Background: LDL plays a key role in development and progression of atherosclerosis. Elevated LDL amplifies the atherosclerotic process but the significance of modified LDL in pathogenesis of vascular complications is unclear. We aimed to assess plasma modified LDL levels and their relationship with vascular function in African American diabetic patients. Methods: 125 patients with type-2 diabetes were enrolled. Levels of glycated LDL (g-LDL), carbamylated LDL (c-LDL), nitrated LDL (n-LDL) and oxidized LDL (ox-LDL) were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI), which assesses changes in digital temperature before and after release of arterial cuff occlusion. Carotid-femoral pulse wave velocity (PWV) assessed arterial stiffness using applanation tonometry. B-mode ultrasound image analysis assessed Carotid intima-media thickness (CIMT). Patient population was divided into well-controlled: HbA1c ≤7.0%, N=54; poorly-controlled: HbA1c >7.0%, N=71. Results: Age 60±8 years; 64% Female, 80% Hypertension, 90% Dyslipidemia and 15% CKD. HbA1c level 8.1±2.2%, diabetes duration 10.29±3.79 years. Mean plasma g-LDL, c-LDL, n-LDL and ox-LDL were 1.56±0.64 mg/dL, 0.85±0.11 mg/dL, 2.33±0.39 ng/mL, and 61.93±9.25 ng/mL. Ox-LDL was positively correlated with CIMT in well-controlled patients (r= 0.45, p=0.001), but not in poorly-controlled (r= 0.12, p=0.30). Multi-regression analysis revealed ox-LDL was independently associated with CIMT, but neither with PWV nor VRI after adjustment for variables such as age, gender, weight, smoking, total cholesterol, HDLc, triglycerides, and LDLc (β= 0.003, p= 0.012; r2= 0.38). Conclusion: Ox-LDL offered better predictive value for CIMT in well-controlled patients than other forms of modified LDL. These data favor ox-LDL as potential marker to identify diabetic patients at risk of developing atherosclerotic vascular complications. Disclosure A.M. Adedayo: None. A. Eluwole: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. J. Lazar: None. A. Bakillah: None.
Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity, and inflammation. The soluble human F11 receptor (sF11R) and annexin A5 (ANXA5) play crucial roles in inflammatory thrombosis and atherosclerosis. We examined the relationship between circulating sF11R and ANXA5 and their impact on endothelial function. The study included 125 patients with T2DM. Plasma levels of sF11R and ANXA5 were quantified by ELISA. Microvascular function was assessed using the vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. The mean age of patients in the study was 59.7 ± 7.8 years, 78% had hypertension, 76% had dyslipidemia, and 12% had CKD. sF11R correlated positively with ANXA5 levels (β = 0.250, p = 0.005), and correlated inversely with VRI and total nitic oxide (NO), (β = −0.201, p = 0.024; β = −0.357, p = 0.0001, respectively). Multivariate regression analysis revealed that sF11R was independently associated with ANXA5 in the total population and in patients with HbA1c > 6.5% (β = 0.366, p = 0.007; β = 0.425, p = 0.0001, respectively). sF11R and ANXA5 were not associated with vascular outcome, suggesting that they may not be reliable markers of vascular dysfunction in diabetes. The clinical significance of sF11R/ANXA5 association in diabetes warrants further investigation in a larger population.
