Association of insulin resistance,insulin and leptin levels with coronary in-stent restenosis

BackgroundIn-stent restenosis remains the major limitation of coronary stent implantation. Leptin is a hormone strongly related to insulin resistance (IR). Moreover, insulin resistance and hyperinsulinemia are common in patients with coronary heart disease (CHD), each of the previous metabolic and hormonal factors might be involved in restenosis after stent implantation.ObjectiveThis study was planned to evaluate the relationship between insulin resistance, insulin, leptin levels and coronary in-stent restenosis after coronary stent implantation in non-diabetic patients with CHD and to determine their value in prediction of restenosis.Patients and methodsThe study included 48 non-diabetic CHD patients with previous successful coronary stent implantation. They were divided into two groups according to the presence of in-stent restenosis on follow-up coronary angiography (6–9 months after stent implantation). The first group was CHD patients with in-stent restenosis which included 20 patients, the second group was CHD patients without restenosis which included 28 patients. All patients were subjected to complete clinical examination including determination of body mass index (BMI), waist to hip ratio (WHR) and laboratory investigations including fasting plasma glucose (FPG), fasting plasma insulin (FP insulin), lipid profile (total cholesterol, HDL-C, LDL-C, TG), glycoselated hemoglobin (HbA1c), plasma leptin, estimation of homeostasis model assessment of IR (HOMA-IR). All subjects were submitted to OGTT with estimation of 2-h post-prandial glucose (2-hPP glucose) and sum post-prandial insulin levels (sum PP insulin). Follow-up coronary angiography was done for all patients with the estimation of minimal luminal diameter (MLD), diameter stenosis % and late lumen loss.ResultsThere was highly significant increase in each of FP insulin, sum PP insulin, HOMA-IR, leptin, diameter stenosis % and late lumen loss (P < 0.001) and a highly significant decrease of MLD (P < 0.001) in CHD patients with in-stent restenosis when compared to CHD patients without in-stent restenosis. MLD is negatively correlated to each of FP insulin (r = −0.49, P < 0.001), sum PP insulin (r = −0.60, P < 0.001) HOMA-IR (r = −0.63, P < 0.001) and leptin (r = −0.55, P < 0.001) while late lumen loss was positively correlated to each of FP insulin (r = 0.98, P < 0.001), sum PP insulin (r = 0.70, P < 0.001), HOMA-IR (r = 0.67, P < 0.001) and leptin (r = 0.72, P < 0.001). Multiple regression analysis revealed that each of FP insulin, sum PP insulin, HOMA-IR and leptin can be considered an independent predictor of in-stent restenosis (P < 0.001).ConclusionOur study revealed that insulin resistance, fasting and post-prandial hyperinsulinemia and hyperliptinemia are considered predictors of coronary in-stent restenosis. Evaluation of HOMA-IR, insulin levels after standard OGTT and leptin levels are important tools in an attempt to recognize subjects at risk of early restenosis among non-diabetic, CHD patients undergoing percutaneous coronary revascularization and stent implantation.     

Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus

ObjectiveElevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal an early response to commonly used medical therapies for T2D.Materials and MethodsA liquid chromatography–mass spectrometry approach was used to measure BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: 1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; 2) two days of twice daily metformin 500 mg orally; and 3) a 75-g OGTT. Percent change in BCAA/AAAs was determined after each intervention.ResultsFollowing glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/AAAs decreased in the IS subjects only (all P < 0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/AAAs increased in the IR subjects at or below P = 0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/AAAs decreased in all subjects (P < 0.05).ConclusionsBCAA/AAAs changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/AAAs may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D.     

Association of Indoxyl Sulfate With Fibroblast Growth Factor 23 in Patients With Advanced Chronic Kidney Disease

