Endothelium-dependent and independent vasodilation studied at normoglycaemia in Type I diabetes mellitus with and without microalbuminuria

Aims/hypothesis. We examined whether endothelial function is impaired in patients with Type I (insulin-dependent) diabetes mellitus under conditions of near-normoglycaemia compared with age-matched healthy control subjects. Our aim was to determine whether microalbuminuria is associated with endothelial dysfunction in Type I diabetes. Methods. Endothelial function, measured as post-ischaemic flow-mediated dilatation of the brachial artery using ultrasound, was compared among 17 microalbuminuric and 17 normoalbuminuric diabetic patients, and 17 control subjects. Glyceryl trinitrate-mediated dilatation of the brachial artery was used to measure endothelium-independent function. All diabetic patients were studied at near-normoglycaemia, using insulin and 5 % dextrose infusions to maintain blood glucose between 3.5 and 8.0 mmol/l. Results. Flow-mediated dilatation was significantly lower in microalbuminuric diabetic patients (3.2 ± 0.3 %) compared with normoalbuminuric diabetic patients (5.4 ± 0.6 %) and control subjects (7.9 ± 0.6 %, p < 0.001). Normoalbuminuric diabetic patients also had significantly lower flow-mediated dilatation than control subjects (p = 0.01). Glyceryl trinitrate mediated dilatation was significantly lower in the microalbuminuric patients compared with the control subjects (11.9 ± 1.1 % vs 20.0 ± 1.2 %, p = 0.001). Albumin excretion rate and glycated haemoglobin showed a significant negative independent correlation with flow-mediated dilatation (both p < 0.05). Conclusion/interpretation. Type I diabetic patients show endothelial dysfunction at near-normoglycaemia compared with the control subjects, and this abnormality is more marked in diabetic patients with microalbuminuria. Endothelial dysfunction in Type I diabetes is related to the albumin excretion rate and glycaemic control. The presence of endothelial dysfunction in normoalbuminuric diabetic patients suggests it could precede microalbuminuria as an early risk marker for cardiovascular disease. [Diabetologia (2001) 44: 593–601] Received: 6 November 2000 and in revised form: 11 January 2001     

Plasma apolipoprotein (a) is increased in Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria

Summary Patients with Type 2 (non-insulin-dependent) diabetes mellitus complicated by microalbuminuria or albuminuria, have an increased risk of developing macrovascular disease and of early mortality. Because lipoprotein abnormalities have been associated with diabetic nephropathy, this study tested the hypothesis that levels of apolipoprotein (a) are elevated in patients with Type 2 diabetes and increased levels of urinary albumin loss. Levels of apolipoprotein (a) in diabetic patients with microalbuminuria (n = 26, geometric mean 195 U/1, 95 % confidence interval 117–324) and albuminuria (n = 19, 281 U/1,165–479) were higher than in non-diabetic control subjects (n = 140,107 U/1, 85–134,p < 0.05), and in the albuminuric group than diabetic patients without urinary albumin loss (n = 58, 114 U/1, 76–169,p < 0.05). Patients with microalbuminuria and albuminuria had levels comparable with patients undergoing elective coronary artery graft surgery (n = 40,193 U/1,126–298). Apolipoprotein (a) levels were higher in diabetic patients with macrovascular disease than in those without (n = 49, 209 U/1, 143–306 vsn = 54, 116 U/1, 78–173,p < 0.05). These preliminary results suggest that raised apolipoprotein (a) levels of Type 2 diabetic patients with microalbuminuria and albuminuria may contribute to their propensity to macrovascular disease and early mortality.     