Previous studies have demonstrated that increased muscle lipid content is associated with reduced muscle strength and physical performance, independent of muscle mass. An association between elevated muscle lipid content with skeletal muscle attenuation has been reported in a large number of studies. The relationship between vitamin D serum levels and muscle strength is well established. Patients with vitamin D deficiency have increased body fat and decreased muscle strength. A similar association between vitamin D levels and muscle strength has been reported both in the elderly and in healthy adolescent postmenarcheal girls. In several studies, skeletal muscle attenuation was demonstrated in vitamin D deficient patients with neuromuscular disorders. It is unclear whether vitamin D insufficiency is also related to adipose tissue infiltration in muscle. In the present study, the investigators hypothesized that there was an inverse relationship between serum vitamin D levels and adipose tissue infiltration in muscle, which is independent of muscle mass. This cross-sectional study tested this hypothesis by examining the relationship between serum 25-hydroxyvitamin D (25OHD) and skeletal muscle lipid content and muscle mass in a cohort of healthy young women. The study subjects were 90 postpubertal females, aged 16 to 22 years. Study outcome measures included anthropometric characteristics, serum 25OHD values determined with radioimmunoassay, and values of fat, muscle mass, and percent muscle fat determined using computed tomography (CT). The participants were divided into 2 groups based on baseline vitamin D levels: 41% (n = 37) were 25OHD sufficient (≥30 ng/mL) and 59% (n = 53) were 25OHD insufficient (≤29 ng/mL); 24% of the latter were 25OHD deficient (≤20 ng/mL). The data demonstrated a strong inverse relationship between serum 25OHD levels and CT measurements of percent muscle fat (r = −0.37; P < 0.0003), whereas no such relationship was found between the 2 vitamin D groups for fat infiltration in the thigh muscle area (r = 0.16; P = 0.14). Multiple regression analysis showed that the association between 25OHD levels and percent muscle fat was independent of body mass or CT measures of subcutaneous and visceral fat. Compared with the vitamin D sufficient group, percent muscle fat was significantly higher in the vitamin D insufficient group (3.15 ± 1.4 vs. 3.90 ± 1.9; P = 0.038). These findings indicate that vitamin D insufficiency has an inverse association with fat infiltration in muscle, which is independent of body mass.
Higher levels of nitrated lipoproteins (NT-HDL and NT-LDL) were found in blood and atherosclerotic plaques of patients with coronary artery disease. We aimed to examine the relationship between plasma NT-HDL and NT-LDL and diabetic vascular dysfunction. The study included 125 African-American patients with T2DM. NT-HDL and NT-LDL were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. In univariate analysis, NT-HDL was associated with VRI in total population and in patients with HbA1c more than or equal to 7.0 percent (beta= -0.178, p= 0.034; beta = -0.265, p= 0.042; respectively). In contrast, NT-LDL was associated with CIMT in total population and in patients with HbA1c more than 7.0 percent (beta = -0.205, p= 0.022; beta = -0.244, p= 0.042; respectively). Multivariable-adjusted regression analysis demonstrated that NT-HDL independently predicted VRI outcome in total population and in well-controlled patients (beta = -0.282, p= 0.014; beta = -0.400, p= 0.035, respectively). These results suggest that NT-HDL could be used as marker to identify diabetic patients at risk of developing early microvascular complications.
Patients with type 2 diabetes mellitus exhibit non-enzymatic glycation of lipoproteins that are considered proatherogenic modification contributing to increased susceptibility of patients with diabetes to atherosclerosis. We postulated that glycated lipoproteins might be associated with vascular outcome. To explore this, we studied the relationship between glycated HDL (gHDL) and glycated LDL (gLDL) with vascular function in African American diabetic patients. Total of 146 diabetic were enrolled over a 6 month period. Levels of plasma gHDL and gLDL were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (C-IMT) was assessed by B-mode ultrasound image analysis. Mean patient age was 60±8 years, 64% were female. 80% had hypertension, 90% had dyslipidemia and 15% had chronic kidney disease. Mean HbA1c levels were 8.1±2.2%. Pearson correlation analysis showed no significant correlation between gHDL and gLDL. Multi-regression analysis revealed that gHDL was negatively associated with VRI (β= -0.006, p= 0.012; r2 = 0.276 for model) in the entire population and in the group of patients with good glycemic control (HbA1c ≤ 7.0; β= -0.007, p= 0.031; r2 = 0.312 for model); whereas gLDL was positively associated with CIMT (β= 0.045, p= 0.051; r2= 0.568 for model) after adjustment for other independent variables such as age, gender, stroke, smoking, hypertension, dyslipidemia, HbA1c, diabetes duration, HDLc, and LDLc. In this cohort, data showed that gHDL was associated with microvascular function, whereas gLDL was mainly correlated with carotid intima media thickness. Further large study is needed to clarify mediating factors of these relationships. Disclosure A. Eluwole: None. A.M. Adedayo: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. J. Lazar: None. A. Bakillah: None.