BackgroundProtein-bound uremic toxins–indoxyl sulfate (IS) and p-cresyl sulfate (PCS)–can not only predict clinical outcomes but also may relate to bone-mineral disorders in patients with chronic kidney disease (CKD). However, the relationship between protein-bound uremic toxins and fibroblast growth factor 23 (FGF23) has not been studied before. The objective of this study was to explore the association of IS and PCS with FGF23 in a CKD-based cohort.MethodsThis is a cross-sectional study that enrolled 80 stable CKD stage 3 to 5 patients who met the inclusion criteria in a single medical center. Serum levels of IS, PCS and FGF23 were measured concurrently. General biochemistry and patient background were also investigated.ResultsSerum FGF23 and IS concentrations were elevated commensurately with deteriorating renal function. Pearson's analysis showed that FGF23 levels were significantly associated with blood urea nitrogen (r = 0.381, P < 0.05), creatinine (r = 0.632, P < 0.01), estimated glomerular filtration rate (r = –0.447, P < 0.05), phosphate (r = 0.543, P < 0.01), intact parathyroid hormone (r = 0.543, P < 0.01), IS (r = 0.432, P < 0.01) and PCS (r = 0.318, P < 0.05). After adjusting other confounding factors by stepwise multiple linear regression analysis, only creatinine (β = 0.82, P < 0.01), phosphate (β = 0.28, P = 0.02) and IS (β = 0.39, P = 0.04) retained statistically significant associations with FGF23. Moreover, serum levels of IS were higher in patients with high FGF23 concentration (> 90 pg/mL, median value) than those with lower FGF23 (P < 0.01).ConclusionsResults indicated that only IS but not PCS correlated independently with FGF23 in worsening CKD. IS may be an independent factor involved in regulation of bone-mineral metabolism.     

Serum sclerostin in acute kidney injury patients

BackgroundMany of the mineral metabolite abnormalities encountered in chronic kidney disease (CKD) patients were found also associated with acute kidney injury (AKI). In the last decade, sclerostin was found to intimately affect bone mineral metabolism in CKD patients. Nothing is known about sclerostin in AKI.ObjectiveWe looked for serum level of sclerostin in AKI patients in comparison to normal control subjects and if there is an impact on metabolic derangement, endothelial function or clinical outcome.Cases and methodsThis is a cross sectional case control observational study of 219 AKI cases (group I) beside 219 age matched normal control subjects (group II). All cases of group I were in the intensive care because of sepsis; 86 had acute on CKD (group Ib), while 133 had de novo AKI (group Ia). All studied subjects underwent estimation of serum sclerostin, parathyroid hormone (PTH), 25 hydroxy vitamin D (25 OH vit D), fibroblast growth factor 23 (FGF23), C-reactive protein (CRP), interleukin 6 (IL6), Homeostatic Model Assessment for Insulin Resistance (Homa IR), beside the routine CBC, kidney and liver function tests, serum calcium, and phosphorus, and flow mediated vasodilation of brachial artery (FMD). Follow-up of group I cases was done till they recovered or passed away.ResultsSerum sclerostin, PTH, FGF23, phosphorus, CRP, IL6, HOMA IR, creatinine, urea, uric acid, ALT, AST and white blood cell count (WBC) were significantly higher while serum calcium, 25 OH vit D, hemoglobin, platelet count and FMD were significantly lower in group I compared to group II (P < 0.001 in all). On the other hand, there was no significant difference in serum sclerostin, PTH, FGfF23, 25 OH vit D, CRP, IL6, Homa IR and FMD between group Ia and Ib. Survivors were younger in age (median 55.5 vs. 60 years, P < 0.04), had lower AST (30.5 vs. 58 units, P < 0.001), had higher platelet count (206 vs 162 × 10⁹/L, P < 0.001), otherwise, there was no significant difference in any of the other parameters between survivors and patients that were lost. Serum sclerostin had strong correlation with FGF23 in group I (r = 0.99, P < 0.001) and group II (r = 1, P < 0.001). Homa IR had positive correlation with serum sclerostin (r = 0.148, P = 0.014) and serum FGF23 (r = 0.142, P = 0.018) in group I.ConclusionSclerostin is intimately related to FGF23. Sclerostin level increases in AKI patients. Both sclerostin and FGF23 might increase insulin resistance but have no impact on FMD. Neither sclerostin nor FGF23 interfere with AKI outcome.     

