Selective processing of food words during insulin-induced hypoglycemia in healthy humans

Rationale Hypoglycemia leads to undernutrition of the brain. Favoring selective processing of food stimuli would be an adaptive cognitive strategy. However, hypoglycemia is known to impair several aspects of cognitive function, and it is unknown whether selective cognitive processing of food stimuli occurs during insulin-induced hypoglycemia.Methods In a single-blind repeated measures design, healthy young adults (n=12, six female, mean age 28 years; mean body mass index 22.5 kg/m²) performed a standard Stroop word-color test, as well as a variant with food words designed to detect selective processing of food cues. Two sessions were scheduled with a 4-week interval. In each session, a hyperinsulinemic clamp method produced a normoglycemic (plasma glucose: 4.7 mmol/l) period, followed on 1 day by a hypoglycemic (2.7 mmol/l) testing period, and on the other day a second normoglycemic testing period (counterbalanced order).Results Color naming verbal reaction time (RT) increased during hypoglycemia (P<0.0001). The extent of the Stroop cognitive interference was independent of plasma glucose level. The key finding is that RT for food words increased more than for non-food control words (P<0.004), and this effect was not predicted by hunger ratings.Conclusions Our data provide new evidence that during hypoglycemia, attention is directed selectively to food-relevant stimuli. The results are discussed in terms of adaptation.     

Naloxone suppresses insulin-induced food intake in novel and familiar environments,but does not affect hypoglycemia

The opiate antagonist naloxone reduced the food intake induced in rats by acute injection of insulin. The suppression was most marked in the first hour after insulin injection. Insulin provoked less food intake when rats were tested in a novel environment compared with those tested in their home cage, but naloxone again significantly suppressed the intake in the first hour. Naloxone had no effect upon insulin-induced hypoglycemia.     

Short-term cost-effectiveness of insulin detemir and insulin aspart in people with type 1 diabetes who are prone to recurrent severe hypoglycemia

Objective: Based on the data of the HypoAna trial (ClinicalTrials.gov NCT00346996), a short-term cost–effectiveness analysis was conducted comparing an all insulin analogue regimen with an all human insulin regimen in people with type 1 diabetes who are prone to recurrent severe hypoglycemia.

Methods: Clinical data from the HypoAna trial and Danish cost data related to the treatment of severe hypoglycemia were used to populate a 1-year cost–effectiveness analysis. Hypoglycemia quality-of-life data were based on previously published utility values, used to calculate the quality-adjusted life-years (QALYs) gained. Sensitivity analyses were conducted to test the robustness of the analysis. The main outcome measure was the incremental cost–effectiveness ratio (ICER).

Results: The insulin analogue regimen was associated with greater total costs compared with the human insulin regimen (20,418 DKK [1972 GBP] vs. 18,558 DKK [1793 GBP], respectively), primarily driven by the difference in insulin costs. Total costs for corrective actions for hypoglycemic events, however, were lower in the insulin analogue group (927 DKK [89 GBP]) compared with the human insulin group (1311 DKK [127 GBP]), primarily due to a lower event rate. QALYs were higher with insulin analogues vs. human insulin (difference 0.0672). The resulting ICER was 27,685 DKK (2674 GBP) per QALY gained, which is well below the generally accepted cost–effectiveness threshold.

Conclusions: The analysis shows that treating people with type 1 diabetes who are prone to recurrent severe hypoglycemia with an insulin analogue regimen is cost-effective compared with a human insulin regimen.     

The burden of severe hypoglycemia in type 1 diabetes

Aims: Approximately 1.25 million people in the US have type 1 diabetes mellitus (T1DM), a chronic metabolic disease that develops from the body’s inability to produce insulin, and requires life-long insulin therapy. Poor insulin adherence may cause severe hypoglycemia (SHO), leading to hospitalization and long-term complications; these, in turn, drive up costs of SHO and T1DM overall. This study’s objective was to estimate the prevalence and costs of SHO-related hospitalizations and their additional longer-term impacts on patients with T1DM using basal-bolus insulin.

