甘精胰岛素联合格列美脲对比联合吡格列酮治疗新诊断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对比联合吡格列酮治疗新诊断HbA1 c＞9.0％的T2DM患者的疗效与安全性. 方法 新诊断的T2DM患者92例随机分为甘精胰岛素联合格列美脲（A）组和联合吡格列酮（B）组,观察治疗前后,两组BMI、FPG、2 hPG、HbA1 c、胰岛β细胞功能、血糖达标时间、胰岛素单日用量及低血糖发生率. 结果 12周后,两组FPG、2hPG、HbA1c、HOMA-IR均比治疗前下降（P＜0.01）;FC-P、2 hC-P、胰岛素功能指数（HOMA-islet）均升高（P＜0.01）;B组治疗后较治疗前体重增加（P＜0.05）,而A组无明显变化（P＞0.05）;与B组比较,A组达标时间短,单日胰岛素用量少、体重增加少,且低血糖发生率低（P＜0.05）. 结论 甘精胰岛素联合格列美脲与联合吡格列酮治疗新诊断T2DM均能较好地控制血糖,但甘精胰岛素联合格列美脲低血糖发生率更低,体重增加更少.     

沙格列汀或格列美脲联合甘精胰岛素对2型糖尿病患者血糖波动影响的观察

目的观察沙格列汀联合甘精胰岛素及格列美脲联合甘精胰岛素对T2DM患者血糖波动的影响。方法 60例未接受胰岛素治疗且血糖控制不佳的T2DM患者被随机分为沙格列汀联合甘精胰岛素组和格列美脲联合甘精胰岛素组,共治疗12周。采用动态血糖监测系统(CGMS)监测血糖波动情况,观察BMI、FPG、HbA1c及胰岛素用量等指标。结果两组血糖控制均改善,沙格列汀联合甘精胰岛素组日内血糖平均波动幅度(MAGE)、日内血糖波动次数(NGE)、日间血糖平均绝对差(MODD)低于格列美脲联合甘精胰岛素组[(2.2±1.0)vs(4.1±1.9)mmol/L;(1.4±1.4)vs(2.6±1.5)次/d;(1.30±0.65)vs(2.60±0.90)mmol/L,P<0.05]。两组治疗后FPG及HbA1c均降低[沙格列汀联合甘精胰岛素组(10.5±2.1)vs(6.2±1.3)mmol/L,(8.7±1.2)%vs(6.3±1.1)%;格列美脲联合甘精胰岛素组(10.4±1.8)vs(6.1±1.4)mmol/L,(8.9±1.4)%vs(6.5±1.2)%](P均<0.01);沙格列汀联合甘精胰岛素组BMI低于格列美脲联合甘精胰岛素组[(22.2±2.4)vs(25.5±2.7)kg/m2](P<0.05)。结论沙格列汀联合甘精胰岛素可有效控制血糖,改善血糖波动,在血糖控制稳定性方面优于格列美脲联合甘精胰岛素。     

西格列汀或格列美脲联合地特胰岛素治疗2型糖尿病的临床研究

目的比较西格列汀联合地特胰岛素与格列美脲联合地特胰岛素治疗T2DM的疗效。方法将80例口服降糖药OAD血糖控制不佳的T2DM患者随机分为西格列汀联合地特胰岛素组(观察组)和格列美脲联合地特胰岛素组(对照组),治疗12周,观察FPG、2 hPG、HbA1c、BMI等指标及低血糖发生情况、胰岛素用量。结果治疗后两组FPG、2 hPG、HbA1c均较治疗前下降(P0.05);观察组与对照组HbA1c达标率分别为87.5%、85.0%(P0.05),但观察组胰岛素用量比对照组减少了10.4%,同时低血糖发生率低,BMI得到控制。结论西格列汀联合地特胰岛素治疗在有效控制血糖和体重同时,减少低血糖事件,同等HbA1c达标情况下,所用的胰岛素剂量更少。     