Apolipoprotein B-48 as a determinant of endothelial function in obese subjects with type 2 diabetes mellitus: effect of fenofibrate treatment

ObjectiveElevated triglyceride-rich lipoproteins may contribute to endothelial dysfunction in obese diabetic subjects. We investigated the association between plasma concentrations of chylomicron-related particles and endothelial function, and the corresponding responses to fenofibrate treatment.MethodsPlasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol concentrations were measured in 28 obese subjects with T2DM. Flow-mediated endothelium-dependent dilation (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) in the brachial artery during reactive hyperaemia were examined by high-resolution ultrasound technique.ResultsIn univariate analysis, plasma apoB-48 and RLP-cholesterol concentrations were inversely associated with brachial artery FMD (r = ?0.425 and ?0.423, respectively, P < 0.05), but not with GTNMD. In regression models including BMI and HOMA score, plasma apoB-48 was an independent predictors (P < 0.05) of brachial artery FMD (β coefficient = ?0.384). Replacing HOMA-IR score with plasma triglyceride, adiponectin or CRP concentrations did not alter the findings. The subjects were then randomized to a 12-week treatment period of either 200 mg micronized fenofibrate or matching placebo. Compared with the placebo group, fenofibrate treatment (200 mg daily for 12 weeks) achieved significant increase in FMD (+34%) and reduction in plasma triglyceride (?42%), apoB-48 (?52%) and RLP-cholesterol (?51%) concentrations. The increase in FMD with fenofibrate was significantly associated with the corresponding decrease in plasma apoB-48 (r = ?0.644, P < 0.02) concentrations.ConclusionsOur findings demonstrate an association between changes in lipid metabolism and improvement in endothelial function in patients with diabetic dyslipidaemia treated with fenofibrate that may involve the effect of apoB-48 on endothelium-dependent vasodilator function.     

Prevalence of metabolic syndrome assessed by IDF and NCEP ATP 111 criteria and determinants of insulin resistance among HIV patients in the Eastern Cape Province of South Africa

AimsTo determine the prevalence of metabolic syndrome (MS) and insulin resistance (IR) and their determinants in HIV on ART, ART naive HIV and HIV negative patients.MethodsCross sectional study. ART experienced HIV, ART naive HIV and HIV negative patients were compared for differences in prevalence of MS and IR. Determinants of MS and IR were assessed.ResultsPrevalence of MS by NCEP criteria was 26.6%, 15.7% and 21.9% (P = 0.3) respectively for HIV on ART, ART naive HIV and HIV negative groups. The MS rates with the IDF definition were 22.7%, 23.2% and 19.3% (P = 0.8) for HIV on ART, ART naive HIV and HIV negative patients respectively. Increased waist circumference by IDF criteria (P = 0.03), visceral to subcutaneous fat ratio (P = 0.049), hypertriglyceredemia (P < 0.001) and high LDL-Cholesterol (P < 0.001) were more common in HIV patients on ART than other groups. IR was found in 12.8%, 3.6% and 2.4% (P = 0.003) of HIV on ART, ART naive HIV and HIV negative groups respectively. Male gender (odds ratio (OR) 11 95% CI 3–48; P < 0.001) was independently associated with MS. HIV patients on ART (OR 6.6 95% CI 1.3–32.3; P = 0.020), IDF definition of MS (OR 3.4 95% CI 1.1–10.7; P = 0.040), NCEP definition of MS (OR 3.2 95% CI 1.01–10.3; P = 0.049) and low HDL-Cholesterol (OR 5.7 95% CI 1.2–27; P = 0.029) were independently associated with IR.ConclusionPrevalence of MS with IDF and NCEP definitions was similar across groups. HIV patients on ART and MS were independently associated with IR while male gender was independently associated with MS.     

Evolution of subcutaneous adipose tissue fibrosis after bariatric surgery

AimObesity is associated with the development of metabolic complications such as insulin resistance (IR). The mechanisms leading to IR remain unclear. This study aimed to investigate the relationship between adipose tissue fibrosis and IR in obese patients before and after bariatric surgery.MethodsThirty-five obese patients awaiting bariatric surgery (12 with type 2 diabetes) were included in the study. Non-diabetic patients were classified as either insulin-sensitive (n = 11) or insulin-resistant (n = 12), based on the Matsuda insulin sensitivity index (ISI_Matsuda). Homoeostasis model assessment (HOMA-IR) was used for longitudinal evaluation of insulin resistance. Fibrosis was quantified by Masson's trichrome staining on microscopy, and mRNA levels of fibrosis-related genes were examined in subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies collected during and 6 months after bariatric surgery (SAT only).ResultsDespite their similar age, body mass index and fat mass, SAT fibrosis was significantly higher in diabetic vs insulin-sensitive patients (P < 0.05), and associated with IR as assessed by both ISI_Matsuda (r = −0.417, P = 0.038) and HOMA-IR (r = 0.464, P = 0.007) at baseline, whereas VAT fibrosis was not. Six months after surgery and significant weight loss, fibrosis levels remained unchanged in SAT, although IR was significantly reduced in all groups (P < 0.0001). No correlation was found between SAT fibrosis and IR after surgery.ConclusionOverall, these results show a significant but, most likely, transient association between SAT fibrosis and IR in obese humans.     

