Adipose tissue depot volume relationships with spinal trabecular bone mineral density in African Americans with diabetes

<div><p>Changes in select adipose tissue volumes may differentially impact bone mineral density. This study was performed to assess cross-sectional and longitudinal relationships between computed tomography-determined visceral (VAT), subcutaneous (SAT), inter-muscular (IMAT), and pericardial adipose tissue (PAT) volumes with respective changes in thoracic vertebral and lumbar vertebral volumetric trabecular bone mineral density (vBMD) in African Americans with type 2 diabetes. Generalized linear models were fitted to test relationships between baseline and change in adipose volumes with change in vBMD in 300 African American-Diabetes Heart Study participants; adjustment was performed for age, sex, diabetes duration, study interval, smoking, hypertension, BMI, kidney function, and medications. Participants were 50% female with mean ± SD age 55.1±9.0 years, diabetes duration 10.2±7.2 years, and BMI 34.7±7.7 kg/m². Over 5.3 ± 1.4 years, mean vBMD decreased in thoracic/lumbar spine, while mean adipose tissue volumes increased in SAT, IMAT, and PAT, but not VAT depots. In fully-adjusted models, changes in lumbar and thoracic vBMD were positively associated with change in SAT (β[SE] 0.045[0.011], p<0.0001; 0.40[0.013], p = 0.002, respectively). Change in thoracic vBMD was positively associated with change in IMAT (p = 0.029) and VAT (p = 0.016); and change in lumbar vBMD positively associated with baseline IMAT (p<0.0001). In contrast, vBMD was not associated with change in PAT. After adjusting for BMI, baseline and change in volumes of select adipose depots were associated with increases in thoracic and lumbar trabecular vBMD in African Americans. Effects of adiposity on trabecular bone appear to be site-specific and related to factors beyond mechanical load.</p></div

Baseline demographic and biochemical parameters of African American-Diabetes Heart Study cohort.

<p>Baseline demographic and biochemical parameters of African American-Diabetes Heart Study cohort.</p

Relationships between baseline adipose volumes with change in thoracic and lumbar volumetric bone mineral density.

<p>Relationships between baseline adipose volumes with change in thoracic and lumbar volumetric bone mineral density.</p

Baseline demographic and biochemical parameters of African American-Diabetes Heart Study cohort.

<p>Baseline demographic and biochemical parameters of African American-Diabetes Heart Study cohort.</p

Relationships between five year change in adipose volumes with change in thoracic and lumbar volumetric bone mineral density.

<p>Relationships between five year change in adipose volumes with change in thoracic and lumbar volumetric bone mineral density.</p

Top meta-analyzed interactions with AIR_g SNPs regressed on T2D risk in ARIC, CARDIA, JHS, MESA, and WFSM.

<p>Top meta-analyzed interactions with AIR_g SNPs regressed on T2D risk in ARIC, CARDIA, JHS, MESA, and WFSM.</p

Characteristics and single-SNP association results for AIR_g SNPs in IRASFS.

<p>Characteristics and single-SNP association results for AIR_g SNPs in IRASFS.</p

A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS)

<div><p>Obesity is growing epidemic affecting 35% of adults in the United States. Previous genome-wide association studies (GWAS) have identified numerous loci associated with obesity. However, the majority of studies have been completed in Caucasians focusing on total body measures of adiposity. Here we report the results from genome-wide and exome chip association studies focusing on total body measures of adiposity including body mass index (BMI), percent body fat (PBF) and measures of fat deposition including waist circumference (WAIST), waist-hip ratio (WHR), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in Hispanic Americans (n_max = 1263) from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Five SNPs from two novel loci attained genome-wide significance (P<5.00x10^-8) in IRASFS. A missense SNP in the isocitrate dehydrogenase 1 gene (<i>IDH1)</i> was associated with WAIST (rs34218846, MAF = 6.8%, P_DOM = 1.62x10^-8). This protein is postulated to play an important role in fat and cholesterol biosynthesis as demonstrated in cell and knock-out animal models. Four correlated intronic SNPs in the Zinc finger, GRF-type containing 1 gene (<i>ZGRF1</i>; SNP rs1471880, MAF = 48.1%, P_DOM = 1.00x10^-8) were strongly associated with WHR. The exact biological function of <i>ZGRF1</i> and the connection with adiposity remains unclear. SNPs with p-values less than 5.00x10^-6 from IRASFS were selected for replication. Meta-analysis was computed across seven independent Hispanic-American cohorts (n_max = 4156) and the strongest signal was rs1471880 (P_DOM = 8.38x10^-6) in <i>ZGRF1</i> with WAIST. In conclusion, a genome-wide and exome chip association study was conducted that identified two novel loci (<i>IDH1 and ZGRF1</i>) associated with adiposity. While replication efforts were inconclusive, when taken together with the known biology, <i>IDH1</i> and <i>ZGRF1</i> warrant further evaluation.</p></div

Significant signals of association from genome-wide and exome chip association analyses in IRASFS.

<p>^aSNP identified from GWAS</p><p>^bSNP identified from exome chip</p><p>^cDominant Model</p><p>^dRecessive Model</p><p>^eMinor allele frequency based on the entire population</p><p>^fMinor/Major allele on the positive strand</p><p>Significant signals of association from genome-wide and exome chip association analyses in IRASFS.</p

Demographic characteristics of the study populations.

<p>^aHTN-IR has only 139 individuals with PBF measurements</p><p>^bValues are expressed as the mean ± standard deviation</p><p>^cIncludes 161 diabetics</p><p>Abbreviations: IRASFS, Insulin Resistance Atherosclerosis Family Study; IRAS, Insulin Resistance Atherosclerosis Study; TRIPOD, Troglitazone in Prevention of Diabetes Study; BetaGene, Family-based study of obesity, insulin resistance, and beta-cell dysfunction; HTN-IR, Hypertension-Insulin Resistance Family Study; MACAD, Mexican-American Coronary Artery Disease Study; NIDDM-Athero, NIDDM-Atherosclerosis Study.</p><p>Demographic characteristics of the study populations.</p