安立泽联合胰岛素治疗单独胰岛素降糖欠佳的高龄 2 型糖尿病患者临床观察

目的：观察安立泽应用于单独胰岛素治疗血糖控制欠佳的高龄2 型糖尿病患者的疗效及安全性。方法：200 例高龄2型糖尿 病胰岛素降糖欠佳的患者（空腹血糖控制在7.8-13.9mmol/L范围内）,随机分成对照组和治疗组,对照组采用胰岛素加安慰剂治 疗80 例;治疗组120 例,分为A、B、C三组,每组40 例,A、B、C三组分别在继续应用胰岛素治疗的基础上加服安立泽4mg/d、 5mg/d、6mg/d,疗程三个月。观测治疗组和对照组治疗前后FPG 及PPG、HbA1C、BMI 和胰岛素用量的改变及治疗的安全性。结 果：对照组和治疗组治疗前的各指标无明显差异（P＞0.05）;A、B、C三组在治疗后1 个月和3 个月FPG、PPG、HbA1C均有明显的 下降（P＜0.05,P＜0.01）,而对照组治疗前后FIG、PPG、HbA1C 略有下降,差异不明显（P＞0.05）;A、B、C 三组胰岛素的用量及体 重指数较治疗前均略有下降,三组间无显著性差异;对照组和治疗组的不良反应发生率无显著差异。结论：对高龄2 型糖尿病单 用胰岛素治疗血糖控制欠佳的患者,加用安立泽治疗,可使糖尿病相关指标得以良好的控制,减少糖尿病患者每日胰岛素用量, 临床毒副作用较小。     

安立泽联合胰岛素治疗单独胰岛素降糖欠佳的高龄2型糖尿病患者临床观察

目的：观察安立泽应用于单独胰岛素治疗血糖控制欠佳的高龄2型糖尿病患者的疗效及安全性。方法：200例高龄2型糖尿病胰岛素降糖欠佳的患者（空腹血糖控制在7．8．13．9mmol／L范围内）,随机分成对照组和治疗组,对照组采用胰岛素加安慰剂治疗80例;治疗组120例,分为A、B、c三组,每组40例,A、B、c三组分别在继续应用胰岛素治疗的基础上加服安立泽4mg／d、5mg／d、6mg／d,疗程三个月。观测治疗组和对照组治疗前后FPG及PPG、HbAlC、BMI和胰岛素用量的改变及治疗的安全性。结果：对照组和治疗组治疗前的各指标无明显差异（P〉0．05）;A、B、c三组在治疗后1个月和3个月FPG、PPG、H1）A1C均有明显的下降（P〈0．05,P〈0．01）,而对照组治疗前后FIG、PPG、HbAlC略有下降,差异不明显（P〉0．05）;A、B、c三组胰岛素的用量及体重指数较治疗前均略有下降,三组间无显著性差异;对照组和治疗组的不良反应发生率无显著差异。结论：对高龄2型糖尿病单用胰岛素治疗血糖控制欠佳的患者,加用安立泽治疗,可使糖尿病相关指标得以良好的控制,减少糖尿病患者每日胰岛素用量,临床毒副作用较小。     