Inflamación y adecuación de la hemodiálisis: ¿están los niveles de proteína C reactiva influidos por la dosis de diálisis recibida?

IntroductionChronic inflammation and the underlying cardiovascular comorbidity are still current problems in chronic hemodialysis patients. There are few studies comparing the “dialysis dose” (Kt/V) with the degree of inflammation in the patient. Our main objective was to determine whether there is a relationship between serum C-reactive protein (CRP) levels and the Kt/V using ionic dialysance.MethodsMulticenter cross-sectional study. A total of 536 prevalent chronic hemodialysis patients were included. CRP levels, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were collected. Kt was obtained by ionic dialysance and urea distribution volume was calculated from the Watson's formula. The sample was divided into 2 groups, taking the median CRP as the cut-off point. Dialysis adequacy obtained in each group was compared. Finally, a logistic regression model was carried out to determine the variables with the greatest influence.ResultsMedian CRP was 4.10 mg/L (q25-q75: 1.67-10) and mean Kt/V was 1.48 ± 0.308. Kt/V was lower in the patients included in the high inflammation group (P = .01). In the multivariate logistic regression, the “high” levels of CRP were directly correlated with the Log neutrophil-lymphocyte ratio (P < .001) and inversely proportional with serum albumin values (P = .014), Kt/V (P = .037) and serum iron (P < .001).ConclusionThe poorer adequacy in terms of dialysis doses (lower Kt/V values) may contribute to a higher degree of inflammation in chronic hemodialysis patients.     

The -250G/A polymorphism in the hepatic lipase gene promoter influences the postprandial lipemic response in healthy men

Background and aimThe −250G/A promoter polymorphism of the hepatic lipase gene has been associated with changes in the activity of the enzyme. We investigated whether this polymorphism modifies the postprandial response of triacylglycerol-rich lipoproteins (TRL) in young normolipemic males.Methods and resultsFifty-one healthy apolipoprotein (apo) E3/E3 male volunteers (30 G/G and 21 carriers of the A allele) underwent a vitamin A fat-loading test and blood samples were drawn every hour until the 6th, and every 2 h and 30 min until the 11th. Total plasma cholesterol and triacylglycerols (TG), as well as cholesterol, TG and retinyl palmitate (RP) in TRL, isolated by ultracentrifugation, were determined.Carriers of the A allele showed a higher response (P = 0.008), a higher area under the curve (AUC; P = 0.022) and a lower RP peak time (P = 0.029) in small TRL during the postprandial response, as well as a lower peak time in total plasma TG levels (P = 0.034) and large TRL-TG (P = 0.033) than subjects who were homozygous for the G allele.ConclusionOur data indicate that the presence of the A allele in the −250G/A promoter polymorphism of the hepatic lipase gene is associated with a higher postprandial lipemic response.     

Abdominal obesity and low-grade systemic inflammation as markers of subclinical organ damage in type 2 diabetes

