Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study

While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)- levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women (P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women

Relationship of the metabolic syndrome to carotid ultrasound traits

BACKGROUND: The metabolic syndrome is associated with increased vascular disease risk. We evaluated two carotid ultrasound measurements, namely intima media thickness and total plaque volume, in a Canadian Oji-Cree population with a high metabolic syndrome prevalence rate. METHODS: As part of the Sandy Lake Complications Prevalence and Risk Factor Study, 166 Oji-Cree subjects (baseline metabolic syndrome prevalence, 44.0%, according to the National Cholesterol Education Program Adult Treatment Panel III guidelines) were examined using a high-resolution duplex ultrasound scanner. RESULTS: Image analysis showed that mean intima media thickness was elevated in subjects with the metabolic syndrome (818 ± 18 vs 746 ± 20 μm), as was total plaque volume (125 ± 26 vs 77.3 ± 17.0 mm(3)). However, after adjustment for age and sex, the differences were significant only for intima media thickness (P = 0.039). Furthermore, a significant trend towards increased intima media thickness was observed with increasing numbers of metabolic syndrome components: mean intima media thickness was highest among individuals with all five metabolic syndrome components compared to those with none (866 ± 55 vs 619 ± 23 μm, P = 0.0014). A similar, but non-significant trend was observed for total plaque volume. CONCLUSION: This is the first study of the relationship between the metabolic syndrome and two distinct carotid ultrasound traits measured in the same individuals. The results suggest that standard intima media thickness measurement shows a more consistent and stronger association with the metabolic syndrome than does total plaque volume

RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

BACKGROUND: The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. RESULTS: The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency. On average, 57 million reads (short reads or short mRNA sequences < ~200 bases) were sequenced, 52 million reads were mapped, and 24,616 known transcripts were quantified according to the bovine reference genome. A comparison of the high- and low-RFI groups revealed 70 and 19 significantly DEGs in Holstein and Jersey cows, respectively. The interaction analysis (high vs. low RFI x control vs. high concentrate diet) showed no interaction effects in the Holstein cows, while two genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. CONCLUSION: We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP’s and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3622-9) contains supplementary material, which is available to authorized users

Plasma Chemokine Levels Are Associated with the Presence and Extent of Angiographic Coronary Collaterals in Chronic Ischemic Heart Disease

In patients with chronic ischemic heart disease (IHD), the presence and extent of spontaneously visible coronary collaterals are powerful determinants of clinical outcome. There is marked heterogeneity in the recruitment of coronary collaterals amongst patients with similar degrees of coronary artery stenoses, but the biological basis of this heterogeneity is not known. Chemokines are potent mediators of vascular remodeling in diverse biological settings. Their role in coronary collateralization has not been investigated. We sought to determine whether plasma levels of angiogenic and angiostatic chemokines are associated with of the presence and extent of coronary collaterals in patients with chronic IHD.We measured plasma concentrations of angiogenic and angiostatic chemokine ligands in 156 consecutive subjects undergoing coronary angiography with at least one ≥90% coronary stenosis and determined the presence and extent of spontaneously visible coronary collaterals using the Rentrop scoring system. Eighty-eight subjects (56%) had evidence of coronary collaterals. In a multivariable regression model, the concentration of the angiogenic ligands CXCL5, CXCL8 and CXCL12, hyperlipidemia, and an occluded artery were associated with the presence of collaterals; conversely, the concentration of the angiostatic ligand CXCL11, interferon-γ, hypertension and diabetes were associated with the absence of collaterals (ROC area 0.91). When analyzed according to extent of collateralization, higher Rentrop scores were significantly associated with increased concentration of the angiogenic ligand CXCL1 (p<0.0001), and decreased concentrations of angiostatic ligands CXCL9 (p<0.0001), CXCL10 (p = 0.002), and CXCL11 (p = 0.0002), and interferon-γ (p = 0.0004).Plasma chemokine concentrations are associated with the presence and extent of spontaneously visible coronary artery collaterals and may be mechanistically involved in their recruitment

The effects of low-dose simvastatin and ezetimibe compared to high-dose simvastatin alone on post-fat load endothelial function in patients with metabolic syndrome: a randomized double-blind crossover trial

