucose control is the primary goal for all patients with diabetes mellitus.In patients with type 1 diabetes mellitus, multiple daily injections of exogenous insulin and frequent monitoring of blood glucose levels are required to achieve tight glycemic control. Patients with type 2 diabetes mellitus may achieve initial glycemic control with diet and lifestyle interventions alone; however, a large percentage of patients will require pharmacological therapy, first with an oral antidiabetic agent and, ultimately, with insulin.Premixed insulin formulations, consisting of fixed ratios of short- and intermediate-acting insulins, are a convenient and effective treatment option which account for ≈40% of insulin use worldwide. Until recently, the only premixed formulations available contained varying proportions of human regular insulin and human isophane insulin suspension (NPH). However, new premixed formulations containing insulin lispro (a rapid-acting insulin analog) and insulin lispro neutral protamine suspension (NPL) [an intermediate-acting insulin analog] are now available.Insulin lispro mix75/25 (Humalog® Mix75/25?) is a premixed formulation containing 25% insulin lispro and 75% NPL which has been investigated for use in patients with type 1 and with type 2 diabetes mellitus. Administered twice daily immediately before breakfast and dinner, insulin lispro mix75/25 provides better control of postprandial blood glucose, provides similar overall glycemic control, appears to be preferred by patients and may reduce nocturnal hypoglycemia compared with a similar premixed formulation containing 30% human regular insulin and 70% NPH (human insulin 70/30; Humulin® 70/30, Novolin® 70/30). Insulin lispro mix75/25 has a rapid onset of action, allowing for administration immediately before a meal, whereas patients need to administer human insulin 70/30 30 to 60 minutes prior to meals. Insulin lispro mix75/25 also improves glycemic control in patients whose type 2 diabetes mellitus is not well controlled by oral agents.

Conclusion

Insulin lispro mix75/25 is suitable for patients wishing to use premixed insulin formulations and may offer several benefits over human insulin 70/30.

     

Addition of Insulin to Parenteral Nutrition for Control of Hyperglycemia

Administration of parenteral nutrition (PN) may result in hyperglycemia in patients with preexisting diabetes or disease‐related insulin resistance, and it can be associated with increased rates of complications. Treatment requires insulin therapy. Insulin can be administered subcutaneously, intravenously via a variable rate sliding scale, or by adding it directly to the PN. The last method is a potentially attractive technique for a number of reasons—it could deliver the insulin intravenously at a steady rate alongside carbohydrates, and in malnourished patients with little subcutaneous tissue, it may prevent the need for frequent insulin injections. Despite such potential advantages, the addition of insulin to PN remains controversial, largely with respect to the bioavailability of insulin in PN and resultant concerns of the risk of hypoglycemia. There is a paucity of long‐term quality controlled studies to address this question. The available literature suggests that, at least in the short term, insulin addition to PN can achieve reasonable glycemic control with low rates of hypoglycemia, and the technique compares favorably with the use of long‐acting insulin preparations. This literature review finds a wide range of values reported for insulin availability via PN, ranging from 44% to 95% depending on the type of PN container material used and the presence of added vitamins and trace elements. Few studies looking at glycemic control among patients receiving home PN were found, and larger prospective trials are needed to assess the efficacy and safety of this technique in this patient group.