Carotid stiffness and microalbuminuria in patients with type 2 diabetes

Microalbuminuria is associated with higher cardiovascular mortality, especially in diabetics. But the direct association between microalbuminuria and vascular wall properties is still not clear. We investigated quantitative carotid stiffness (QCS) index in relation to microalbuminuria in 260 Chinese diabetic patients. In categorical analyses, patients with elevated urinary albumin-to-creatinine ratio (uACR) had higher QCS than those with normal uACR (P < 0.001). The corresponding values for QCS values were 4.4 and 5.9, respectively. In multiple stepwise regression analyses, QCS was significantly associated with age, uACR, plasma glycosylated hemoglobin A_1C (HbA_1C), and current smoking (P < 0.05 for all). In conclusion, carotid stiffness as measured by QCS, a local functional measurement of the arterial wall, is increased in type 2 diabetes with microalbuminuria. Wei-Wei Zhan and Yu-Hong Chen have contributed equally to this article.     

2型糖尿病尿微量白蛋白与心血管病危险因素的研究

目的探讨2型糖尿病（T2DM）患者尿微量白蛋白与心血管病危险因素（血糖、血脂、血压、尿酸等）的关系。方法选择192例确诊为T2DM住院患者,分为微量白蛋白尿（MAU）组（n=60）和正常微量白蛋白尿（NAU）组（n=132）,检测患者体质指数（BMI）、血脂、血压、尿酸等相关危险因素,并进行对比分析;同时以尿微量白蛋白为因变量,各相关危险因素为自变量进行了多元线性回归分析,以明确影响2型糖尿病患者尿微量白蛋白增加的因素。结果 MAU组糖化血红蛋白水平（HbA1c）、入院时收缩压（SBP）、舒张压（DBP）水平、血肌酐（Cr）、尿酸（UA）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）水平及TC、LDL-C、UA、SBP和DBP的异常率明显高于NAU组,而高密度脂蛋白胆固醇（HDL-C）水平明显低于NAU组（P〈0.05～0.01）,多元线性回归分析发现MAU与BMI、SBP、DBP、TC、TG、LDL-C、HbA1c、UA和Cr呈正相关,而与HDL-C呈负相关（P〈0.05～0.01）。结论血脂、血压等多种危险因素的异常影响T2DM患者尿微量白蛋白水平。     

High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study

Aims/hypothesis  High-dose supplements of thiamine prevent the development of microalbuminuria in experimental diabetes. The aim of this pilot study was to assess whether oral supplements of thiamine could reverse microalbuminuria in patients with type 2 diabetes. Methods  Type 2 diabetic patients (21 male, 19 female) with microalbuminuria were recruited at the Diabetes Clinic, Sheikh Zayed Hospital, Lahore, Pakistan, and randomised to placebo and treatment arms. Randomisation was by central office in sequentially numbered opaque, sealed envelopes. Participants, caregivers and those assessing the outcomes were blinded to group assignment. Patients were given 3 × 100 mg capsules of thiamine or placebo per day for 3 months with a 2 month follow-up washout period. The primary endpoint was change in urinary albumin excretion (UAE). Other markers of renal and vascular dysfunction and plasma concentrations of thiamine were determined. Results  UAE was decreased in patients receiving thiamine therapy for 3 months with respect to baseline (median −17.7 mg/24 h; p < 0.001, n = 20). There was no significant decrease in UAE in patients receiving placebo after 3 months of therapy (n = 20). UAE was significantly lower in patients who had received thiamine therapy compared with those who had received placebo (30.1 vs 35.5 mg/24 h, p < 0.01) but not at baseline. UAE continued to decrease in the 2 month washout period in both groups, but not significantly. There was no effect of thiamine treatment on glycaemic control, dyslipidaemia or BP. There were no adverse effects of therapy. Conclusions/interpretation  In this pilot study, high-dose thiamine therapy produced a regression of UAE in type 2 diabetic patients with microalbuminuria. Thiamine supplements at high dose may provide improved therapy for early-stage diabetic nephropathy. Trial registration: CTRI (India) CTRI/2008/091/000112 Funding: Pakistan Higher Education Commission     

