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Thomas C Register,
Jasmin Divers,
Donald W Bowden,
J Jeffrey Carr,
Leon Lenchik,
Lynne E Wagenknecht,
R Caresse Hightower,
Jianzhao Xu, S Carrie Smith,
Keith A Hruska,
Carl D Langefeld,
Barry I Freedman
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ABSTRACT: Context:Adiposity, bone mineral density (BMD), and calcified atherosclerotic plaque (CP) exhibit complex interrelationships that are not well understood. Adipokines vary in relation to changes in body composition and may play roles in regulation of BMD and risk of cardiovascular disease.Objective:Our objective was to examine the relationship between serum adiponectin and quantitative computed tomography-derived measures of volumetric BMD (vBMD) in thoracic and lumbar vertebrae, adipose tissue volumes, and CP in coronary, carotid, and infrarenal aortoiliac arteries. Generalized linear models were fitted to test for associations between adiponectin and measured phenotypes.Participants:A total of 479 unrelated African Americans with type 2 diabetes, 57% female with a mean ± SD (median) age of 55.6 ± 9.5 (55.0) years and diabetes duration of 10.3 ± 8.2 (8.0) years.Results:Serum adiponectin was 8.26 ± 7.41 (6.10) μg/mL, coronary artery CP mass score was 280 ± 634 (14), carotid artery CP was 47 ± 133 (0), and aortoiliac CP was 1616 ± 2864 (319). Women had significantly higher body mass index and serum adiponectin and lower coronary and carotid artery calcium than males (all P < .05). Before and after adjusting for age, sex, body mass index, mean arterial pressure, smoking status, hemoglobin A1c, thiazolidinedione use, and low-density lipoprotein-cholesterol, adiponectin was inversely associated with thoracic and lumbar vertebral vBMD [parameter estimates (PEs) of -0.06 and -0.021, respectively; both P < .0005], visceral adipose tissue (PE -0.02; P < 0.0001), and C-reactive protein (PE -0.07; P < .0001) and positively associated with intermuscular adipose tissue (PE 0.01; P = .03). After covariate adjustment, significant associations were not observed between adiponectin and CP in any vascular bed (P > .1).Conclusion:Serum adiponectin levels were inversely associated with cross-sectional measures of thoracic and lumbar vertebral vBMD, inflammation, and visceral adiposity in African Americans but not with vascular CP after adjustment for covariates. The data support a regulatory/signaling role for adiponectin in the modulation of bone density.
The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
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Diabetes care 03/2013; 36(3):e34-5. · 8.09 Impact Factor
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Jasmin Divers,
Nicholette D Palmer,
Lingyi Lu,
Thomas C Register,
J Jeffrey Carr,
Pamela J Hicks,
R Caresse Hightower, S Carrie Smith,
Jianzhao Xu,
Amanda J Cox, [......],
Kathleen F Kerr,
Y-D Ida Chen,
Walter Palmas,
Jerome I Rotter,
Christina L Wassel,
Alain Bertoni,
David Herrington,
Lynne E Wagenknecht,
Carl D Langefeld,
Barry I Freedman
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ABSTRACT: BACKGROUND: -The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping (AM) may be informative for identifying genetic variants associated with subclinical cardiovascular disease (CVD). METHODS AND RESULTS: -AM of CAC was performed in 1,040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study (AA-DHS), Multi-Ethnic Study of Atherosclerosis (MESA), and Family Heart Study (FamHS) using the Illumina custom ancestry informative marker (AIM) panel. All cohorts obtained computed tomography scanning of the coronary arteries using identical protocols. For each AIM, the probability of inheriting 0, 1, and 2 copies of a European-derived allele was determined. Linkage analysis was performed by testing for association between each AIM using these probabilities and CAC, accounting for global ancestry, age, gender and study. Markers on 1p32.3 in the GLIS1 gene (rs6663966, LOD=3.7), 1q32.1 near CHIT1 (rs7530895, LOD=3.1), 4q21.2 near PRKG2 (rs1212373, LOD=3.0) and 11q25 in the OPCML gene (rs6590705, LOD=3.4) had statistically significant LOD scores, while markers on 8q22.2 (rs6994682, LOD=2.7), 9p21.2 (rs439314, LOD=2.7), and 13p32.1 (rs7492028, LOD=2.8) manifested suggestive evidence of linkage. These regions were uniformly characterized by higher levels of European ancestry associating with higher levels or odds of CAC. Findings were replicated in 1,350 AAs without diabetes and 2,497 diabetic European Americans from MESA and the Diabetes Heart Study. CONCLUSIONS: -Fine mapping these regions will likely identify novel genetic variants that contribute to CAC and clarify racial differences in susceptibility to subclinical CVD.