甘精胰岛素和预混胰岛素用于老年2型糖尿病患者的疗效和不良反应对比分析

目的评价甘精胰岛素和预混胰岛素在老年T2DM治疗中的优越性。方法68例老年T2DM患者随机分为甘精胰岛素组（Gla组）和预混胰岛素组（Pre组）,比较两组治疗前后FBG、2hBG、HbA1c、空腹C肽（FC-P）及75g OGTT后2hC肽（2hC-P）水平、体重变化、低血糖发生率及患者满意度。结果治疗后两组FBG、2hBG、HbA1c水平均较治疗前显著降低（P〈0．01）,Gla组FBG、HbA1c水平较Pre组显著降低（P〈0.05）,Pre组2hC-P水平较治疗前显著增加（P〈0.05）。Gla组体重增加、低血糖发生率显著低于Pre组（P〈0.05或P〈0．01）。结论老年T2DM患者应用甘精胰岛素是有益的治疗方案。     

门冬胰岛素联合甘精胰岛素治疗2型糖尿病的疗效观察

目的探讨三餐前门冬胰岛素联合甘精胰岛素对血糖控制较差的糖尿病患者的疗效。方法选择血糖控制较差的糖尿病患者60例,随机分为两组：一组以三餐前门冬胰岛素联合睡前甘精胰岛素治疗（Asp＋Gla组）,另一组以三餐前诺和灵R联合睡前诺和灵N治疗（RI＋NPH组）。比较两组治疗后血糖达标时间、FBG、2hBG、血糖波动、胰岛素用量、低血糖发生率。结果Asp＋Gla组降糖快速稳定,血糖达标时间短,治疗后FBG、2hBG更理想,日内血糖波动幅度小,低血糖发生率低,优于RI＋NPH组（P均〈0．05）。结论对血糖控制较差的2型糖尿病患者,三餐前门冬胰岛素联合睡前甘精胰岛素治疗,低血糖发生率低,降糖效果显著。     

预混胰岛素转换为甘精胰岛素联合口服降糖药有效性与安全性的观察

目的 评价应用预混胰岛素治疗血糖控制不佳的T2DM患者转换为甘精胰岛素联合口服药物治疗的有效性及安全性. 方法 选择62例应用预混胰岛素治疗但血糖控制不佳的T2DM患者,将其治疗方案转换为甘精胰岛素联合口服药治疗16周.以治疗前后FPG、2hPG及HbA1c的变化评价方案的有效性和低血糖发生率及BMI的变化评价治疗的安全性,采用调查问卷评分比较治疗前后满意度. 结果 治疗16周后,FPG、2hPG及HbA1c较治疗前下降(P＜0.01),HbA1c下降幅度大于1％者占63.79％;治疗期间共有16例发生非重度日间低血糖27次;患者对治疗的满意度较治疗前增加(P＜0.01). 结论 应用预混胰岛素治疗但血糖控制不佳的T2DM患者转换为甘精胰岛素联合口服药物治疗具有安全性、有效性.     

地特胰岛素用于治疗口服降糖药控制不佳的2型糖尿病患者疗效观察

目的观察地特胰岛素对口服降糖药（OAD）控制不佳的2型糖尿病（T2DM）患者临床疗效。方法33例OAD血糖控制不佳的T2DM患者,加用地特胰岛素每日睡前皮下注射,共24周。观察用药前后FBG、2hBG、HbA1c、BMI等的变化。结果治疗后T2DM患者FBG、2hBG、HbA1C均明显下降（P〈0．01）。日间低血糖发生率9．1％,无夜间症状性低血糖发生,体重无明显增加。结论OAD控制不佳的T2DM患者加用地特胰岛素可有效控制血糖,低血糖发生率低,体重增加不明显。     

亚莫利联合甘精胰岛素治疗2型糖尿病疗效观察

目的探讨磺酰脲类降糖药亚莫利联合甘精胰岛素治疗2型糖尿病（T2DM）的临床疗效。方法将130例T2DM患者随机分为两组,对照组单用亚莫利治疗,观察组加用甘精胰岛素治疗。观察两组治疗前及治疗后3个月空腹血糖（FPG）、餐后2h血糖（2hPG）、糖化血红蛋白（HbA1c）及体质量指数（BMI）变化。结果治疗后3个月观察组FPG、2hPG、HbA1c,BMI较治疗前明显下降（P均〈0．05）,对照组治疗前后各指标比较差异无统计学意义。结论亚莫利联合甘精胰岛素治疗T2DM安全、有效。     