2型糖尿病微量白蛋白尿患者血浆血小板活化因子的检测及其临床意义

目的研究2型糖尿病微量白蛋白尿患者血浆血小板活化因子(PAF)的水平及其与尿白蛋白排泄率(UAER)的相互关系.方法采用生物学方法和放免法分别测定30例健康人(正常对照组)、30例2型糖尿病正常白蛋白尿患者、28例2型糖尿病微量白蛋白尿患者血浆PAF和UAER水平.结果 (1)正常对照组与正常白蛋白尿组相比UAER、血浆PAF均无显著性差异(P>0.05);(2)在排除代谢因素影响后,2型糖尿病组中微量白蛋白尿组与正常白蛋白尿组相比血浆PAF有非常显著性差异(P<0.01);(3)UAER与PAF正相关,相关系数0.68,尤其在微量白蛋白尿组,相关系数达0.74.结论血浆PAF增高可能参与了2型糖尿病微量白蛋白尿的发生、发展过程,它的检测可作为早期糖尿病肾病的诊断、治疗、预后观察的一个临床指标.     

An acceptable exercise test to study microalbuminuria in type 1 diabetes

A modified test for studying the response of urinary albumin excretion (UAV) to exercise in diabetic patients is described. It is designed to produce a standardized increase in pulse rate (by 90-110%) rather than a standardized workload. Thirty-three normotensive Type 1 diabetic patients with normal pre-exercise UAV (less than 10 micrograms min-1) on the day of the test were compared with 25 non-diabetic subjects matched for age and sex. The patients developed a significantly greater increase in the median UAV (p less than 0.05) and systolic blood pressure (p less than 0.01) during exercise, despite the use of lower workloads (p less than 0.05). During exercise, the albumin excretion in the patients was not related to their heart rate, blood pressure, workload or fall in blood glucose; nor was it related to duration of diabetes, glycosylated haemoglobin or insulin dose. An exercise UAV greater than 15 micrograms min-1 was found in 10 of the 33 patients; it was significantly correlated (p less than 0.01) with the frequency of previous overnight microalbuminuria (greater than 10 micrograms min-1), and was associated with a greater progression of microalbuminuria (p less than 0.05) over a mean period of 24 months. Retinol-binding protein excretion rate was also measured as an indicator of proximal tubular function and did not increase in either group.     

Serum lipids and lipoproteins in type 2 diabetic patients with persistent microalbuminuria

To investigate whether persistent microalbuminuria is related to altered levels of both lipids and apolipoproteins in Type 2 diabetes mellitus serum total-cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein A-I, and apolipoprotein B were measured by standard methods in a group of Type 2 diabetic patients affected by persistent microalbuminuria (albumin excretion rate (AER) 20-200 micrograms min-1) as compared with a group of sex- and age-matched non-microalbuminuric patients (AER less than 20 micrograms min-1). The groups were stratified according to a short (less than or equal to 5 years) or a longer (greater than 5 years) duration of diagnosed diabetes. Microalbuminuria was not associated with significant changes of serum total-cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, and apolipoproteins in the group of patients with a duration of disease greater than 5 years, while microalbuminuric patients less than or equal to 5 years from diagnosis (n = 11) had serum total-cholesterol, triglycerides, LDL-cholesterol, and apoprotein B higher than non-microalbuminuric control patients (n = 26) (cholesterol 6.2 +/- 0.9 vs 5.1 +/- 1.0 mmol l-1 (p = 0.003); triglycerides 2.1 +/- 0.7 vs 1.7 +/- 1.3 mmol l-1 (p = 0.03); LDL-cholesterol 4.1 +/- 0.8 vs 3.0 +/- 0.7 mmol l-1 (p less than 0.001); apo-B 1.3 +/- 0.3 vs 1.1 +/- 0.3 g l-1 (p = 0.02). In these patients with shorter duration of diabetes many of the serum lipid measures correlated positively with AER.     

Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients

Aims/hypothesis  This study examined the relationship, if any, between glucose-induced oxidative stress, antioxidant status and microalbuminuria in patients with type 2 diabetes. Methods  The study involved 99 consecutive type 2 diabetic patients (57 men, 42 women). Patients with persistent microalbuminuria were identified and the following variables evaluated: fasting plasma glucose, HbA_1c, malonyldialdehyde (MDA), pentosidine, AGE, the total radical-trapping antioxidant parameter (TRAP), vitamin E, creatinine, estimated GFR and lipid profile. Results  Patients were divided into two groups, i.e. 37 individuals without microalbuminuria (AER <20 μg/min) and 62 with microalbuminuria (AER ≥20 μg/min). The following variables were significantly higher in patients with microalbuminuria than in those without microalbuminuria (mean ± SD): fasting plasma glucose 9.41 ± 2.88 vs 8.19 ± 1.93 mmol/l, p < 0.05; HbA_1c 7.97 ± 1.51 vs 7.39 ± 1.03%, p < 0.05; MDA 1.18 ± 0.35 vs 1.02 ± 0.29 μmol/l, p < 0.05; pentosidine 98.5 ± 24.6 vs 82.9 ± 20.9 pmol/ml, p < 0.005; and AGE 13.2 ± 4.8 vs 10.6 ± 3.8 μg/mg protein, p < 0.01. However, vitamin E and TRAP did not differ between the two groups. Serum creatinine values and estimated GFR were similar in the two groups. Only in patients with microalbuminuria were significant linear correlations seen between AER and both oxidation (HbA_1c r = 0.33, p < 0.01; MDA r = 0.59, p < 0.001; pentosidine r = 0.48, p < 0.001; and AGE r = 0.44, p < 0.001) and antioxidation variables (vitamin E r = −0.55, p < 0.001; TRAP r = −0.49, p < 0.001). Considering all variables together, multiple regression revealed a correlation between microalbuminuria and vitamin E, TRAP, HbA_1c and MDA, but not pentosidine or AGE. Conclusions/interpretation  Our data suggest that microalbuminuria in type 2 diabetic patients might be promoted by an insufficient counter-regulation of the antioxidant system in the event of increased glyco-oxidation/glycation.     

微量清蛋白尿与2型糖尿病合并冠心病的关系

目的:探讨2型糖尿病患者微量清蛋白尿(MA)与冠心病的关系。方法:342例2型糖尿病患者根据冠状动脉(冠脉)造影结果分为合并冠心病组(106例)和不合并冠心病组(236例),测定2组24h尿清蛋白、血糖、糖化血红蛋白及血脂等相关指标;比较MA阳性组(139例)和MA阴性组(203例)冠心病的发病率及冠脉造影特点。采用多元Logistic回归方法分析2型糖尿病患者冠脉病变的危险因素。结果:糖尿病合并冠心病组MA水平明显高于不合并冠心病组(P<0.01),多元逐步回归分析也表明MA与糖尿病患者冠心病的发生显著相关(P<0.05);MA阳性组冠心病发病率明显高于MA阴性组(42.5%比23.2%,P<0.01);此外,与MA阴性组比较,MA阳性组重度血管狭窄、弥漫性和闭塞性病变更多(P0.05)。结论:MA是2型糖尿病患者冠脉病变的重要危险因素,且伴MA的2型糖尿病合并冠心病患者冠脉病变更严重。     

Microalbuminuria predicts the development of serum lipoprotein abnormalities favouring atherogenesis in newly diagnosed type 2 (non-insulin-dependent) diabetic patients

