地特胰岛素联合二甲双胍、那格列奈在门诊血糖控制不佳2型糖尿病患者中的应用

目的观察在门诊的2型糖尿病患者中,使用二甲双胍联合那格列奈控制血糖不佳,不改变口服药,加用每天注射1次地特胰岛素或低精蛋白锌胰岛素,比较两种胰岛素方案的疗效。方法血糖控制不佳的2型糖尿病患者78例,随机分成2组。治疗组为40例,平均年龄（46土9．8）岁,男性25例,女性15例,予联用地特胰岛素治疗;对照组38例,平均年龄（45±8．9）岁,男性22例,女性16例,予联用低精蛋白锌胰岛素,疗程12周。结果各组治疗前后的空腹血糖、餐后2h血糖、糖化血红蛋白（HbAlc）有显著差异俨〈0．05）。治疗后治疗组的空腹血糖由（9,9±1．3）mmol／L降至（6．9±0．9）mmol／L,餐后血糖从（12．2±2．2）mmol／L降至（8．4±0．7）mmol／L,糖化血红蛋白从（8．8±0．5）％降至（6．6±0．9）％。对照组空腹血糖由（9．8±1．2）mmol／L降至（7．0±0．8）mmol／L,餐后血糖从（12．5±2．3）mmol／L降至（8．5±0．6）mmol／L,糖化血红蛋白从（8．7±0．6）％降至（6．7±0．8）％。对照组体质量指数增加,但与治疗组仍无统计学差异。治疗组发生低血糖事件5次,对照组发生低血糖事件11次,治疗组脱落3例（3／40,7．5％）,对照组脱落5例（5／38,13．8％）。结论地特胰岛素联合那格列奈、二甲双胍治疗2型糖尿病,血糖控制达标率提高,不增加体质量,低血糖发生率低,临床使用较安全、放便,患者依丛性高。     

L-赖氨酸对克隆的胰岛β细胞株INS-1E细胞的急性作用

目的:探讨L-赖氨酸刺激INS-1E细胞分泌胰岛素(INS)的作用。方法:INS-1E细胞经传代培养2d后,在Krebs-Ringer缓冲液中37℃培养箱预培养30min,再用含有不同浓度葡萄糖和不同浓度L-赖氨酸的改良Krebs-Ringer缓冲液培养60min,然后留取上清液进行胰岛素测定并用细胞蛋白含量校正胰岛素。结果:在1.1～6.7mmol/L葡萄糖范围内,随着葡萄糖浓度的增加,INS分泌量逐渐增加。L-赖氨酸在0.1～20mmol/L范围促进了葡萄糖刺激的INS-1E细胞的胰岛素分泌,随剂量增大而增强。结论:INS-1E细胞分泌胰岛素随葡萄糖浓度的增加而增加。L-赖氨酸能增加葡萄糖诱导的INS-1E细胞分泌胰岛素的作用。     

Effects of Glimepiride vs Glibenclamide on Ischaemic Heart Disease Risk Factors and Glycaemic Control in Patients with Type 2 Diabetes Mellitus