BACKGROUND AND AIMS: Insulin resistance is associated with postprandial hyperlipidemia and endothelial dysfunction. Patients with metabolic syndrome, characterized by insulin resistance, are at increased cardiovascular risk. The aim of the present study was to investigate whether a similar low-density lipoprotein cholesterol (LDL-c) reduction with combination therapy of low-dose simvastatin and ezetimibe or with high-dose simvastatin alone has similar effects on (post-fat load) endothelial function. METHODS: Randomized, double blind, crossover trial in 19 male obese patients with metabolic syndrome with high-dose simvastatin 80 mg versus combination therapy of low-dose simvastatin 10 mg with ezetimibe 10 mg. Fasting and post-fat load lipids and endothelial function (brachial artery flow-mediated dilation) were determined. RESULTS: Fasting LDL-c concentrations (2.1 +/- 0.5 mmol/L) and fasting endothelial function (6.9 +/- 0.8 vs. 7.6 +/- 1.2%) were the same after both treatments. Although post-fat load plasma triglycerides concentrations were higher (3.2 +/- 0.4 vs. 2.6 +/- 0.2 mmol x h/L) with combination therapy compared to monotherapy, ApoB particles were comparable (0.9 +/- 3.3 vs. -0.2 +/- 2.3 g x h/L). Combination therapy did not decrease post-fat load endothelial function (7.6 +/- 1.2 vs. 7.7 +/- 1.6%), contrary to high-dose simvastatin monotherapy (6.9 +/- 0.8 vs. 4.3 +/- 0.6%). CONCLUSIONS: Combination therapy with low-dose simvastatin and ezetimibe preserved post-fat load endothelial function, contrary to treatment with high-dose simvastatin monotherapy in male metabolic syndrome patients. There were no differences in fasting lipid profiles and endothelial functio

Carotid arterial stiffness is marginally higher in the metabolic syndrome and markedly higher in type 2 diabetes mellitus in patients with manifestations of arterial disease

Insulin resistance is generally considered to be of major importance in the pathophysiology of the metabolic syndrome and type 2 diabetes mellitus, both high-risk conditions for cardiovascular complications. Carotid artery stiffness is increasingly recognized as an important predictor of cardiovascular morbidity and mortality. Therefore, in the present study we determined whether the metabolic syndrome (MetSyn) and type 2 diabetes mellitus (DM2) are associated with carotid artery stiffness in patients with already clinical manifestations of arterial disease. A cross-sectional study in 2105 patients with manifest arterial disease (cerebral, coronary or peripheral artery disease, renal artery stenosis or an aneurysm of the abdominal aorta) was performed. The difference in carotid stiffness between patients with and without MetSyn and with and without DM2 was studied with linear regression analysis. Compared to patients without DM2 (N=1112), patients with DM2 (N=301) had significantly higher arterial stiffness (distension -18.5 (-35.1;-1.9) 95% CI/distensibility -1.8 (-2.2;-1.4) 95% CI). Generally, there was a trend of higher carotid stiffness in patients with MetSyn (N=922) compared to patients without (N=1112) MetSyn (distension -9.6 (-21.5;2.3) 95% CI/distensibility -2.0 (-2.6;-1.4) 95% CI). Excluding the patients with also DM2 (N=230) from the MetSyn-group diminished this relation (distension -5.7 (-18.8;7.4) 95% CI/distensibility -1.1 (-1.6;-0.6) 95% CI). Furthermore, in the population as a whole, carotid artery stiffness increased with increasing number of components of the metabolic syndrome (p=0.08 for distension/p <or =0.001 for distensibility). In addition, this association was not as clear after exclusion of the patients with DM2 from the MetSyn-group (p=0.24 for distension/p <0.001 for distensibility). From all the components of the MetSyn only high blood pressure and high fasting glucose influenced the carotid artery stiffness. We concluded that (increasing number of components of) the metabolic syndrome were associated with marginally higher carotid artery stiffness, while type 2 diabetes was associated with a marked increase in carotid artery stiffness, in patients with already clinical manifestations of arterial diseas