Methods: Using Truven MarketScan claims, we identified adult T1DM patients using basal-bolus insulin regimens who were hospitalized for SHO (inpatient SHO patients) during 2010–2015. Two comparison groups were defined: those with outpatient SHO-related encounters only, including emergency department (ED) visits without hospitalization (outpatient SHO patients), and those with no SHO- or acute hyperglycemia-related events (comparison patients). Lengths of stay and SHO-related hospitalization costs were estimated and propensity score and inverse probability weighting methods were used to adjust for baseline differences across the groups to evaluate longer-term impacts.

Results: We identified 8,734 patients, of which 4.2% experienced at least one SHO-related hospitalization. Among those who experienced SHO (i.e. of those in the inpatient and outpatient SHO groups), 31% experienced at least one SHO-related hospitalization, while 9% were treated in the ED without subsequent hospitalization. Approximately 79% of patients were admitted directly to the hospital; the remainder were first assessed or treated in the ED. The inpatient SHO patients stayed in the hospital, including time in the ED, for 1.7 days and incurred $3551 in costs. About one-third of patients were hospitalized again for SHO. Inpatient SHO patients incurred significantly higher monthly costs after their initial SHO-related hospitalization than patients in the two other groups ($2084 vs $1313 and $1372), corresponding to 59% or 52% higher monthly costs for inpatient SHO patients.

Limitations: These analyses excluded patients who did not seek ED or hospital care when faced with SHO; events may have been miscoded; and we were not able to account for clinical characteristics associated with SHO, such as insulin dose and duration of diabetes, or unmeasured confounders.

Conclusions: The burden associated with SHO is not negligible. About 4% of T1DM patients using basal-bolus insulin regimens are hospitalized at least once due to SHO. Not only did those patients incur the costs of their SHO hospitalization, but they also incur red at least $712 (52%) more in costs per month after their hospitalization than outpatient SHO or comparison patients. Reducing SHO events can help decrease the burden associated with SHO among patients with T1DM.     

2型糖尿病合并低血糖实施人性化护理干预对提高患者生存质量的作用

目的：探讨人性化护理对2型糖尿病合并低血糖患者生存质量的影响,并总结经验体会。方法回顾性分析2012年1月~2013年6月期间来我院诊治的146例2型糖尿病合并低血糖患者,将其平均分为观察组和对照组,各73例。对照组实施普通护理,观察组则在普通护理基础上实施人性化护理,比较两组患者的生存质量。结果观察组患者实施人性化护理后,患者的生存质量评分明显高于对照组,且患者的满意度高,差异具有统计学意义（P＜0.05）。结论人性化护理可以显著改善2型糖尿病合并低血糖患者的病情,提高患者的生存质量,值得在临床护理中推广使用。     

The burden of severe hypoglycemia in type 2 diabetes

Aims: More than 29 million people in the US have type 2 diabetes mellitus (T2DM), a chronic metabolic disorder characterized by a progressive deterioration of glucose control, which eventually requires insulin. Abnormally low levels of blood glucose, a feared side-effect of insulin treatment, may cause severe hypoglycemia (SHO), leading to emergency department (ED) admission, hospitalization, and long-term complications; these, in turn, drive up the costs of T2DM. This study’s objective was to estimate the prevalence and costs of SHO-related hospitalizations and their additional longer-term impacts on patients with T2DM using insulin.

Methods: Using Truven MarketScan claims, we identified adult T2DM patients using basal and basal-bolus insulin regimens who were hospitalized for SHO (inpatient SHO patients) during 2010–2015. Two comparison groups were defined: those with outpatient SHO-related encounters only, including ED visits without hospitalization (outpatient SHO patients), and those with no SHO- or acute hyperglycemia-related events (comparison patients). Lengths of stay and SHO-related hospitalization costs were estimated, and propensity score and inverse probability weighting methods were used to adjust for baseline differences across the groups to evaluate longer-term impacts.