OBJECTIVE: This study aimed to compare the effects of glimepiride and glibenclamide on glycaemic control and a range of risk factors for ischaemic heart disease (IHD), including concentrations of insulin-like molecules. PATIENTS: A double-blind, placebo-controlled, randomised, crossover comparison of 4 weeks of treatment with glibenclamide 2.5 to 20 mg/day and glimepiride 1 to 8 mg/day was undertaken in 29 type 2 (non-insulin-dependent) diabetic patients. The average (mean +/- SD) duration of diabetes was 8.5 (+/- 5.9) years. RESULTS: Compared with placebo, fasting plasma glucose was significantly lower on both drugs [placebo (P): mean (SD) 11.9 (3.3) mmol/L, glibenclamide: 9.5 (3.2); p < 0.0005, glimepiride: 10.6 (3.4); p = 0.01] and lower on glibenclamide than glimepiride (p = 0.003). The integrated, meal-stimulated rise in glucose was lower with glimepiride, but not glibenclamide, compared with placebo [P: 588.1 (372.2) mmol/L.min, glimepiride: 443.0 (346.9) mmol/L.min; p = 0.010, glibenclamide: 586.4 (366.2) mmol/L.min; p = 0.630]. There was no between-drug difference (p = 0.145). Fasting insulin did not differ compared with placebo [P: 92.3 (61.3) pmol/L, glimepiride: 91.8 (60.6) pmol/L; p = 0.787, glibenclamide: 87.8 (51.6) pmol/L; p = 0.379] and there was no between-drug difference (p = 0.601). There were no significant differences in effect upon fasting concentrations of C-peptide, proinsulin, des 31,32 proinsulin or the ratio of proinsulin-like to total insulin-like molecules. The integrated insulin and C-peptide responses to a meal were significantly greater on both drugs than on placebo [insulin: median (25th, 75th percentile), P: 7073 (2430-18296) pmol/L.min, glibenclamide: 18045 (4290-35850) pmol/L.min; p = 0.0005, glimepiride: 14355 (5880-32820) pmol/L.min; p = 0.0001; C-peptide mean (SD): P: 51.89 (49.01) nmol/L.min, glibenclamide: 90.15 (59.44) nmol/L.min; p = 0.006, glimepiride: 89.75 (61.78) nmol/L.min; p = 0.007], but there was no between-drug difference [integrated insulin (p = 0.923), integrated C-peptide (p = 0.680)]. Compared with placebo, plasminogen activator inhibitor (PAI) antigen was significantly lower on glibenclamide but not glimepiride [P: 28.8 (19.7) microg/L, glimepiride: 24.4 (15.2) microg/L; p = 0.300, glibenclamide: 20.0 (10.9) microg/L; p = 0.003]. PAI activity was similar with all agents, as was low density lipoprotein (LDL)-cholesterol [P: 4.4 (1.2) mmol/L, glimepiride: 4.2 (0.9) mmol/L; p = 0.225, glibenclamide: 4.5 (1.4) mmol/L; p = 0.174]. Corrected for fasting plasma glucose, LDL was 0.5 mmol/L lower on glimepiride than on glibenclamide (95% confidence interval: -0.8, -0.2), a clinically significant difference. There were no significant differences in other measured factors. CONCLUSION: Both drugs improved glycaemia without adversely affecting a range of IHD risk factors.     

Biphasic insulin aspart 30 treatment in patients with type 2 diabetes poorly controlled on prior diabetes treatment: results from the PRESENT study

ABSTRACT

Aim: The safety and efficacy of biphasic insulin aspart (BIAsp30) were evaluated in patients uncontrolled on previous treatment (human insulin ± oral hypoglycaemic agent [OHA] or OHA only) in routine clinical practice.

Methods: This was a large, multi-national, multi-centre, prospective, 6-month study in type 2 diabetes mellitus patients who were prescribed BIAsp30. Changes in glycated haemoglobin (HbA_1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), proportion who achieved target HbA_1c < 7% and rate of hypoglycaemic episodes were assessed. This paper evaluates outcomes in patients by diabetes duration (< 5, 5–10, 10–20 or ≥ 20 years) stratified by prior therapy.

Results: After 6 months of treatment, glycaemia improved significantly across the duration subgroups. The improvement was better in insulin-naïve group versus prior insulin group: HbA_1c decreased ~ 2.2%-points versus ~ 1.6%-points, FPG decreased ~ 4.5?mmol/L versus ~ 2.9?mmol/L and PPPG decreased ~ 6.8?mmol/L versus ~ 5.0?mmol/L. Target HbA_1c was achieved by about one in four patients although insulin-naïve patients achieved this at comparatively lower BIAsp30 dose. Body weight remained relatively unchanged. Hypoglycaemic episodes appeared to be more frequent in the prior insulin group which decreased during the treatment period.

Conclusions: According to this observational study, in clinical practice, initiating or transferring uncontrolled patients to biphasic insulin aspart improved glycaemic control without using a strict insulin algorithm.     

