川芎嗪联合左旋精氨酸对缺血—再灌注损伤兔心肌线粒体功能的影响

目的探讨川芎嗪联用左旋精氨酸对心肌缺血-再灌注损伤时心肌细胞线粒体功能的影响。方法选用日本大耳白兔50只,随机分为正常对照组(A组)、心肌缺血-再灌注组(B组)、心肌缺血—再灌注 川芎嗪治疗组(C组)、心肌缺血—再灌注 左旋精氨酸治疗组(D组)和心肌缺血—再灌注 川芎嗪 左旋精氨酸治疗组(E组)。观察心肌线粒体呼吸功能、Ca2 浓度、丙二醛浓度、超氧化物歧化酶活性和心肌组织三磷酸腺苷(ATP)和能荷的变化。结果与A组比较,B组线粒体呼吸控制率、Ⅲ态呼吸速率和超氧化物歧化酶明显降低,Ⅳ态呼吸速率、Ca2 浓度和丙二醛显著升高,心肌组织ATP和能荷明显降低。与B组比较,C组、D组和E组线粒体呼吸控制率、Ⅲ态呼吸速率和超氧化物歧化酶明显升高,Ⅳ态呼吸速率、Ca2 浓度、丙二醛显著降低,心肌组织ATP和能荷明显增高;且与A组比较,E组上述指标均无明显差异。结论川芎嗪联用左旋精氨酸可通过降低氧自由基水平和减轻钙超载,而改善缺血—再灌注损伤心肌的线粒体功能。     

Measurement of HbA1c from stored whole blood samples in the Atherosclerosis Risk in Communities study

Background: The aims of the present study were to demonstrate the reliability of HbA1c measurements during two time periods and to compare these measurements with HbA1c distribution in the general US population. Methods: HbA1c was measured in 14 069 whole blood samples in the Atherosclerosis Risk in Communities (ARIC) study using different HPLC instruments across two time periods, namely 2003–2004 and 2007–2008. At the time of measurement, samples had been in storage at ?70°C for up to 18 years. To assess differences in values, HbA1c measurements were repeated in 383 samples at both periods. Indirect comparisons were made by comparing our measurements against those from a nationally representative study. Results: The coefficients of variation for quality control samples were 1.8% (n = 89) in 2003–2004 and 1.4% (n = 259) in 2007–2008. The correlation between measurements at the two time points was high (r = 0.99), but with a slight bias: 0.29% points higher in 2007–2008 vs 2003–2004 (n = 383; P < 0.0001). The comparison yielded the following Deming regression equation: y_{(2007–2008)} = 0.073 + 1.034x_{(2003–2004)}. After alignment using this equation, the distribution of HbA1c in the ARIC study was similar to that in the national study using fresh samples. Conclusions: Measurements of HbA1c from samples stored for up to 18 years are highly reliable when using state‐of‐the‐art HPLC instruments, but with some bias introduced over time. The HbA1c data now available in the ARIC study should be invaluable for investigations into the clinical utility of HbA1c as a diagnostic test for diabetes.     

UKPDS 50: Risk factors for incidence and progression of retinopathy in Type II diabetes over 6 years from diagnosis

Aims/hypothesis. To determine risk factors related to the incidence and progression of diabetic retinopathy over 6 years from diagnosis of Type II (non-insulin-dependent) diabetes mellitus. Methods. This report describes 1919 patients from within the United Kingdom Prospective Diabetes Study (UKPDS), with retinal photographs taken at diagnosis and 6 years later and with complete data available. Photographs were centrally graded for lesions of diabetic retinopathy using the modified Early Treatment of Diabetic Retinopathy Study Final scale. Risk factors were assessed after 3 months diet from the time of diagnosis of diabetes. Patients were seen every 3 months in a hospital setting. Biochemical measurements were done by a central laboratory. End points of vitreous haemorrhage and photocagulation were confirmed by independent adjudication of systematically collected clinical data. The main outcome measures were incidence and progression of retinopathy defined as a two-step Early Treatment of Diabetic Retinopathy Study (ETDRS) final scale change. Results. Of the 1919 patients, 1216 (63 %) had no retinopathy at diagnosis. By 6 years, 22 % of these had developed retinopathy, that is microaneurysms in both eyes or worse. In the 703 (37 %) patients with retinopathy at diagnosis, 29 % progressed by two scale steps or more. Development of retinopathy (incidence) was strongly associated with baseline glycaemia, glycaemic exposure over 6 years, higher blood pressure and with not smoking. In those who already had retinopathy, progression was associated with older age, male sex, hyperglycaemia (as evidenced by a higher HbA_{1 c}) and with not smoking. Conclusion/interpretation. The findings re-emphasise the need for good glycaemic control and assiduous treatment of hypertension if diabetic retinopathy is to be minimised. [Diabetologia (2001) 44: 156–163] Received: 13 June 2000 and in revised form: 15 September 2000     