AimThis study aimed to explore the associations between abdominal obesity, inflammatory markers and subclinical organ damage in 740 middle-aged patients with type 2 diabetes.MethodsWaist circumference (WC) and sagittal abdominal diameter (SAD) were measured, and blood samples were analyzed for C-reactive protein (CRP) and IL-6. Carotid intima–media thickness (IMT) was evaluated by ultrasonography, and aortic pulse wave velocity (PWV) measured with applanation tonometry.ResultsAbdominal obesity as determined by SAD and WC was significantly correlated with IL-6 (WC: r = 0.27, P < 0.001; SAD: r = 031, P < 0.001), CRP (WC: r = 0.29, P < 0.001; SAD: r = 0.29, P < 0.001), IMT (WC: r = 0.09, P = 0.013; SAD: r = 0.11, P = 0.003) and PWV (WC: r = 0.18, P < 0.001; SAD: r = 0.21, P < 0.001). In multiple linear regressions with IMT and PWV as dependent variables, and age, gender, statin use, systolic blood pressure (SBP), body mass index (BMI), CRP and HbA_1c as independent variables, both SAD and WC remained associated with IMT and PWV. On stepwise linear regression and entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.ConclusionBoth SAD and WC are feasible measures of obesity, and both provide information on inflammation, atherosclerosis and arterial stiffness in type 2 diabetes, while SAD appears to be slightly more robustly associated with subclinical organ damage than WC.     

Studying progression from glucose intolerance to type 2 diabetes in obese children

AimIdentification of metabolic and genetic factors capable to mediate progression from normal glucose tolerance (NGT) through impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in childhood obesity.Patients and methodsThree groups of obese children with NGT (n = 54), IGT (n = 35), and T2D (n = 62) were evaluated. A control group of non-obese normal children (n = 210) was also studied. In obese patients, an oral glucose tolerance test (OGTT) was performed. Insulin resistance (IR) was assessed using HOMA-IR index. Insulin sensitivity (IS) was assessed according to the Matsuda formula. Genomic DNA from obese and control children was genotyped for genetic variants of PPARG, ADIPOQ, ADIPOR1, FTO, TCF7L2, and KCNJ11 using a real-time PCR strategy. The unpaired Student's t-test and Kruskal–Wallis one-way test were used to compare quantitative data in two and more groups. To assess the extent to which the various genetic variants were associated with pathology, ORs (odds ratios) and 95% CI (confidence interval) were estimated.ResultsIn T2D children, HOMA-IR value (7.5 ± 3.1) was significantly (P < 0.001) higher than that in IGT (4.21 ± 2.25) and NGT (4.1 ± 2.4) subjects. The Matsuda IS index was significantly increased in normoglycemic patients compared to IGT individuals (2.8 ± 1.75 vs. 2.33 ± 1.2, P < 0.05). The Pro12Ala polymorphism of PPARG was significantly associated with obesity (OR = 1.74, 95% CI = 1.19–2.55, P = 0.004) and T2D in obesity (OR = 2.01, 95% CI = 1.24–3.26, P = 0.004).ConclusionIR is a major risk factor that mediates progression from NGT to clinical T2D in Russian obese children. This progression may be genetically influenced by the Pro12Ala variant of PPARG.     

Vitamin D levels in patients with Behçet’s disease: Significance and impact on disease measures

Aim of the workThis study aimed to investigate serum levels of vitamin D in patients with Behçet’s disease (BD) and to evaluate their relationship to disease activity as well as different disease measures.Patients and methodsForty-two patients with BD were enrolled into this study. These patients were subjected to detailed history taking, thorough clinical examination including assessment of disease activity according to Behçet’s Disease Current Activity Form (BDCAF) score and performed laboratory investigations including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum calcium, serum phosphorus and serum alkaline phosphatase. Serum 25-hydroxyvitamin D (vitamin D) levels were determined using Enzyme-Linked-Immunosorbent Assay (ELISA). A control group of 41 age and sex matched healthy controls was also included.ResultsThe mean level of 25-hydroxyvitamin D (30.65 ± 12.87 ng/ml) was significantly decreased in BD patients compared to the controls (37.98 ± 15.76 ng/ml) (p = 0.02). Significant negative correlations of serum vitamin D levels with patients’ ages (p = 0.03), ESR (p < 0.001), CRP (p < 0.001) and BDCAF (p = 0.003) were found; whereas, there was no significant correlation with disease duration (p = 0.6). In multivariate regression analysis age (p = 0.02), colchicine therapy (0.008), ESR (0.02) and CRP (0.03) were found to be the independent effectors on vitamin D serum levels.ConclusionSerum levels of vitamin D were significantly lower in BD patients compared to controls. Associations were found between vitamin D levels and age, BDCAF as well as ESR and CRP in BD patients. Low vitamin D may predispose BD patients to active disease, especially in older subjects.     

