Serum adiponectin is increased in type 1 diabetic patients with nephropathy

OBJECTIVE: To elucidate whether serum adiponectin is associated with renal function, low-grade inflammatory markers, metabolic control, and insulin resistance in type 1 diabetic patients with and without nephropathy. RESEARCH DESIGN AND METHODS: A total of 189 type 1 diabetic patients from the Finnish Diabetic Nephropathy Study were divided into three groups based on their urinary albumin excretion rate (AER): patients with normal AER (n = 66) had no antihypertensive medication, while patients with microalbuminuria (n = 63) or macroalbuminuria (n = 60) were all treated with an ACE inhibitor. Renal function was estimated with the Cockcroft-Gault formula. Adiponectin was measured by an in-house time-resolved immunofluorometric assay. RESULTS: Adiponectin concentrations were higher in women than in men, but since there was no significant difference in sex distribution between the groups, data were pooled. Adiponectin concentrations were higher in patients with macroalbuminuria (19.8 +/- 12.0 mg/l) than in patients with microalbuminuria (13.1 +/- 4.8 mg/l) or normoalbuminuria (11.8 +/- 4.2 mg/l). In a univariate analysis, adiponectin was positively associated with creatinine (r = 0.41; P < 0.0001), AER (r = 0.33; P < 0.0001), interleukin-6 (r = 0.22; P = 0.002), systolic blood pressure (r = 0.22; P = 0.004), HbA(1c) (r = 0.17; P = 0.02), total cholesterol (r = 0.16; P = 0.03), and HDL cholesterol (r = 0.16; P = 0.03) and negatively with estimated glomerular filtration rate (GFR; r = -0.52; P < 0.0001) and waist-to-hip ratio (WHR; r = -0.16; P = 0.03). In a multiple linear regression analysis including the above variables, estimated GFR, AER, and WHR were independently associated with adiponectin levels (r(2) = 0.32). CONCLUSIONS: Serum adiponectin concentrations are increased in type 1 diabetic patients with nephropathy, and levels are further associated with renal insufficiency.     

Urinary transforming growth factor-beta1 and alpha1-microglobulin in children and adolescents with type 1 diabetes

OBJECTIVE: Transforming growth factor (TGF)-beta1 is an important mediator in the pathogenesis of diabetic nephropathy. Urinary TGF-beta1 reflects TGF-beta1 production in the kidney, and alpha1-microglobulin tubular dysfunction. These 2 markers were studied in the early phases of type 1 diabetes. RESEARCH DESIGN AND METHODS: There were 113 type 1 diabetic children and adolescents (mean +/- SD: age 14.1 +/- 2.9 years, and diabetes duration 7.4 +/- 2.9 years, HbA1c 9.3 +/- 1.5%) and 39 healthy subjects (age 13.8 +/- 2.8 years) who participated in the study. Of the diabetic patients, 105 were normoalbuminuric (2-3 consecutive overnight urinary albumin excretion rates [AERs] <20 microg/min) and 8 had microalbuminuria (at least 2 AERs 20-200 microg/min). Overnight urinary TGF-beta1 and alpha1-microglobulin levels were measured and the results expressed as the ratio to urinary creatinine concentration. RESULTS: Data are medians (range). Diabetic patients had higher urinary TGF-beta1 levels than those of control subjects: 0.9 ng/mg (0.05-122.3) vs. 0.3 ng/mg (0.05-2.2) creatinine, respectively (P = 0.003). Urinary TGF-beta1 levels correlated with urinary glucose (r = 0.2, P = 0.03) and alpha1-microglobulin (r = 0.2, P = 0.02) levels, but not with HbA1c, AER, age, or duration of diabetes. In 43 patients with urinary TGF-beta1 above the control levels, urinary TGF-beta1 levels correlated with urinary glucose (r = 0.6, P < 0.001) and alpha1-microglobulin (r = 0.6, P < 0.001) levels. Diabetic patients had higher urinary alpha1-microglobulin levels than those of control subjects: 4.8 microg/mg (0.6-48.8) vs. 2.7 microg/mg (0.8-11.6) creatinine, respectively (P < 0.001). Alpha1-microglobulin levels correlated with AER (r = 0.2, P = 0.02), HbA1c (r = 0.3, P = 0.001), urinary glucose (r = 0.5, P < 0.001), and urinary TGF-beta1 levels. CONCLUSIONS: An early rise in urinary TGF-beta1 levels was observed in young type 1 diabetic patients. Urinary TGF-beta1 is associated with 2 interrelated tubular markers, alpha1-microglobulin and urinary glucose.     

