甘精胰岛素联合诺和灵R强化治疗初发2型糖尿病的疗效与安全性

目的探讨甘精胰岛素联合诺和灵R强化治疗初发2型糖尿病(T2DM)患者的疗效及安全性。方法选择36例初诊、未使用降糖药物的T2DM患者,随机分为甘精胰岛素组18例、精蛋白人胰岛素(NPH)组18例,每日22:00分别皮下注射1次甘精胰岛素或NPH,每日3餐前均注射诺和灵R,疗程12周。观察两组治疗前后空腹血糖(FPG)、餐后2 h血糖(2 h PG)、3:00血糖、空腹C肽(FCP)、餐后2 h C肽(PCP)及血糖达标率、低血糖发生率等。结果两组治疗后FPG、2 h PG、3:00血糖均明显下降,但治疗前后比较均无统计学差异(P均>0.05)。甘精胰岛素组血糖达标率为83.3%、NPH组为50.0%,两组比较有统计学差异(P<0.01);甘精胰岛素组低血糖发生率为5.6%、NPH组为22.2%,两组比较有统计学差异(P<0.01)。结论甘精胰岛素联合诺和灵R短期强化治疗初发T2DM不但可以获得良好的降糖效果,还可改善胰岛功能,且低血糖发生率较低。     

2种预混胰岛素对初诊2型糖尿病的疗效观察

64例初诊T2DM患者随机分为两组,各32例,A组（门冬胰岛素30组）及B组（诺和灵30R组）,比较两组治疗12周后FBG、PBG、GHbA1c、血糖达标所需时间、血糖达标时胰岛素用量及低血糖的情况。结果结果2种预混胰岛素方法均可使血糖达标,A组较B组显著降低（P〈0.01或P〈0.05）;A组血糖达标所需时间和所需胰岛素用量明显少于B组（P〈0.01或P〈0.05）。A组低血糖发生次数为6.67%,B组低血糖发生次数为20.0%。结论对于初诊T2DM患者,应用门冬胰岛素30注射液疗效优于诺和灵30R注射液,可较理想控制全天血糖。     

阿卡波糖联合甘精胰岛素与门冬胰岛素30治疗老年2型糖尿病患者疗效观察

选取2016年9月～2018年9月老年T2DM患者84例,随机平分为A组给予门冬胰岛素30治疗,B组给予阿卡波糖、甘精胰岛素联合治疗。结果总有效率B组88. 10%高于A组69. 05%(P 0. 05); B组胰岛素用量、低血糖发生率较A组低(P 0. 05); B组平均血糖水平(MBG)高于A组,日平均血糖波动幅度(MAGE)低于A组(P 0. 05)。结论阿卡波糖联合甘精胰岛素治疗老年T_2DM患者,可减少胰岛素用量,降低血糖波动、低血糖发生率。     

每日3次诺和锐30治疗2型糖尿病疗效观察

目的 比较不同胰岛素强化治疗对T2DM的疗效.方法 240例T2DM患者随机分为两组:诺和锐30组(124例)日3次诺和锐30皮下注射;诺和灵组(116例)日4次重组人胰岛素治疗(三餐前半小时注射诺和灵R,睡前注射诺和灵N).结果 两组相比,诺和锐30组控制血糖更快,胰岛素用量更少,低血糖发生率更低.结论 日3次注射诺和锐30,能更有效控制血糖,但需警惕低血糖发生.     

甘精胰岛素对血糖控制不良2型糖尿病患者的临床疗效

目的探讨甘精胰岛素对血糖控制不良2型糖尿病（T2DM）患者的临床疗效。方法将60例T2DM患者随机分为两组各30例,A组皮下注射甘精胰岛素,B组皮下注射诺和锐30,两组疗程均为12周。治疗前后检测两组空腹血糖、餐后2 h血糖、血糖波动程度,观察其低血糖发生率。结果在血糖控制方面,两组比较无统计学差异（P〉0.05）;但A组的血糖波动程度、低血糖发生率明显低于B组（P均〈0.05）。结论对血糖控制不良T2DM患者,甘精胰岛素与诺和锐30的降糖疗效相当,但前者的血糖波动程度及低血糖发生率明显低于后者,可提高患者的顺应性。     

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.     