Molecular methods for the study of the genetic determinants of nephropathy in type 1 (insulin-dependent) diabetes

Recently, evidence has accumulated that genetic factors may contribute to the development of diabetic nephropathy in patients with type 1 (insulin-dependent) diabetes mellitus. To identify variation at a gene locus, newly developed methods are introduced which employ denaturing gradient gel electrophoresis (DGGE) to study sequence differences in polymerase chain reaction (PCR)-amplified DNA fragments as well as in genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, we found no DNA sequence difference in the part of the angiotensinogen gene coding for angiotensin I. We did find, however, different distributions of a DNA polymorphism detected with the probe corresponding to exons 7 and 8 of the insulin receptor gene inRsaI DGGE blots in a comparison of patients with slow and fast progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiological data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected so that genetic studies will be possible.     

Quality of care for patients with Type 2 diabetes mellitus--a long-term comparison of two quality improvement programmes in the Netherlands.

AIM: To compare two intervention programmes, aimed at improving the quality of care provided for patients with Type 2 diabetes in the longer term. METHODS: A retrospective comparison of data derived from two non-randomized trials with 3.5 years of follow-up. In the first intervention group 401 patients were included, 413 in the second intervention group and 105 in the reference group. The first programme focused on improving the skills and knowledge of general practitioners (GPs) with regard to Type 2 diabetes, and supported them in making organizational changes in their practice (GP care only). Centralized shared diabetes care was implemented in the second programme in which the GPs received therapy advice according to a protocol for each individual patient. The patients were also encouraged in self-management, and received structured diabetes education (Diabetes Service). The main patient outcomes were HbA1c, blood pressure and serum lipid levels. Multilevel analysis was applied to adjust for dependency between repeated observations within one patient and for clustering of patients within general practices. RESULTS: The HbA1c levels of patients of GPs who were supported by the Diabetes Service improved significantly more than the HbA1c levels of patients receiving GP care only (-0.28% [95% confidence interval (CI) -0.45; -0.11]). In contrast, the systolic blood pressure of patients receiving GP care only decreased more than that of patients of GPs supported by the Diabetes Service [4.14 mmHg (95% CI 1.77, 6.51)]. CONCLUSION: A Diabetes Service, providing GPs with individual therapy advice and patient education, resulted in better glycaemic control over 3.5 years than an intervention aimed at improving the skills of GPs in combination with organizational changes in the general practice.     

Risk factors for Type 2 (non-insulin-dependent) diabetes mellitus. Thirteen and one-half years of follow-up of the participants in a study of Swedish men born in 1913

Summary This report presents data on antecedents of Type 2 (non-insulin-dependent) diabetes mellitus in a homogeneous sample of randomly selected 54-year-old men from an urban Swedish population with a diabetes incidence of 6.1% during 13.5 years of follow-up. The increased risk leading to diabetes for those in the top quintile compared to the lowest quintile of the distribution of statistically significant risk factors were: body mass index = 21.7, triglycerides = 13.5, waist-to-hip circumference ratio = 9.6, diastolic blood pressure = 6.7, uric acid = 5.8, glutamic pyruvic transaminase = 3.9, bilirubin = 3.2, blood glucose = 2.7, lactate = 2.4 and glutamic oxaloacetic transaminase = 2.0. Those with a positive family history of diabetes had 2.4-fold higher risk for developing diabetes than those without such a history. In a multivariate analysis glutamic pyruvic transaminase, blood glucose, body mass index, bilirubin, systolic blood pressure, uric acid and a family history of diabetes were all significantly associated with the development of diabetes. Our study demonstrates the great importance of adiposity and body fat distribution for the risk of diabetes. A number of established risk factors for coronary heart disease are risk factors for diabetes as well. Disturbed liver function and increased levels of lactate are early risk factors for diabetes — presumably indicators of the presence of impaired glucose tolerance and/or hyperinsulinaemia.     

Treatment intensification in patients with inadequate glycemic control on basal insulin: rationale and clinical evidence for the use of short‐acting and other glucagon‐like peptide‐1 receptor agonists

A substantial proportion of patients with type 2 diabetes mellitus do not reach glycemic targets, despite treatment with oral anti‐diabetic drugs and basal insulin therapy. Several options exist for treatment intensification beyond basal insulin, and the treatment paradigm is complex. In this review, the options for treatment intensification will be explored, focusing on drug classes that act via the incretin system and paying particular attention to the short‐acting glucagon‐like peptide‐1 receptor agonists exenatide and lixisenatide. Current treatment guidelines will be summarized and discussed. © 2016 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.