白细胞介素-18和CRP及mALB在2型糖尿病患者早期肾损害中的临床意义

目的探讨血清白细胞介素-18(IL-18)、C-反应蛋白(CRP)、24 h尿微量白蛋白(mALB)与2型糖尿病早期肾损害的关系。方法根据尿白蛋白排泄率(UAER)将105例2型糖尿病患者分为正常白蛋白尿组、微量白蛋白尿组、临床白蛋白尿组,另选40例健康人作为对照组,观察各组血中IL-18、CRP、mALB水平并进行比较,同时进行相关分析。结果 2型糖尿病各组IL-18、CRP、mALB均高于对照组,各组间比较差异有统计学意义(P<0.05),且IL-18与CRP、mALB呈正相关(分别r=0.453,r=0.579,P均<0.01)。结论血清IL-18、CRP是2型糖尿病肾病发生的重要炎性反应介质,2型糖尿病患者血清IL-18、CRP、mALB水平的升高可能在糖尿病患者早期肾损害的发生及发展中起着重要作用。     

踝臂指数及踝臂脉搏波传导速度与糖尿病慢性并发症的相关性研究

目的探讨踝臂指数（Ankle brachial lndex,ABI）及踝臂脉搏波传导速度（brachial ankle Pulse Wave Velocity,baWV）与糖尿病慢性并发症之间的相关性。方法对101例糖尿病患者进行baPWV、ABI测量以及临床资料的回顾性分析,探讨baPWV、ABI与糖尿病慢性并发症（如糖尿病足、糖尿病视网膜病变、糖尿病肾病）的患病风险之间的关系。结果①ABI与糖尿病足的发生（B=2.778,P=0.007）及分级（r=-0.669,P〈0.001）密切相关;②ABI与糖尿病视网膜病变的发生（B=3.245,P=0.014）和严重程度（r=-0.473,P〈0.001）相关;③baPWV与糖尿病肾脏受累的发生（B=0.002,P=0.014）可能有关。结论 ABI的异常是糖尿病足病、糖尿病视网膜病变的独立危险因素,且与并发症的严重程度呈现相关性,baPWV的升高与糖尿病性肾脏受累情况相关。因此ABI和baPWV的测量可用于评估糖尿病慢性并发症的患病风险和严重程度。     

Serum and urinary nitrites and nitrates and Doppler sonography in children with diabetes

OBJECTIVE: The aim of the present study was to evaluate serum and urinary nitric oxide (NO) concentrations in children and adolescents with diabetes compared with age-matched healthy control subjects to find out whether Doppler ultrasonography could be used to detect changes in renal resistive indexes (RIs) in children with diabetes and to assess whether there are correlations between these parameters and NO excretion. RESEARCH DESIGN AND METHODS: We studied 42 children with type 1 diabetes and 41 matched healthy control subjects, both divided into prepubertal or pubertal children. Serum and urinary nitrite and nitrate (NO2-+NO3-) concentrations were evaluated as an index of NO production. Doppler ultrasonographic registration of intrarenal RI was performed. RESULTS: Compared with healthy control subjects, children with diabetes had significantly increased concentrations of serum (30.26 +/- 6.52 vs. 24.47 +/- 7.27 mmol/l, P = 0.001) and urinary NO2-+NO3- (345.07 +/- 151.35 vs. 245.86 +/- 80.25 mmol/l, P = 0.002); the same was true for Doppler RI values (0.64 +/- 0.03 vs. 0.60 +/- 0.04, P = 0.035). This occurs in both prepubertal and the pubertal children. A significant positive correlation was found between serum and urinary NO2-+NO3- levels (P = 0.002, r = 0.374). Serum NO2-+NO3- concentrations also correlated positively with Doppler RI (P = 0.032, r = 0.262) and HbA1c (A1C) (P = 0.004, r = 0.329); urinary NO2-+NO3- concentrations correlated positively with A1C (P = 0.001, r = 0.394). Doppler RI correlated positively with A1C (P = 0.000, r = 0.424). CONCLUSIONS: This study demonstrates that in children with diabetes, chronic hyperglycemia may act through a mechanism that involves increased NO production and/or action and contributes to generating intrarenal hemodynamic abnormalities, which are detectable by Doppler ultrasonography even in early diabetic nephropathy.     