Results: We identified 66,179 patients using basal and 81,876 patients using basal-bolus insulin, of which ～1.1% (basal) to 3.2% (basal-bolus) experienced at least one SHO-related hospitalization. Among those who experienced SHO (i.e. those in the inpatient and outpatient SHO groups), 27% (basal) and 40% (basal-bolus) experienced at least one SHO-related hospitalization. One-third of basal and about one-quarter of basal-bolus patients were admitted directly to the hospital; the remainder were first assessed or treated in the ED. Inpatient SHO patients using basal insulin stayed in the hospital, including time in the ED, for 2.8 days and incurred $6896 in costs; patients using basal-bolus insulin stayed in the hospital for 2.6 days and incurred costs of $5802. Forty-to-fifty percent of inpatient SHO patients were hospitalized again for SHO. Inpatient SHO patients using basal insulin incurred significantly higher monthly costs after their initial SHO-related hospitalization than patients in the other two groups ($2935 vs $1819 and $1638), corresponding to 61% and 79% higher monthly costs; patients using basal-bolus insulin also incurred significantly higher monthly costs than patients in the other groups ($3606 vs $2731 and $2607), corresponding to 32% and 38% higher monthly costs.

Limitations: These analyses excluded patients who did not seek ED or hospital care when faced with SHO; events may have been miscoded; and we were not able to account for clinical characteristics associated with SHO, such as insulin dose and duration of diabetes, or unmeasured confounders.

Conclusions: The burden associated with SHO is not negligible. Nearly one in three patients using only basal insulin and one in four patients using basal-bolus regimens who experienced SHO were hospitalized at least once due to SHO. Not only did those patients incur the costs of their SHO hospitalization, but they also incurred at least $1,116 (62%) and $875 (70%) more per month than outpatient SHO or comparison patients. Reducing SHO events can help decrease the burden associated with SHO among patients with T2DM.     

基于Roy适应理论的健康宣教配合智慧平台在T1DM带泵治疗患儿中的应用

目的　探讨基于Roy适应理论的健康宣教配合智慧平台在1型糖尿病（T1DM）带泵治疗患儿中的应用效果。方法　纳入2020年5月至2022年5月经郑州儿童医院收治的84例T1DM带泵治疗患儿及主要监护人作前瞻性研究,按随机数字表法设为对照组（患儿42例,主要监护人42例）及观察组（患儿42例,主要监护人42例）。对照组予以常规健康宣教,观察组则于对照组基础上,基于Roy适应理论的健康宣教配合智慧平台实施干预,比较两组主要监护人健康教育知识掌握程度、照护水平及患儿血糖控制效果、治疗依从性。统计学方法采用χ²检验、t检验。结果　两组主要监护人干预前健康教育知识掌握度、照护者负担水平（ZBI）、家庭关怀度（APGAR）比较,差异均无统计学意义;两组干预后健康教育知识掌握度、APGAR均有提高,ZBI有所降低,观察组健康教育知识掌握度［（68.15±7.36）分比（54.62±10.18）分］、APGAR［（8.03±1.35）分比（6.72±1.13）分］均高于对照组,ZBI［（26.87±5.21）分比（30.24±5.48）分］低于对照组（t=6.98、4.822、2.888,均P<0.05）;两组患儿干预前HbA1c、FBG比较,差异无统计学意义。两组干预后糖化血红蛋白（HbA1c）、空腹血糖（FBG）均有降低,观察组HbA1c［（6.51±0.58）%］、FBG［（6.76±0.65）mmol/L］低于对照组［（7.44±0.86）%、（7.83±0.91）mmol/L］,差异均有统计学意义（t=5.810、6.201,均P<0.05）,且观察组干预后HbA1c、FBG合格率高于对照组（χ²=7.244、5.833,均P<0.05）;经Redit分析,两组患儿治疗依从性比较,差异有统计学意义（χ²=2.090,P<0.05）,且观察组MMAS-8评分高于对照组,差异有统计学意义（t=11.770,P<0.05）。结论　基于Roy适应理论的健康宣教配合智慧平台应用于T1DM带泵治疗患儿,可提升主要监护人健康教育知识掌握程度,提高照护水平,且患儿血糖控制效果良好,治疗依从性上升。     

Cost-effectiveness of insulin detemir compared to NPH insulin for type 1 and type 2 diabetes mellitus in the Canadian payer setting: modeling analysis*

ABSTRACT

Objective: This study was conducted to quantify the long-term cost-effectiveness of insulin detemir (Levemir^?) versus intermediate-acting neutral protamine Hagedorn (NPH) insulin for the treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in Canada, and to assess the sensitivity of results to dis-utilities for hypoglycemic events.