Summary We studied the relationship of slight albuminuria (microalbuminuria) to serum lipid and lipoproteins in a representative group of middle-aged Type 2 (non-insulin-dependent) diabetic patients. A random sample of non-diabetic control subjects was also examined. Diabetic patients had both at diagnosis and after five years higher total, LDL- and VLDL-triglyceride levels and higher VLDL-cholesterol, but lower HDL-cholesterol levels than non-diabetic subjects. No consistent difference was found in LDL-cholesterol levels between diabetic and non-diabetic subjects. The prevalence of microalbuminuria (>35 mg/24 h) remained about the same in diabetic patients at both examinations (19–20%). The diabetic patients with persistent microalbuminuria were slightly hyperglycaemic and they tended to have lower creatinine clearance at the 5-year examination than those without persistent microalbuminuria. There were no differences in the blood pressure levels or the occurrence of hypertension between the diabetic groups with and without microalbuminuria. At the baseline examination, no differences were seen in serum lipids and lipoproteins between diabetic patients with and without microalbuminuria. In patients with persistent microalbuminuria. a statistically significant increase in VLDL-cholesterol (p<0.05) and VLDL- and LDL-triglyceride levels (p<0.05) and a decrease in HDL-cholesterol level (p<0.05) was seen at the 5-year follow-up. These changes could not be explained by age, sex, body mass index or HbA₁. In conclusion, persistent microalbuminuria predicts and aggravates abnormalities in lipoprotein composition and a decrease in HDL-cholesterol in patients with Type 2 diabetes mellitus. The excess cardiovascular morbidity and mortality in diabetic patients with increased albuminuria may, in part, be explained by these lipoprotein abnormalities.     

The natural history and associations of microalbuminuria in type 2 diabetes during the first year after diagnosis

The prevalence of microalbuminuria was assessed in 149 consecutive, newly-diagnosed and untreated patients with Type 2 diabetes, 129 of whom were followed up for 1 year, with at least three urine specimens being obtained during this period. At initial presentation, 39 (26%) patients had a urinary albumin to creatinine ratio (ACR) of greater than 2.5 mg mmol-1 and compared with patients who had a normal ACR, they were older (64 (11) (SD) vs 58 (11) yr, p less than 0.002), with higher random blood glucose (14.4 (4.5) vs 12.3 (4.4) mmol l-1, p less than 0.02) and glycosylated haemoglobin (13.0 (3.1) vs 11.3 (2.7)%, p less than 0.01) concentrations. An elevated ACR was also associated with a higher systolic blood pressure (149 (22) vs 140 (22), p less than 0.05) and the presence of macrovascular disease, particularly peripheral vascular disease (p less than 0.001), with this association persisting after adjustment for the effect of age. Ten patients reverted to normal albumin excretion on improving blood glucose control, this group having a significantly higher glycosylated haemoglobin concentration at initial presentation than the group with a persistently elevated ACR (14.4 (2.5) vs 12.0 (3.0)%, p less than 0.05). The 21 (16%) patients with a persistently elevated ACR from diagnosis of Type 2 diabetes were older than those with normal albumin excretion throughout (64 (7) vs 58 (10) yr, p less than 0.02) and it is probable that these patients have abnormal albumin excretion secondary to established renal pathology.     

Impact of an educational intervention in the management of individuals with uncontrolled type 2 diabetes mellitus using insulin therapy

ObjectiveTo investigate the effects of problematizing intervention in the treatment of individuals with type 2 diabetes mellitus.MethodologyA randomized clinical trial was conducted in 41 patients ages 18 to 64 with type 2 diabetes who were treated with insulin and had glycosylated hemoglobin greater than 7.0%. The mean age of participants was 55.9 (SD = 5.49). A high percentage of patients had comorbidities such as hypertension (92.7%), dyslipidemia (68.3%), overweight (95%), retinopathy (41%), and neuropathy (39%). The patients in the intervention group participated in 6 educational groups using problematization methodology, whereas the patients in the control group attended only routine consultations. Sociodemographic, clinical, behavioral, and lifestyle variables were assessed.ResultsAfter 6 months of follow-up, no statistically significant difference in glycemic control and anthropometric parameters was observed between participants in either study group. The intervention group showed an increase in knowledge about the disease, and an improvement in total cholesterol and uric acid levels.ConclusionThe use of a problematizing intervention provided an improvement in behavioral as well as specific clinical parameters, compared to routine diabetes care. However, longer follow-up time for these patients could bring benefits regarding glycemic control.     