Serum type IV collagen in diabetic patients at risk for nephropathy

OBJECTIVE: Whereas increased urinary excretion of type IV collagen, which is believed to reflect renal overproduction of this extracellular matrix protein in early diabetic nephropathy, has been confirmed in several studies, examination of serum concentrations of this analyte has yielded conflicting results. We sought to clarify the relationship between early renal dysfunction in diabetes and circulating type IV collagen concentrations. RESEARCH DESIGN AND METHODS: We measured serum (human) collagen IV concentrations by immunoassay in 109 patients with type 1 or type 2 diabetes and various amounts of albuminuria extending from the normo- to the macroalbuminuric range, and we examined its relationship to albumin excretion and to serum creatinine levels. RESULTS: Serum collagen IV concentrations (mean +/- SEM) were not significantly different in normoalbuminuric (219 +/- 10 ng/ml), microalbuminuric (209 +/- 6 ng/ml), or macroalbuminuric (206 +/- 7 ng/ml) diabetic subjects or in nondiabetic normal volunteers (206 +/- 10 ng/ml). Collagen IV concentrations showed no significant correlation (P > 0.25) with albumin excretion (r = -0.001), HbA(1c) (r = 0.030), or serum creatinine (r = -0.161) and were unrelated to urinary excretion of collagen IV in the subset of subjects in whom these data were available. CONCLUSIONS: The results of this cross-sectional analysis discount the utility of measurement of the serum concentration of collagen IV as an indicator of early renal dysfunction in diabetes. Increased urine excretion of collagen IV without a significant change in the serum concentration is consistent with a renal origin of this analyte in early diabetic nephropathy.     

Prospective study of lipoprotein(a) as a risk factor for deteriorating renal function in type 2 diabetic patients with overt proteinuria

OBJECTIVE: The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic nephropathy has not been evaluated yet. The aim of this study was to determine whether Lp(a) is an independent risk factor for deteriorating renal function in type 2 diabetic patients with nephropathy. RESEARCH DESIGN AND METHODS: We conducted this prospective study in type 2 diabetic patients with overt proteinuria. Patients were divided into two groups according to their baseline serum Lp(a) level. Group 1 had Lp(a) levels < or =30 mg/dl (n = 40) and group 2 had Lp(a) levels >30 mg/dl (n = 41). Patients were followed for 2 years. Progression of diabetic nephropathy was defined as a greater than twofold increase of follow-up serum creatinine concentration from the baseline value. RESULTS: At baseline and during the follow-up, there was no difference in HbA(1c) and lipid profile between groups 1 and 2. However, serum creatinine was significantly higher in group 2 than in group 1 after 1 year (148.3 +/- 78.0 vs. 108.1 +/- 34.9 micromol/l, P = 0.004) and after 2 years (216.9 +/- 144.5 vs. 131.3 +/- 47.3 micromol/l, P = 0.001), although baseline serum creatinine did not differ significantly between groups. In all, 13 of 14 patients with progression of diabetic nephropathy (progressors) were from group 2. Baseline Lp(a) levels were higher in the progressors than in the nonprogressors (62.9 +/- 26.7 vs. 33.5 +/- 27.5 mg/dl, P < 0.001). Multiple logistic regression showed that baseline Lp(a) level was a significant and independent predictor of the progression of diabetic nephropathy. CONCLUSIONS: Our study demonstrated that Lp(a) is an independent risk factor for the progression of diabetic nephropathy in type 2 diabetic patients with overt proteinuria.     