Research design and methods: The web-based IMS-CORE diabetes model has a menu-driven interface programmed in hypertext markup language (HTML). It was used to project lifetime (60 years for T1DM and 35 years for T2DM) clinical and economic outcomes for patients on detemir vs. NPH. Cohort characteristics, utilities, and costs were derived from published literature. For T1DM, clinical trial data for HbA_1c improvement (detemir ?0.94%?±?1.07; NPH ?0.82%?±?1.01) from baseline, and rates of hypoglycemic events (major events: 0.20 vs. 0.80 per patient-year for detemir vs. NPH, respectively) were modeled. For T2DM, observational study data for HbA_1c improvement (detemir ?0.18%) from baseline, and reductions in hypoglycemic events (major events: 0.0995 vs. 1.33 per patient-year for detemir vs. NPH, respectively) were modeled. Base-case hypoglycemia dis-utilities were ?0.0118 for major and ?0.0035 for minor events. Sensitivity analyses were conducted on discount rate and hypoglycemia dis-utility.

Outcome measures: Outcomes included costs of treatment/management and costs (and incidence) of diabetes-related complications. Incremental cost-effectiveness ratios (ICERs) were calculated from differences in total costs and quality-adjusted life-years (QALYs).

Results: Average total costs for T1DM were $CAN 83?622?±?4585 for detemir and $CAN 72?016?±?4593 for NPH. QALYs increased by 0.475 years with detemir, with an ICER of $CAN 24?389/QALY. Average direct costs for T2DM were $CAN 74?919?±?6391 (detemir) and $CAN 69?230?±?6840 (NPH). QALYs increased by 0.305 years. The ICER was $CAN 18?677. Although detemir was associated with slightly lower costs for most complications, results were driven by the differences in rates and costs for hypoglycemic events, and their assumed dis-utility. Study limitations include the use of single trials for clinical assumptions and the lack of analyses for patient risk sub-groups.

Conclusions: Findings provide evidence for the cost-effectiveness of detemir vs. NPH in treating T1 and T2DM in Canada, and support the key role of assumptions regarding the impact of hypoglycemic events. Additional work is needed to determine the extent to which results are robust for different sub-groups of patients and for variation in assumptions around HbA_1c improvements and hypoglycemic event rates.     

4‐Phenyl butyric acid does not generally reduce glucose levels in rodent models of diabetes

1. Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of diabetes. The aim of the present study was to investigate the effect of 4‐phenyl butyric acid (PBA), a novel chemical chaperone reducing ER stress, on serum glucose level in different strains of normal and diabetic rodents. 2. 4‐Phenyl butyric acid (1 g/kg per day, i.g.) was administered to ob/ob Type 2 diabetic mice, alloxan‐induced Type 1 diabetic mice and hydrocortisone (HC)‐induced Type 2 diabetic mice as well as normal C57BL/6J mice and Kumming mice for 14 days to evaluate its effect on serum glucose levels. In addition, mice were treated simultaneously with PBA (1 g/kg per day) and HC for 9 days to determine its preventive effect against the development of insulin resistance. PBA (0.7 and 1.4 g/kg per day) was administered to non‐obese Type 2 diabetic Goto‐Kakizaki (GK) and normal Wistar‐Kyoto (WKY) rats for 14 and 7 days, respectively, to determine its effects on serum glucose levels. 3. 4‐Phenyl butyric acid significantly reduced serum glucose levels in obese Type 2 diabetic ob/ob mice. Normoglycaemia was obtained in ob/ob mice after 4 days of PBA treatment and was maintained for up to 14 days treatment. 4. 4‐Phenyl butyric acid had no glucose‐lowering effect in alloxan‐induced Type 1 diabetic mice, HC‐induced Type 2 diabetic mice and non‐obese Type 2 diabetic GK rats. In addition, it had no beneficial effects on insulin resistance in HC‐treated mice. 5. 4‐Phenyl butyric acid did not affect normal serum glucose levels in C57BL/6 J mice, Kunming mice or WKY rats. 6. In conclusion, PBA does not generally reduce glucose levels in rodent models of diabetes, although it can normalize glucose levels in ob/ob diabetic mice, indicating that restoration of ER function as diabetes therapy is limited to conditions under which ER stress is involved in the high glucose levels.     