甘精胰岛素和诺和灵N胰岛素对老年2型糖尿病的临床观察

目的探讨甘精胰岛素和诺和灵N胰岛素在老年2型糖尿病治疗上的临床效果。方法从该院所收治的老年2型糖尿病患者当中选取80例为研究对象,将这些患者随机分为A组和B组,每组各40例。A组患者采用甘精胰岛素治疗,B组患者采用诺和灵N胰岛素治疗,对比分析两组患者各项指标变化情况以及低血糖发生率。结果两组患者空腹血糖、餐后血糖以及糖化血红蛋白等各项指标变化差异无统计学意义(P0.05)。两组患者低血糖发生率差异有统计学意义(P0.05)。结论甘精胰岛素和诺和灵N胰岛素均能有效治疗老年2型糖尿病,但相比较而言,使用甘精胰岛素低血糖发生率较少。     

来得时联合餐时速效胰岛素治疗2型糖尿病疗效观察

60例应用口服降糖药血糖控制不理想的T2DM患者随机分为甘精胰岛素组(n=30)采用每晚8点注射来得时,当某餐餐后血糖控制不良时,即加用诺和锐。强化治疗组(n=30)采用三餐前30min皮下注射诺和灵R,每晚10点注射诺和灵N。目标为空腹血糖≤7.0mmol/L和餐后2h血糖≤10.0mmol/L。结果治疗后两组FBG、P2BG均较前明显下降,P2BG及血糖达标时间比较无统计学意义(P0.05),但甘精胰岛素组FBG低于强化治疗组,低血糖事件明显少于强化治疗组,每日注射4次胰岛素患者明显少于强化组,且患者坚持用药时间明显长于强化治疗组(P0.05)。结论甘精胰岛素联合餐时超短效胰岛素可以良好地控制高血糖,且低血糖发生率低。     

2 型糖尿病短期CSII强化治疗后转换为3种皮下注射胰岛素疗效比较

目的 观察比较2型糖尿病患者经过短期持续皮下输注胰岛素(CSII)强化治疗血糖达标后分别转换为甘精胰岛素与门冬胰岛素或赖脯胰岛素联合多次皮下注射(MDI)治疗、人胰岛素R与中性鱼精蛋白锌胰岛素(NPH)联合MDI治疗及预混人胰岛素30R每天2次注射治疗后的血糖迭标率、血糖控制情况及低血糖的发生率.方法 对大连市中心医院2006-2008年2型糖尿病患者CSII治疗7 d后血糖达标者分为3组,甘精胰岛素与门冬胰岛素或赖脯胰岛素联合MDI治疗组(A组),人胰岛素R与NPH联合MDi治疗组(B组),预混人胰岛素30R每天2次注射治疗组(C组),当血糖控制平稳达标时入组分析,比较转换治疗后3组之间血糖达标率、日内平均血糖、日内血糖波动幅度、低血糖发生率.结果 血糖达标率A组与B组差异无统计学意义(P>0.05),A组高于C组,差异有统计学意义(P<0.001),B组高于C组差异有统计学意义(P<0.05);日内平均血糖及日内血糖波动幅度3组之间差异均无统计学意义(P>0.05);低血糖发生率A组与B组及B组与C组差异均无统计学意义(P>0.05),A组低于C组差异有统计学意义(P<0.05).结论 3种治疗方式若能均使血糖控制达标的情况下可以获得相似的血糖控制状态,A组与B组治疗较C组治疗血糖控制达标率高,低血糖发生率低,临床上有较好的有效性和安全性.     

双相门冬胰岛素与预混人胰岛素治疗老年2型糖尿病的临床疗效观察

老年2型糖尿病(T2DM)患者每日注射两次预混胰岛素30R(诺和灵30 R)较为普遍,但在部分病人中无论怎样调整两次的剂量,空腹血糖(FPG)及(或)餐后血糖(PBG)仍难以控制.本文旨在探讨双相门冬胰岛素(诺和锐30)及诺和灵30R 治疗老年T2DM的疗效,及在两次注射的基础上加用诺和锐30对FPG及PBG的控制情况,并观察体重指数(BMI)及低血糖事件的发生情况.     