原发性IgA肾病患者血清白细胞介素-17、血管内皮生长因子与肾功能指标的相关性

目的探讨原发性IgA肾病患者血清白细胞介素-17(IL-17)、血管内皮生长因子(VEGF)与肾功能指标的相关性。方法选取47例IgA肾病患者为观察组,选取44例健康人群作为对照组。结果观察组患者eGFR显著低于对照组(P0.001),24 h尿蛋白显著高于对照组(P0.001);观察组患者血清IL-17(P0.001)、VEGF(P0.001)水平显著高于对照组;Pearson相关性检验分析发现,观察组患者IL-17与24 h尿蛋白(r=0.461,P=0.001)呈正相关,与eGFR呈负相关(r=-0.571,P0.001)。VEGF与24 h尿蛋白(r=0.571,P0.001)呈正相关,与eGFR呈负相关(r=-0.596,P0.001)。结论原发性IgA肾病患者IL-17、VEGF的表达上调可破坏肾小球的滤过功能。     

Urinary levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), and renal injuries in patients with type 2 diabetic nephropathy

We examined the correlation among the levels of urinary monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), hyperglycemia, and renal injuries in patients with type 2 diabetic nephropathy. The levels of urinary MCP-1, IL-8, protein excretion, blood urea nitrogen (BUN), serum creatinine (s-Cr), glycohemoglobin A1c (HbA1c), and fasting plasma glucose (FPG) were measured in 24 patients with type 2 diabetic nephropathy and 14 healthy adults as controls. Diabetic nephropathy was classified into three stages: stage 1 = normoalbuminuric, stage 2 = microalbuminuric, and stage 3 = macroalbuminuric. All of the patients showed normal ranges in renal function tests. Levels of urinary MCP-1 in all patients with diabetic nephropathy were significantly higher than those in healthy adults (P < 0.05). The levels of urinary MCP-1 in patients with diabetic nephropathy increased gradually according to the clinical stage of this disease. In contrast, the levels of urinary IL-8 in patients with diabetic nephropathy increased in stages 2 and 3. There was a significant correlation between the levels of urinary IL-8 and those of HbA1c. High glucose may stimulate MCP-1 and/or IL-8 production and their excretion into the urine independently of the phases or pathological lesions of this disease. It appears that IL-8 increased in the early stage of diabetic nephropathy, and MCP-1 increased in the advanced stage of this disease. It was concluded that measurement of urinary MCP-1 and IL-8 may be useful for evaluating the degree of renal injuries in patients with type 2 diabetic nephropathy.     

2型糖尿病肾病患者炎性反应相关因子检测与分析

目的探讨糖尿病肾病患者的血清C反应蛋白、可溶性白细胞介素-2受体(sIL-2R)、白细胞介素-6(IL-6)和血清转化生长因子-β1(IGF-β1)水平的变化在糖尿病肾病发生、发展中的作用。方法将98例糖尿病肾病患者24 h尿微量清蛋白排泄率分为:无蛋白尿组(UAER<20 g/min,n=32)、微量蛋白尿组(UAER<290 g/min,n=35)和大量蛋白尿组(UAER>200 g/min,n=31)。观察各组患者CRP、slL-2RI、L-6和TGF-β1水平的变化,并与健康对照组(n=32)进行比较。结果无蛋白尿组、微量蛋白尿组及大量蛋白尿组的CRP、slL-2R、IL-6及TGF-β1水平均明显高于健康对照组(P<0.01);微量蛋白尿组的CRP、slL-2RI、L-6及TGF-β1水平明显高于无蛋白尿组(P<0.05);大量蛋白尿组的CRP、slL-2RI、L-6及TGF-β1水平明显高于微量蛋白尿组(P<0.01)。结论早期检测血清CRP、slL-2RI、L-6及TGF-β1水平的变化可以作为临床观察糖尿病肾病病情及判断糖尿病预后的参考指标。     

Increased plasma fibronectin concentration in diabetic patients with microalbuminuria

