Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in Hispanic and African Americans.

Context: Vitamin D deficiency is associated with many adverse health outcomes, yet little is known about the genetic epidemiology of vitamin D or its metabolites.

Objective: Our objective was to examine the relationship among three vitamin D-related genes and levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in Hispanics (HAs) and African Americans (AAs).

Design And Setting: The cross-sectional Insulin Resistance Atherosclerosis Family Study recruited and examined subjects in: Los Angeles, California (AAs; 513 individuals from 42 families); San Luis Valley (SLV), Colorado (HAs; 513 individuals from 30 families); and San Antonio (SA), Texas (HAs; 504 individuals from 58 families).

Visceral fat and prevalence of hypertension among African Americans and Hispanic Americans: findings from the IRAS family study.

Background: We examined the relationship between visceral adipose tissue (VAT), independent of overall adiposity, and prevalent hypertension among adults enrolled in the Insulin Resistance Atherosclerosis (IRAS) Family Study. We also examined the role of insulin sensitivity (S(I)) upon hypertension. This was a cross-sectional epidemiological study in which African-American and Hispanic-American families were recruited from three clinical sites.

Quantitative trait analysis of type 2 diabetes susceptibility loci identified from whole genome association studies in the Insulin Resistance Atherosclerosis Family Study.

Objective: Evaluate type 2 diabetes susceptibility variants identified from genome-wide association studies in Hispanic Americans and African Americans from the Insulin Resistance Atherosclerosis Family Study (IRAS-FS) for association with quantitative measures of glucose homeostasis and determine their biological role in vivo.

Research Design And Methods: Seventeen type 2 diabetes-associated single nucleotide polymorphisms (SNPs) were genotyped in 1,268 Hispanic- and 581 African-American participants from the IRAS-FS. SNPs were tested for association with quantitative measures of glucose homeostasis, including insulin sensitivity index (S(I)), acute insulin response (AIR), and disposition index.

Genome-wide admixture mapping for coronary artery calcification in African Americans: the NHLBI Family Heart Study.

Coronary artery calcification (CAC) is an important measure of subclinical coronary atherosclerosis and an independent predictor of coronary heart disease. To identify the genetic loci contributing to CAC, we conducted a genome-wide scan with 374 microsatellite markers by applying admixture mapping to 618 African American participants in the US National Heart, Lung, and Blood Institute Family Heart Study, in which 868 European American participants from family heart study and 157 Africans genotyped by the Marshfield Medical Genetics Center were used as the two reference founding populations for the African Americans, and a computer program based on a Markov Chain Monte Carlo algorithm, STRUCTURE 2.1, was used to estimate European and African ancestries among African Americans.

Do inflammation and procoagulation biomarkers contribute to the metabolic syndrome cluster?

Context: The metabolic syndrome (MetS), in addition to its lipid, metabolic, and anthropomorphic characteristics, is associated with a prothrombotic and the proinflammatory state. However, the relationship of inflammatory biomarkers to MetS is not clear.

Objective: To study the association between a group of thrombotic and inflammatory biomarkers and the MetS.

Kidney volume associations with subclinical renal and cardiovascular disease: the Diabetes Heart Study.

Background: The prognostic significance of total kidney volume (TKV) in subjects with type 2 diabetes mellitus (T2DM) is unknown.

Methods: One hundred and seventy unrelated Caucasians with T2DM underwent multidetector-row computed tomography of the neck, chest, and abdomen to measure calcified plaque in the coronary artery (CorCP), carotid artery (CarCP), and infrarenal aorta (AorCP). Spearman's rank correlation coefficients were used to assess associations between TKV and subclinical renal and cardiovascular disease.

Calcified atherosclerotic plaque and bone mineral density in type 2 diabetes: the diabetes heart study.

The purpose of the present study was to determine the relationships between atherosclerotic calcified plaque (CP) and bone mineral density (BMD) in subjects with type 2 diabetes mellitus (DM2). CP in the coronary arteries, carotid bifurcation, and abdominal aorta was measured using computed tomography (CT) in 1023 diabetic subjects from 453 families. Trabecular volumetric BMD in thoracic (T-vBMD) and lumbar (L-vBMD) spine was measured with quantitative CT (QCT), while areal BMD (aBMD) in the lumbar spine and hip was measured by dual X-ray absorptiometry (DXA).