The changes of serum sKlotho and NGAL levels and their correlation in type 2 diabetes mellitus patients with different stages of urinary albumin

ObjectiveTo investigate the changes of serum anti-aging protein Klotho and neutrophil gelatinase-associated lipocalin (NGAL) levels and their correlation in type 2 diabetes mellitus (T2DM) patients at different stages of diabetic kidney disease (DKD) determined by urinary albuminuria.Methods462 cases with T2DM were divided into three groups: normoalbuminuric [N-UAlb; urinary albumin to creatinine ratio (UACR) < 30 mg/g, n = 180], microalbuminuric [M-UAlb; UACR 30–300 mg/g, n = 158], macroalbuminuric [L-UAlb; UACR > 300 mg/g, n = 124]. The levels of serum soluble-Klotho (sKlotho), NGAL, 8-isoprostane prostaglandin F2α (8-iso-PGF2α), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) were determined by enzyme-linked immunosorbent assay (ELISA) in all cases and 160 control subjects.ResultsCompared with control, serum sKlotho levels were significantly decreased (P < 0.001), and serum NGAL levels increased significantly (P < 0.001) in T2DM patients. Furthermore, serum sKlotho and NGAL levels were significantly negatively correlated (P < 0.001). Serum sKlotho levels negatively correlated with UACR, TG, CHO, LDL, 8-Iso-PGF2α, MCP-1, TNF-α, TGF-β1 (P < 0.001), but positively correlated with LDL (P < 0.001). Serum NGAL levels positively correlated with UACR, 8-Iso-PGF2α, MCP-1, TNF-α, TGF-β1 (P < 0.001). In addition, serum NGAL levels and LDL were significantly positively correlated (P = 0.005), and HDL was significantly negatively correlated (P < 0.001).ConclusionSerum Klotho and NGAL levels may become new biomarkers of the early diagnosis of DKD in T2DM. Klotho may participate in the development of DKD pathological mechanism such as oxidative stress related to inflammation, renal fibrosis, lipid metabolic disorders, modulating the pathological process of diabetic kidney tissue. NGAL may play a part in these mechanisms.     

Association of Hepatitis C Virus Seropositivity With Inflammatory Markers and Heart Failure in Persons With Coronary Heart Disease: Data From the Heart and Soul Study

BackgroundHow hepatitis C virus (HCV) affects coronary heart disease (CHD) risk factors and outcomes is largely unknown.Methods and ResultsAmong a cohort of patients with stable CHD, we examined the association between HCV seropositivity and levels of inflammatory markers (C-reactive protein [CRP], fibrinogen, interleukin-6, and tumor necrosis factor [TNF]-α) and risk for the following outcomes: death, cardiovascular (CV) events, and heart failure events. A total of 84 (8.6%) participants were found to be seropositive for HCV. HCV-seropositive patients were found to have significantly lower adjusted mean levels of CRP (2.6 vs. 4.4; P < .01) and fibrinogen (340 vs. 398; P < .01), but higher levels of TNF-α (7.1 vs. 4.8; P < .01). Age-adjusted rates for HCV seropositive vs. seronegative were as follows: death 93 vs. 42/1,000 p-y (P < .01), CV events 62 vs. 40 (P = .13), and heart failure 76 vs. 29 (P < .01). After adjustment for demographic and clinical factors, HCV remained significantly associated with an increased risk for heart failure events (HR = 2.13; 95% CI: 1.19–3.80).ConclusionsIn this cohort with CHD, HCV seropositive participants had higher rates of death, CV events, and heart failure hospitalizations during follow-up. After adjustment for CV risk factors, HCV seropositivity remained independently associated with risk for heart failure events.     

Association between sleep-disordered breathing,aminoterminal pro-brain natriuretic peptide (NT-proBNP) levels and insulin resistance in morbidly obese young women