TNF-α inhibition for potential therapeutic modulation of SARS coronavirus infection

ABSTRACT

Objective: To describe and compare the differences in subject characteristics, glycaemic control, diabetes complications, and treatment between 1998 and 2006 in patients with type 2 diabetes.

Research design and methods: Subjects who had been registered for diabetes care at the diabetes clinic (defined as any clinic treating over 100 patients/month) for over 12 months were enrolled. The data were retrospectively reviewed, including diabetes history, treatment regimens and laboratory assessments. HbA_1c was measured at a central laboratory. All data were tabulated and statistical analyses were performed.

Results: The Diabcare studies included 2246 subjects (mean age: 59.7 years) in 1998 and 2702 subjects (mean age: 61.9 years) in 2006. The mean duration of diabetes was 8.2 years in 1998 and 8.7 years in 2006 and mean BMI was 23.8 kg/m² in 1998 and 24.6 kg/m² in 2006. The mean glycaemic control improved significantly from 1998 (8.7 ± 2.0%) to 2006 (7.6 ± 1.6%) and significantly more patients reached HbA_1c < 7% or ≤ 6.5% in 2006. The mean fasting plasma glucose (FPG) values were 9.0 ± 3.4 mmol/L in 1998 and 7.7 ± 2.5 mmol/L in 2006. From 1998 to 2006, cataract, neuropathy and background retinopathy remained the most frequently observed diabetes complications. The percentage of the subjects treated with oral antidiabetic drugs (OADs) alone decreased from ～75% in 1998 to ～50% in 2006, while the proportion of patients on insulin only and on OADs in combination with insulin was greater in 2006 than 1998. The majority of subjects rated their quality of life as good or acceptable in 2006.

Conclusion: Glycaemic control, diabetes therapy and patient care were improved in 2006. However, the gap between therapeutic guidelines and glycaemic control strongly suggests that promoting awareness of treat-to-target treatment and continuing medical education in clinical practice are still needed.     

Clinical potential of insulin therapy in critically ill patients

Stress of critical illness is often accompanied by hyperglycaemia, whether or not the patient has a history of diabetes mellitus. This has been considered to be part of the adaptive metabolic response to stress. The level of hyperglycaemia in patients with acute myocardial infarction (MI) or stroke upon admission to the hospital has been related to the risk of adverse outcome. However, until recently, there was no evidence of a causal relationship and thus stress-induced hyperglycaemia was only treated with exogenous insulin when it exceeded 12 mmol/L (220 mg/dL). In patients with known diabetes, even higher levels were often tolerated. Recently, new data became available in support of another approach. In this review, we focus on the new evidence and the clinical aspects of managing hyperglycaemia with insulin in critically ill patients, drawing a parallel with diabetes management. Particularly, the 'Diabetes and Insulin-Glucose infusion in Acute Myocardial Infarction (DIGAMI) study' and the 'insulin in intensive care study' have provided novel insights. The DIGAMI study showed that in patients with diabetes, controlling blood glucose levels below 12 mmol/L for 3 months after acute MI improves long-term outcome. In the recent study of predominantly surgical intensive care patients, the majority of whom did not previously have diabetes, it was shown that an even tighter control of blood glucose with exogenous insulin, aiming for normoglycaemia, dramatically improved outcome. Indeed, in this large prospective, randomised, controlled study, 1548 intensive care patients had been randomly allocated to either the conventional approach, with insulin infusion started only when blood glucose levels exceeded 12 mmol/L, or intensive insulin therapy, with insulin infused to maintain blood glucose at a level of 4.5-6.1 mmol/L (80-110 mg/dL). Intensive insulin therapy reduced intensive care mortality by more than 40% and also decreased a number of morbidity factors including acute renal failure, polyneuropathy, ventilator-dependency and septicaemia. Future studies will be needed to further unravel the mechanisms that explain the beneficial effects of this simple and cost-saving intervention. Although available evidence supports implementation of intensive insulin therapy in surgical intensive care, the benefit for other patient populations, such as patients on medical intensive care units or hospitalised patients who do not require intensive care but who do present with stress-induced hyperglycaemia, remains to be investigated.     