Glomerular charge selectivity and the influence of improved blood glucose control in Type 1 (insulin-dependent) diabetic patients with microalbuminuria

Summary We first compared glomerular charge selectivity index in two matched groups of Type 1 (insulin-dependent) diabetic patients with micro and normoalbuminuria respectively, and secondly, investigated prospectively in a randomized clinical trial, the influence of improved metabolic control on selectivity index in diabetic patients with microalbuminuria. In Study 1, 27 patients with microalbuminuria (albumin excretion >-15 g/min in at least two out of three overnight urine samples) were matched (age, diabetes duration, mean 1-year HbA_1c, gender) with normoalbuminuria patients (n=24), and in Study 2, 23 microalbuminuric patients were randomly allocated to either intensive (continuous subcutaneous insulin infusion) or conventional treatment. Glomerular charge selectivity index was measured as IgG/IgG₄ selectivity index, i.e. total IgG/IgG₄ clearance ratio in timed overnight urine samples. The microalbuminuric patients had a significantly reduced selectivity index compared to the normoalbuminuric patients: 1.20 (0.92–1.40) vs 1.68 (1.22–2.21), median and 95% confidence interval (p<0.01). In Study 2, the HbA_1c improved in the intensive-treatment group compared to the conventional-treatment group: at 2, 6 and 12 months the difference in mean percentage HbA_1c between the groups was 1.1, 1.2 and 1.4, respectively (p<0.01). A sharp 50% increment in IgG/IgG₄ selectivity index was seen in the intensive-treatment group during the first 6 months (p<0.05 compared to the conventional group). We conclude that adolescents and young adults in an early stage of diabetic nephropathy have reduced glomerular charge selectivity, which may be improved by reducing the mean blood glucose level.     

The cost-effectiveness of different management strategies for Type I diabetes: a Swiss perspective

Aims/hypothesis. A computer model was developed to determine the health outcomes and economic consequences of different combinations of diabetes interventions in newly diagnosed patients with Type I (insulin-dependent) diabetes in Switzerland.¶Methods. We modelled seven complications of diabetes: hypoglycaemia, ketoacidosis, acute myocardial infarction, stroke, lower extremity amputation, nephropathy, and retinopathy. Transition probabilities and costs were taken from published literature. The Swiss health insurance payer perspective was taken. Various combinations of diabetes management strategies, including intensive or conventional insulin therapy and screening and treatment strategies for renal and eye disease were defined. Life expectancy, cumulative incidences of complications, and mean expected total lifetime costs per patient were calculated under six different management strategies. Incremental cost-effectiveness ratios were calculated in terms of costs per life-year gained compared with conventional insulin therapy alone.¶Results. The addition of screening for microalbuminuria and retinopathy followed by appropriate treatment, if detected, were cost saving, with reduction in cumulative incidence of end stage renal disease and blindness respectively, and, in the case of microalbuminuria screening and treatment, an improvement in life expectancy. Intensive therapy improved life expectancy but increased total lifetime costs.¶Conclusion/interpretation. Optimal management of Type I diabetic patients, including secondary and tertiary prevention, leads to reduced complications and improved life expectancy, with the increased costs of prevention offset to varying degrees by cost savings due to complications avoided. [Diabetologia (2000) 43: 13–26]     

原发性高血压患者昼夜血压节律异常与尿微量白蛋白的关系

目的 研究原发性高血压患者昼夜血压节律变化与尿微量白蛋白的关系.方法 将188例原发性高血压患者根据夜间收缩压下降百分比分为A（非杓型组）、B（杓型组）两组,并设30例健康体检人群为对照（C组）,记录各组患者一般资料、24h动态血压、空腹血糖、胆固醇以及尿微量白蛋白并比较,分析昼夜血压节律变化与尿微量白蛋白的关系.结果 A组患者尿微量白蛋白水平较B组、C组明显升高（P＜0.01）;A组患者尿微量白蛋白水平受多种因素影响,其中日间平均收缩压（dSBP）、24h平均收缩压（24 h SBP）以及24h平均舒张压（24 h DBP）可能是其关键的独立危险因素.结论 原发性高血压患者昼夜血压节律异常与尿微量白蛋白的关系密切,其中dSBP、24hSBP以及24 h DBP可能是其关键的独立危险因素.     

