2型糖尿病患者高敏C-反应蛋白与糖尿病肾病的关系

目的:探讨2型糖尿病肾病(DN)不同时期血清高敏C-反应蛋白(hs-CRP)的浓度变化与DN的关系。方法:采用速率散射比浊法测定144例2型糖尿病患者和49名正常对照的血清hs-CRP水平。根据尿白蛋白排泄率(UAER)将2型糖尿病患者分为3组:正常蛋白尿组53例、微量白蛋白尿组57例和临床蛋白尿组34例。结果:(1)2型糖尿病组的血清hs-CRP值较对照组显著升高(U=1458.5,P<0.001);(2)hs-CRP值随UAER的增加而增加(H=74.068,P<0.001);(3)hs-CRP值与空腹血糖、血尿酸、纤维蛋白原成正相关(r=0.26、0.33、0.30,P均<0.001),与高密度脂蛋白呈负相关(r=-0.14,P<0.05)。结论:C-反应蛋白可能参与了2型糖尿病和糖尿病肾病的发生发展。     

Diabetic nephropathy is associated with increased albumin and fibrinogen production in patients with type 2 diabetes

Aims/hypothesis Hyperfibrinogenaemia and albuminuria are cardiovascular risk factors, often coexisting in diabetic and non-diabetic people. Albuminuria in turn is associated with a compensatory albumin overproduction in non-diabetic patients. It is not known whether the presence of albuminuria in patients with type 2 diabetes mellitus is associated with greater albumin and fibrinogen production rates than in normoalbuminuric patients.Subjects, materials, and methods Using leucine isotope methods, we measured fractional and absolute synthesis rates (FSR, ASR) of albumin and fibrinogen in post-absorptive type 2 diabetic patients with either normal (n=11) or increased (n=10) urinary albumin excretion.Results In albuminuric patients, albumin FSR (16.2±1.5%/day) and ASR (20.5±1.9 g/day) were greater (p<0.02 and p<0.05, respectively) than in normoalbuminuric patients (FSR=11.5±1.1%/day; ASR=15.7±1.2 g/day). Fibrinogen FSR was similar between patients with normal and increased albumin excretion, but concentration, the circulating pool and ASR of fibrinogen were 40 to 50% greater (p<0.035) in patients with albuminuria. Albuminuria was positively correlated with albumin ASR, with fibrinogen concentration, the fibrinogen pool and ASR, whereas albumin synthesis was inversely correlated with calculated oncotic pressure.Conclusions/interpretation Synthesis of albumin and fibrinogen is upregulated in type 2 diabetic patients with increased urinary albumin excretion. Albuminuria is associated with enhanced fibrinogen and albumin synthesis.     

2型糖尿病患者血中炎症因子、尿MCP-1与尿白蛋白排泄率的关系

观察84例不同尿白蛋白排泄率(UAE)的2型糖尿病患者血中炎症因子超敏C反应蛋白(hs-CRP)、肿瘤坏死因子α(TNF-α)及红细胞沉降率(ESR)与尿单核细胞趋化蛋白1(MCP-1)水平的变化及临床意义.结果 发现2型糖尿病患者hs-CRP、TNF-α、尿MCP-1和ESR水平明显高于对照组,其中前三项指标随着UAE的增加而显著增加.提示糖尿病肾病与炎症反应相关.     

不同分期糖尿病肾病患者血清IL-18、CRP水平的变化及意义

目的探讨不同分期糖尿病肾病（DN）患者血清IL-18、C反应蛋白（CRP）水平的变化及意义。方法选择97例2型糖尿病患者,根据尿白蛋白排泄率（UAER）分为3组：正常白蛋白尿组35例、微量白蛋白尿组30例和大量白蛋白尿组32例,另选健康体检者35例作为对照组。采用ELISA法检测各组患者血清IL-18、CRP水平,并对其影响因素进行分析。结果 2型糖尿病患者血清IL-18、CRP水平明显高于对照组（P均〈0.05）,且随着UAER的增加,IL-18水平逐渐增高（P均〈0.01）。Pearson相关分析显示,血清CRP、IL-18均与病程、收缩压、糖化血红蛋白、空腹血糖、TG、TC、LDL-C、尿素氮、血肌酐、UAER呈正相关（rIL-18分别为0.766、0.628、0.568、0.388、0.375、0.400、0.512、0.516、0.698、0.792;rCRP分别为0.777、0.701、0.416、0.327、0.308、0.307、0.449、0.611、0.817、0.893,P均〈0.01）,与HDL-C呈负相关（rIL-18=-0.652、rCRP=-0.546,P均〈0.01）,且两者互呈正相关（r=0.890,P〈0.01）。结论血清IL-18、CRP与DN的发生、发展有关,两者联合检测有助于DN的早期诊断。     