ObjectiveSleep-disordered breathing (SDB) is often encountered in morbid obesity (MO) in conjunction with insulin resistance (IR) and several cardio-vascular risk factors. Aminoterminal pro-brain natriuretic peptide (NT-proBNP) is a promising marker for left ventricular dysfunction (LVD) in MO. The aim of this study was to look for possible correlations between SDB, IR, heart structure and function indexes and NT-proBNP levels in MO female subjects.Materials and methodsCross-sectional study involving 110 MO (44.5 ± 0.7 kg m^{? 2}) apparently healthy, young (37.8 ± 1.0 y.o.) female patients. NT-proBNP was measured using an ELISA kit (Roche). Echo-cardiograms were performed to quantify left ventricular ejection fraction values (LVEF), cardiac output (CO), left ventricular mass (LVM), left atria size (LA) and left ventricular filling pressures (the E/Em ratio). The Berlin Questionnaire (BQ) was used to assess the risk of SDB. IR and sensitivity were assessed using the HOMA index and adiponectin measurements, respectively.ResultsAll patients had a normal LVEF (> 50%). Hypertension and Type 2 diabetes mellitus prevalences were 34.5 and 4.5% (respectively). Log-transformed NT-proBNP levels correlated with BQ categories (P < 0.0005), creatinine (P < 0.001), age (P < 0.05), LVM (P < 0.001), CO (P < 0.001), LA (P < 0.0005) and E/Em (P < 0.01). NT-proBNP levels, LVD and LVM increased significantly along with BQ scores (P < 0.0001). Stepwise multiple regression analysis identified BQ and log-transformed HOMA as independent variables predicting as much as 48.0% of log-transformed NT-proBNP's variability (dependent variable).ConclusionsNT-proBNP levels are independently predicted by SDB and IR in asymptomatic MO women. Additionally, SDB worsens along with LVH and diastolic dysfunction. Larger prospective studies are warranted.     

Gender differences in the lipid profile of dyslipidemic subjects

ObjectiveWe evaluated the gender-associated differences in lipid profile of subjects intended to receive lipid-lowering therapy with emphasis on the associations between triglycerides (TG) and other plasma lipid variables.DesignLipid profiles of 1385 patients [aged 55 ± 11 years, 549 women (40%)] were evaluated. Eligible subjects fulfilled one or more of the following criteria: total cholesterol (TC) ≥ 6.2 mmol/l, TG ≥ 1.7 mmol/l, and high-density lipoprotein cholesterol (HDL-C) < 1.0 mmol/l. Patients were divided into subgroups according to TG and HDL-C levels.ResultsWomen aged on average 3.5 years older, had higher TC and HDL-C, lower TG and a correspondingly lower TC/HDL-C ratio than men. High TG and low HDL-C in tandem appeared twice more frequently in men. Inverse correlations between HDL-C and TG levels were found to exist in the entire cohort (r = ? 0.354, p < 0.001) and in all various subgroups. In the subgroup with TG < 1.7 mmol/l, women had higher TC and HDL-C, lower TG levels and lower TC/HDL-C ratio compared with men. In the subgroup with TG ≥ 1.7 mmol/l, women had higher TC and HDL-C levels and lower TC/HDL ratio compared with men. In the subgroup with HDL-C ≥ 1.0 mmol/l women had higher HDL-C, lower TG levels and lower TC/HDL-C ratio compared with men.ConclusionsElevated TG levels and low HDL-C in tandem are common lipid abnormalities in the clinical setting of primary and secondary preventions. Gender-associated differences in the lipid profile are evident in subjects presenting with dyslipidemia and might be of potential relevance for diagnostics and therapy for the prevention of atherosclerosis.     

FGF21 deficiency is associated with childhood obesity,insulin resistance and hypoadiponectinaemia: The BCAMS Study

ObjectiveFibroblast growth factor 21 (FGF21) exerts beneficial effects on metabolic homoeostasis and has been reported to be regulated by adiponectin, leptin and resistin. However, while an association between increased circulating FGF21 and metabolic disorders has been reported in adults, paediatric-specific data are lacking.Design and methodsThis study investigated the relationship between FGF21 levels and obesity, insulin resistance (IR), the metabolic syndrome (MetS) and adipokines (adiponectin, leptin and resistin) in a cohort of 3231 Chinese youngsters aged 6–18.ResultsThere were gender- and puberty-related differences in FGF21 levels. Unexpectedly, FGF21 levels were decreased in children with obesity, and negatively correlated with insulin, HOMA-IR and leptin levels after adjusting for age, gender, puberty and lifestyle factors. Moreover, multiple regression analyses showed that serum FGF21 positively predicted adiponectin levels while resistin positively predicted FGF21 levels independent of BMI (P < 0.05). Children in the lowest FGF21 quintile were more likely to have IR (OR: 1.85, 95% CI: 1.41–2.42; P = 0.002) and MetS (OR: 1.62, 95% CI: 1.14–2.28; P = 0.007) than those in the highest quintile. Further adjusting for BMI and/or the three adipokines modified the association of FGF21 with MetS (P > 0.10) but not with IR (P < 0.01).ConclusionAlthough the associations between adiponectin, leptin, resistin and metabolic abnormalities in our paediatric population were similar to those in adults, correlations of FGF21 levels with obesity, IR and MetS were the inverse of those found in adults. Our present findings suggest that FGF21 deficiency, rather than resistance, contribute to IR and hypoadiponectinaemia independently of obesity in young people.     

