Inconsistency in albuminuria predictors in type 2 diabetes: a comparison between neural network and conditional logistic regression.

Albuminuria is a sensitive marker to predict future cardiovascular events in patients with type 2 diabetes mellitus. However, current studies only use conventional regression models to discover predictors of albuminuria. We have used 2 different statistical models to predict albuminuria in type 2 diabetes mellitus: a multilayer perception neural network and a conditional logistic regression. Neural network models were used to predict the level of albuminuria in patients with type 2 diabetes mellitus, which include a matched case-control study for the population. For each case, we randomly selected 1 control matched by age and body mass index (BMI). The input variables were sex, duration of diabetes, systolic and diastolic blood pressure, glomerular filtration rate, high-density lipoprotein, low-density lipoprotein, triglyceride, high-density lipoprotein/triglyceride ratio, cholesterol, fasting blood sugar, and glycated hemoglobin. Age and BMI were included only in the neural network model. This model included 4 hidden layers and 1 bias. Relative error of predictions was 0.38% in the training group, 0.52% in the testing group, and 1.20% in the holdout group. The most robust predictors of albuminuria were high-density lipoprotein (21%), cholesterol (14.4%), and systolic blood pressure (9.7%). Using the conditional logistic regression model, glomerular filtration rate, time of onset to diabetes, and sex were significant indicators in the onset of albuminuria. Using a neural network model, we show that high-density lipoprotein is the most important factor in predicting albuminuria in type 2 diabetes mellitus. Our neural network model complements the current risk factor models to improve the care of patients with diabetes.

Oxidized low-density lipoprotein is associated with viral load and disease activity in patients with chronic hepatitis C.

BACKGROUND: The mechanisms of liver injury in chronic hepatitis C virus (HCV) infection are poorly understood. Recent evidence suggests that oxidative stress and lipid-peroxidation play a major role. The purpose of this study was to determine the serum level of oxidized low-density lipoprotein (ox-LDL), and evaluate its association with different clinically valuable parameters of liver disease in patients with chronic hepatitis C. METHODS: Forty-five untreated chronic hepatitis C patients and 45 healthy adult volunteers, matched for age, sex and BMI, were enrolled. Blood samples were collected after 12 h of fasting, and serum bilirubin, albumin, liver aminotransferases, lipid profile, prothrombin time and ox-LDL were measured. Viral load of HCV was determined in patients. Liver biopsy was performed in patients and the stage of fibrosis and grade of necroinflammatory activity were determined. Healthy controls did not undergo liver biopsy. RESULTS: Ox-LDL was significantly higher in HCV patients (42.54 ± 3.82 vs. 30.98 ± 1.66 µ/l, P < 0.01). Ox-LDL was significantly correlated to viral load (r = 0.457, P < 0.01), and grade of inflammation (r = 0.293, P < 0.05) in HCV patients. Ox-LDL was significantly higher in cirrhotic vs. noncirrhotic patients. No significant association was found between ox-LDL and Child-Pugh classification, serum albumin, liver enzymes, or prothrombin time. CONCLUSION: This study provided new data from an in vivo setting which suggests the contribution of ox-LDL to HCV pathogenesis. Our results encourage further clinical studies to evaluate the potential diagnostic and therapeutic implications of ox-LDL in HCV patients.

Increased serum HSP70 levels are associated with the duration of diabetes.

The evolutionary conserved family of heat shock proteins (HSP) is responsible for protecting cells against different types of stress, including oxidative stress. Although the levels of HSPs can be readily measured in blood serum, the levels of HSP70 in patients with different durations of diabetes have not been studied before. We quantified serum HSP70 levels in a healthy control group (n = 36) and two groups of type 2 diabetic patients, defined as newly diagnosed diabetes (n = 36) and patients with diabetes duration of more than 5 years (n = 37). The clinical characteristics and biochemical parameters were evaluated in the studied population. We found that serum HSP70 levels were significantly higher in patients with diabetes when compared with controls (p < 0.001) and it was higher in patients with disease for more than 5 years than in newly diagnosed patients (p < 0.001). Serum HSP70 was inversely correlated with fasting blood sugar in patients with diabetes for more than 5 years (r = -0.500, p = 0.002), positively correlated with the history of hypertension in newly diagnosed patients (p < 0.001), and positively correlated with age in patients with diabetes (r = 0.531, p = 0.001). Serum level of HSP70 is significantly higher in patients with diabetes and correlates with the duration of disease. Higher HSP70 in prolonged diabetes versus newly diagnosed diabetes may be an indicator of metabolic derangement in the course of diabetes.