The association of serum total sialic acid/total protein ratio with diabetic parameters in young type 1 diabetic patients

Abstract Sialic acid is a terminal component of the non-reducing end of carbohydrate chains of glycoproteins and glycolipids. The purpose of this study was to estimate serum total sialic acid (TSA) concentrations and serum TSA/serum total protein (TP) ratios in young type 1 diabetic subjects and to investigate their association with diabetes-related parameters in that population. Twentyfour young type 1 diabetic patients and 20 healthy controls were enrolled in this study. Serum TSA and serum TSA/TP ratio were measured in both groups. Moreover, we looked for correlation among serum TSA, serum TSA/TP ratio and clinically relevant parameters such as urinary albumin excretion, blood pressure, diabetes duration, HbA1c, daily insulin dose, serum lipids and magnesium in type 1 diabetic patients. Serum TSA concentrations and serum TSA/TP ratio showed no statistical difference between patients and controls (p>0.05). While serum TSA concentrations only correlated with urinary albumin excretion (r=0.44, p=0.028), serum TSA/TP ratio correlated with diastolic blood pressure (r=0.48, p=0.015), diabetes duration (r=0.46, p=0.022) and urinary albumin excretion (r=0.53, p=0.007) in the diabetic subjects. We concluded that serum TSA/TP ratio might be a better indicator than serum TSA as an index of diabetic complications.     

2型糖尿病患者血超敏C反应蛋白和微血管并发症的关系

目的分析2型糖尿病患者各种微血管并发症和血超敏C反应蛋白(hsCRP)的关系。方法以2003年5月至2006年6月北京协和医院内分泌科321例2型糖尿病住院患者为研究对象。根据尿白蛋白排泄率(UAER)分为无肾病组(UAER<20μg/min)213例,早期肾病组(20μg/min≤UAER<200μg/min)62例和临床肾病组(UAER≥200μg/min)46例;根据眼底镜检查分为无糖尿病视网膜病变组238例、有糖尿病视网膜病变组83例;根据肌电图检查分为无糖尿病神经病变组255例和有糖尿病神经病变组66例。观察3种并发症中各组hsCRP的变化。结果只有糖尿病肾病和血hsCRP相关,hsCRP随尿白蛋白的增加而升高。Pearson相关分析显示,hsCRP与UAER(r=0.448,P=0.002)、三酰甘油(r=0.385,P=0.008)及体重指数(r=0.261,P=0.004)呈正相关。逐步线性回归表明,UAER、三酰甘油、体重指数是影响hsCRP的主要因素。结论hsCRP与糖尿病肾病相关,其水平与糖尿病肾病的程度具有一致性。     