Background: Diabetes is a robust risk factor for cardiovascular events which is marked in African Americans for reasons that may be attributed to socioeconomic and biologic vulnerabilities. Both structural (arterial thickening) and functional (arterial stiffness) abnormalities of the vasculature are predictive of incidental clinical events. Study objective was to determine the risk factors and relationship between large artery stiffness and carotid intimal thickness in African Americans with type II diabetes. Methods: 125 patients with diabetes were recruited from medical clinics. Medical information was obtained via interview and electronic medical record review. Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV) using applanation tonometry. Carotid Intimal Medial Thickness (CIMT) was obtained using B-mode ultrasound image analysis of the common carotid artery. Statistical analysis was done using SPSS version 23. Results: Mean age 60±8 years, 64% female. 82% hypertension, dyslipidemia 83%, diabetes duration 10.2±7.6 years, Mean HbA1C= 8.1±2.2%. Mean CIMT=0.68±0.15, PWV= 8.6±2.9. There was no significant association between PWV and CIMT. CIMT positively correlated with gender (r=0.302, p=0.001), smoking (r=0.278, p=0.002), creatinine (r=0.260, p=0.006), triglycerides (r=0.279, p=0.002), pooled cohort score (r=0.353, p=0.001), and negatively with HDL (r= -0.196, p=0.031). PWV positively correlated with creatinine (r=0.300, p=0.001), duration of diabetes (r=0.195, p=0.037) and age (β=0.359, p<0.0001) and pooled cohort score (r=0.248, p=0.003). After adjusting for cardiovascular risk factors, gender (β=-2.000, p=0.019), and age (β=0.119, p=0.018) independently predict PWV but not CIMT. Conclusion: Our findings indicate that PWV and CIMT differ in risk factor profile in African Americans with type II diabetes mellitus. Further studies are needed to clarify mediating factors. Disclosure A. Eluwole: None. A.M. Adedayo: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. A. Bakillah: None. J. Lazar: None.
Vitamin D insufficiency has now reached epidemic proportions and has been linked to increased body fat and decreased muscle strength. Whether vitamin D insufficiency is also related to adipose tissue infiltration in muscle is not known.The objective of the study was to examine the relationship between serum 25-hydroxyvitamin D (25OHD) and the degree of fat infiltration in muscle.This was a cross-sectional study. OUTCOME MEASURES AND SUBJECTS: Measures were anthropometric measures, serum 25OHD radioimmunoassay values, and computed tomography (CT) values of fat, muscle mass, and percent muscle fat in 90 postpubertal females, aged 16-22 yr, residing in California.Approximately 59% of subjects were 25OHD insufficient (< or = 29 ng/ml), of which 24% were deficient (< or = 20 ng/ml), whereas 41% were sufficient (> or = 30 ng/ml). A strong negative relationship was present between serum 25OHD and CT measures of percent muscle fat (r = -0.37; P < 0.001). In contrast, no relationship was observed between circulating 25OHD concentrations and CT measures of thigh muscle area (r = 0.16; P = 0.14). Multiple regression analysis indicated that the relation between 25OHD and muscle adiposity was independent of body mass or CT measures of sc and visceral fat. Percent muscle fat was significantly lower in women with normal serum 25OHD concentrations than in women with insufficient levels and deficient levels (3.15 +/- 1.4 vs. 3.90 +/- 1.9; P = 0.038).We found that vitamin D insufficiency is associated with increased fat infiltration in muscle in healthy young women.