Raised levels of plasma fibronectin (PF), an alpha 2-glycoprotein produced by vascular endothelia, have been previously described in diabetic patients with retinopathy and overt nephropathy. The aim of this study was to investigate whether the presence of microalbuminuria is associated with increased PF concentrations. Twenty Albustix-negative diabetic outpatients with microalbuminuria [median albumin excretion rate (AER): 30.2 micrograms/min; range 12.1-194 micrograms/min] were compared with 58 sex- and age-matched patients without microalbuminuria (median AER 3.1 micrograms/min; range 0.8-12 micrograms/min) and 34 control subjects (median AER 2.8 micrograms/min; range 0.8-12.1 micrograms/min). Mean PF was significantly higher in the group with microalbuminuria (406.7 +/- 85.5 micrograms/ml) than in the group without it (325.3 +/- 76.5 micrograms/ml or in control subjects (334.5 +/- 76 micrograms/ml; P less than .05). PF increase associated with microalbuminuria was independent of the presence of retinopathy. Furthermore, in the whole group of diabetic patients, PF was significantly correlated with AER (r = .33; P = .003). Such correlation also remained significant (P = .0002) after covariance analysis by a stepwise discriminant procedure taking into account age, duration of disease, sex, blood pressure, body weight, therapy, and HbA1. In conclusion, PF increase is associated with microalbuminuria independent of the other considered variables; its role as a possible marker for early diabetic nephropathy remains to be fully clarified.     

Erythrocyte spermidine levels in IDDM patients.

OBJECTIVES--To evaluate whether erythrocyte levels of polyamines spermidine and spermine (expressed in nmol/ml packed erythrocytes [PRBCs]) are modified in insulin-dependent diabetes mellitus (IDDM) and are associated with the presence of retinopathy or nephropathy. RESEARCH DESIGN AND METHODS--We studied erythrocyte spermidine and spermine levels in 38 IDDM patients with or without persistent microalbuminuria (urinary albumin excretion rate [AER] between 20 and 200 micrograms/min), macroalbuminuria (AER greater than 200 micrograms/min), or retinopathy compared with 60 sex- and age-matched control subjects. RESULTS--Mean +/- SD erythrocyte spermine content was similar in both diabetic (9.7 +/- 5.5 nmol/ml PRBCs) and control (8.8 +/- 3.5 nmol/ml PRBCs) subjects, whereas spermidine was higher in diabetic (19.1 +/- 7.2 nmol/ml PRBCs) than in control (14.5 +/- 4 nmol/ml PRBCs, P = 0.0007) subjects. Moreover, spermidine was significantly higher in the groups with microalbuminuria (n = 11, 22.5 +/- 9.2 nmol/ml PRBCs) and macroalbuminuria (n = 4, 22.2 +/- 5.7 nmol/ml PRBCs) than in both normoalbuminuric (n = 23, 16.9 +/- 5.6 nmol/ml PRBCs) and control (F = 9.78, P = 0.0001) subjects, and correlated with log AER (r = 0.41, P = 0.009). Similarly, proliferative retinopathy was associated with a significant increase in spermidine (n = 5, 20 +/- 7 nmol/ml PRBCs compared with control subjects [P = 0.0009]). CONCLUSIONS--Our data suggest that erythrocyte spermidine content is increased in IDDM patients associated with both diabetic nephropathy and advanced retinopathy.     

血清同型半胱氨酸测定在糖尿病肾病中的临床意义

目的 探讨分析糖尿病肾病中血清同型半胱氨酸（Hcy）的变化和其炎症因子的相关性。 方法 选取2012年2月~2016年8月于我院就诊的2型糖尿病肾病患者共160例,根据尿白蛋白排泄率和血肌酐水平分为单纯糖尿病组（DM组）、早期糖尿病肾病组（EDN组）、糖尿病肾病组（CDN组）和肾功能衰竭组（CRF组）,以40例健康体检者作为对照组,比较各组患者的Hcy值及生化指标,分析Hcy其糖尿病肾病患者炎症因子IL-1、IL-6、TNF-α和hsCRP的相关性。 结果 5组患者比较,其GLU、HbA1c、UREA、Cr、TP、ALB、TCH和TG差异均有统计学意义（P<0.01）;Hcy差异有统计学意义（F=27.452,P<0.01）;hsCRP、TNF-α、IL-1和IL-6差异有统计学意义（P<0.01）;血清Hcy水平和hsCRP存在显著的正相关（r=0.624,P<0.01）、和TNF-α存在正相关（r=0.557,P<0.01）、和IL-1存在显著正相关（r=0.568,P<0.01）、和IL-6存在显著正相关（r=0. 417,P=0.017）。 结论 Hcy在糖尿病肾病中病情进展中具有重要作用,可作为糖尿病肾病患者肾血管损伤及病情进展评价的重要指标,且与hsCRP、IL-1、IL-6和TNF-α具有显著的相关性。       