维生素B1水平与糖尿病肾病进展的关联性分析

目的：检测2型糖尿病患者血浆、红细胞及尿液中维生素B1水平,分析其与糖尿病肾病进展的关联性,阐明2型糖尿病肾病的代谢营养机制。方法：根据尿微量白蛋白水平将90例2型糖尿病患者分为糖尿病无肾病组（NDN组）、早期肾病组（EDN组）和临床肾病组（CDN组）,每组30例;30名志愿者作为正常对照组（NC组）,采用高效液相色谱法（HPLC）测定其血浆、红细胞及尿液中维生素B1的水平,分析尿微量白蛋白与血浆维生素B1水平的相关性。结果：NC组血浆维生素B1水平为(7.1±3.3) μg?L-1,NDN组、EDN组和CDN组血浆维生素B1水平分别是(4.0±2.3)、(3.1±1.0)和(2.3±0.6) μg?L-1,3组较正常组分别下降了43.7%、56.3%和67.6% (P<0.05)。NC组、NDN组、EDN组和CDN组尿液中维生素B1排泄量分别是(2.9±0.8)、(9.0±4.7)、(11.7±3.9)和(15.6±5.0) μg?L-1,3组较正常组分别增加了2、3和4.4倍（P<0.05）。尿微量白蛋白与血浆维生素B1水平呈负相关关系(r =－0.62,P=0.013)。结论：2型糖尿病患者肾病早期即发生维生素B1缺乏,且与肾病的进展密切关联,补充维生素B1可能有助于改善糖尿病肾病患者的病情。     

Increased Inflammatory Markers Are Associated with Obesity and Not with Target Organ Damage in Newly Diagnosed Untreated Essential Hypertensive Patients

The aim of this study was to investigate whether inflammatory markers are associated with hypertensive end organ damage or obesity in patients with hypertension. Seventy newly diagnosed essential hypertensive patients (29 men and 41 women aged 49.6 ± 9.5 y) and 25 age–sex-matched normotensive subjects (12 men and 13 women aged 45.8 ± 7.3 y) were asked about their family history of hypertension and smoking habits, and body mass index (BMI) was recorded and blood samples were taken to measure fibrinogen, C-reactive protein (CRP), and homocysteine levels. In hypertensive patients, creatinine clearance, urinary albumin extraction, and left ventricular mass index were determined. Hypertensive patients had significantly higher BMIs and inflammatory markers when compared with normotensive healthy controls. The CRP was positively associated with BMI (P < .05), diastolic blood pressure (P < .05), fibrinogen (P < .01), urinary albumin extraction (P < .01), and left ventricular mass index (P < .05). The BMI and serum fibrinogen level were independently associated with CRP. The effect of inflammation on the development of hypertensive end organ damage may be associated with obesity, so that control of obesity may eliminate the inflammatory state in hypertensive patients and also hypertensive end organ damage.     

Prognostic factors in resistant hypertension: implications for cardiovascular risk stratification and therapeutic management

Resistant hypertension (RH) is defined as uncontrolled office blood pressure (BP) in spite of the use of at least three antihypertensive medications. Although its condition has a high prevalence, it is still understudied, and its prognosis is not well established. Some prospective studies evaluated the prognostic value of ambulatory BP monitoring, ECG and renal parameters. They pointed out that ambulatory BPs are important predictors of cardiovascular morbidity and mortality, whereas office BP has no prognostic value. The diagnosis of true RH and the nondipping pattern are also valuable predictors of cardiovascular outcomes. Moreover, several ECG (prolonged ventricular repolarization, serial changes in the strain pattern and left ventricular hypertrophy) and renal parameters (albuminuria and reduced glomerular filtration rate) are also powerful cardiovascular risk markers in RH. These markers and others yet unexplored, such as arterial stiffness and serum biomarkers, may improve cardiovascular risk stratification in these very high-risk patients.