The effects of insulin glargine treatment and an educational programme on glycaemic control in type 2 diabetes patients in clinical practice

OBJECTIVE: This retrospective analysis was performed to establish the effect of initiating insulin glargine (LANTUS; sanofi-aventis, Paris, France), a once-daily basal insulin analogue, in combination with an educational programme on glycaemic control and body weight in sub-optimally controlled patients with Type 2 diabetes in clinical practice. RESEARCH DESIGN AND METHODS: We undertook a retrospective review of the medical records of 46 patients (mean age 61.5 +/- 8.6 years) with Type 2 diabetes. These patients had previously been treated with oral antidiabetic agents (OADs; n = 18) or insulin only (n = 28) and had then received insulin glargine in combination with OADs or prandial insulin, for 30 months. Records of metabolic control and body weight data were analysed at 9 and 30 months. Patients had taken part in a diabetes educational programme before initiation of insulin glargine and received continued physician consultations throughout. RESULTS: Following initiation of insulin glargine, patients showed a significant decrease in HbA1c from 8.14 +/- 1.7% to 7.18 +/- 0.9% at 30 months (p < 0.001). When the results were analysed by pre-treatment, patients pre-treated with OADs showed a reduction in HbA1c of 2.3% at 30 months (p < 0.001), while patients pre-treated with insulin only showed a decrease in HbA1c of 0.4% (p < 0.005). There was no significant change in body weight. No unexpected adverse events or episodes of severe hypoglycaemia (blood glucose < 40 mg/dL [< 2.2 mmol/L]) occurred. CONCLUSIONS: Insulin glargine in combination with educational support and close clinical supervision significantly improved metabolic control without significant weight change in patients with Type 2 diabetes in clinical practice over 30 months. Additional studies are required to establish if similar results can be obtained in a larger cohort of patients.     

Insulin clearance from plasma in type I (insulin-dependent) diabetic patients: influence of glycaemic level

The influence of the actual glycaemic level on the kinetics of insulin disappearance from plasma was studied in 16 type I diabetic patients. Constant intravenous infusion of insulin (1-5 mU.kg-1.min.-1) was used to achieve different levels of steady state plasma free insulin concentrations, while the blood glucose level was clamped at normoglycaemia, 4.1 +/- 0.1 mmol/l (mean +/- S.E.M.), and mild hyperglycaemia, 8.2 +/- 0.1 mmol/l. The experimentally determined data were compared using a previously validated model of first order kinetics for insulin disappearance from plasma in diabetic patients. At the physiological insulin concentration range the median clearance rate of insulin was 23 ml.kg-1.min-1 (range 16-26) at normoglycaemia and 23 ml.kg-1.min-1 (19-35) at hyperglycaemia (P = 0.45). At supraphysiological levels, insulin was cleared at a lower rate at normoglycaemia than at hyperglycaemia. No correlation was observed between the insulin clearance rate and the duration of diabetes or the haemoglobin A1C level (both Spearman's rho = 0.08). In conclusion, the insulin clearance rate from plasma is independent of the actual glycaemic level and hardly influenced by the long-term glycaemic level in type I diabetic patients.     