Influence of ambient glucose and insulin concentrations on adipocyte insulin binding

To elucidate factors of importance for insulin binding, fat cells from humans and rats were incubated under various experimental conditions for different periods of time. Human adipocytes incubated for 24 hours in the absence of insulin showed no significant difference in insulin binding compared with cells from freshly excised tissue. After 48 hours, however, an increased rate of binding (average 54%; P less than 0.05) was obtained. The addition of insulin (2000 microU/ml) to the culture medium resulted in a decrease in insulin binding (average 33%; P less than 0.05) compared with cells maintained in the absence of insulin. There was no apparent difference in receptor affinity, indicating that the altered binding was due to a change in receptor number. In the absence of insulin, elevating the glucose concentration of the medium from 0.8 mM to 22.4 mM did not significantly influence insulin binding. Rat adipocytes showed similar but more rapid changes. Thus, incubation for 24 hours without insulin caused an increase in insulin binding (average 37%; P less than 0.05). This up-regulation was seen even in a high glucose concentration (28 mM) but was completely prevented by the presence of insulin in the medium. Furthermore, when rat adipocytes were incubated with insulin in the presence of a high glucose concentration (28 mM) there was a significant further decrease in insulin binding compared with that of parallel incubations performed in 5.6 mM glucose. Thus, even in the absence of TRIS buffer, insulin-dependent regulation of the number of binding sites is shown for both human and rat adipocyte tissue in vitro. Although this perturbation could be directly due to hormone-receptor interaction at the membrane level, the finding of rat adipocytes that the ambient glucose concentration can modulate this effect suggests the importance of post-receptor events.     

Sex and insulin sensitivity

To analyze whether enhanced adiposity in females as compared with males is associated with a decreased sensitivity to insulin, a group of healthy normal weight females (n = 13, age 21 ± 1 years) and males (n = 11, age 23 ± 1 year, mean ± SEM) was studied. In each subject, body composition (% fat and % muscle), maximal aerobic power (V_O2 max) and whole body insulin-mediated glucose metabolism were measured. The group of women had a higher percentage of fat to total body weight (P < 0.001) and a lower percentage of muscle (P < 0.001) than the group of men. The higher percentage of fat in women compared with males was due to enhanced peripheral fat accumulation in the arm and thigh regions. V_O2 max levels were comparable in both groups (48 ± 1 mL/kg/min for women, 53 ± 2 mL/kg/min for men, P = NS). The rate of glucose metabolism (M) was comparable in women (8.78 ± 0.74 mg/kg/min), and men (8.31 ± 0.89 mg/kg/min) when expressed per kilogram of total body weight, but when expressed per kilogram of muscle tissue (M_m), it was 45% higher in women (29.4 ± 2.4 mg/kg/min) than in men (20.2 ± 1.6 mg/kg/min, P < 0.005). Partial correlation analysis indicated that the percentage of fat was inversely related to M and M_m in both women (P < 0.05) and men (P < 0.05), but not to percentage of muscle or V_O2 max. Conclusions: (1) Insulin-mediated glucose disposal is inversely related to adiposity in normal weight healthy males and females. (2) Women and men utilize equal amounts of glucose despite a higher adiposity in females. (3) Since muscle tissue utilizes most of intravenously administered glucose, this result indicates enhanced glucose uptake by muscle tissue in females compared with males. (4) Elevated glucose uptake by muscle in women may provide a mechanism by which women are protected against excessive hyperglycemia despite their smaller amount of glucose-consuming tissue.     

