Association of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes.

BACKGROUND: Osteoprotegerin is a member of the tumor necrosis factor-related family and inhibits RANK stimulation of osteoclast formation as a soluble decoy receptor. The goal of this study was to determine the relationship of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes. METHODS: The subjects were 124 patients with type 2 diabetes mellitus, including 88 males and 36 females with a mean (± SD) age of 65.6 ± 8.2 years old. Serum levels of osteoprotegerin, osteocalcin, fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D3 and adiponectin were measured by ELISA. Vascular calcification in the cervical artery was examined by ultrasound sonography. The subjects were divided into 4 quartiles depending on serum osteoprotegerin levels. RESULTS: Vascular calcification was significantly higher in the 4th quartile and significantly lower in the 1st quartile of serum osteoprotegerin levels, compared to other quartiles. There were no differences in serum osteoprotegerin and vascular calcification among patients with different stages of diabetic nephropathy, but serum FGF23 levels were elevated in those with stage 4 diabetic nephropathy. Simple regression analysis showed that serum osteoprotegerin levels had significant positive correlations with age, systolic blood pressure and serum adiponectin levels, and significant negative correlations with BMI and serum 25-hydroxyvitamin D3. CONCLUSIONS: These findings suggest that elevated serum osteoprotegerin may be involved in vascular calcification independently of progression of diabetic nephropathy in patients with type 2 diabetes.

Association of subcutaneous and visceral fat mass with serum concentrations of adipokines in subjects with type 2 diabetes mellitus.

The goal of the study was to examine the association of subcutaneous and visceral fat mass with serum concentrations of adipokines in 130 subjects with type 2 diabetes mellitus. The levels of serum high sensitivity C-reactive protein (HS-CRP), adiponectin, high-molecular-weight (HMW) adiponectin, interleukin-18, and retinol-binding protein 4 were measured. Percentage body fat was determined by dual energy X-ray absorptiometry, and subcutaneous and visceral fat areas were measured by abdominal CT. HS-CRP had significant positive correlations with percentage body fat and subcutaneous fat area, and a particularly significant positive correlation with visceral fat area. Serum adiponectin had a negative correlation with the subcutaneous and visceral fat areas, with the strongest correlation with the visceral fat area. Similar results were obtained for HMW adiponectin. Serum adiponectin had a negative correlation with visceral fat area in subjects with a visceral fat area < 100 cm², but not in those with a visceral fat area ≥ 100 cm². In contrast, serum HS-CRP showed a positive correlation with visceral fat area in subjects with visceral fat area ≥ 100 cm², but not in those with a visceral fat area < 100 cm². These findings indicate that an increased visceral fat area is associated with inflammatory changes, and that inflammatory reactions may alter the functional properties of visceral fat in type 2 diabetes mellitus.

Prompt increases in retinol-binding protein 4 and endothelial progenitor cells during acute exercise load in diabetic subjects.

The present study was undertaken to determine whether acute exercise load alters serum retinol-binding protein 4 (RBP4) and numbers of endothelial progenitor cells (EPC) in diabetic subjects. Sixty-two subjects with type 2 diabetes mellitus were enrolled in the present study. They were 50 males and 12 females with the ages of 65.1±8.1 (mean ± SD) years. Cardio-pulmonary exercise stress test (CPX) was carried out, and the numbers of EPC and serum RBP4 levels before and after the CPX were measured. RBP4 is a cytokine synthesized in hepatocytes, white adipose tissues and skeletal muscles, and serum RBP4 was determined by ELISA. EPC was determined as CD34(+)/133(+) cells by FACS. The subjects were subgrouped into two groups with or without nephropathy. Serum RBP4 levels promptly increased from 48.2±4.3 (mean±SEM) to 54.3±4.2 µg/mL after the CPX (mean exercise time of 8 min) in the diabetic subjects without nephropathy (p=0.0006), but did not in those with nephropathy. There was a positive correlation between changes in serum RBP4 during the exercise and estimated glomerular filtration rate (r=0.30, p=0.018). Also, an acute exercise load promptly increased the number of EPCs in the diabetic subjects with and without nephropathy. These findings suggest that a prompt increase in exercise-induced RBP4 is retarded by progression of nephropathy, and that an exercise-induced mobilization of EPCs could maintain endothelial cells in diabetic subjects.

An increase in serum retinol-binding protein 4 in the type 2 diabetic subjects with nephropathy.

