口服葡萄糖耐量试验诊断DM、IGT、IFG的临床意义

目的　探讨空腹血糖 (FPG) <7.0mmol/L ,OGTT试验诊断糖尿病 (DM )、糖耐量减低 (IGT)及空腹血糖损害 (IFG)的价值。方法　挑选经体检确认FPG >7.0mmol/L人群作为观察对象 ,经馒头餐后 2h PG≥ 6.7mmol/L人员 ,施以OGTT ,根据 1999年WHO标准分为三组 :DM组、IGT组及IFG组。给每一组人员检查 2 4h尿微量白蛋白 (UmALB)。结果　DM、IGT及IFG男性检出率分别为 6.6%、10 .5 %及 5 .1% ,女性为 5 .1%、12 .5 %及 3 .3 % ,男性DM及IFG检出率高于女性 (P <0 .0 5 ) ,女性IGT检出率显著高于男性 (P <0 .0 1) ;2 4hUmALB ,FPG诊断DM组为 43 .2± 14 .3mg、OGTT诊断DM组为 3 0 .4± 15 .3mg、IGT组为 2 1.7± 8.5mg、IFG组为 7.7± 3 .6mg、正常对照组 7.5± 4.6mg ,DM组、IGT组均显著高于正常对照组 (P <0 .0 1) ,IFG组与正常对照组无差异 (P >0 .0 5 )。结论　对于FPG <7.0mmol/L者 ,应以OGTT试验来筛查患者是否有糖尿病或糖耐量异常。     

Association of Dysglycemia and All-Cause Mortality Across the Spectrum of Coronary Artery Disease

ObjectiveTo assess the association between fasting plasma glucose (FPG) and all-cause mortality across the spectrum of coronary artery disease (CAD).Patients and MethodsThe study included 18,999 patients during a study period of April 1, 2004, through October 31, 2010. The primary end points were in-hospital and follow-up all-cause mortality. According to the quartiles of FPG levels, patients were categorized into 4 groups: quartile 1, less than 5.1 mmol/L; quartile 2, 5.1 to less than 5.9 mmol/L; quartile 3, 5.9 to less than 7.5 mmol/L; and quartile 4, 7.5 mmol/L or greater. The conversion factor for units of plasma glucose is 1.00 mmol/L equals 18 mg/dL. Presented as mg/dL, the 4 quartile ranges of plasma glucose concentrations used in our data analysis are ≤90.0 mg/dL, 90.1-106.0 mg/dL, 106.1 mg/dL-135.0 mg/dL and ≥135.1 mg/dL. Quartile 1 was recognized as the lower glycemic group, quartiles 2 and 3 as the normoglycemic groups, and quartile 4 as the higher glycemic group.ResultsIn patients with acute myocardial infarction, all-cause mortality for the dysglycemic groups was higher than for the normoglycemic groups: in-hospital mortality for quartiles 1, 2, 3, and 4 was 1.0%, 0.9%, 0.2%, and 1.5%, respectively (P=.001); follow-up mortality for quartiles 1, 2, 3, and 4 was 1.7%, 0.9%, 0.3%, and 1.8%, respectively (P<.001). In patients with stable CAD, no significant differences in mortality were found among groups. However, in patients with unstable angina pectoris, the normoglycemic groups had lower follow-up mortality and roughly equal in-hospital mortality compared with the dysglycemic groups. After adjusting for confounding factors, this observation persisted.ConclusionThe association between lower FPG level and mortality differed across the spectrum of CAD. In patients with acute myocardial infarction, there was a U-shaped relationship. In patients with stable CAD or unstable angina pectoris, mildly to moderately decreasing FPG level was associated with neither higher nor lower all-cause mortality.     

Estimate of a predictive cut-off value for serum 25-hydroxyvitamin D reflecting abdominal obesity in Korean adolescents

Vitamin D deficiency is a serious global issue. Although the serum 25-hydroxyvitamin D [25(OH)D] test is generally the most accurate way to assess vitamin D levels, the optimal range of 25(OH)D has yet to be established. Moreover, the optimal level may vary according to race, region, and age. Suboptimal vitamin D status is associated with obesity and metabolic syndrome, which are the major risk factors for cardiovascular disorders; however, these relationships in children and adolescents have yet to be clearly determined. Therefore, we identified the best predictive cut-off value for reflecting abdominal obesity and, based on this value, we investigated the relationship between suboptimal 25(OH)D status and the risk for having abdominal obesity, being overweight or obese, and having metabolic syndrome in Korean adolescents. We performed a cross-sectional analysis of 713 Korean adolescents, between 12-19 years of age, and used data collected from the 2008 Korea National Health and Nutrition Examination Survey (KNHANES). Receiver operation characteristic curve analysis was used to identify the cut-off value that reflected abdominal obesity. The cut-off value of serum 25(OH)D that reflected abdominal obesity in Korean adolescents was 17.6 ng/mL. After making adjustments for gender, age, and regular physical exercise, the group that had lower levels of serum 25(OH)D compared to the cut-off value had a significantly higher risk for abdominal obesity, obesity, and metabolic syndrome than the group with 25(OH)D levels higher than the cut-off value. Suboptimal vitamin D status based on this value is associated with increased risk for abdominal obesity, obesity, and metabolic syndrome among Korean adolescents.     