Inhaled insulin: recent advances in the therapy of Type 1 and 2 diabetes

There are promising data in the field of inhaled insulin. This article describes the current devices being developed for insulin delivery via inhalation. Encouraging advanced clinical data are available in Type 1 diabetes, where inhaled insulin is used in conjunction with basal insulin. Moreover, patients with Type 2 diabetes who have failed oral therapy show improved control when inhaled insulin therapy is initiated. Safety data show that cough is the most common side effect. Pulmonary function tests have shown some changes in carbon monoxide diffusion in the lung. Further studies are needed to clarify the significance of this finding. Inhaled insulin appears to be a non-invasive, well-tolerated and -liked modality of treatment, with potential in both Type 1 and 2 diabetes.     

Hyperglycaemia as a determinant of cognitive decline in patients with type 1 diabetes

Individuals with type 1 diabetes show mild performance deficits in a range of neuropsychological tests compared to healthy controls, but the mechanisms underlying this cognitive deterioration are still poorly understood. Basically, two diabetes-related mechanisms can be postulated: recurrent severe hypoglycaemia and/or chronic hyperglycaemia. Intensive insulin therapy in type 1 diabetes, resulting in a durable improvement of glycaemic control, has been shown to lower the risk of long-term microvascular and macrovascular complications. The down side of striving for strict glycaemic control is the considerably elevated risk of severe hypoglycaemia, sometimes leading to seizure or coma. While retrospective studies in adult patients with type 1 diabetes have suggested an association between a history of recurrent severe hypoglycaemia and a modest or even severe degree of cognitive impairment, large prospective studies have failed to confirm this association. Only fairly recently, better appreciation of the possible deleterious effects of chronic hyperglycaemia on brain function and structure is emerging. In addition, it can be hypothesized that hyperglycaemia associated microvascular changes in the brain are responsible for the cognitive decline in patients with type 1 diabetes. This review presents various pathophysiological considerations concerning the cognitive decline in patients with type 1 diabetes.     

Cognitive function and blood pressure control in hypertensive patients over 60 years of age: COGNIPRES study

ABSTRACT

Background and aims: The aim of the COGNIPRES study was to analyze the prevalence of cognitive impairment in hypertensive individuals over 60 years of age, treated in primary care centres in the context of routine clinical practice. Degree of blood pressure control and treatment compliance, as well as other possible factors that influence cognitive function, were also evaluated.

Methods: An epidemiological, multicentre cross-sectional study was made. Demographic, clinical, therapeutic and blood pressure data for the first three hypertensive patients aged over 60 years seen in the primary care centre, and for the first patient visited at home by the physician were recorded. The study was carried out by 477 physicians in 333 primary care centres throughout Spain. Cognitive impairment was assessed using the Mini Mental State Examination (MMSE), and therapeutic compliance was assessed using the Haynes-Sacket and Morisky-Green tests.