Elevated levels of mannan-binding lectin in patients with type 1 diabetes

The hepatic protein mannan-binding lectin (MBL) activates the complement system on binding to carbohydrate patterns and is involved in first-line defense against invading microorganisms. Emerging evidence indicates that in some situations MBL may cause inexpedient complement activation and tissue injury through binding to endothelial glycosylations. MBL levels are suppressed by insulin treatment in critically ill patients, and, hypothetically, hepatic portal hypoinsulinemia could lead to increased levels of MBL in patients with type 1 diabetes. We measured MBL and C-reactive protein (CRP) levels in 132 normoalbuminuric type 1 diabetic patients and 66 healthy age- and sex-matched controls. The median MBL concentration was higher in diabetic patients than in healthy controls [1290 micro g/liter (interquartile range, IQR 354-2961 micro g/liter) vs. 970 micro g/liter (IQR 277-1607 micro g/liter), P = 0.025], whereas CRP concentrations were similar among patients and controls [1.42 mg/liter (IQR 0.95-2.21) vs. 1.21 mg/l (IQR 0.74-2.13), NS]. In diabetic subjects, CRP levels correlated with poor glycemic control as indicated by hemoglobin A(1c) and daily insulin dose, which was not the case with MBL. MBL concentrations were positively correlated with urinary albumin excretion (r = 0.22; P = 0.013) and increased with increasing urinary albumin excretion tertile (P = 0.036). In conclusion, our data demonstrate that circulating MBL concentrations are significantly elevated in patients with type 1 diabetes and suggest a possible role of MBL in the pathogenesis of renovascular complications in diabetes.     

Serum sIL-2r,IL-6, IL-10 and TNF-α level in familial Mediterranean fever patients

 In this study we investigated cytokine levels in patients with familial Mediterranean fever (FMF). Twenty patients and 20 healthy controls were included. Ten patients had acute attacks of FMF, whereas the other 10 were in the silent period. Patients with the acute exacerbation of FMF had higher soluble interleukin-2 receptor (sIL-2r), interleukin-6 (IL-6), tumour necrosis factor-α, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen levels than those in the silent period (P<0.001) and controls (P<0.001). In patients with acute attacks of FMF, interleukin-10 (IL-10) levels were not significantly different from those in the other patients or the controls (P>0.05). In FMF patients IL-6, TNF-α, sIL-2r, ESR, CRP and fibrinogen levels increased with the acute-phase reaction, especially in the attack period. On the other hand, anti-inflammatory cytokine IL-10 levels did not increase as much as did the inflammatory cytokines. The balance between the cytokines may help us to understand the pathophysiology of FMF and to develop therapies. We conclude that the levels of the acute-phase reactants and the cytokines could be useful for diagnosis of acute exacerbations, follow-up and treatment. However, the cost of cytokine measurement analyses seems disadvantageous at present. Received: 13 May 2002 / Accepted: 28 October 2002     

Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients

Aims/hypothesis Increased concentrations of C-reactive protein and interleukin-6, a finding suggestive of the presence of inflammation, have been observed in Type 2 diabetes. In such patients, C-reactive protein was predictive of diabetic nephropathy. Studies on low-grade inflammatory markers and nephropathy in Type 1 diabetic patients have shown conflicting results. Therefore we studied whether low-grade inflammation is associated with diabetic nephropathy in Type 1 diabetic patients.Methods We divided 194 Type 1 diabetic patients into three groups from the Finnish Diabetic Nephropathy Study based upon their albumin excretion rate. Patients with normoalbuminuria (n=67) had no antihypertensive medication or signs of cardiovascular disease, while patients with microalbuminuria (n=64) or macroalbuminuria (n=63) were all treated with an angiotensin-converting enzyme inhibitor, a drug that could attenuate low-grade inflammation. As a measure of insulin sensitivity we used estimated glucose disposal rate. C-reactive protein was measured by radioimmunoassay and interleukin-6 by high sensitivity enzyme immunoassay.Results C-reactive protein was higher in micro- and macroalbuminuric patients compared to normoalbuminuric patients (normoalbuminuria 2.0±1.7, microalbuminuria 2.6±1.7, macroalbuminuria 2.9±2.5 mg/l; p=0.016), while interleukin-6 increased in parallel with the severity of the renal disease (1.9±1.5, 2.9±3.3, 3.6±3.1 ng/l; p<0.0001). In multiple regression analysis albumin excretion rate was the only variable independently associated with C-reactive protein (p=0.03), whereas albumin excretion rate (p=0.0003), HDL-cholesterol (p=0.0135) and duration of diabetes (p=0.0176) were independently associated with interleukin-6.Conclusions/interpretation Low-grade inflammatory markers are associated with diabetic nephropathy in Type 1 diabetic patients. The predictive value needs to be assessed.Abbreviations DN diabetic nephropathy - CRP C-reactive protein - eGDR estimated glucose disposal rate - FinnDiane finnish diabetic nephropathy study - MDRD modification of diet in renal disease     