Effects of 3-monochloropropane-1,2-diol (3-MCPD) and its metabolites on DNA damage and repair under in vitro conditions

3-monochloropropane-1,2-diol (3-MCPD) is a food contaminant that occurs during industrial production processes and can be found mainly in fat and salt containing products. 3-MCPD has exhibited mutagenic activity in vitro but not in vivo, however, a genotoxic mechanism for the occurrence of kidney tumors has not so far been excluded. The main pathway of mammalian 3-MCPD metabolism is via the formation of β – chlorolactatic acid and formation of glycidol has been demonstrated in bacterial metabolism. The aim of this study was to investigate genotoxic and oxidative DNA damaging effects of 3-MCPD and its metabolites, and to provide a better understanding of their roles in DNA repair processes. DNA damage was assessed by alkaline comet assay in target rat kidney epithelial cell lines (NRK-52E) and human embryonic kidney cells (HEK-293). Purine and pyrimidine base damage, H₂O₂ sensitivity and DNA repair capacity were assessed via modified comet assay. The results revealed in vitro evidence for increased genotoxicity and H₂O₂ sensitivity. No association was found between oxidative DNA damage and DNA repair capacity with the exception of glycidol treatment at 20 μg/mL. These findings provide further insights into the mechanisms underlying the in vitro genotoxic potential of 3-MCPD and metabolites.     

舒洛地特联合瑞格列奈治疗糖尿病肾病的临床研究

目的研究舒洛地特联合瑞格列奈治疗糖尿病肾病的临床疗效。方法选取2014年5月—2015年2月重庆市南岸区人民医院收治的糖尿病肾病患者200例,随机分为对照组和治疗组,每组各100例。对照组口服瑞格列奈片,0.5 mg/次,2次/d,连续使用2周后根据患者表现出来的具体症状调整用药剂量。治疗组在对照组治疗基础上口服舒洛地特软胶囊,1粒/次,2次/d。两组均连续治疗4个月。观察两组的临床疗效,同时比较治疗前后两组患者空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb A1c)、体质量指数(BMI)、24 h尿蛋白、血肌酐(Scr)、尿素氮(BUN)、IL-6、IL-10、TNF-α的变化情况。结果治疗后,对照组和治疗组的总有效率分别为88.0%、96.0%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者FPG、2 h PBG、Hb A1c、24 h尿蛋白、Scr、BUN、IL-6、IL-10、TNF-α均显著降低,同组治疗前后差异有统计学意义(P0.05);治疗后治疗组这些观察指标的改善程度优于对照组,两组比较差异有统计学意义(P0.05);治疗后治疗组患者BMI较治疗前显著降低,对照组无明显变化,两组比较差异有统计学意义(P0.05)。结论舒洛地特联合瑞格列奈治疗糖尿病肾病具有较好的临床疗效,可较好的控制患者的血糖水平,减轻肾脏损害,具有一定的临床推广应用价值。     

Associations of intra-renal arterial resistance index with chronic kidney disease and carotid intima-media thickness in type 2 diabetes mellitus

Renal dysfunction can be evaluated by increased intra-renal arterial resistance index (RI). We evaluated 113 Chinese men with type 2 diabetes on their RI. Results suggest that RI is associated with chronic kidney disease and subclinical arteriosclerosis. RI may help monitoring the deterioration of intra-renal hemodynamics.     

Changes in serum adiponectin concentrations and endothelial function after intensive insulin treatment in people with newly diagnosed type 2 diabetes: a pilot study

Aims

We aimed to assess changes in serum adiponectin and endothelial function after intensive insulin treatment in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Methods

Patients with newly diagnosed T2DM were randomly assigned to Group A (intensive insulin treatment) or Group B (conventional insulin treatment). Before treatment and 2 weeks after plasma glucose concentrations had been maintained at the specified concentrations, blood samples were obtained to measure serum adiponectin and nitric oxide (NO) concentrations. A total of 21 patients were randomized to each Group.