胰岛素吸入粉雾剂的体外沉降及大鼠体内吸收促进剂的药效学评价

目的采用喷雾干燥法制备胰岛素吸入粉雾剂，对吸入粉雾剂体外沉降性质进行考察，并对其吸收促进剂在大鼠体内的药效学进行初步研究。方法采用中国药典(2000版)附录XH的装置测定粉末的体外有效部位沉积量，以葡糖氧化酶法（GOD-PAP法）测定大鼠的血糖浓度来评价其降血糖效果。结果喷雾干燥法制得的胰岛素吸收粉雾剂沉积量在各湿度下均大于40％，在气流量≥18 L·min^-1的情况下其有效部位沉积量变化不大。8 mmol·L^-1/dose牛黄胆酸钠［PA=59.91%,C_nadir=(33±6)%］和10 mmol·L^-1/dose去氧胆酸钠［PA=47.46%，C _nadir=(32±7)%］对胰岛素肺部吸收促进作用明显。而1%辛酸钠、1%十二烷基硫酸钠、250 μg/dose卵磷脂和10 mmol·L^-1/dose EDTA并未显示明显效果。结论制得的胰岛素吸收粉雾剂沉积量受湿度影响小，环境湿度依赖性和吸气流量依赖性小。8 mmol·L^-1/dose牛黄胆酸钠和10 mmol·L^-1/dose去氧胆酸钠可有效促进胰岛素干粉吸入剂的降血糖效果。     

L-丙氨酸对INS-1E细胞胰岛素分泌功能的影响

目的:探讨L-丙氨酸对胰岛B细胞株INS-1E细胞分泌胰岛素(INS)的刺激作用及其葡萄糖依赖性。方法:INS-1E细胞经传代培养2d后,在Krebs-Ringer缓冲液中于37°C培养箱预培养30min,再在含相同浓度葡萄糖、不同浓度L-丙氨酸(观察剂量依赖性)和不同浓度葡萄糖、相同浓度L-丙氨酸(观察葡萄糖依赖性)的改良Krebs-Ringer缓冲液培养60min,留取上清液进行胰岛素测定。结果:L-丙氨酸在0.1～20mmol/L范围促进了葡萄糖(16.7mmol/L)诱导的INS-1E细胞的胰岛素分泌,随剂量增大而增强;在1.1～25mmol/L葡萄糖范围内,随着葡萄糖浓度的增加,INS分泌量逐渐增加。在1.1～3.3mmol/L葡萄糖的情况下,10mmol/LL-丙氨酸未显示增加胰岛素分泌的作用;在6.7～25mmol/L葡萄糖范围内,10mmol/LL-丙氨酸显著促进了葡萄糖诱导的胰岛素分泌。结论:在高血糖状态下,随着L-丙氨酸浓度的增加,INS-1E细胞分泌胰岛素量逐渐增加。L-丙氨酸促进INS-1E细胞分泌胰岛素的作用依赖于一定水平的葡萄糖。     

Pioglitazone is effective therapy for elderly patients with type 2 diabetes mellitus

BACKGROUND: Pioglitazone as monotherapy and in combination with sulfonylurea, metformin, or insulin has consistently demonstrated improved glycaemic and lipid parameters in patients with type 2 diabetes mellitus. OBJECTIVE: We performed a subanalysis to examine the effect of pioglitazone on glycaemia and lipids in patients <65 and > or =65 years of age in two double-blind, placebo-controlled monotherapy studies and in three separate multi-centre trials. METHOD: In Study 1, 197 patients were randomised to receive pioglitazone 30 mg/day or placebo for 16 weeks. Study 2 was a forced dose-titration trial in patients randomised to receive pioglitazone 7.5/15/30 mg/day, pioglitazone 15/30/45 mg/day, or placebo daily for 26 weeks. Each of the lower dosages was given for at least 4 weeks and the highest dosage for 16 weeks. The three combination studies evaluated efficacy of pioglitazone 30 or 45 mg/day over a 24-week period in combination with sulfonylureas, metformin, or insulin. RESULTS: In both placebo-controlled monotherapy studies, at 16 weeks, and at maximum pioglitazone dosage, 0.53-0.55% and 0.57-1.27% mean reductions from baseline in glycosylated haemoglobin (HbA(1c)) were seen in patients aged <65 (n = 225) and > or =65 (n = 45) years, respectively. There were statistically significant differences between the placebo and pioglitazone groups in each age cohort. Similar effects were observed in fasting plasma glucose (FPG) levels, with 2.03-2.59 mmol/L and 3.20-4.44 mmol/L mean reductions from baseline, respectively, which were significantly different from the changes in the placebo group, but there was no difference between pioglitazone groups. At treatment endpoint in combination trials, pioglitazone added to sulfonylurea produced a mean decrease in HbA(1c) of 0.78-1.61%, and 1.64-1.96% in patients aged <65 (n = 557) and > or =65 (n = 115) years, respectively. Pioglitazone added to metformin produced a mean decrease in HbA(1c) of 0.78-1.03% and 0.78-0.98% in patients aged <65 (n = 686) and > or =65 (n = 112) years, respectively. Pioglitazone added to insulin produced a mean decrease in HbA(1c) of 1.13-1.37% and 1.39-1.66% in patients aged <65 (n = 500) and > or =65 (n = 156) years, respectively. In patients aged > or =65 years, hypoglycaemia was observed in 1 of 14 patients and in 0 of 13 patients in the two monotherapy studies. In the combination studies, the incidence of hypoglycaemia among patients aged > or =65 years was as follows: 26.7-28.8% combined with sulfonylurea; 0-4.4% combined with metformin; and 53.4-56.4% combined with insulin. CONCLUSION: Pioglitazone monotherapy, or added to a sulfonylurea, metformin, or insulin demonstrated no significant differences in effectiveness while exhibiting similar adverse events in patients aged > or =65 years compared with patients aged <65 years. Well-controlled randomised clinical trials are recommended to confirm the impact of pioglitazone therapy on the glycaemic and lipid control in elderly patients with type 2 diabetes.     