?Results: Of 1579 patients included in the study, 12.3% (95%CI 10.7–14.0) (n = 195) had cognitive impairment. This was significantly associated with patients over 80 years of age (OR 4.97; 95%CI 2.98–8.29), exclusive home care (OR 1.84; 95%CI 1.19–2.83), anxiety (OR 1.84; 95%CI 1.19–2.83), stroke or transient ischemic attack (OR 4.37; 95%CI 2.81–6.78), Parkinson's disease (OR 8.15; 95%CI 2.54–26.12), essential tremor (OR 2.25; 95%CI 1.34–3.79), uncontrolled blood pressure (OR 0.60; 95%CI 0.39–0.94) and poor treatment compliance (OR 0.53; 95%CI 0.37–0.75). Overall, 28.3% of the patients showed controlled blood pressure, and 33.6% showed poor adherence to antihypertensive treatment.

Conclusions: In this study, the prevalence of cognitive impairment in hypertensive patients aged over 60 years was 12.3%. Less than a third of the patients had good blood pressure control. Compliance with therapy and good control of blood pressure are associated with better MMSE scores.     

The value of short- and long-acting glucagon-like peptide-1 agonists in the management of type 2 diabetes mellitus: experience with exenatide

Background:

Only about half of patients with type 2 diabetes treated with antihyperglycemic drugs achieve glycemic control (HbA1c <7%), most commonly due to poor treatment adherence. Glucagon-like peptide-1 (GLP-1) receptor agonists act on multiple targets involved in glucose homeostasis and have a low risk of causing hypoglycemia. While GLP-1 receptor (GLP-1R) agonists share the same mechanism of action, clinical profiles of individual agents differ, particularly between short- and long-acting agents. In this article, recent findings regarding the pharmacology of GLP-1 agonists are reviewed, and the clinical effects of short- versus long-acting agents are compared.

Data sources:

Relevant articles were identified through a search of PubMed using the keywords glucagon-like peptide-1, GLP-1, glucagon-like peptide-1 receptor agonist, GLP-1R agonist, and exenatide for publications up to 22 May 2015. Supporting data were obtained from additional searches for albiglutide, dulaglutide, liraglutide and lixisenatide as well as from the bibliographies of key articles.

Findings:

Short-acting GLP-1R agonists produce greater reductions in postprandial glucose levels by slowing gastric emptying, whereas long-acting GLP-1R agonists produce greater reductions in fasting blood glucose by stimulating insulin secretion from the pancreas. These characteristics can be exploited to provide individualized treatment to patients. A large body of evidence supports the benefits of short- and long-acting exenatide as add-on therapy in patients with inadequate glycemic control despite maximum tolerated doses of metformin and/or sulfonylurea. Exenatide is generally well tolerated and no new safety concerns were identified during long-term follow-up of up to 5 years. A limitation of this review of short-and long-acting GLP-1 receptor agonists is that it focuses on exenatide rather than all the drugs in this class. However, the focus on a single molecule helps to avoid any confusion that may be introduced as a result of differences in molecular structure and size.

Conclusions:

Short-acting GLP-1R agonists including exenatide are well suited to patients with type 2 diabetes with exaggerated postprandial glucose excursions and for co-administration with basal insulin therapy. Long-acting GLP-1R agonists including once weekly exenatide offer greater convenience and are well suited to patients who require specific control of fasting hyperglycemia.     