Association of macroalbuminuria with oxidized LDL and TGF-beta in type 2 diabetic patients: a case-control study.

The pathogenesis of diabetic nephropathy, mainly characterized by macroalbuminuria, is still poorly understood, but it is reported that transforming growth factor-beta (TGF-beta) plays a key role. In vitro evidence suggests that administration of oxidized LDL (ox-LDL) can lead to upregulation of TGF-beta by human glomerular mesangial cells. This study aimed to evaluate the association between macroalbuminuria, ox-LDL, and TGF-beta in diabetic patients. A total of 77 type 2 diabetic patients with macroalbuminuria (albumin excretion rate: AER > or = 300 mg/24 h) and 66 patients with normoalbuminuria (AER < or = 30 mg/24 h) were recruited. Fasting blood samples were obtained and serum levels of ox-LDL and TGF-beta were determined. Ox-LDL and TGF-beta were significantly higher in patients with macroalbuminuria than in those with normoalbuminuria (98.93 + or - 3.99 vs. 72.45 + or - 2.48 U/l; P < 0.001 and 6.46 + or - 0.74 vs. 2.49 + or - 0.39 ng/ml; P < 0.001, respectively). In patients with macroalbuminuria, there was a significant correlation between Ox-LDL and TGF-beta (r = 0.376; P < 0.01). AER was significantly correlated to ox-LDL (r = 0.302; P < 0.05) and TGF-beta (r = 0.306; P < 0.05) in macroalbuminuric patients. This association remained significant after adjustment for potential confounders. Adjustment for TGF-beta (ox-LDL), attenuated the association of ox-LDL (TGF-beta) with AER. In conclusion, this study demonstrated the association of TGF-beta and ox-LDL with albuminuria in macroalbuminuric type 2 diabetic patients, and suggested that this relationship is highly mediated through the correlation between TGF-beta and ox-LDL.

Association of oxidized low-density lipoprotein and transforming growth factor-beta in type 2 diabetic patients: a cross-sectional study.

Recent in vitro evidence suggests that oxidized low-density lipoprotein (ox-LDL) stimulates the expression of transforming growth factor-beta (TGF-beta) by human glomerular epithelial cells. An elevated level of TGF-beta, which is a multifunctional growth cytokine, is also reported in diabetic patients. This study aimed to determine the association between ox-LDL and TGF-beta in healthy and type 2 diabetic participants. A total of 80 type 2 diabetic patients, who were referred to the outpatient diabetes clinic of a university general hospital, and 80 healthy controls matched for sex, age, and body mass index (BMI) were recruited. Fasting blood samples were obtained, and fasting plasma glucose, cholesterol, high-density lipoprotein-cholesterol (HDL-c), LDL-cholesterol, triglycerides, creatinine, HbA1C, ox-LDL, and TGF-beta were measured. Ox-LDL and TGF-beta were significantly greater in diabetic patients than healthy controls (72.66 +/- 3.11, 46.02 +/- 1.64, P < 0.001 and 4.75 +/- 0.43, 2.06 +/- 0.31, P < 0.001, respectively). Ox-LDL was significantly correlated to TGF-beta in diabetic patients (r = 0.318, P = 0.004). This significant association was not observed in healthy controls (r = 0.148, P = 0.191). In multivariate linear regression analysis after adjustment for age, sex, BMI, and creatinine, ox-LDL was a significant independent predictor of TGF-beta (beta = 0.308, P = 0.007). In conclusion, this study demonstrated that ox-LDL is significantly correlated to TGF-beta in type 2 diabetic patients.