New developments in the treatment and monitoring of type 1 diabetes mellitus

In recent years, insulin analogues are the benefits of the use in functional intensive insulin therapy for the treatment of diabetes. Shortacting insulin (lispro, aspart and glulisine) and long-acting insulin (glargine and detemir) have been developed for the management of diabetes. Short-acting insulin analogues are an alternative to regular human insulin before meals. These new short-acting insulin analogues show more rapid onset of activity and a shorter duration of action. As a result of these pharmacokinetic differences, an improved postprandial glycemic control is achieved, without increasing the risk of hypoglycemia. In addition, these insulin analogues can be administered immediately before a meal. The long-acting insulin analogues provide basal insulin levels for 24 h when administered once (glargine) or two (detemir) daily. Compared with previous intermediate- or long-acting conventional insulin, these insulins shows a flat profile of plasma insulin levels . The use of these long-acting insulin analogues appears to be associated with a reduced incidence of hypoglycemia, especially at night. The availability of these new insulin analogues has the potential to significantly improve long-term control over blood glucose in diabetic patients. In recent years more and more frequently the method of multiple daily injections (MDI) of insulin is being replaced by the method of continuous subcutaneous insulin infusion (CSII). It is the most physiological way to administer insulin. In recent years treatment with insulin pumps has been used more frequently in the pediatric patients and in the treatment of diabetes in pregnancy. Use of continuous glucose monitoring systems enables detection of glycemia fluctuations unrevealed by selfmonitoring of blood glucose, such as night hypoglycemias and early postprandial hyperglycemias. Real-time systems allow to reduce HbA1c levels and limit number of excursions. Non-invasive glucose measurement devices are introduced. Fully automated continuous glucose monitoring systems integrated with insulin pumps operating in closed-loop model, requiring no patient assistance, are still being researched. Commercially available systems operate in open-loop model, where the patient has to decide on administration and dose of insulin.     

Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial.

Alpha-lipoic acid (ALA), a naturally occuring compound and a radical scavenger was shown to enhance glucose transport and utilization in different experimental and animal models. Clinical studies described an increase of insulin sensitivity after acute and short-term (10 d) parenteral administration of ALA. The effects of a 4-week oral treatment with alpha-lipoic acid were evaluated in a placebo-controlled, multicenter pilot study to determine see whether oral treatment also improves insulin sensitivity. Seventy-four patients with type-2 diabetes were randomized to either placebo (n = 19); or active treatment in various doses of 600 mg once daily (n = 19), twice daily (1200 mg; n = 18), or thrice daily (1800 mg; n = 18) alpha-lipoic acid. An isoglycemic glucose-clamp was done on days 0 (pre) and 29 (post). In this explorative study, analysis was done according to the number of subjects showing an improvement of insulin sensitivity after treatment. Furthermore, the effects of active vs. placebo treatment on insulin sensitivity was compared. All four groups were comparable and had a similar degree of hyperglycemia and insulin sensitivity at baseline. When compared to placebo, significantly more subjects had an increase in insulin-stimulated glucose disposal (MCR) after ALA treatment in each group. As there was no dose effect seen in the three different alpha-lipoic acid groups, all subjects receiving ALA were combined in the "active" group and then compared to placebo. This revealed significantly different changes in MCR after treatment (+27% vs. placebo; p < .01). This placebo-controlled explorative study confirms previous observations of an increase of insulin sensitivity in type-2 diabetes after acute and chronic intravenous administration of ALA. The results suggest that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type-2 diabetes. The encouraging findings of this pilot trial need to be substantiated by further investigations.     

Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised,double blind,placebo controlled trial (the DIABHYCAR study)

Objective To investigate whether a low dose of the angiotensin converting enzyme (ACE) inhibitor ramipril lowers cardiovascular and renal events in patients with type 2 diabetes who have microalbuminuria or proteinuria.Design Randomised, double blind, parallel group trial comparing ramipril (1.25 mg/day) with placebo (on top of usual treatment) for cardiovascular and renal outcomes for at least three years.Setting Multicentre, primary care study conducted mostly by general practitioners in 16 European and north African countries.Participants 4912 patients with type 2 diabetes aged >50 years who use oral antidiabetic drugs and have persistent microalbuminuria or proteinuria (urinary albumin excretion ≥ 20 mg/l in two consecutive samples), and serum creatinine ≤ 150 μmol/l.Main outcome measures The primary outcome measure was the combined incidence of cardiovascular death, non-fatal myocardial infarction, stroke, heart failure leading to hospital admission, and end stage renal failure.Results Participants were followed for 3 to 6 (median 4) years. There were 362 primary events among the 2443 participants taking ramipril (37.8 per 1000 patient years) and 377 events among the 2469 participants taking placebo (38.8 per 1000 patient years; hazard ratio 1.03 (95% confidence interval 0.89 to 1.20, P = 0.65)). None of the components of the primary outcome was reduced. Ramipril lowered systolic and diastolic blood pressures (by 2.43 and 1.06 mm Hg respectively after two years) and favoured regression from microalbuminuria (20-200 mg/l) or proteinuria (> 200mg/l) to normal level (< 20 mg/l) or microalbuminuria (P < 0.07) in 1868 participants who completed the study.Conclusions Low dose (1.25 mg) ramipril once daily has no effect on cardiovascular and renal outcomes of patients with type 2 diabetes and albuminuria, despite a slight decrease in blood pressure and urinary albumin. The cardiovascular benefits of a daily higher dose (10 mg) ramipril observed elsewhere are not found with an eightfold lower daily dose.     