TIMP-1在糖尿病肾病中的水平变化及临床意义

目的观察金属蛋白酶组织抑制因子-1（TIMP-1）在糖尿病肾病不同临床阶段的变化规律，进而探讨TIMP-1在糖尿病肾病发生、发展过程中的作用。方法选取健康对照组（NC）20例，2型糖尿病组（DM）20例，临床期糖尿病肾病组（ON）20例及糖尿病肾病肾衰竭组（DNF）20例为研究对象，利用酶联免疫吸附实验（ELISA）分别检测各试验对象血清中TIMP-1的含量，并比较各组TIMP-1水平的差异性，分析TIMP-1水平与年龄及尿蛋白量的相关性。结果正常对照组血清TIMP-1水平为（825．97±137．34）ng/ml，糖尿病组（1259．05±218．47）ng／ml，临床期糖尿病肾病组（1508．31±282．57）ng／ml，糖尿病肾病肾衰竭组（2131．42±441．25）ng／ml。TIMP-1血清水平在性别间的差异无统计学意义。在DM组和DNF组，TIMP-1水平与年龄正相关。在DN组，TIMP-1与24h尿蛋白定量正相关（r=0．84，P〈0．01）。结论随着糖尿病肾病的病情进展，血清中TIMP-1水平逐渐增高，且与尿蛋白量呈显著正相关，提示TIMP-1可能参与了糖尿病患者动脉硬化、动脉粥样斑块的形成及高血压的血管重塑过程；TIMP-1可能介导了肾小球细胞外基质（ECM）积聚、肾小球基底膜（GBM）重塑、肾小球硬化，在糖尿病肾病发生、发展过程中起着重要作用。     

Increased urinary transferrin excretion predicts microalbuminuria in patients with type 2 diabetes.

OBJECTIVE: We studied whether increased urinary transferrin excretion rates (TERs) (urinary transferrin-to-urinary creatinine ratio > or = 107 micrograms/mmol, which is the sum of an average and 2 SDs in 431 healthy nondiabetic individuals) would predict the development of microalbuminuria (urinary albumin-to-urinary creatinine ratio > or = 2.8 mg/mmol) in patients with type 2 diabetes and normal urinary albumin excretion rates (AERs) (albumin-to-creatinine ratio < 2.8 mg/mmol). We also studied the influence of blood pressure, glycemic control, and serum levels of lipids and apolipoproteins on the later development of microalbuminuria. RESEARCH DESIGN AND METHODS: In 77 diabetic patients with normal AER, AER and TER were measured at baseline and after 24 months of follow-up. Blood pressure, glycemic control, and serum levels of lipids and apolipoproteins were measured at 1- to 2-month intervals during the follow-up period. RESULTS: Of the 16 patients who initially had increased TER, 5 (31%) developed microalbuminuria. In contrast, of the 61 who initially had normal TER, 4 (7%) developed microalbuminuria (P = 0.016). At baseline, no difference was found in age, sex, diabetes duration, diabetic medications, prevalence of hypertension, blood pressure, HbA1c levels, or serum lipid and apolipoprotein concentrations between the two group of patients with normal and increased TER. There was also no difference in duration of hypertension and prevalence of users of ACE inhibitors between two subgroups of hypertensive patients with normal and increased TER. During the 24 month follow-up period, those whose condition progressed to microalbuminuria had increased serum levels of triglycerides (1.87 +/- 0.49 vs. 1.29 +/- 0.64 mmol/l, P = 0.003) and apolipoprotein B (114 +/- 20 vs. 102 +/- 24 mg/dl, P = 0.05) and tended to have increased HbA1c levels (7.7 +/- 1.0 vs. 7.1 +/- 1.1%, P = 0.10) compared with those in whom microalbuminuria did not develop. Blood pressure, however, did not differ. In multivariate stepwise logistic regression analysis, the association between increased TER at baseline and subsequent development of microalbuminuria was significant (odds ratio 7.04 [95% CI 1.02-48.5], P = 0.04). CONCLUSIONS: In patients with type 2 diabetes and normal AER, increased TER may predict the development of microalbuminuria and abnormalities in triglyceride-rich lipoprotein metabolism, and poor glycemic control may be associated with this progression.     