Disordered glycemic control in women with type 2 diabetes is associated with increased TNF receptor-2 levels

BackgroundEvidence implicates tumor necrosis factor (TNF) in the pathophysiology of Type 2 Diabetes (T2D) through unclear mechanisms. We hypothesized that disordered glycemic control leads to TNF activation and increases in soluble-TNF (sTNF) and its receptors-1 (sTNFR1) and -2 (sTNFR2).MethodsWe characterized 265 T2D and non-diabetic Latin American subjects and assessed the relationship between the TNF system and fasting plasma glucose (FPG), hemoglobin-A1C (A1C), insulin (FPI), C-peptide and HOMA-Beta.ResultssTNF and sTNFR2 but not sTNFR1 levels were higher in T2D than non-diabetics (P < 0.0001). In T2D, sTNFR2 was associated with A1C and C-peptide (R² = 0.354, b = 0.504, P < 0.0001; b = 0.167, P = 0.049). Also, T2D patients with disordered glycemic control had increased sTNFR2 levels that correlated with FPG (Rho:0.393, P < 0.001), A1C (Rho:0.451, P < 0.001) and HOMA-Beta (Rho:-0.308, P = 0.005); events not observed in T2D patients with adequate glycemic control. Furthermore, sex-based comparative analyses of T2D patients showed that women compared to men had higher sTNFR2 levels (P = 0.017) that correlated with FPG, A1C, FPI and HOMA-Beta.ConclusionsDisordered glycemic control is associated with sTNF and sTNFR2. sTNFR2 levels were higher in T2D women than men. Thus, increased sTNFR2 levels may be an important biomarker for disordered glucose and inflammatory complications in T2D patients and women in particular.     

Plasma adiponectin levels are related to obesity,inflammation, blood lipids and insulin in type 2 diabetic and non-diabetic Trinidadians

AimsTo determine the relationship between plasma adiponectin levels and obesity, inflammation, blood lipids and insulin resistance in type 2 diabetics (T2DM) and non-diabetics in a patient population in Trinidad.MethodsA cohort study of a total of 126 type 2 diabetic (42 males and 84 females) and 140 (43 males and 97 females) non-diabetic public clinic attendees were assessed between December 2008 and July 2009. Along with clinical history and anthropometry, adiponectin, TNF-α, IL-6, CRP, lipid profile, glucose, and insulin were measured in fasting blood samples and insulin resistance (HOMA-IR) was calculated.ResultsDiabetics had higher (p < 0.05) glucose, insulin, HOMA-IR, triglycerides (TG), VLDL and systolic blood pressure than non-diabetics, but lower (p < 0.05) HDL and adiponectin levels. Adiponectin levels were lower (p < 0.05) in obese than in non-obese individuals regardless of diabetic status. There were significant gender differences in HDL, LDL and TG. Among non-obese persons, adiponectin correlated negatively with triglycerides (r = ?0.280; adiponectin), IL-6 (r = ?0.216; p < 0.005), HOMA-IR (r = ?0.373; p = 000) and positively correlated with HDL (r = 0.355; p = 0.000). Diabetic status (p = 0.025), TNF-α (p = 0.048) and BMI (p = 0.027) were identified as useful predictors of adiponectin by multiple linear regression methods. In addition binary logistic regression analysis found glucose (p = 0.001) and adiponectin (p = 0.047) to be useful indicators of type 2 diabetes.ConclusionsAdiponectin decreases with increasing adiposity and insulin resistance. Adiponectin and TNF-α appear to be related to differences in the insulin mediated glucose turnover.