Comparison of human versus porcine insulin in treatment of diabetes in children.

The blood glucose control obtained when using semi-synthetic monocomponent human insulin (insulin A) was compared with that using standard monocomponent porcine insulin (insulin B) in 14 children in a double blind crossover study. At the start of the study age, duration of diabetes, insulin dose, and daily carbohydrate intake were the same in both groups. After a one month run in period of standard treatment with porcine insulin the children were randomly divided into group 1 (three months of insulin A followed by three months of insulin B) and group 2 (three months of insulin B followed by three months of insulin A). During each treatment period blood glucose control was assessed by clinical symptoms, glycosylated haemoglobin, and home blood glucose monitoring. Although a significant difference in the period after lunch during 24 hour blood glucose profiles suggested a shorter onset time and faster peak action time of human insulin, no significant difference in the overall diabetic control was seen between the two types of insulin. There was a trend towards improved blood glucose control (irrespective of insulin) as the trial progressed. No clinical reactions to human insulin occurred, and there was no significant difference in the daily insulin dose between porcine and human insulin.     

Lispro insulin and metformin versus other combination in the diabetes mellitus type 2 management after secondary oral antidiabetic drug failure

The purpose of the study was to find out differences between treatments of diabetes type 2 after secondary oral antidiabetic drug failure. Three different methods of treatment were compared: lispro insulin in combination with metformin, glimepiride and metformin combination or two daily doses of biphasic insulin 30/70 together with bed-time NPH insulin. The study included 87 patients with diabetes mellitus type 2 randomly distributed into 3 different treatment groups. Fasting and postprandial glucose were analyzed by enzymatic colorimetric method and HbA1c was measured by ion exchange chromatography. HbA1c significantly decreased in all three study groups. The decrease was mostly expressed among patients treated with lispro and metformin. When focused on postprandial glucose control, antihyperglycemic metformin and insulin lispro therapy has greater impact on the overall metabolic control (decrease in level of HbA1c) in comparison with the above mentioned more traditional approaches.     

Suppression of overt diabetes in NOD mice by anti-thymocyte serum or anti-Thy 1, 2 antibody

Effects of anti-thymocyte serum (ATS) and anti-Thy 1, 2 monoclonal antibody on the spontaneously occurring diabetes in NOD mice were examined. Spontaneous diabetes in female mice was markedly suppressed by intravenous injection of rabbit anti-mouse thymocyte serum diluted to 1:4 on three consecutive days during the time period from 70 to 100 days after birth; the cumulative incidence of overt diabetes upto 195 days of age was greatly reduced and the onset of diabetes was delayed. Similar effect was observed with anti-Thy 1, 2 antibody treatment. These findings suggest that T lymphocytes play a role in the production of spontaneous diabetes in this mouse strain.     