Increased fructose concentrations in blood and urine in patients with diabetes

OBJECTIVE: To investigate fructose metabolic changes in patients with diabetes. RESEARCH DESIGN AND METHODS: Serum and urinary fructose concentrations were determined in healthy subjects (n = 23) and in nondiabetic (n = 23) and diabetic patients (n = 26). Fructose was measured using our newly developed method, and (13)C(6)-fructose was used as the internal standard. After adding sample to a fixed amount of internal standard, ion-exchange resins and high-performance liquid chromatography pretreatments were performed. Then, the amount of fructose in the sample was measured by gas chromatography-mass spectrometry. RESULTS: Serum fructose concentrations in patients with diabetes (12.0 +/- 3.8 micromol/l) were significantly higher than those in healthy subjects (8.1 +/- 1.0 micromol/l, P < 0.001) and nondiabetic patients (7.7 +/- 1.6 micromol/l, P < 0.001), and daily urinary fructose excretion was significantly greater in patients with diabetes (127.8 +/- 106.7 micromol/day) than in nondiabetic patients (37.7 +/- 23.0 micromol/day, P < 0.001). In patients with diabetes (n = 20), serum fructose concentrations (8.6 +/- 1.8 micromol/l, P < 0.001) and daily urinary fructose excretion (63.4 +/- 63.8 micromol/day, P < 0.01) significantly decreased by week 2 after admission. CONCLUSIONS: The present results differed from those of previous studies in that we found that the serum and urinary fructose concentrations decreased rapidly, concomitant with an improvement in glycemia. Therefore, hyperglycemia was associated with increased serum and urinary fructose concentrations in patients with diabetes.     

Preventing diabetic nephropathy: an audit.

In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary albumin excretion rate (AER) of 6% to 14%/year and a risk for the development of diabetic nephropathy of 3% to 30%/year have previously been reported. The aim of the present study was to audit the effect of angiotensin converting enzyme (ACE) inhibition on the progression of microalbuminuria and development of diabetic nephropathy. We consecutively identified 227 type 1 diabetic patients with persistent microalbuminuria (urinary AER between 30 and 300mg/24h, ELISA). According to the level (> or = 100 or < 100mg/24 h) and/or rate of progression in urinary AER (>6% or < or =6%/year), patients were divided into a high-risk group (n= 177) and a low-risk group (n= 50) for development of diabetic nephropathy. According to international guidelines, all patients at high-risk were recommended ACE-inhibitor treatment. Throughout the study, 67% of the patients were treated with an ACE inhibitor. Urinary AER significantly declined by 8.3%/year (95% CI: 2.8 to 13.9) in the whole group of patients, and the risk for the development of diabetic nephropathy during follow-up was 3.5%/year. Glycaemic control and blood pressure remained unchanged during the study. The implementation of modified international guidelines regarding the use of ACE inhibition in the treatment of microalbuminuric type 1 diabetic patients reduced progression to diabetic nephropathy comparable to what has previously been reported in intervention trials.     