Hypersensitivity vasculitis and cytokines

OBJECTIVE: Hypersensitivity vasculitis (HSV) is secondary vasculitis due to an immune response to exogenous substances. Because of the relative rarity of the vasculitides there are no reports on the role cytokines. This report evaluates some of cytokines which might be involved in pathophysiological events of HSV. MATERIAL AND METHODS: Patients with HSV ( n=20) were classified as active ( n=12) ornd inactive ( n=8) according to a vasculitis activity index for systemic necrotizing vasculitis (VAI). All the patients were males. A control group was formed from 20 healthy male employees of our department. We performed tests for serum interleukins 6, IL-10, sIL-2 receptor, tumor necrosis factor (TNF) alpha, C-reactive protein (CRP) levels using enzyme-linked immunosorbent assay and erythrocyte sedimentation rate (ESR). RESULTS: The mean ESR value, CRP, and fibrinogen levels were significantly different in both active and inactive HSV from those in the healthy group; they were also significantly higher in the active than in the inactive group. There was no significant difference between healthy and inactive groups for serum IL-10, IL-6, sIL-2 receptor, and TNFalpha levels. However, it was also significantly higher for in active HSV patients than in the healthy group. Similar results were obtained comparing active and inactive groups, namely, all cytokine levels were significantly higher for all patients. The most striking finding is the high correlation of ESR (also for CRP, fibrinogen) with serum levels of TNFalpha and IL-10, but not with IL-6 and IL2R. CONCLUSIONS: These data show that serum TNFalpha and IL-10 levels can be studied in comparison to traditional markers of inflammation such as sedimentation rate or C-reactive protein. This may lead to new approaches to treating or managing HSV.     

Correlation between urinary activity of N-acetyl-β-d-glucosaminidase (NAG) and albumin excretion rate in type II (non-insulin-dependent) diabetic subjects

Summary Different kidney diseases are often associated with high urinary excretion of N-acetyl-β-D-glucosaminidase (NAG), a lysosomal enzyme involved in the breakdown of glycoproteins, whose activity is also increased in diabetic patients with poor metabolic control or vascular complications. In order to evaluate the relationship between renal function and urinary NAG levels in diabetes mellitus, 30 type II diabetic patients without evidence of kidney disease and 18 control subjects were studied. In each subject 24-h urinary excretion rates of NAG (fluorimetric method), albumin and β₂-microglobulin (radioimmunoassay), together with⁵¹Cr-EDTA clearance were performed. In diabetic patients urinary levels of NAG (356±25vs 162±9.2 nmol/h/mg creatinine, p<0.0001) and albumin (21±2.5vs 4.3±0.5 mg/24h, p<0.0001) were significantly higher than in the controls, while β₂-microglobulin levels and⁵¹Cr-EDTA clearance did not differ in the two groups. Moreover in diabetic patients NAG and albumin levels were positively and significantly correlated (r=0.63, p<0.001). These results suggest that urinary NAG excretion rate may be altered early in diabetic patients with apparently normal renal function; its diagnostic value seems to be similar to that of the albumin excretion rate.     

Haptoglobin gene polymorphism in type 2 diabetic patients with and without nephropathy: An Egyptian study