UNLABELLED: The present study was undertaken to determine retinol-binding protein 4 (RBP4) levels in subjects with diabetic nephropathy. A total of 149 type 2 diabetic subjects and 19 control subjects were enrolled. Serum levels of RBP4 were measured by a method of ELISA. Serum RBP4 levels were significantly greater in the subjects with type 2 diabetes mellitus than the controls (70.5 +/- 35.3 vs. 40.1 +/- 13.0 microg/ml, mean +/- SD, p<0.01). Serum RBP4 levels were gradually increased according to the progression of diabetic nephropathy (p value in trend test: <0.001). Its elevation was significantly greater in the diabetic subjects with stages 1, 3B and 4 than the control subjects (Stage 1: 64.6 +/- 29.7, Stage 3B: 123.3 +/- 71.8, Stage 4: 91.4 +/- 33.8 vs. CONTROL: 40.1 +/- 13.0 microg/ml, p<0.01). Similar results were obtained in the subjects based on the amount of albuminuria (Normo-: 64.6 +/- 29.7, Micro-: 63.7 +/- 29.4, and Marcoalbuminuria: 90.3 +/- 44.6 microg/ml, p <0.001). Serum RBP4 levels had a positive correlation with serum creatinine levels(r = 0.377, p<0.001), and a negative correlation with 1/creatinine (r = -0.420, p<0.001). Also, there was a negative correlation between serum RBP4 and the estimated glomerular filtration rate(r = -0.436, p<0.001). Multiple regression analysis showed that estimated glomerular filtration rate was an independent determinant for increased serum RBP4 levels. There was no difference in serum RBP4 levels between the advanced nephropathy with and without macrovascular diseases. These results indicate an increase in serum RBP4 levels in the type 2 diabetic subjects, particularly complicated with advanced renal impairment.

Endothelial impairment and bone marrow-derived CD34(+)/133(+) cells in diabetic patients with erectile dysfunction.

AIMS/INTRODUCTION: The present study was undertaken to determine vascular endothelial impairment and endothelial progenitor cells (EPCs) in patients with type 2 diabetes mellitus and erectile dysfunction (ED). MATERIALS AND METHODS: A total of 100 type 2 diabetic men were enrolled. Flow-mediated dilatation (FMD) and anaerobic threshold (AT) were measured. Also, EPCs in the peripheral blood were determined by flow cytometry. RESULTS: In the 42 ED diabetic patients, FMD and AT were significantly less than those in the 58 patients with normal erectile function (FMD 2.84 vs 3.82%, P = 0.038, and AT 11.2 vs 12.7 mL/kg/min, P = 0.022). Exercise tolerance significantly increased the number of EPCs in the patients with and without ED (49-60 cells/100 µL, P = 0.015, and 72-99 cells/100 µL, P = 0.003). In the diabetic patients without autonomic neuropathy, FMD was significantly reduced in the patients with ED than those without ED (P = 0.015). In response to exercise tolerance, the number of EPCs increased in both the diabetic patients with ED (P = 0.003) and without ED (P = 0.007). In contrast, in the diabetic patients with autonomic neuropathy, there was no difference in FMD between the patients with and without ED. The exercise tolerance increased the number of EPCs in the patients without ED (P = 0.023), but it disappeared in those with ED. CONCLUSIONS: ED diabetic patients have endothelial impairment during the early period of diabetic complications, whose deranged endothelial function is concomitantly repaired by promoting bone marrow-derived EPCs.

Elevation of plasma retinol-binding protein 4 and reduction of plasma adiponectin in subjects with cerebral infarction.

The present study was undertaken to determine plasma retinol-binding protein 4 (RBP4) and adiponectin levels in subjects with cerebral infarction. Fifty-eight subjects with cerebral infarction and 53 age- and sex-matched control subjects were enrolled. Plasma RBP4, adiponectin, and high-molecular-weight adiponectin were measured by the method of enzyme-linked immunosorbent assay. Plasma RBP4 was 16.4 +/- 2.8 microg/mL in the subjects with cerebral infarction, a value significantly greater than that of 10.1 +/- 1.2 microg/mL in the controls (P = .044). Inversely, plasma adiponectin was significantly less in the subjects with cerebral infarction than the control subjects (8.1 +/- 0.8 vs 10.8 +/- 0.7 microg/mL, P = .015). However, there was no difference in plasma high-molecular-weight adiponectin between the 2 groups of subjects. In the control subjects, there were negative correlations between plasma RBP4 and adiponectin and between plasma RBP4 and high-molecular-weight adiponectin levels; and they totally disappeared in the subjects with cerebral infarction. The multiple regression analysis showed that adiponectin and hypertension were independent factors contributing to cerebral infarction (P < .001). These findings indicate that hypoadiponectinemia is concomitantly involved in the pathogenesis of atherosclerosis, and that an elevation of plasma RBP4 may be a useful marker for the development of atherosclerosis, in subjects with cerebral infarction.