Whole-grain intake and carotid artery atherosclerosis in a multiethnic cohort: the Insulin Resistance Atherosclerosis Study.

Background: Whole-grain intake has been shown to be inversely associated with cardiovascular events, but an association with atherosclerosis is less well established.

Objective: We sought to evaluate the association of whole-grain intake with carotid intimal medial thickness (IMT) and IMT progression in a multiethnic cohort.

Design: This study evaluated 1178 participants in the Insulin Resistance Atherosclerosis Study.

A comparison of risk factors for calcified atherosclerotic plaque in the coronary, carotid, and abdominal aortic arteries: the diabetes heart study.

The extent of shared risk factors for calcified atherosclerotic plaque (CAP) of the coronary, carotid, and abdominal aortic arteries is unknown. CAP was measured by computed tomography in 1,125 individuals in families affected with diabetes. Statistical methods adjusted for the lack of independence between observations.

Alanine aminotransferase and directly measured insulin sensitivity in a multiethnic cohort: the Insulin Resistance Atherosclerosis Study.

Objective: The objective of the present analysis was to evaluate the association of alanine aminotransferase (ALT) with directly measured insulin sensitivity (S(i)) in a large, multiethnic cohort of U.S. adults and to determine whether ALT adds to existing metabolic risk definitions in identifying subjects with insulin resistance.

Associations of adiponectin with body fat distribution and insulin sensitivity in nondiabetic Hispanics and African-Americans.

Context: Hypoadiponectinemia has emerged as an independent risk factor for type 2 diabetes and cardiovascular disease. Although associations of adiponectin with central obesity and insulin resistance have been reported, very little data are available from studies using detailed measures of insulin sensitivity (S(I)) and/or body fat distribution in ethnic groups at high risk for metabolic disease.

Objective: The aim of the study was to identify the correlates of adiponectin in 1636 nondiabetic Hispanics and African-Americans.

Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.

Objective: The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes 1-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events.

Research Design And Methods: This study consisted of a multicentered, randomized, controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with BMI >25 kg/m2 (>27 kg/m2 if taking insulin).

Baseline characteristics of the randomised cohort from the Look AHEAD (Action for Health in Diabetes) study.

Objective: The Look AHEAD (Action for Health in Diabetes) study is a 16-centre randomised clinical trial in overweight and obese individuals with type 2 diabetes, designed to evaluate the long-term effects (up to 11.5 years) of intensive weight loss intervention on the time to incidence of major cardiovascular events.

Research Design And Methods: Eligibility requirements are diagnosis of type 2 diabetes (determined by self-report and verification) in individuals aged 4574 years and body mass index (BMI) > 25 kg/m2 (> 27 kg/m2 if currently taking insulin).

Serum uric acid predicts incident hypertension in a biethnic cohort: the atherosclerosis risk in communities study.

Serum uric acid has been positively associated with incident hypertension, but previous studies have had limited ability to explore this relationship across sex and ethnic strata. We sought to evaluate this association in a biethnic cohort of middle-aged men and women. Participants in the Atherosclerosis Risk in Communities (ARIC) study who were free of hypertension at baseline (N=9104) were evaluated for hypertension at 3-year intervals over 4 examinations.

Heritability and expression of C-reactive protein in type 2 diabetes in the Diabetes Heart Study.

Elevated C-reactive protein (CRP) levels are associated with both prevalent and incident cardiovascular disease. In this study, familial aggregation was estimated, and we tested for association between serum CRP levels and polymorphisms within the CRP and APOE genes in sib-ships with type 2 diabetes mellitus, a population at increased risk for cardiovascular disease. CRP levels were determined in 461 diabetes-affected subjects from 224 sibships from the Diabetes Heart Study (DHS).

Haplotypes in the lipoprotein lipase gene influence fasting insulin and discovery of a new risk haplotype.

Context: Prior studies of Mexican Americans described association of lipoprotein lipase (LPL) gene haplotypes with insulin sensitivity/resistance and atherosclerosis. The most common haplotype (haplotype 1) was protective, whereas the fourth most common haplotype (haplotype 4) conferred risk for insulin resistance and atherosclerosis.

Objective: In this study of Hispanics in the Insulin Resistance Atherosclerosis Study Family Study, we sought to replicate LPL haplotype association with insulin sensitivity/resistance.