Insulin infusion therapy for myocardial infarction

In the last 10 years, there has been considerable interest in the administration of insulin as part of the management of myocardial infarction. This review examines the clinical trials of insulin infusion for myocardial infarction in the era of reperfusion therapy, and discusses the implications of the recently completed HI-5 (Hyperglycaemia: Intensive Insulin Infusion In Infarction) study. The clinical trials of insulin therapy for myocardial infarction can be divided into those with a primary aim of delivering insulin (insulin focus), and those with a primary aim of achieving tight glycaemic control (glycaemia focus). The evidence suggests that protocols with an insulin focus do not improve the outcome of myocardial infarction. However, the trials with a glycaemia focus are inconclusive and it remains possible that glycaemic control is beneficial.     

Insulin infusion therapy for myocardial infarction

In the last 10 years, there has been considerable interest in the administration of insulin as part of the management of myocardial infarction. This review examines the clinical trials of insulin infusion for myocardial infarction in the era of reperfusion therapy, and discusses the implications of the recently completed HI-5 (Hyperglycaemia: Intensive Insulin Infusion In Infarction) study. The clinical trials of insulin therapy for myocardial infarction can be divided into those with a primary aim of delivering insulin (insulin focus), and those with a primary aim of achieving tight glycaemic control (glycaemia focus). The evidence suggests that protocols with an insulin focus do not improve the outcome of myocardial infarction. However, the trials with a glycaemia focus are inconclusive and it remains possible that glycaemic control is beneficial.     

Effect of caffeine on response of rabbit isolated corpus cavernosum to high K+ solution, noradrenaline and transmural electrical stimulation

1. Caffeine has wide-ranging activities on smooth muscles, including contractile and relaxant effects. The aim of the present study was to examine the activity of caffeine on rabbit corpus cavernosum (RCC). 2. The effects of caffeine (0.5-4.0 mmol/L) on the response of RCC to high K+ solution, noradrenaline (NA) and transmural electrical stimulation (EFS) were studied in a tissue bath system. 3. Caffeine did not contract the RCC. However, 0.5-4.0 mmol/L caffeine caused concentration-dependent relaxation of tension development in high-K+ (120 mmol/L) solution in contrast with the solvent control. At 4.0 mmol/L caffeine, high-K+ solution-induced tone of the RCC was reduced by 73.4 +/- 7.3%. Caffeine (0.5-4.0 mmol/L) also concentration-dependently relaxed NA (12.5 micro mol/L)-induced tonic contraction of the RCC. At 4.0 mmol/L caffeine, NA-induced tone of the RCC was reduced by 41.1 +/- 7.0%. Incubation of RCC in 2.0 mmol/L caffeine for 30 min prior to EFS (1-40 Hz) caused a marked rightward shift in the frequency-response curve. 4. The results of the present study suggest that caffeine exhibits relaxant activity on rabbit cavernosal smooth muscle and the mechanism of this activity possibly involves inhibition of Ca2+ signalling.     