Type 2 diabetes in childhood: the American perspective

The incidence of type 2 diabetes mellitus is steadily escalating throughout the world in people from a wide range of ethnic groups and all social and economic levels. Type 2 diabetes is no longer a disease only of adults: parallel with the global epidemic of type 2 diabetes in adults, an 'emerging epidemic' of type 2 diabetes has been observed in youth over the last decade. Research and clinical experience in adults have established that insulin resistance is a major risk factor for type 2 diabetes. However, insulin resistance alone is not sufficient to cause diabetes, which will develop only when insulin secretion by the beta-cells fails. This review discusses the recent emergence of type 2 diabetes in children and adolescents, its risk factors, pathophysiologic mechanisms and treatment modalities.     

沙格列汀联合二甲双胍对2型糖尿病的疗效与安全性分析

目的:探讨沙格列汀联合二甲双胍对2型糖尿病的疗效与安全性。方法:选取200例2型糖尿病患者,按随机数字表法分为两组,沙格列汀组(102例)口服沙格列汀联合二甲双胍治疗,阿卡波糖组(98例)口服阿卡波糖联合二甲双胍治疗。通过观察并记录治疗前后糖代谢情况与体重指数水平,SF-36量表各项评分,治疗期间不良反应情况,评价沙格列汀联合二甲双胍对2型糖尿病的疗效与安全性。结果:治疗后,两组HbAlc,BMI,FBG,2hPBG水平均明显下降(P0.05),且沙格列汀组患者HbAlc,BMI,FBG,2 hPBG水平明显低于阿卡波糖组(P0.05);治疗后3个月两组患者SF-36表各项评分均明显提高(P0.05),但两组间差异没有统计学意义(P0.05);随访期间,两组不良反应率相比,差异没有统计学意义(P0.05)。结论:沙格列汀联合二甲双胍可以明显控制患者血糖水平,减轻患者体重,提高患者生活质量用药安全性好,值得临床推广使用。     

Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice

Human acatalasemia may be a risk factor for the development of diabetes mellitus. However, the mechanism by which diabetes is induced is still poorly understood. The impact of catalase deficiency on the onset of diabetes has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of diabetogenic alloxan. The incidence of diabetes was higher in acatalasemic mice treated with a high dose (180 mg/kg body weight) of alloxan. A higher dose of alloxan accelerated severe atrophy of pancreatic islets and induced pancreatic β cell apoptosis in acatalasemic mice in comparison to wild-type mice. Catalase activity remained low in the acatalasemic pancreas without the significant compensatory up-regulation of glutathione peroxidase or superoxide dismutase. Furthermore, daily intraperitoneal injection of angiotensin II type 1 (AT1) receptor antagonist telmisartan (0.1 mg/kg body weight) prevented the development of alloxan-induced hyperglycemia in acatalasemic mice. This study suggests that catalase plays a crucial role in the defense against oxidative-stress-mediated pancreatic β cell death in an alloxan-induced diabetes mouse model. Treatment with telmisartan may prevent the onset of alloxan-induced diabetes even under acatalasemic conditions.     

肠道菌群在2型糖尿病并发抑郁症中的作用探析

抑郁症作为2型糖尿病常见并发症,不仅严重危害人体的健康,而且增加了疾病的治疗难度。临床中对于本病的治疗通常将二者分开,采用降糖与抗抑郁联合的方法,却忽视了抑郁症作为2型糖尿病的并发症,两者必定存在内在联系。研究表明,2型糖尿病患者肠道菌群存在明显失衡,而肠道菌群与抑郁症的发生密切相关,因此肠道菌群可能在2型糖尿病并发抑郁症中起着重要作用,本文通过论述三者的关系,认为肠道菌群失调可能是糖尿病并发抑郁症的关键因素,提出肠道菌群可能是干预2型糖尿病并发抑郁的新靶点,以期为2型糖尿病并发抑郁症的治疗提供新的途径。     

Effectiveness of intensive insulin therapy by multiple daily injections and continuous subcutaneous infusion: a comparison study in type 2 diabetes with conventional insulin regimen failure.