BACKGROUND: The development and progression of diabetic microvascular complications including nephropathy are related to the degree of glycemic control and oxidative stress and may be influenced by genetic factors. The aim of the present study was to investigate the association between haptoglobin (Hp) gene polymorphism and the occurrence of diabetic nephropathy in patients with type 2 diabetes mellitus and to find a possible link between Hp phenotypes and the inflammatory parameters; serum C-reactive protein (CRP), interleukin- 6 (IL-6), and Hp. METHODS: The study included 60 normotensive type 2 diabetic patients (>5 years duration) categorized into three equal groups (normo-, micro-, and macroalbuminuric), according to urinary albumin excretion (UAE). In addition, 20 age- and sex-matched individuals were selected to serve as a control group. Serum CRP, IL-6, and Hp concentrations were measured and Hp phenotyping was conducted using polyacrylamide gel electrophoresis. RESULTS: The frequency of Hp phenotype 1-1 (Hp 1-1) in diabetic patients with normoalbuminuria was 7/20 (35%) as compared with 1/20 (5%) in diabetics with macroalbuminuria (p=0.02). However, the frequency of Hp 2-2 was greater in diabetics with macroalbuminuria (12/20, 60%) than in those with normoalbuminuria or controls (5/20, 25%; p=0.03). Patients with diabetic nephropathy (micro- or macroalbuminuria) had higher levels of serum CRP, IL-6, and Hp than those without nephropathy (normoalbuminuria). Serum Hp levels in type 2 diabetics were higher in Hp phenotype 2-2 than in Hp 1-1; however, serum CRP and IL-6 levels did not differ significantly between Hp phenotype groups. Moreover, there were significant positive correlations between UAE and serum levels of CRP, IL-6, and Hp in diabetic patients. CONCLUSIONS: Hp phenotype 2-2 is considered to be a major susceptibility gene for the development of nephropathy in type 2 diabetic patients. In addition, the significant association between inflammatory parameters and UAE indicates that inflammation may be a pathogenic mechanism of renal injury in type 2 diabetics. Moreover, serum IL-6 and Hp may be good prognostic factors for the development of nephropathy in the course of diabetes mellitus. Future research on the use of anti-inflammatory therapy may result in a new approach to the treatment and prevention of diabetic nephropathy.     

Thrombogenic factors are related to urinary albumin excretion rate in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients

Summary Parameters of haemostasis, endothelial cell markers and lipid peroxide levels were studied in 64 Type 1 (insulin-dependent) and 94 Type 2 (non-insulin-dependent) diabetic patients according to their urinary albumin excretion rate in comparison with age-matched control subjects. We determined plasma levels of fibrinogen (Clauss' method), coagulation factor VII:activity (clotting assay), factor VII antigen, protein C and S antigen, von Willebrand factor antigen,d-dimer concentration (ELISA), and lipid peroxide levels (thiobarbituric acid) in relation to urinary albumin excretion rate (RIA). Significant positive correlations were found between urinary albumin excretion rate and plasma fibrinogen (p<0.005,p<0.02), factor VII activity (p<0.0002,p<0.002), factor VII antigen (p<0.0001,p<0.001), protein C (p<0.003,p<0.05), and lipid peroxides (p<0.02,p<0.004) in Type 1 as well as in Type 2 diabetes. Von Willebrand factor (p<0.001) and protein S (p<0.0005) correlated with albuminuria only in patients with Type 1 diabetes. Although most of the haemostatic abnormalities are already found in normoalbuminuric patients, the significant positive correlations to urinary albumin excretion indicate that endothelial cell damage and coagulation disorders deteriorate with the progression of diabetic nephropathy.     

Rheumatoid arthritis treated with tenidap and piroxicam clinical associations with cytokine modulation by tenidap

Objective. To compare the effects of tenidap and piroxicam on acute-phase protein and cytokine levels in the blood of rheumatoid arthritis (RA) patients and to explore their associations with clinical disease activity. Methods. A double-blind, randomized, crossover trial in 49 patients with active RA compared 6 weeks of treatment with tenidap (120 mg/day) versus 6 weeks of treatment with piroxicam (20 mg/day). Results. Median values for C-reactive protein (CRP), Westergren erythrocyte sedimentation rate (ESR), serum amyloid A (SAA) protein, and interleukin-6 (IL-6) were significantly lower after tenidap treatment compared with piroxicam treatment, even in the presence of stable background treatment with prednisone, methotrexate, or prednisone plus methotrexate. The median within-patient treatment differences (after tenidap minus after piroxicam) in the CRP, ESR, SAA, and IL-6 values were –1.7 mg/dl, –10.0 mm/hour, –22.0 μg/ml, and –3.7 pg/ml, respectively, and represent –60.4%, –17.7%, –35.5%, and –26.1% of the respective baseline levels. IL-6 levels were positively correlated with CRP and SAA. Plasma IL-1β was generally below the level of detection. Tumor necrosis factor α levels were similar after tenidap and after piroxicam. Treatment differences for 4 of 7 clinical parameters favored tenidap, but did not reach statistical significance. IL-6, CRP, and ESR were significantly correlated with clinical treatment differences. Tenidap and piroxicam toleration were similar, although tenidap treated patients exhibited a reversible increase in urinary protein excretion. Conclusion. Tenidap was differentiated from piroxicam by lower levels of acute-phase proteins, ESR, and IL-6 after tenidap treatment. These treatment differences were significantly correlated with clincial parameters.     