口服降糖药血糖控制不佳的老年2型糖尿病患者加用甘精胰岛素的疗效观察

目的通过比较甘精胰岛素和诺和灵N对口服降糖药血糖控制不佳的老年2型糖尿病患者的治疗效果,探讨甘精胰岛素在老年2型糖尿病患者血糖达标治疗中的临床运用价值。方法44例口服降糖药治疗空腹血糖控制不佳的老年2型糖尿病患者随机分为两组：甘精胰岛素治疗组22例,诺和灵N治疗组22例,治疗12周。观察两组治疗前后的糖化血红蛋白（HbA1c）值、空腹血糖（FBG）、餐后两小时血糖（2hPG）、体重指数（BMI）和每日所需的胰岛素剂量以及两组治疗过程中低血糖发生的频率。结果治疗12周后两组HbA1c、FBG、2hPG与治疗前比较差异有统计学意义（P〈0．05）;而两组间HbA1c、2hPG、低血糖事件的发生率比较差异有统计学意义（P〈0．05）,每日胰岛素的用量、BMI、FBG比较差异无统计学意义（P〉0．05）。结论加用甘精胰岛素对口服降糖药血糖控制不佳的老年2型糖尿病患者能更有效更安全地控制血糖。     

格列美脲联合利格列汀对2型糖尿病合并肥胖患者血糖控制及体质指数变化的影响

选取2016年4月至2017年4月收诊的74例T_2DM合并肥胖患者,随机平分为对照组采用格列美脲治疗,观察组采用格列美脲+利格列汀治疗。结果治疗前,观察组与对照组空腹血糖(FBG)、餐后2 h血糖(2 hBG)及BMI指数对比(P0.05);治疗2个月后,观察组FBG、2 hBG水平及BMI指数低于对照组(P0.05)。结论格列美脲联合利格列汀治疗T2DM合并肥胖患者,可改善患者血糖水平,降低患者BMI指数。     

Precipitin reactions between insulin,proinsulin, insulin chains and insulin antibody

Summary Insulin antibody was produced in guinea pigs and the precipitins tested by double diffusion in agarose gel. Pork, beef and monocomponent insulin produced precipitin lines. Proinsulin also produced a precipitin line with these antisera but no lines appeared with either the A-chain or the B-chain of insulin. There was good correlation between the precipitin titre and the radioimmunoassay titre.     

ATP sensitizes the insulin receptor to insulin

Insulin receptor with high insulin binding and tyrosine kinase activities has been prepared from human placenta. Based on a molecular mass of 306 kDa for the receptor (the value obtained from the sum of the amino acid residues), this preparation is capable of binding 1.48 mol of insulin per mol of receptor. The receptor is free from phosphatase and ATPase activity and is not stimulated by sodium vanadate. Autophosphorylation is linear with respect to receptor concentration, and the 32P incorporated is stable even in the presence of a 100-fold excess of unlabeled ATP. The Km for ATP is 208 microM. N-Ethylmaleimide inhibits autophosphorylation. Alkylation with 3H-labeled N-ethylmaleimide results in the incorporation of 1.13 +/- 0.37 mol of N-ethylmaleimide per mol of insulin binding activity exclusively into the beta subunit of the receptor. The nonhydrolyzable ATP analog adenosine 5'-[beta,gamma-imido]triphosphate stimulates autophosphorylation of the receptor, an effect that is evident at ATP concentrations below 1 mM. The stimulatory effect of adenosine 5'-[beta,gamma-imido]triphosphate is the result of increasing the binding of insulin to the alpha subunit, and this reflects itself in a shift to the left of the insulin dose-response curve for autophosphorylation. The same is true for ATP. As a consequence, it is now possible to reconcile the concentration of insulin necessary for stimulating the autophosphorylation reaction with physiological levels and with the levels of insulin required for its classical biological effects.     

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.     

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.