OBJECTIVE: To compare the effectiveness of two intensified insulin regimens, i.e., pump delivery versus multiple daily injections in patients with type 2 diabetes not optimally controlled with conventional insulin therapy. RESEARCH DESIGN AND METHODS: Seventeen type 2 diabetes patients uncontrolled by two daily injections of regular plus NPH were randomly assigned in a cross-over fashion to either three daily injections of lispro plus NPH or pump device delivering lispro. HbA1c, 6 points capillary blood glucose, 24-hour continuous glucose monitoring system tracings and global satisfaction score were evaluated at the end of each 12-week treatment period. RESULTS: HbA1c decreased from 9.0+/-1.6% to 8.6+/-1.6% with multiple injections and 7.7+/-0.8% with pump device (p<0.03). Capillary blood glucose was lowered at all time-points with pump, but only at morning with multiple injections (p<0.01). Compared to conventional therapy, pump reduced hyperglycemic area under curve by 73% (p<0.01), but multiple injections by only 32% (p=0.08). Rate of hypoglycemia was not increased and patient's satisfaction was comparable with both intensive treatments. CONCLUSIONS: Pump therapy provides a better metabolic control than injection regimens, and seems to be safe and convenient in patients with type 2 diabetes who fail to respond to conventional insulin therapy.     

The intricate relationship between diabetes,obesity and pancreatic cancer

Pancreatic cancer is one of the leading determinants of global cancer mortality, and its incidence is predicted to increase, to become in 2030 the second most common cause of cancer-related death. Obesity and diabetes are recognized risk factors for the development of pancreatic cancer. In the last few decades an epidemic of diabetes and obesity has been spreading worldwide, forewarning an increase in incidence of pancreatic cancer. This review considers the most recent literature, covering the multiple molecular axis linking these three pathologies, aiming to draw a more comprehensive view of pancreatic cancer for a better theragnostic stratification of the population.     

大剂量胰岛素联合西格列汀对老年2 型糖尿病患者的疗效

目的:研究大剂量胰岛素联合西格列汀对老年2型糖尿病患者的疗效。方法:选择2012年1月~2015年12月在我院进行诊治的老年2型糖尿病患者82例,随机分为两组,观察组采用大剂量胰岛素联合西格列汀治疗,对照组采用大剂量胰岛素治疗,两组均治疗3个月。比较两组治疗前后的甘油三酯、总胆固醇、低密度脂蛋白和高密度脂蛋白水平,餐后2 h血糖、空腹血糖、糖化血红蛋白,胰岛素抵抗指数、胰岛素分泌指数、每日胰岛素总量和低血糖发生次数。结果:对照组治疗前后的血脂水平无明显差异(P0.05),观察组治疗后的甘油三酯、总胆固醇和低密度脂蛋白明显降低(P0.05),高密度脂蛋白明显升高(P0.05);治疗后,两组的餐后2 h血糖、空腹血糖、糖化血红蛋白均明显降低(P0.05),且观察组降低更为明显(P0.05);对照组治疗前后的胰岛素抵抗指数、胰岛素分泌指数和每日胰岛素总量均无明显差异(P0.05),观察组治疗后的胰岛素抵抗指数和每日胰岛素总量均明显降低(P0.05),胰岛素分泌指数明显升高(P0.05);两组治疗前后低血糖发生次数和身体质量指数均无明显差异(P0.05)。结论:大剂量胰岛素联合西格列汀能有效控制老年2型糖尿病患者的血糖水平,改善胰岛β细胞功能,减少胰岛素用量,是一种安全有效的治疗方法。     

Current aspects of the mechanism of action of calcium antagonists in patients with diabetes mellitus]