Abnormalities of coagulation in hypertensive patients with reduced creatinine clearance

PURPOSE: The prothrombotic state that occurs in uremic patients may increase their cardiovascular risk. We studied hypertensive patients with mild-to-moderate impairment of renal function to determine if they had evidence of abnormalities in the coagulation system. SUBJECTS AND METHODS: Renal function was assessed in 382 patients with essential hypertension, in whom 24-hour creatinine clearance, urinary protein excretion, and microalbuminuria were measured. We evaluated the function of the coagulation system by measurement of platelet counts, prothrombin time, partial thromboplastin time, and plasma antithrombin III, fibrinogen, D-dimer, and prothrombin fragment 1 + 2 levels. RESULTS: Impaired renal function, defined as a creatinine clearance of 30 to 89 mL per minute per 1.73 m(2) of body surface area, was found in 168 (44%) of the patients. Age, blood pressure, duration of hypertension, and plasma levels of fibrinogen, D-dimer, prothrombin fragment 1 + 2, and lipoprotein(a) were significantly greater in these patients than in those with normal renal function; these differences persisted after adjustment for potential confounders. Creatinine clearance was significantly and inversely correlated with levels of plasma fibrinogen (Spearman's rho = -0.26, P <0.001), D-dimer (rho = -0.33, P <0.001), and prothrombin fragment 1 + 2 (rho = -0.20, P <0.001). Levels of plasma fibrinogen (P = 0.009) and D-dimer (P = 0.003) were correlated with renal function independent of age, blood pressure, duration of hypertension, triglyceride level, urinary protein excretion, and erythrocyte sedimentation rate. Lipoprotein(a) levels were correlated with fibrinogen (rho = 0.16, P = 0.003) and D-dimer (rho = 0.26, P <0.001) levels. CONCLUSIONS: Increased plasma levels of fibrinogen, D-dimer, and prothrombin fragment 1 + 2 are present in hypertensive patients with mildly decreased creatinine clearance, suggesting that the coagulation system is activated in these patients.     

Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes

We measured serum concentrations of advanced glycation endproducts (AGEs) in patients with type 2 diabetes, to elucidate the mechanisms underlying the elevated serum concentrations of AGEs and to clarify the relationship between serum AGE concentrations and the development of microangiography and macroangiopathy. Serum AGEs were significantly higher in diabetic patients than in age-matched control subjects (p < 0.0001). In diabetic patients, serum AGEs were positively correlated with HbA1c (r = 0.47, p < 0.0001), urinary albumin excretion (UAE) (r = 0.42, p < 0.0001), diabetes duration (r = 0.31, p = 0.0030), and fasting plasma glucose (r = 0.34, p = 0.0010). Multiple regression analysis disclosed that only the HbA1c and UAE levels independently correlated with serum AGE levels. Serum AGEs in diabetic patients with progressive retinopathy and overt nephropathy were significantly higher than in those with less severe retinopathy and nephropathy. Serum AGEs were significantly higher in the diabetic patients with coronary heart disease (CHD) than in those without CHD. These results suggest that the HbA1c and UAE levels are independent risk factors for increased serum AGE concentrations in type 2 diabetic patients, and that higher serum AGE concentrations are associated with increased severity of diabetic retinopathy and nephropathy. Serum AGE concentrations may be a useful marker not only for the severity of diabetic microangiopathy but also for the development of CHD in patients with type 2 diabetes mellitus. Received: 8 May 2000 / Accepted in revised form: 5 September 2000     

Elevation of urinary betaig-h3, transforming growth factor-beta-induced protein in patients with type 2 diabetes and nephropathy