Results

Adiponectin, NO, endothelium-dependent vasodilation (EDD), and endothelium-independent vasodilation (EID) measures were significantly higher post-treatment than pre-treatment in Group A (all P < 0.05). Only EID was significantly higher in Group B (P < 0.05). Post-treatment adiponectin and NO concentrations, and EDD were significantly higher in Group A compared with Group B (all P < 0.05). Both treatment regimens were well tolerated (all patients completed the study). The most common adverse event was hypoglycemia. Thus, early intensive insulin therapy can increase serum adiponectin and NO concentrations and improve endothelial function in patients with newly diagnosed T2DM.

Conclusions

These effects may underlie the reduced incidence of microvascular and macrovascular in patients who receive early intensive hypoglycemic therapy.     

The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus

Solid-organ transplantation is the optimal long-term treatment for most patients with end-stage organ failure. After solid-organ transplantation, short-term graft survival significantly improved (1). However, due to chronic allograft nephropathy and death with functioning graft, long-term survival has not prolonged remarkably (2). Posttransplant immunosuppressive medications consist of one of the calcineurin inhibitors in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroids. All of them have different adverse effects, among which posttransplant diabetes mellitus (PTDM) is an independent risk factor for cardiovascular (CV) events and infections causing the death of many transplant patients and it may directly contribute to graft failure (3). According to the criteria of the American Diabetes Association (4), diabetes mellitus (DM) is defined by symptoms of diabetes (polyuria and polydipsia and weight loss) plus casual plasma glucose concentration ≥ 11.1 mmol/L or fasting plasma glucose (FPG) ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). This metabolic disorder occurring as a complication of organ transplantation has been recognized for many years. PTDM, which is a combination of decreased insulin secretion and increased insulin resistance, develops in 4.9/15.9% of liver transplant patients, in 4.7/11.5% of kidney recipients, and in 15/17.5% of heart and lung transplants [cyclosporine A (CyA)/tacrolimus (Tac)-based regimen, respectively] (5). Risk factors of PTDM can be divided into non-modifiable and modifiable ones (6), among which the most prominent is the immunosuppressive therapy being responsible for 74% of PTDM development (7). Emphasizing the importance of the PTDM, numerous studies have determined the long-term outcome. On the basis of these studies, graft and patient survival is tendentiously (8) or significantly (9, 10) decreased for those developing PTDM.     

Genetic association analyses of fast plasma glucose level in pre-menopausal Chinese women: potential interaction between osteocalcin and oestrogen receptor α

Background: Fasting plasma glucose (FPG) levels are usually tightly regulated within a narrow physiologic range. Variation of FPG levels is clinically important and is strongly heritable. Several lines of evidence suggest the importance of the oestrogen receptor α (ER-α) and osteocalcin (also known as BGP, for bone Gla protein) in determining FPG; however, whether their polymorphisms are associated with FPG variation is not well understood.

Aim: To investigate whether ER-a PvuII and BGP HindIII genetic polymorphisms and their potential interaction are associated with FPG variation.

Subjects and methods: The study subjects were 328 unrelated pre-menopausal Chinese women aged 21 years and over (mean age?±?SD, 33.2?±?5.9 years), with an average FPG of 4.92 (SD?=?0.81). All subjects were genotyped at the ER-α PvuII and BGP HindIII loci using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP).

Results: The ER-α PvuII genotypes were significantly associated with FPG (p?=?0.007). In addition, a significant interaction was observed of the ER-α PvuII polymorphism with BGP HindIII polymorphism on FPG variation (p?=?0.013), although the BGP HindIII polymorphism was not shown to be individually associated with FPG.

Conclusion: The PvuII polymorphism of the ER-α gene and its potential interaction with the HindIII polymorphism of the BGP gene were associated with FPG in pre-menopausal Chinese women.     

Utilization of model-based meta-analysis to delineate the net efficacy of taspoglutide from the response of placebo in clinical trials

The objective of this study was to develop quantitative models to delineate the net efficacy of taspoglutide on fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) from the response of placebo in type 2 diabetes patients, and further find pharmacodynamic potency of taspoglutide and FPG for half of maximum reduction responses of FPG and HbA1c, respectively. Several PD data about taspoglutide treatments for type 2 diabetes patients were digitalized from the published papers related with the clinical development of taspoglutide. The model based meta-analysis (MBMA) studies for FPG and HbA1c were performed with Monolix 4.2 software. The MBMA successfully described the effects of placebo and taspoglutide on pharmacological indexes of FPG and HbA1c through mono and multiple combination therapies in clinical trials. The pharmacodynamic potency (25.3 pmol/l) produced 50% of maximum responses of FPG (−2.39 mmol/l) from the responses of placebo for FPG (−0.371 mmol/l); the response change of FPG (−1.81 mmol/l) affected 50% of maximum response change (−1.74%) for HbA1c from the response of placebo (−0.253%). The leveraging prior knowledge from the longitudinal MBMA will be utilized to guide clinical development of taspoglutide and further support study designs including optimization of dose and duration of therapy.