Metabolic syndrome and cardiovascular disease in older people: The cardiovascular health study.

Objectives: To assess the prospective association between metabolic syndrome (MetS) and cardiovascular disease (CVD) in older people and to evaluate the effect of lowering the threshold for impaired fasting glucose (IFG) on the prevalence of IFG and MetS and the risk of CVD.

Design: Prospective cohort study.

Setting: Four field centers in U.

A functional polymorphism in the lymphotoxin-alpha gene is associated with carotid artery wall thickness: the Diabetes Heart Study.

Background: The lymphotoxin-alpha (LTA) gene has been implicated in the pathogenesis of atherosclerosis. We tested for an association between a functional polymorphism, LTA 252A/G, and common carotid artery intima-media thickness in 1088 siblings from 435 Diabetes Heart Study families.

Methods: Intima-media thickness was measured by high-resolution B-mode carotid ultrasonography.

Coincident linkage of type 2 diabetes, metabolic syndrome, and measures of cardiovascular disease in a genome scan of the diabetes heart study.

Cardiovascular disease (CVD) is a major contributor to morbidity and mortality in type 2 diabetes, but the relationship between CVD and type 2 diabetes is not well understood. The Diabetes Heart Study is a study of type 2 diabetes-enriched families extensively phenotyped for measures of CVD, type 2 diabetes, and metabolic syndrome. A total of 977 Caucasian subjects from 358 pedigrees (575 type 2 diabetic relative pairs) with at least two individuals with type 2 diabetes and, where possible, unaffected siblings were included in a genome scan.

Genome-wide linkage of plasma adiponectin reveals a major locus on chromosome 3q distinct from the adiponectin structural gene: the IRAS family study.

Adiponectin (APM1) is an adipocyte-derived peptide that contributes to glucose, lipid, and energy homeostasis. We assessed the genetic basis of plasma adiponectin in Hispanic-American and African-American families enrolled through the Insulin Resistance Atherosclerosis Study Family Study. A 10-cM genome scan was performed in two batches: an original set (set 1) consisting of 66 families (45 Hispanic American and 21 African American) and a replication set (set 2) consisting of 66 families (45 Hispanic American and 21 African American).

Racial differences in the association of coronary calcified plaque with left ventricular hypertrophy: the National Heart, Lung, and Blood Institute Family Heart Study and Hypertension Genetic Epidemiology Network.

Studies have reported a lower burden of calcified atherosclerotic plaque in coronary arteries in African-Americans than in whites. Findings from autopsy studies of sudden cardiac death have suggested a link between left ventricular hypertrophy and severity of coronary atherosclerosis. Echocardiograms and cardiac computed tomograms were analyzed in 334 African-American (84% hypertensive) and 196 white (66% hypertensive) adults with no history of coronary heart disease or revascularization procedures at study entry.

Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident type 2 diabetes.

Background: Several studies have shown that fibrinolytic and coagulation abnormalities as well as low-grade inflammation predict cardiovascular disease and type 2 diabetes. We studied in the Insulin Resistance Atherosclerosis Study the relation of incident diabetes to dynamic changes of plasminogen activator inhibitor-1 (PAI-1) and fibrinogen.

Methods And Results: After a follow-up of 5.

The natural course of beta-cell function in nondiabetic and diabetic individuals: the Insulin Resistance Atherosclerosis Study.

Data from the UKPDS (U.K. Prospective Diabetes Study) indicate a continuous decline in beta-cell function in patients with type 2 diabetes.

Genetic mapping of disposition index and acute insulin response loci on chromosome 11q. The Insulin Resistance Atherosclerosis Study (IRAS) Family Study.

Glucose homeostasis, a defining characteristic of physiological glucose metabolism, is the result of complex feedback relationships with both genetic and environmental determinants that influence insulin sensitivity and beta-cell function. Relatively little is known about the genetic basis of glucose homeostasis phenotypes or their relationship to risk of diabetes. Our group previously published a genome scan for glucose homeostasis traits in 284 African-American subjects from 21 pedigrees in the Insulin Resistance Atherosclerosis Study Family Study (IRASFS) and presented evidence for linkage to disposition index (DI) on chromosome 11q with a logarithm of odds (LOD) of 3.