硫氧还蛋白 1、活化 T细胞趋化因子在脑梗死病人血清中的水平及与认知功能、预后的关系

目的探究硫氧还蛋白 1(Trx1)、活化 T细胞趋化因子( RANTES)在脑梗死病人血清中的水平及与认知功能、预后的关系。方法选取 2020年 3月至 2022年 6月在无锡市人民医院诊治的 168例脑梗死病人作为观察组,及同期 165例健康体检志愿者作为对照组进行研究。参照蒙特利尔认知评估量表( MoCA)评分对所有病人的认知能力进行评估,分为认知功能障碍组 112例,认知功能正常组 56例;根据改良 Rankin量表( MRS)评分分为预后良好组 90例,预后不良组 78例。采用酶联免疫吸附测定( ELISA)法检测血清 Trx1、RANTES水平; Spearman法分析脑梗死病人血清中 Trx1、RANTES水平与 MoCA评分的相关性;对影响脑梗死病人发生认知功能障碍及预后的因素进行 logistic回归分析;受试者操作特征曲线( ROC曲线)分析血清 Trx1、 RANTES水平对脑梗死病人发生认知功能障碍的诊断价值。结果与对照组相比,观察组病人血清 Trx1水平显著降低［( 6.78±1.62)μg/L比( 11.05±1.89)μg/L,P<0.05］,RANTES水平明显升高［( 35.12±4.84)ng/L比( 23.51±3.28)ng/L,P<0.05］;认知功能障碍组脑梗死病人血清 Trx1水平明显低于认知功能正常组［(6.02±1.59)μg/L比( 8.30±1.68)μg/L,P<0.05］,RANTES水平显著高于认知功能正常组［( 38.57±5.25)ng/L比( 28.22±4.02)ng/L,P<0.05］;与预后良好组对比,预后不良组脑梗死病人血清 Trx1水平明显降低［( 5.42±1.55)μg/L比( 7.96±1.68)μg/L,P<0.05］,血清 RANTES水平显著升高［( 38.58±5.29)ng/L比( 32.12±4.45)ng/L,P<0.05］;脑梗死病人血清 Trx1水平与 MoCA评分呈正相关( r=0.40,P<0.05),RANTES水平与 MoCA评分呈负相关s(r=-0.56,P<0.05); logistic回归分析显示,受教育程度、 Trx1是影响脑梗死病人发生认知功能障碍及预后的保护因素( P<0.05),脑梗死区域、 RANTES是影响脑梗死病人发生认知功能障碍及预后的危险因素( P<0.05)。 ROC曲线显示,血清 Trx1、 RANTES、二者联合诊断脑梗死病人发生认知功能障碍的 ROC曲线下面积( AUC)分别为 0.82、0.94、0.97,二者联合诊断均优于其各自单独诊断( Z二者联合 -Trx1=4.00,P<0.001;Z二者联合 -RANTES=2.03,P=0.021)。结论脑梗死病人血清 Trx1水平降低, RANTES水平升高,二者均与认知功能及预后有密切关系。     

初发2型糖尿病患者糖化血红蛋白水平对胰岛素抵抗及胰岛功能的影响

目的探讨初发2型糖尿病（T2DM）患者糖化血红蛋白水平与胰岛功能的关系,为合理选择降糖药物和有效控制血糖提供理论依据。方法对新诊断的126例2型糖尿病患者（男76例,女50例）分别测量身高、体重、血脂、空腹血糖（FPG）、空腹胰岛素（FINS）、糖化血红蛋白（HbA1C）。按HbA1C水平分为A组（HbA1C〈7．0％）、B组（7．0％≤HbAIC〈9．0％）及C组（HbA1C≥9．0％）3组,并分别计算胰岛素抵抗指数（HOMA—IR）、胰岛B细胞功能（HOMA—B）及胰岛索敏感性指数（ISI）。结果3组平均年龄和体重指数差异无统计学意义（P〉0．05）;随着HbA1C的增加,TG依次递增,HDL—C则依次递减。C组的FPG明显高于其他两组（P〈0．05）。B组表现为HOMA—IR明显增高,ISI下降。C组HOMA—B较其他两组明显降低,差异有统计学意义（P〈0．05）。结论初发2型糖尿病患者随着糖化血红蛋白的增高胰岛素敏感性下降,B细胞分泌能力减弱。     

Elevated catalase and heme oxygenase-1 may contribute to improved postischaemic cardiac function in long-term type 1 diabetes