2型糖尿病肾病患者血清TNF-α、IL-18、ADPN水平测定

目的探讨血清炎症因子TNF-α、IL-18、ADPN在2型糖尿病肾病中的变化。方法随机选择T2DM患者50例,根据尿蛋白排泄率分为糖尿病无肾病组(DN组)25例;糖尿病肾病组(NDN组)25例。并选择健康对照组(CTL组)25例。用酶联免疫吸附法测定受试者血清TNF-α、IL-18、ADPN浓度。结果 (1)糖尿病各组的血清TNF-α、IL-18浓度高于CTL组,DN组血清ADPN浓度显著高于CTL组,NDN组血清ADPN浓度低于CTL组,差异均有统计学意义。(2)血清TNF-α、IL-18、ADPN水平在DN组显著高于NDN组,差异有统计学意义。(3)直线相关分析显示TNF-α与FBG、HbAIC、UAER呈正相关;IL-18与FBG、HbAIC、UAER呈显著正相关;ADPN与UAER呈显著正相关,与BMI、FBG、HbA1C呈负相关。结论血清TNF-α、IL-18、ADPN的高低与糖尿病肾病的病变阶段密切相关,可作为判断2型糖尿病肾病受损程度以及预后的指标。     

No evidence of an exaggerated albuminuric response to physical exercise in non-diabetic siblings of type 1 diabetic patients with diabetic nephropathy

Substantial evidence suggests a role for genetic factors in the development of diabetic nephropathy in both type 1 and type 2 diabetes. In support of this view, non-diabetic relatives of type 2 diabetic patients with nephropathy have been found to display abnormalities of urinary albumin excretion rate (AER) both when measured at rest and during physical exercise. The aim of the present study was to assess the albuminuric response to physical exercise in non-diabetic relatives of type 1 diabetic patients with nephropathy. AER was measured from urine collections performed (i) overnight, (ii) during an oral glucose tolerance test (OGTT), and (iii) during a submaximal bicycle ergometer test in 21 and 24 non-diabetic siblings of type 1 diabetic patients with (DN+; AER > 200 microg/min) and without diabetic nephropathy (DN-; AER < 20 microg/min). No difference was found in AER (median [range]) measured overnight (DN+ vs DN-: 3.8 [1.3-24.1] vs 3.5 [2.0-21.0] microg/min; P=NS), during the OGTT (DN+ vs DN-: 6.3 [3.2-26.0] vs 4.8 [1.9-15.7] microg/min; P = NS) or during the exercise test (DN+ vs DN-: 44.8 [7.0-535] vs 30.0 [3.4-1614] microg/min; P = NS). In conclusion, we found no evidence of an exaggerated albuminuric response to physical exercise in non-diabetic relatives of type 1 diabetic patients with nephropathy. This differs from previous findings in type 2 diabetes and may suggest differences in the mode of inheritance of albuminuria between type 1 and type 2 diabetes.     

The determination of AGE-peptides by flow injection assay, a practical marker of diabetic nephropathy.

BACKGROUND: Increasing evidence has suggested that advanced glycation end products (AGEs) might play a central role in the pathogenesis of diabetic complications. Serum AGEs concentration may serve as a useful marker for monitoring pathological processes and progression of diabetic complications. METHODS: A flow injection assay (FIA) system was developed using high performance liquid chromatography (HPLC) to detect low molecular mass AGEs (AGE-peptides, AGE-P). Serum from diabetic patients (n=126), normal controls (n=54) and diabetic mice (n=20) and matched controls (n=20) were collected. RESULTS: The coefficient of variance for intra-assay and inter-assay were 1.2% and 6.3%, respectively. The range of recoveries was 94.9-101.9%. The serum AGE-P concentration was significantly increased both in diabetic patients (2.976+/-0.247 vs. 1.385+/-0.131 U/ml, P<0.0001) and mice (6.71+/-0.50 vs. 2.49+/-0.10 U/ml, P<0.0001) than their respective controls. Concentration of AGE-P was positively correlated with serum creatinine (Scr) (r=0.7133, P<0.0001), 24-h urinary protein (24-h UPro) (r=0.8704, P<0.0001) and urinary albumin excretion (UAE) (r=0.5989, P<0.0001). CONCLUSIONS: The present study suggested that FIA might be a reliable method for measuring the serum AGE-P. Furthermore, our results supported the notion that AGE-P might be a valuable marker for predicting the severity of diabetic nephropathy (DN).