BackgroundIngestion of polyunsaturated fatty acids (PUFAs) has been proposed to influence several chronic diseases including coronary heart disease (CHD) and type-2 diabetes (T2D).There is strong evidence that omega-3 (n-3) PUFAs provide protection against CHD and biomarkers of atherosclerosis. In contrast, there is more limited and inconsistent data for T2D. Few studies have examined the impact of n-3 PUFA-containing botanical oils on T2D.MethodsFifty-nine subjects with early-stageT2D or metabolic syndrome participated in an 8-week, randomized, single-blind, parallel intervention study and were provided PUFA-containing oils. Individuals received either corn oil (CO), a botanical oil (BO) combination (borage [Borago officinalis L.]/echium oil [Echium plantagineum L.]) or fish oil (FO). The BO combination was enriched in alpha-linolenic, gamma-linolenic, and stearidonic acids and the FO in eicosapentaenoic and docosahexaenoic acids. Serum fatty acids and other serum lipids(triglycerides and total, HDL and LDL cholesterol), as well as markers of inflammation (leptin, and C-reactive protein) and glucose regulation (glucose and hemoglobin A1c) were assessed from fasting participants at baseline and after the intervention.ResultsCompliance was verified by expected increases in specific PUFAs in each of the three oil arms. Participants in the CO group showed no differences in serum lipids, markers of inflammation or glucose regulation between pre- and post-treatment measures. Supplementation with BO significantly lowered total and LDL cholesterol levels and FO reduced serum triglycerides, hemoglobin A1c and increased HDL-cholesterol.ConclusionShort-term dietary supplementation with BO and FO improved biomarkers associated with T2D/metabolic syndrome.Trial registrationClinicaltrial.gov NCT01145066

No abstract

Integrative multiomics analyses of adipose and muscle tissue transcripts, S, and genotypes revealed novel genetic regulatory mechanisms of insulin resistance in African Americans.

Evidence for Inflammation as a Cause of Hypocholesterolemia in Older People

Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes were evaluated by mining GWAS datasets. eQTL analysis identified 1,971 and 2,078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2, were identified in both tissues. 62.1% of top cis-eSNPs were within ±50kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes, (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu) and identified genetically-regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes.

Chronic IL-6 injections cause acquired hypocholesterolemia, hypoalbuminemia, and weight loss in nonhuman primates. These changes are similar to those seen in older persons with acquired hypocholesterolemia.

Objective-Increased carotid artery intima-media thickness (IMT) and increased coronary artery calcium (CAC) are noninvasive surrogate indices of prevalent coronary artery disease (CAD). We compared CAC to IMT for noninvasive detection of prevalent CAD in participants whose coronary status was identified by coronary angiography. Methods and Results-Male and female CAD patients (Ն50% stenosis in one or more coronary artery, nϭ79) and controls (no lumen irregularities, nϭ93) were identified using coronary angiography. Mean maximum carotid IMT was quantified using B-mode ultrasound and total CAC was measured using ECG-gated helical computed tomography (HCT). Carotid IMT was Ϸ20% higher in CAD cases compared with controls (PϽ0.001), whereas mean CAC was 1000% higher in CAD cases than controls (PϽ0.0001). In multivariable models adjusted for age and sex, IMT greater than the median (1.13 mm) was associated with 2-fold increase in likelihood of prevalent CAD compared with scores below that cut point (Pϭ0.015). CAC scores that exceeded the median score of 92 were associated with 28-fold increase in likelihood of prevalent CAD (PϽ0.0001). Although associations of increased IMT with prevalent CAD were similar in males and females, CAC scores above the median in females were associated with 39-fold increase in odds of prevalent CAD, whereas males with elevated CAC had 19-fold risk of CAD. Key Words: calcification Ⅲ computed tomography Ⅲ coronary artery disease Ⅲ intima-media thickness Ⅲ ultrasound C arotid artery intima-media thickness (IMT) quantified by B-mode ultrasound has proven validity as a noninvasive index of risk for vascular disease. [1][2][3][4][5][6][7] Recent research suggests that computed tomography (CT) may be used to quantify coronary artery calcification (CAC) as an alternative noninvasive indicator of vascular disease. Conclusion-HCT-measuredPresence and/or extent of CAC is associated with traditional CAD risk factors, including age, 8 -13 sex, 8 -13 ethnicity, 12,13 cholesterol, 8,11,12 hypertension, 8,9,12 and history of smoking. 8,9,12,13 Cross-sectional studies have also shown that elevated CAC is strongly associated with prevalent CAD identified by coronary angiography and/or with clinically manifest cardiovascular disease (CVD). 14 -20 The substantial evidence for the association of elevated CAC with prevalent CVD, along with more limited data regarding the association of CAC with incident disease, has been extensively reviewed by 2 expert panels. 19,20 Most studies to date have measured CAC using cardiacgated electron beam CT (EBCT), which was developed and implemented in the mid 1980s. 14,15 Recent improvements in more widely available helical CT systems have increased temporal resolution and made CAC measurement possible with this technology. Cardiac-gated helical CT (HCT) has since been validated against EBCT measurement of CAC. 21 Because CT directly images the coronary vasculature, it is reasonable for researchers to expect that quantification of CAC would reflect coronary disease better t...

No abstract