Effects of structured Ramadan Nutrition Plan on glycemic control and variability using continuous glucose monitoring in individuals with type 2 diabetes: A pilot study

Background and aimsContinuous glucose monitoring (CGM) has been increasingly used in recent years to evaluate glycemic control and variability in individuals with diabetes observing Ramadan fasting. However, the effectiveness of the Ramadan Nutrition Plan (RNP) in individuals with type 2 diabetes (T2D) using CGM-derived measures has not been investigated. The study aimed to evaluate the effects of structured RNP versus standard care using CGM in individuals with T2D.MethodsThis parallel non-randomized interventional study with patients’ preference design involved 21 individuals with T2D (mean age: 49 ± 10 years, BMI: 30.0 ± 6.2 kg/m²). Participants chose to receive either structured RNP (sRNT; structured Ramadan Nutrition Therapy group; n = 14) or standard care (SC; n = 7). Participants wore CGM 5 days before Ramadan and during Ramadan. CGM-derived measures of glycemic variability were calculated using Glyculator version 2.0.ResultsCompared to the SC group, the sRNT group significantly reduced their fasting blood glucose levels, HbA1c, total cholesterol, diastolic blood pressure, and increased dietary fiber intake. CGM data showed the sRNT group had significantly lower average sensor glucose, peak sensor value, estimated A1c, percentage and duration of time-above-range, J-index, mean amplitude of glycemic excursion (MAGE), and continuous overall net glycemic action (CONGA); and a significantly higher percentage of time-in-range (TIR).ConclusionsThe structured RNP significantly improved clinical outcomes, glycemic control and variability in individuals with T2D. The study highlights the importance of utilizing CGM sensor data to monitor glycemic excursions during Ramadan fasting. Adequately powered randomized controlled trials are needed to confirm the findings.     

Limited impact of lifestyle education in patients with Type 2 diabetes mellitus and microalbuminuria: results from a randomized intervention study.

AIMS: To assess the effect of intensified education on lifestyle (diet, exercise and smoking) as part of an intensified multifactorial intervention over a 4-year period in patients with Type 2 diabetes mellitus with microalbuminuria. METHODS: Patients, aged 45-65 years, were randomly assigned either to an intensive group focusing on change of behaviour as well as polypharmacological treatment (n = 80) or to a control group receiving conventional treatment (n = 80). Diet intervention focused on dietary fat and carbohydrate. Food intake was estimated by dietary history interviews and nutrients were calculated from food tables. Exercise and smoking habits were evaluated by interviews. RESULTS: Mean follow-up was 3.8 (SD 0.3) years. The decrease in total fat intake (% of energy intake) was larger in the intensive group as compared to the control group (41.2 (6.2) to 34.2 (6.0) vs. 41.9 (6.5) to 38.3 (6.4)%, P = 0,0001). The decrease in saturated fatty acids (% of total fat intake) was from 47 (4) to 44 (6)% with intensive therapy vs. 45 (5) to 46 (5)%, P = 0.001 and the increase in polyunsaturated fatty acids was from 14 (4) to 18 (6) vs. 16 (5) to 14 (4)%, P < 0.0001. Also the increase in carbohydrate was larger with intensive therapy. However, changes in exercise and smoking habits did not differ between groups. CONCLUSION: Despite the many resources invested in behaviour modification in this study, only modest changes were obtained in nutrient intake. Further studies are required to determine the best method of inducing long-lasting changes in behaviour in Type 2 diabetic patients.     

原发性高血压并2型糖尿病患者脉压与蛋白尿的相关性探讨

目的　研究 2型糖尿病及高血压病患者脉压 (PP)与尿微量白蛋白的关系。方法　对 2 4 1例患者 ,高血压 (EH)患者 75例、2型糖尿病 (T2 DM)患者 77例和高血压病合并 2型糖尿病 (EH +T2 DM)患者 89例进行血压检测和尿微量白蛋白测定。结果　T2 DM组微量白蛋白与收缩压 (SBP)相关性不显著 (P >0 .0 5 ) ;而与PP显著正相关 (P <0 .0 5 )。EH组微量白蛋白与SBP和PP呈显著正相关 (P <0 .0 5 ) ;EH +T2 DM组微量白蛋白与SBP和PP呈显著正相关 (P <0 .0 5 ) ,微量白蛋白与PP相关性在EH +T2 DM组最大。反映肾功能的其它指标则与SBP、PP无相关性。结论　在上述 3种患者中只PP与早期肾损害相关 ,故为防止DM和EH患者肾脏损害加重 ,降低PP很重要。     

The Natural Course of Microalbuminuria among African Americans with Type 2 Diabetes: A 3-Year Study

Background

The natural course of microalbuminuria in African Americans (AA) with type 2 diabetes is not well established.