门冬胰岛素与人正规胰岛素对不规律进食老年2型糖尿病患者血糖影响的研究

目的：研究门冬胰岛素与人正规胰岛素对不规律进食老年2型糖尿病患者血糖的影响。方法：2006年2月至2007年4月老年2型糖尿病患者共33例[男性18例，女性15例，平均年龄（65．82±2．85）岁]被纳入研究，先后用方案A和方案B治疗，各4个月。方案A：三餐前30min皮下注射人正规胰岛素＋睡前皮下注射人低精蛋白锌胰岛素；方案B：三餐后10～15min皮下注射门冬胰岛素＋睡前皮下注射人低精蛋白锌胰岛素。每周检测2次空腹血糖（FBG）和早、午、晚餐后2h血糖；并对患者低血糖发生次数及其严重程度、糖化血红蛋白（HbA1c）变化进行对比观察。结果：患者的FBG和早、午、晚餐后2h血糖，在方案A治疗期间分别为（7．37±4．22）mmol／L、（9．73±3．38）mmol／L、（10．23±3．96）mmol／L和（10．85±3．36）mmol／L，在方案B治疗期间分别为（7．01±1．74）mmol／L、（9．23±1．58）mmol／L、（9．22±1．28）mmol／L和（9．76±1．32）mmol／L，差异有统计学意义（均P〈0．01）；方案B较方案A的餐后血糖波动幅度明显降低；治疗前后HbA1c的差值在方案A、B分别为（3．08±0．96）％和（3．37±0．47）％（P〈0．01）；低血糖发生次数及中重度低血糖发生率，在方案A治疗中分别为68例次及36．7％，在方案B治疗中分别为21例次及19．05％，差异有统计学意义（P〈0．001）。结论：门冬胰岛素餐后皮下注射可有效降低老年2型糖尿病患者的血糖，减小餐后血糖波动幅度，减少低血糖的发作次数并降低其严重程度，对不规律进食的老年糖尿病患者安全有效。     

二甲双胍在慢性高胰岛素处理的Hep G2细胞对胰岛素受体后信号转导的调节作用(英文)

目的:研究慢性高胰岛素对胰岛素受体后信号转导的影响及其与胰岛素抵抗的关系,并探讨二甲双胍治疗胰岛素抵抗是否通过胰岛素信号转导途径的介导。方法:人类肝癌细胞系(Hep G2)在无血清条件下首先与100nmol/L高浓度胰岛素预温育16h以产生胰岛素抵抗细胞模型,并观察不同浓度(0.01-10mmol/L)的二甲双胍对胰岛素受体后磷酯酰肌醇3激酶(PI3K)途径信号转导的影响。结果:高浓度胰岛素100nmol/L慢性处理引起了IRβ、IRS1和IRS2的酪氨酸磷酸化和蛋白表达水平的下调,p85与IRS的相互作用也有显著降低。生理治疗浓度的(0.01-0.1mmol/L)二甲双胍逆转了这种慢性高胰岛素引起的信号下调,细胞用0.1mmol/L二甲双胍预温育后,IRB、IRS1和IRS2的磷酸化反应水平分别增加了2.7倍(P<0.01),6.8倍(P<0.01)和2.3倍(P<0.01),p85与IRS1的相互作用从34％增加至86％(P<0.01),与IRS2的相互作用从30％增加至92％(P<0.01)。相反,药物浓度(1-10mmol/L)的二甲双胍进一步抑制了IRB、IRS的磷酸化及IRS与p85的相互作用。结论:高浓度胰岛素慢性处理可引起胰岛素受体后PI3K途径信号转导的下调,二甲双胍对胰岛素信号转导的作用可能是其治疗胰岛素抵抗的主要分子机制。     