1. Although increased oxidative stress has been shown repeatedly to be implicated in diabetes, the cardiovascular anti-oxidant state and heart response to ischaemia in long-term Type 1 diabetes remain largely unknown. The present study was designed to observe heart tolerance to ischaemia-reperfusion and endogenous anti-oxidants in the cardiovascular system in long-term hyperglycaemic rats. 2. Hearts from Sprague-Dawley rats surviving up to 6 months with streptozocin-induced severe hyperglycaemia (blood glucose > 20 mmol/L) were isolated and subjected to global ischaemia and reperfusion. Cardiac function, electrocardiogram and anti-oxidants in the myocardium and aorta were examined. In addition, the morphology of the myocardial mitochondria and the in vitro function of aortic vessels were assessed. 3. Hearts from diabetic rats demonstrated lower baseline heart function but had higher postischaemic coronary flow and left ventricular developed pressure compared with their respective controls (P < 0.05). In addition, hearts from diabetic animals had fewer arrhythmias (P < 0.01) and lower left ventricular end-diastolic pressure during reperfusion (P < 0.05). Higher catalase and heme oxygenase-1 content was found in the aorta and myocardium from diabetic rats (P < 0.01). In aortas from diabetic animals, acetylcholine-induced vasodilatation was enhanced and was approximately 15% after inhibition of nitric oxide synthase, compared with 0% in controls. The 15% relaxation was abrogated by heme oxygenase blockade. Mitochondria from the myocardium of diabetic rats showed significant increases in both size and number (P < 0.05). 4. Hearts of long-term Type 1 diabetic rats demonstrated improved recovery of postischaemic cardiac function and reduced reperfusion arrhythmia. Hyperglycaemia may enhance cardiovascular anti-oxidant capacity and mitochondrial neogenesis, which renders the heart resistant to ischaemia and oxidative injury.     

应用Simpson法评价老年2型糖尿病患者胆囊收缩功能

目的 应用Simpson法测量技术评价老年2型糖尿病(T2DM)对患者胆囊收缩功能的影响.方法 53例老年T2DM患者(A)组和36例对照(B)组采用高脂餐试验,采集胆囊长轴切面声像图,应用改良Simpson法直接测量高脂餐前后两组胆囊的容积,并统计胆囊排空率.结果 与B组相比,A组空腹胆囊的容积及脂餐后1-h胆囊残余容积明显增大(P<0.01);A组胆囊排空率明显减低(P<0.01).结论 改良Simpson法测量胆囊容积简便易行.     

Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial

ABSTRACT

Objective: To compare the effect of add-on glimepiride or pioglitazone in subjects with type 2 diabetes inadequately controlled on metformin monotherapy.

Research design and methods: Multicenter, randomized, parallel-group, open-label, forced-titration study involving 203 adults with poorly controlled type 2 diabetes (A1C 7.5–10%) on metformin monotherapy. Subjects were randomized to receive glimepiride or pioglitazone, titrated to the maximum dose for 26 weeks. Subjects were evaluated for A1C changes, fasting plasma glucose (FPG), insulin, C‐peptide, and lipid levels. Safety outcomes and diabetes-related healthcare resource utilization were also evaluated.

Results: Both treatment groups achieved similar and significant mean decreases from baseline to endpoint (week 26) in A1C (?p = 0.0001) and FPG (?p < 0.05). Glimepiride therapy, however, resulted in a more rapid decline in A1C levels at weeks 6, 12, and 20 vs. pioglitazone (?p < 0.05). A mean A1C ≤ 7% was reached faster in the glimepiride group (median, 80–90 days vs. 140–150 days [p = 0.024]). Total and LDL cholesterol were significantly higher with pioglitazone treatment than with glimepiride at endpoint (?p < 0.05). Glimepiride treatment was associated with an increased risk of hypoglycemia and pioglitazone with higher rate of peripheral edema. Healthcare resource utilization was similar between groups, but total healthcare costs were significantly lower for glimepiride versus pioglitazone over the course of the study, driven largely by drug costs. The use of fasting C‐peptide concentration ≥ 0.27?nmol/L in the inclusion criteria was a potential limitation as it may have included those patients with an improved probability for glimepiride or pioglitazone response. In addition, a larger patient population would have provided a greater degree of data applicability.

Conclusions: In patients with type 2 diabetes inadequately controlled on metformin monotherapy, add-on glimepiride or pioglitazone results in similar overall improvements in glycemic control. Compared with pioglitazone, glimepiride is associated with faster glycemic control, lower total and LDL cholesterol levels and reduced short-term healthcare costs.