Method

Longitudinal analysis of 186 African Americans with type 2 diabetes enrolled in Project Sugar, a randomized controlled trial of primary care-based interventions to improve diabetes control.

Results

Mean age was 59.4 years and 85% were female. Mean estimated glomerular filtration rate and urinary albumin-to-creatinine ratio were 75.90 mL/min/1.73 m² and 1.62, respectively. Thirty-nine patients had macroalbuminuria and significantly higher systolic blood pressure compared with those with microalbuminuria (P = .01). Sixty patients had microalbuminuria, 19 progressed to macroalbuminuria, and none regressed. Progression was associated significantly with systolic blood pressure ≥115 mm Hg and requirement for blood pressure medication in the univariate model. In the multivariate model, the degree of albumin-to-creatinine ratio (odds ratio 35.51, 95% confidence interval, 2.21-571.65) and need for blood pressure medication (odds ratio 8.96, 95% confidence interval, 1.35-59.70) were independently associated with progression. No association was observed with the use of specific antihypertensive agent.

Conclusion

This study suggests that African Americans with type 2 diabetes and microalbuminuria experience irreversible disease that not infrequently progresses to overt proteinuria. The degree of microalbuminuria and blood pressure are key determinants in this process and should be primary targets in treating this population regardless of the antihypertensive class used.     

Microalbuminuria: Prognostic and Therapeutic Implications in Diabetes Mellitus

Thirty years following the development of the first radioimmunoassay for albumin, microalbuminuria is widely acknowledged as an important predictor of overt nephropathy in patients with Type 1 diabetes and of cardiovascular mortality in Type 2 diabetes. In addition, there is accumulating evidence to suggest that diabetic patients with microalbuminuria may have more advanced retinopathy, higher blood pressure, and worse dyslipidaemia than patients with normal albumin excretion rates. Recent studies have focused on the role of intervention, principally with antihypertensive therapy and intensive glycaemic control, in reducing microalbuminuria. While successful in reducing urinary albumin excretion it remains to be established whether such therapies will be translated into a reduction in renal failure and decreased cardiovascular mobidity and mortality.     

Serum Ferritin level,microalbuminuria and non-alcoholic fatty liver disease in type 2 diabetic patients

BackgroundNon-alcoholic fatty liver disease (NAFLD) was considered one of the most common causes of chronic liver disease and is considered the hepatic manifestation of type 2 diabetes mellitus (T2DM). The factors that lead to marked fibrosis and liver cell injury in NAFLD are still remaining undiscovered.Patients and methodsThis study included (40) type 2 diabetic patients with NAFLD and (40) diabetic patients without NAFLD beside 15 healthy persons as a control group. All of them were subjected to full history taking, thorough clinical examination with especial stress on body weight (BW), height, body mass index (BMI), waist-hip ratio, blood pressure. Laboratory tests included serum total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL), fasting blood glucose (FBG) and 2-h postprandial blood glucose (PBG), serum Ferritin and urine microalbuminuria (MAU).ResultsDuration of diabetes, BW, BMI and blood pressure were significantly higher in NAFLD group (P = 0.001). FBG, PBG, TC, TG, LDL, serum Ferritin and MAU were significantly increased in NAFLD group with significant difference between two studied groups as regard HDL. There was a highly significant correlation between serum Ferritin with BW, BMI, duration of diabetes, TC, TG, LDL and MAU. There was a significant correlation between serum Ferritin with age, waist hip ratio, duration of diabetes, SBP, FBG, PBG and HDL. There was a significant correlation between MAU and age, weight, BMI, waist hip ratio, duration of diabetes, DBP, FBG TC, TG, LDL and HDL.ConclusionNAFLD is a common liver disorder in diabetic patients. NAFLD is significantly associated with microalbuminuria and elevated serum Ferritin.