The review summarizes recent data about the use of calcium channel blockers for the treatment of cardiovascular complications in patients with diabetes mellitus. It is shown that disturbances of Ca ion homeostasis play an important role in the pathogenesis of such diabetic complications as cardiomyopathy, microangiopathy, hypertension and the use of modern calcium channel antagonists for their treatment seems to be quite justified. However, despite definite positive effects of such treatment, these drugs should be used with care, especially if combined with derivatives of sulphonylurea as activators of the beta-cell function. Calcium channel blockers may intervene in the mechanism of the activity of beta-cells in which activation of the calcium channels is an obligatory link for triggering insulin secretion. Nevertheless, according to most of the authors, in such cases Ca antagonists can be recommended in moderate doses under continuous control of the hormonal status of the patient.     

Bile acid pool changes and regulation of cholate synthesis in experimental diabetes

The effect of alloxan-diabetes and insulin treatment in bile acid pool size and composition, bile acid secretion and cholic acid synthesis was investigated in the rat. The size of the cholate pool was significantly increased 4 days after diabetes induction. It reached a constant size three times that of control animals after 2 weeks of diabetes. Changes in bile acid pool size and secretion were directly dependent of the insulin deficiency state since they were reversed by insulin treatment and were not influenced by the caloric intake of the animal nor the pharmacologic effect of alloxan. Biliary cholate secretion was also 3-fold increased in diabetic rats and it accounted for more than 80% of the total bile acids compared to 60% in the control group. The calculated daily rate of cholate synthesis was increased in diabetic rats and the circadian rhythm of cholate synthesis was abolished in this condition. Therefore, it was shown that the negative feedback mechanism that regulates bile acid snythesis was deleted in diabetes. This mechanism was partially restored after 2 weeks of insulin treatment. These studies demonstrated that bile acid metabolism was profoundly changed in alloxan-diabetic rats and suggested that insulin may play an important role in the regulation of bile acid snythesis and intestinal absorption.     

Effect of maternal diabetes and ethanol interactions on embryo development in the mouse

The aim of this study was to determine the possible fetal effects of interaction between maternal diabetes and acute doses of alcohol. Pregnant TO mice were made diabetic by a single injection of streptozotocin (STZ) on gestation day (GD) 2. Single dose of 0.003 or 0.03 ml/g body weight of fresh ethanol (25% v/v of absolute alcohol in normal saline) was injected into groups of diabetic and nondiabetic animals on GD 7 or 8. One group of diabetic animals had a daily dose of 6-8 IU of insulin subcutaneously. Fetuses were collected on GD 18. There was a significant increase in the incidence of implantation failure in the diabetes plus ethanol groups and insulin control group. Ethanol injection on GD 7 accentuated diabetes-related embryonic resorption and intrauterine growth retardation (IUGR). This effect was less marked in the diabetic group treated with ethanol on GD 8. Diabetes alone produced a greater incidence of IUGR than ethanol alone. Midfacial hypoplasia and minor anomalies were found more frequently in the combination treatment groups. Holoprosencephaly and thymus hypoplasia observed in diabetic groups were found to be reduced in frequency in the diabetes plus ethanol groups, suggesting an antagonistic type of ethanol-diabetes interaction, stage-dependently. Since severely malformed embryos are known to be resorbed/killed in utero in mice, this reduction might reflect the magnitude of early death of severely malformed embryos. These data suggest that the interaction effects are possibly related to alterations in fundamental developmental processes of early embryos.     

New and future immunomodulatory therapy in type 1 diabetes

Type 1 diabetes is a common autoimmune disease that affects millions of people worldwide and has an incidence that is increasing at a striking rate, especially in young children. It results from the targeted self-destruction of the insulin-secreting β cells of the pancreas and requires lifelong insulin treatment. The effects of chronic hyperglycemia - the result of insulin deficiency - include secondary endorgan complications. Over the past two decades our increased understanding of the pathogenesis of this disease has led to the development of new immunomodulatory treatments. None have yet received regulatory approval, but this report highlights recent progress in this area.