Transforming growth factor-beta (TGF-beta) is a pro-sclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. betaig-h3 is an extracellular matrix protein which is induced in many cells by TGF-beta. This study examined urinary betaig-h3 excretion in diabetic patients with elevated urinary albumin excretion and the clinical application of urinary betaig-h3 as a marker of diabetic nephropathy. Urinary and serum betaig-h3 levels were determined by enzyme-linked immunosorbent assay in 163 type 2 diabetic patients and 101 healthy control subjects of comparable age and weight. The ratio of urinary betaig-h3 and TGF-beta to creatinine was analyzed in patients with different degree of nephropathy. The betaig-h3 to creatinine ratio in urine was elevated in all groups of type 2 diabetics with normoalbuminuria (101.6 +/- 9.27), microalbuminuria (120.2 +/- 14.48), and overt proteinuria (146.3 +/- 16.34), when compared with control subjects (64.8 +/- 7.14) (P < 0.01). There was a positive correlation between urinary betaig-h3 and TGF-beta excretion rate and a positive correlation between urinary betaig-h3 and albumin excretion rate (AER). These data show that urinary levels of betaig-h3 are elevated in type 2 diabetic patients with nephropathy and may be used as a marker of diabetic nephropathy.     

Haemostatic Measures in Type 2 Diabetic Patients with Microalbuminuria

The major cause of disability and early mortality in Type 2 diabetes is cardiovascular disease. An enhanced urinary albumin excretion is strongly predictive of increased mortality, but the causal relationship behind this association is unclear. Abnormalities in the haemostatic system may be involved in the vascular pathology. We therefore studied the level of von Willebrand factor (vWf:Ag), factor VIII (VIII:Ag), fibrinogen, and fibronectin in male diabetic patients 50–70 years of age, with normal albumin excretion (n = 14), microalbuminuria (n = 14), and frank albuminuria (n = 7). Fourteen healthy age-matched males served as a reference group. There were no significant differences between normo-and micro-albuminuric patients but vWf:Ag (p < 0.01), VIII:Ag (p < 0.01), and fibrinogen (p < 0.05) were increased in those with frank albuminuria. Urinary albumin excretion rate was significantly correlated to vWf:Ag (r = 0.46, p = 0.005), VIII:Ag (r = 0.45, p = 0.007), and fibrinogen (r = 0.49, p = 0.003). The known duration of diabetes was correlated to vWf and F VIII. The increased level of vWf:Ag in Type 2 diabetes and the significant association to the urinary albumin excretion rate may suggest a linkage between albuminuria and cardiovascular disease. However, the present study demonstrated no increase in haemostatic variables in patients with microalbuminuria as compared with those with normal albumin excretion.     

Leptin, triglycerides, and interleukin 6 are independently associated with C-reactive protein in Japanese type 2 diabetic patients

The aim of the present study was to investigate the factors contributing to the concentration of serum C-reactive protein in type 2 diabetic patients. One hundred and 48 Japanese type 2 diabetic patients were studied. In conjunction with C-reactive protein (CRP), BMI, systolic and diastolic blood pressure, glycosylated hemoglobin (HbA1c), fasting concentrations of plasma glucose, and serum lipids (triglycerides, HDL cholesterol, and total cholesterol), interleukin 6 (IL-6), and leptin were measured. Insulin resistance was also estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). With univariate analysis, serum CRP was positively correlated with BMI (r=0.281, P<0.001), diastolic blood pressure (r=0.176, P=0.048), triglycerides (r=0.293, P<0.001), HOMA-IR (r=0.294, P<0.001), IL-6 (r=0.323, P<0.001), and leptin (r=0.330, P<0.001), and negatively correlated with HDL cholesterol (r=-0.181, P=0.028). Multiple regression analyses showed that serum CRP was independently predicted by the level of IL-6 (P<0.001, F=4.04), leptin (P<0.001, F=7.09), and triglycerides (P<0.001, F=15.13), which explained 17.6% of the variability of serum CRP concentration in these patients. From these results, it can be concluded that along with IL-6 and triglycerides, leptin is another important independent factor that is associated with CRP in Japanese type 2 diabetic patients.