Failure of insulin infusion during euglycemia to influence endogenous basal insulin secretion

Despite some evidence of self-regulation of insulin secretion, it is unclear whether endogenous insulin influences insulin secretion independently of blood glucose. The aim of the present study was to examine this question in humans. Seven healthy fasting men were given two-hour porcine insulin infusions (40 mU/min) with and without maintenance of euglycemia (glucose clamp). Intravenous glucose required to maintain basal blood glucose levels (4.2 ± 0.1 mmole/liter) during insulin infusion was 34.3 ± 3.0 gm with a mean rate of 273 ± 29 mg/min in the second hour of insulin infusion. During the glucose clamp, mean C-peptide levels were not significantly altered from fasting levels of 1.91 ± 0.24 ng/ml, but when blood glucose levels fell by approximately 1 mmole/liter, C-peptide fell to 0.37 ± 0.07 ng/ml. Plateau insulin levels were significantly higher during euglycemia than during mild hypoglycemia (53.2 ± 5.6 mU/liter versus 38.5 ± 3.6 mU/liter, P < 0.01). Plasma nonesterified fatty acids were suppressed equally in the two studies. However, a rise in plasma glucagon seen during mild hypoglycemia was absent when euglycemia was maintained. We conclude that insulin self-regulation (either direct or neurally mediated) is not physiologically important in the basal state in normal humans and that the blood glucose-insulin feedback loop dominates in the short-term control of basal insulin secretion.     

Effects of dietary changes on cellular insulin binding and in vivo insulin sensitivity

The effect of a low-sucrose, low-fat diet on insulin sensitivity, insulin binding to monocytes, and insulin secretion in nonketotic diabetic patients was studied. Ten obese diabetics were studied for 1 yr before and during treatment with a 1200–1500-kcal diet, whereas six diabetics of normal weight were studied for 3 mo before and after treatment with a 2200–2400-kcal diet. In the obese group, no change was found in the insulin response to i.v. injection of glucose during treatment (p > 0.1), but the insulin sensitivity was normalized after 1 yr (p < 0.01). The clinical normalization and the improvement of insulin sensitivity were accompanied by a parallel normalization of the binding of insulin to monocytes (p < 0.01). In the group of normal-weight diabetics, both the insulin sensitivity (p < 0.05) and the insulin binding to monocytes (p < 0.05) were normalized after a 3-mo treatment period, but the insulin secretion increased (p < 0.05) without reaching normal values. We conclude that most nonketotic diabetic patients can be controlled by diet treatment alone. The mechanism of action of the low-fat, low-sucrose diet seems for the greatest part to be a normalization of the insulin sensitivity, which is partly caused by a normalization of the cellular insulin binding.     

Suppression of basal, but not of glucose-stimulated insulin secretion by human insulin in healthy and obese hyperinsulinemic subjects

To evaluate the suppressive effect of biosynthetic human insulin (BHI; 2.5 U/m2 . h) on basal and glucose-stimulated insulin secretion in healthy and obese hyperinsulinemic subjects, the plasma C-peptide response was measured during maintenance of euglycemia and hyperglycemia by means of the glucose clamp technique. In five healthy subjects in whom arterial insulin concentration was increased to 94 +/- 8 microU/mL, but euglycemia was maintained at the fasting level. C-peptide concentration fell from 1.3 +/- 1.0 ng/mL by 21 +/- 8% (P less than 0.05). When hyperglycemia of 7 mmol/L above basal was induced by a variable glucose infusion, the C-peptide response was similar in the control (5.0 +/- 0.6 ng/mL) and BHI experiments (4.7 +/- 0.6 ng/mL) and was paralleled by an identical increase in plasma insulin above the prevailing insulin concentration. In seven obese patients plasma C-peptide fell from 3.5 +/- 0.4 to 2.8 +/- 0.5 ng/mL (P less than 0.05) when BHI was infused at the same rate of euglycemia maintained as in the lean subjects. As in healthy subjects, however, the plasma C-peptide response to the hyperglycemic stimulus (8.7 +/- 0.9 ng/mL) was not altered by BHI (7.9 +/- 0.8 ng/mL). Glucose utilization as determined by the glucose infusion rate necessary to maintain the desired glucose level was reduced by half in the obese patients compared with that of normal subjects. From these data we conclude that in healthy as well as obese hyperinsulinemic subjects, insulin at concentrations capable of suppressing its basal secretion fails to suppress its glucose-stimulated secretion.     

