RESUMO
BACKGROUND: Type 2 diabetic patients with albuminuria have an increased risk for vascular complications. Albuminuria is related to endothelial dysfunction and plaque instability. YKL-40 is also associated with both and elevated in nondiabetic vascular patients. We investigated YKL-40 and its association with vascular disease in type 2 diabetic patients with albuminuria. MATERIAL AND METHODS: Two hundred and four patients with type 2 diabetes were included in a cross-sectional study: One hundred and six normo- (No-A), 64 micro- (Mi-A) and 34 macroalbuminuric (Ma-A) patients that did not differ for age, diabetes duration, HbA1c, body-mass-index, blood pressure, lipids and creatinine. YKL-40 was measured in serum samples and determined by ELISA. RESULTS: YKL-40 was significantly different in No-A: 87±57 vs. Mi-A 119±68 vs. Ma-A 157±75ng mL(-1) ; P<0·001. Patients with macrovascular disease showed higher YKL-40 than those without: 115±72 vs. 87±49ng mL(-1) , P=0·003. In correlation analysis, YKL-40 was associated with urinary albumin excretion rate (AER), plasma creatinine, creatinine clearance (CC) and age. Two multivariate regression analyses were conducted: in the first one, AER and CC remained associated with YKL-40 and in the second one AER and age. CONCLUSIONS: This is the first report of a significant elevation of YKL-40 in type 2 diabetic patients with albuminuria. In addition, we observed a significant association with macrovascular disease. Because we detected an association between YKL-40 with renal, micro- and macrovascular disease, this protein could play an important for the increased risk of type 2 diabetic patients with albuminuria for the development of cardiovascular disease.
Assuntos
Albuminúria/complicações , Diabetes Mellitus Tipo 2/complicações , Glicoproteínas/sangue , Lectinas/sangue , Adipocinas , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Proteína 1 Semelhante à Quitinase-3 , Estudos Transversais , Glicoproteínas/metabolismo , Humanos , Lectinas/metabolismo , Pessoa de Meia-Idade , Valores de Referência , Análise de Regressão , Fatores de RiscoRESUMO
OBJECTIVE: The intercellular adhesion molecule-1 (ICAM-1/CD54) and its ligand, CD11a/CD18, mediate endothelial adhesion of leukocytes and their consecutive transmigration. Anti-inflammatory effects of statins are considered to be exerted in part through inhibition of leukocyte-endothelial interactions. We investigated the in vivo effects of simvastatin treatment in hypercholesterolemic patients and the influence of various statins on expression of cellular adhesion molecules in vitro. METHODS AND RESULTS: A total number of 107 hypercholesterolemic patients were treated with 20 mg (n=52) or 40 mg (n=55) of simvastatin daily. After 6 weeks of treatment, peripheral blood mononuclear cells (PBMCs) expressed lower amounts of CD54-, CD18-, and CD11a-mRNA compared with pretreatment values. Surface expression of CD54 and CD18/CD11a on CD14+-monocytes also decreased significantly in both groups of patients. Moreover, simvastatin, atorvastatin, and cerivastatin were found to downregulate tumor necrosis factor (TNF)-alpha-induced expression of CD54 and CD18/CD11a in isolated PBMCs obtained from normal donors as well as TNF-alpha-dependent expression of these CAMs in cultured human umbilical vein endothelial cells (HUVECs). Furthermore, all three statins were found to reduce the binding of PBMCs to TNF-alpha-stimulated HUVECs in vitro. CONCLUSIONS: Statin-induced inhibition of expression of CD54 and CD18/CD11a in PBMCs and HUVECs with consecutive loss of adhesive function may contribute to the anti-inflammatory effects of these drugs and some of their beneficial clinical activities.
Assuntos
Moléculas de Adesão Celular/efeitos dos fármacos , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Monócitos/metabolismo , Sinvastatina/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo , Idoso , Antígenos CD11/metabolismo , Antígenos CD18/metabolismo , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Endotélio Vascular/metabolismo , Feminino , Humanos , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/metabolismo , Lipoproteínas LDL/sangue , Lipoproteínas LDL/efeitos dos fármacos , Antígeno-1 Associado à Função Linfocitária/biossíntese , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/efeitos dos fármacos , Veias UmbilicaisRESUMO
Background. Asymmetric dimethylarginine (ADMA) is associated with macrovascular disease and possibly with microangiopathy in type 2 diabetes (T2DM). We tested the hypothesis that ADMA is related to diabetic retinopathy (DR) independently of macrovascular disease. Methods. This cross-sectional study included 127 T2DM patients selected to achieve equal distributions of patients with and without macrovascular disease in the groups with and without DR. Results. Patients with DR had increased ADMA, longer diabetes duration, and reduced glomerular filtration rate (GFR). ADMA correlated with GFR (ρ = -0.35; P < .001), diabetes duration (ρ = 0.19; P = .048), and age (ρ = 0.19; P = .033). Logistic regression analysis revealed an association of ADMA with DR. After adjustment for macrovascular disease, this association remained significant (OR 1.48; 95% CI: 1.02-2.15; P = .039). Inclusion of GFR and T2DM duration into the model abolished this significant relationship. GFR remained the only independent predictor for DR. A 10 mL/min/1.73 m(2) GFR decrease was associated with DR in a multivariate model (OR 1.30; 95% CI: 1.08-1.56; P = .006). Conclusions. These findings indicate an association between ADMA and DR in T2DM independent of macrovascular disease. This relationship is modified by GFR, the only parameter significantly related to DR in multivariate analysis.
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INTRODUCTION: The efficacy of tight glycemic control for the prevention of death and renal failure in the general diabetic population is well established. However, in diabetic renal-allograft recipients, the effect of different treatment strategies on outcomes is undetermined. METHODS: We conducted a cohort study of 798 diabetic, renal-allograft recipients transplanted at the Medical University of Vienna between 1990 and 2004. We studied the influence of glucose parameters and diabetes treatment on mortality and graft loss. Marginal-structural models and multivariable Cox regression analysis were used to control for confounding. RESULTS: Maximal glucose levels but not HbA1c were independently associated with mortality. Being in the highest quartile of maximal glucose increased the adjusted risk of death by a factor of 2.2 (P value for trend 0.009). Furthermore, in patients receiving insulin, the risk of death was increased 1.7-fold (95% confidence interval 0.9-3.1) compared with diet and 2.0-fold (95% confidence interval 1.1-3.7) compared with oral medication. Maximal glucose, HbA1c, or diabetes treatment did not influence death-censored functional graft survival. DISCUSSION: In conclusion, maximal glucose levels and insulin treatment were independently associated with higher rates of mortality in our cohort of diabetic, renal-allograft recipients. However, graft survival was unaffected.