HADK2MAG-61K MilliporeMILLIPLEX MAP Human Adipokine Magnetic Bead Panel 2 - Endocrine Multiplex Assay

Early benefits of Roux-en Y gastric bypass (RYGB) are partly mediated by the caloric restriction that patients undergo before and acutely after the procedure. Altered DNA methylation occurs in metabolic diseases including obesity, as well as in skeletal, muscle eight months after RYGB. The objective of this study was to test whether promoter methylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1 A), pyruvate dehydrogenase kinase isozyme-4 (PDK4), transcription factor A (TFAM), interleukin-1 beta (IL1 B), interleukin-6 (IL6) and tumor necrosis factor-α (TNF) is altered in blood after a very low calorie diet (VLCD) or RYGB.Obese nondiabetic patients (n = 18, body mass index [BMI] 42.3± 4.9 kg/m(2)) underwent a 14-day VLCD followed by RYGB. Nonobese patients (n = 6, BMI 25.7± 2.1 kg/m(2)) undergoing elective cholecystectomy served as controls. DNA methylation of selected promoter regions was measured in whole blood before and after VLCD. A subgroup of seven patients was studied 1-2 days and 12± 3 months after RYGB. Promoter methylation was measured using methylated DNA capture and quantitative real-time polymerase chain reaction (PCR).VLCD decreased promoter methylation of PPARGC1 A. Methylation of PPARGC1 A, TFAM, IL1 B, IL6, and TNF promoters was changed two days after RYGB. Similar changes were also seen on day one after cholecystectomy. Moreover, methylation increased in PDK4, IL1 B, IL6, and TNF promoters 12 months after RYGB.RYGB induced more profound epigenetic changes than VLCD in promoters of the tested genes in whole blood. Changes in DNA methylation may contribute to the improved overall metabolic health after RYGB.

Growth differentiation factor 15 (GDF-15) is a relatively new biomarker that predicts mortality in patients with chronic stable angina or acute coronary syndrome. However, the association of GDF-15 with cardiovascular (CV) events and the mechanisms of this association are not well understood.We measured plasma GDF-15 and cardiac disease severity in 984 patients with stable ischemic heart disease who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent CV events (myocardial infarction, stroke, and CV death), hospitalization for heart failure, and all-cause mortality were determined by chart review during an average of 8.9-year follow-up.Each doubling in GDF-15 was associated with a 2.5-fold increased rate of CV events (hazard ratio [HR] 2.53, 95% CI 2.13-3.01, P < .001). This association persisted after extensive adjustment for covariates including comorbid conditions, measures of cardiac disease severity, cardiac function, inflammatory markers, and adipokines (HR 1.44, 95% CI 1.11-1.87, P < .01). Participants who had GDF-15 levels in the highest tertile had higher mortality compared with those in the lowest tertile (HR 2.73, 95% CI 1.80-4.15, P ≤ .001 adjusted for all covariates). Addition of GDF-15 to existing risk factors resulted in a 50% change in net reclassification of patients' risk for mortality.Higher levels of GDF-15 are associated with major CV events in patients with stable ischemic heart disease. This suggests that GDF-15 is capturing an element of risk not explained by other known risk factors.

To assess whether waist-to-height-ratio (WHtR) is a better estimate of body fat percentage (BF%) and a better indicator of cardiometabolic risk factors than BMI or waist circumference (WC) in young children.WHtR, WC and BMI were measured by trained staff according to standardized procedures. (2)H2O and (2)H2(18)O isotope dilution were used to assess BF% in 61 children (3-7 years) from the general population, and bioelectrical impedance (Horlick equation) was used to assess BF% in 75 overweight/obese children (3-5 years). Cardiometabolic risk factors, including diastolic and systolic blood pressure, HOMA2-IR, leptin, adiponectin, triglycerides, total cholesterol, HDL- and LDL-cholesterol, TNFα and IL-6 were determined in the overweight/obese children.In the children from the general population, after adjustments for age and gender, BMI had the highest explained variance for BF% compared to WC and WHtR (R(2) = 0.32, 0.31 and 0.23, respectively). In the overweight/obese children, BMI and WC had a higher explained variance for BF% compared to WHtR (R(2) = 0.68, 0.70 and 0.50, respectively). In the overweight/obese children, WHtR, WC and BMI were all significantly positively correlated with systolic blood pressure (r = 0.23, 0.30, 0.36, respectively), HOMA2-IR (r = 0.53, 0.62, 0.63, respectively), leptin (r = 0.70, 0.77, 0.78, respectively) and triglycerides (r = 0.33, 0.36, 0.24, respectively), but not consistently with other parameters.In young children, WHtR is not superior to WC or BMI in estimating BF%, nor is WHtR better correlated with cardiometabolic risk factors than WC or BMI in overweight/obese children. These data do not support the use of WHtR in young children.

To determine the associations between insulin resistance, fibroblast growth factor 23 (FGF-23), and coronary artery calcification (CAC) in chronic kidney disease (CKD) patients.FGF-23 is associated with atherosclerosis and cardiovascular disease, but its association with insulin resistance in CKD has not been explored.Cross sectional study of 72 stage 3-5 CKD patients receiving care in Ontario, Canada.Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR), FGF-23 was measured by carboxyl terminal enzyme linked immunoassay (ctFGF-23) and CAC was measured by multi-slice computed tomography.Median HOMA-IR was 2.19μU/ml (interquartile range 1.19 to 3.94). Patients with HOMA-IR>2.2 had greater ctFGF-23 (179.7 vs 109.6; P=0.03), and 40% higher log CAC scores (2.09±0.87 vs 1.58±1.26; P=0.049). Multivariable linear regression adjusted for 1,25 dihydroxyvitamin D, kidney function, and parathyroid hormone revealed insulin resistance was a risk factor for greater log ctFGF-23 levels (log HOMA IR β=0.37; 95% confidence interval 0.14 to 0.59; P=0.002).Insulin resistant CKD patients demonstrated higher FGF-23 levels, and increased CAC, while PO4 levels remained normal, suggesting a potential link between insulin resistance and PO4 homeostasis in CKD.

Blacks show higher levels of HbA1c in studies with different populations and are disproportionately affected by most diabetes-related complications.The study aims to investigate if the prevalence of altered glycated hemoglobin (HbA1c) varies with skin color and if there is a familial aggregation of either skin color and HbA1c.The study used the CAMELIA study (Cardio-Metabolic-Renal familiar) population, conducted between June 2006 and December 2007 (cross sectional). Families were recruited from 13 Family Doctor Program Unities of Niteroi, Brazil, a highly miscegenated population. The visits included questionnaire, medical consultation, anthropometric and nutritional assessment. Blood pressure, blood/urine samples were collected. The dosage of HbA1c was performed by immunoturbidimetry in Labmax 240 equipment.We compare data of 241 (25.5%) Blacks, versus 422 (44.7%) Mulattos or 272 (28.8%) Whites. The groups did not differ significantly with regard to most measures. Blacks had the lowest levels of income/education, higher frequency of diabetes and hypertension (p<0.20) as higher levels of HbA1c (p<0.05) that persisted after adjusting for possible confounders. Among blacks, the correlations between siblings of HbA1c were higher than among white/mulatto, reaching 86% versus 50%, respectively.Those results indicate that Brazilian Blacks patients must have more attention, focusing on diabetes preventive care. Longitudinal studies are needed to address the question if the altered level of HbA1c has a real clinical impact.