Alteration in insulin action: role of IRS-1 serine phosphorylation in the retroregulation of insulin signalling

Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine phosphorylation, PI 3-kinase activity and glucose transport. Recent findings demonstrate that "diabetogenic" factors such as FFA, TNFalpha, hyperinsulinemia and cellular stress, increase the serine phosphorylation of IRS-1 and identified Ser307/612/632 as phosphorylated sites. Moreover, several kinases able to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases and defining the precise role of serine phosphorylation events in IRS-1 regulation represent important goals. Such studies may enable rational drug design to selectively inhibit the activity of the relevant enzymes and generate a novel class of therapeutic agents for type 2 diabetes.     

Closed-loop insulin delivery utilizing pole placement to compensate for delays in subcutaneous insulin delivery

Background

We have previously used insulin feedback (IFB) as a component of a closed-loop algorithm emulating the β cell. This was based on the observation that insulin secretion is inhibited by insulin concentration. We show here that the effect of IFB is to make a closed-loop system behave as if delays in the insulin pharmacokinetic (PK)/pharmacodynamic (PD) response are reduced. We examine whether the mechanism can be used to compensate for delays in the subcutaneous PK/PD insulin response.

Method

Closed-loop insulin delivery was performed in seven diabetic dogs using a proportional-integral-derivative model of the β cell modified by model-predicted IFB. The level of IFB was set using pole placement. Meal responses were obtained on three occasions: without IFB (NONE), reference IFB (REF), and 2xREF, with experiments performed in random order. The ability of the insulin model to predict insulin concentration was evaluated by correlation with the measured profile and results reported as R². The ability of IFB to improve the meal response was evaluated by comparing peak and nadir postprandial glucose and area under the curve (AUC; repeated measures analysis of variance with post hoc test for linear trend).

Results

Insulin concentration was well predicted by the model (median R² = 0.87, 0.79, and 0.90 for NONE, REF, and 2xREF, respectively). Peak postprandial glucose (294 ± 15, 243 ± 21, and 247 ± 16 mg/dl) and AUC (518.2 ± 36.13, 353.5 ± 45.04, and 280.3 ± 39.37 mg/dl·min) decreased with increasing IFB (p < .05, linear trend). Nadir glucose was not affected by IFB (76 ± 5.4, 68 ± 7.3, and 72 ± 4.3 mg/dl; p = .63).

Conclusions

Insulin feedback provides an effective mechanism to compensate for delay in the insulin PK/PD profile.     

Glucosamine-induced insulin resistance in L6 muscle cells

Background:  Glucosamine increases flux through the hexosamine pathway, causing insulin resistance and disturbances similar to diabetic glucose toxicity.
Aim:  This study examines the effect of glucosamine on glucose uptake by cultured L6 muscle cells as a model of insulin resistance.
Methods:  Glucose uptake by L6 myotubes was measured using the non-metabolized glucose analogue 2-deoxy- d -glucose after incubation with glucosamine for 4 and 24 h, with and without insulin and several other agents (metformin, peroxovanadium and d -pinitol) that improve glucose uptake in diabetic states.
Results:  After 4 h, high concentrations of glucosamine (5 × 10⁻³ and 10⁻² M) reduced basal and insulin-stimulated glucose uptake by up to 50%. After 24 h, the effect of insulin was completely abolished by 10⁻² M glucosamine and reduced over 50% by 5 × 10⁻³ M glucosamine. Lower concentrations of glucosamine did not significantly alter glucose uptake. The effect of glucosamine could not be attributed to cytotoxicity assessed by the Trypan Blue test. Metformin, peroxovanadium and d -pinitol, each of which increased glucose uptake by L6 cells, did not prevent the decrease in glucose uptake with glucosamine.
Conclusion:  Glucosamine decreased insulin-stimulated glucose uptake by L6 muscle cells, providing a potential model of insulin resistance with similarities to glucose toxicity. Insulin resistance induced by glucosamine was not reversed by three agents (metformin, peroxovanadium and d -pinitol) known to enhance or partially mimic the effects of insulin.