Severe hypoglycemia in an elderly patient treated with metformin

The following case of severe hypoglycemia was reported during a systematic evaluation of hospital admissions caused by adverse drug reactions (supported by BfArM). HISTORY AND FINDINGS ON ADMISSION: A 79-year-old diabetic woman was admitted to hospital in a stuporous and unresponsive state. The initial physical examination revealed no other abnormal findings. Serum blood glucose was found to be 2.0 mmol/l and HbA1c was 4.6%. The patient had been started on antidiabetic therapy with metformin 2 months earlier. Treatment with other drugs being taken at that time, an ACE inhibitor, an NSAID and nitrofurantoin, remained unchanged. DIAGNOSIS, TREATMENT AND FOLLOW-UP: Laboratory tests excluded lactic acidosis and renal insufficiency. Cerebral computed tomography findings were normal. The patient improved dramatically following administration of glucose. Other laboratory findings confirmed the diagnosis of hypoglycemia. Blood glucose concentrations ranged between 4.0 and 10.0 mmol/l in the subsequent days and the patient could be discharged in full health. CONCLUSIONS: Drug-induced hypoglycemia is possible even in diabetics not receiving insulin or oral antidiabetic agents increasing insulin secretion. The risk of drug-induced hypoglycemia should be particularly considered when drugs containing blood glucose-lowering components are combined. Metformin does not usually cause hypoglycemia when administered as monotherapy. We suspected that hypoglycemia in this patient was caused by additional blood glucose-lowering effects of the ACE inhibitor and the NSAID possibly combined with a suboptimal nutrition. The indications for metformin administration undergo critical scrutiny.     

Similar effects of succinic acid dimethyl ester and glucose on islet calcium oscillations and insulin release

The relative contribution of glycolysis vs. oxidative metabolism to the stimulus secretion coupling mechanism of beta-cells was investigated in isolated islets. For that purpose, the secretory and intracellular calcium responses of islets to both glucose and succinic acid dimethyl ester (SAD) were compared. After 45 min of rat islet perifusion in the absence of substrates, the maximum secretory responses to glucose (20 mmol/L) and SAD (10 mmol/L) were qualitatively and quantitatively indistinguishable. Malonic acid dimethyl ester (a permeable citric acid cycle inhibitor) suppressed the insulin secretory response to both 20 mmol/L glucose and 10 mmol/L SAD (-70% on average). The inhibitor decreased within 70% the rate of 14CO2-production from 10 mmol/L [2-(14)C]pyruvate without affecting the rate of 20 mmol/L D-[5-(3)H]glucose utilization. Both, 11.1 mmol/L glucose and 10 mmol/L SAD, elevated the intracellular calcium concentration and induced a similar pattern of oscillations that were rapidly ablated by 20 mmol/L malonic acid dimethyl ester. However, the intracellular concentration of calcium declined to basal values several minutes after the introduction of the inhibitor in the presence of SAD whereas it remained elevated in the case of glucose. In conclusion: (1) An exclusive increase of mitochondrial metabolism in pancreatic islets was sufficient to mimic the effects of glucose on intracellular calcium and insulin secretion. (2) Islet glycolysis and/or the re-oxidation of cytoplasmic NADH allowed the maintenance of an elevated, though non-oscillating, intracellular calcium concentration, but a reduced response to glucose.     

Hospital pharmacists' role in type 2 diabetes management

Non insulin dependent diabetes mellitus is strongly influenced by environmental and lifestyle factors Fifty patients with haemoglobin A1c higher than 8 per cent and one or more diabetic complications were given education and counselling and their HbA1c values were reviewed every three months The patients' mean fasting blood glucose level fell from 13.6 to 7.5mmol/L and their mean haemoglobin A1c level fell from 13.6 to 8.3 per cent, demonstrating a significant improvement in glycaemic control Patients showed increased self‐esteem and motivation towards diabetes management, increased satisfaction, responsive service, improved health, and more public awareness The study shows that pharmacist‐led educational programmes for diabetes patients can have a significant impact on glycaemic control and improve patients' understanding and their quality of life