Circulation Cardiovascular Genetics 12/2012; · 6.11 Impact Factor
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Mariana Murea,
Thomas C Register,
Jasmin Divers,
Donald W Bowden,
J Jeffrey Carr,
Caresse R Hightower,
Jianzhao Xu, S Carrie Smith,
Keith A Hruska,
Carl D Langefeld,
Barry I Freedman
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ABSTRACT: BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP- 1 concentration and early nephropathy and subclinical cardiovascular disease (CVD) were assessed in African Americans (AAs) with type 2 diabetes (T2D). METHODS: Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and atherosclerotic calcified plaque (CP) in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP. RESULTS: Participants were 57% female, with mean +/- SD (median) age 55.6+/-9.5 (55.0) years, diabetes duration 10.3+/-8.2 (8.0) years, urine ACR 149.7+/-566.7 (14.0) mg/g, CKD-EPI eGFR 92.4+/-23.3 (92.0) ml/min/1.73m2, MCP-1 262.9+/-239.1 (224.4) pg/ml, coronary artery CP 280.1+/-633.8 (13.5), carotid artery CP 47.1+/-132.9 (0), and aorta CP 1616.0+/-2864.0 (319.0). Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04) and negatively associated with eGFR (parameter estimate 0.0003, P=0.001). MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes. CONCLUSIONS: Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.
BMC Nephrology 11/2012; 13(1):148. · 2.18 Impact Factor
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Thomas C Register,
Keith A Hruska,
Jasmin Divers,
Donald W Bowden,
Nicholette D Palmer,
J Jeffrey Carr,
Lynne E Wagenknecht,
R Caresse Hightower,
Jianzhao Xu, S Carrie Smith,
Dennis J Dietzen,
Carl D Langefeld,
Barry I Freedman
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ABSTRACT: Background:Bone mineral density (BMD) and atherosclerotic arterial calcified plaque (CP) demonstrate inverse relationships through unknown mechanisms. Dickkopf-1 (DKK1) is an endogenous inhibitor of bone formation, and serum DKK1 has been associated with impaired osteoblast activation and susceptibility to bone loss. Plasma DKK1, BMD in the spine, and CP in three arterial beds were assessed in African-Americans (AAs) to determine relationships of serum DKK1 with atherosclerotic vascular calcification.Methods:Plasma DKK1, computed tomography-derived trabecular volumetric BMD (vBMD) in thoracic and lumbar vertebrae, and coronary artery, carotid artery, and aortoiliac CP were measured in 450 unrelated AAs with type 2 diabetes. Generalized linear models were fitted to test for associations between DKK1, vBMD, and CP.Results:Participants were 56% female with mean/sd/median age of 55.4/9.5/55.0 yr, diabetes duration of 10.3/8.2/8.0 yr, plasma DKK1 of 481.6/271.8/417 pg/ml, coronary artery CP mass score of 284/648/13, carotid artery CP mass score of 46/132/0, and aortoiliac CP mass score of 1613/2910/282. Adjusting for age, sex, body mass index, mean arterial blood pressure, smoking, hemoglobin A(1c), and low-density lipoprotein-cholesterol, DKK1 was inversely associated with coronary artery and aortoiliac CP [parameter estimates -0.0011 (P = 0.0137) and -0.0010 (P = 0.0214), respectively], with a trend for carotid artery CP (P = 0.1404). No associations were observed between DKK1 and vBMD in the thoracic or lumbar vertebrae.Conclusions:Plasma DKK1 levels were inversely associated with coronary artery and aortoiliac CP, but not vBMD, in this cross-sectional study of AAs with type 2 diabetes. DKK1 may play a role in vascular mineral metabolism in this clinical setting.
The Journal of clinical endocrinology and metabolism 11/2012; · 6.50 Impact Factor
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Jasmin Divers,
Christina Hugenschmidt,
Kaycee M Sink,
Jeffrey D Williamson,
Yaorong Ge, S Carrie Smith,
Donald W Bowden,
Christopher T Whitlow,
Eric L Yders,
Joseph A Maldjian,
Barry I Freedman
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ABSTRACT: Previous studies involving inner city populations detected higher cerebral white matter hyperintensity (WMH) scores in African Americans (AAs) compared with European Americans (EAs). This finding might be attributable to the higher prevalence of cardiovascular disease (CVD) risk factors and poorer access to healthcare in AAs. Despite racial differences in CVD risk factor profiles, AAs have paradoxically lower levels of subclinical CVD. We hypothesized that AAs with diabetes and good access to healthcare would have comparable or lower levels of WMH as EAs. Racial differences in the distribution of WMH were analyzed in 46 AAs and 156 EAs with type 2 diabetes enrolled in the Diabetes Heart Study (DHS)-Mind, and replicated in a sample of 113 AAs and 61 EAs patients who had clinically indicated cerebral magnetic resonance imaging. Wilcoxon 2-sample tests and linear models were used to compare the distribution of WMH in AAs and EAs and to test for association between WMH and race. The unadjusted mean WMH score from the Diabetes Heart Study-Mind was 1.9 in AAs and 2.3 in EAs (P = .3244). Among those with clinically indicated magnetic resonance imaging, the mean WMH score was 2.9 in AAs and 3.9 in EAs (P = .0503). Adjustment for age and sex produced no statistically significant differences in WMH score between AAs and EAs. These independent datasets reveal comparable WMH scores in AAs and EAs, suggesting that disparities in access to healthcare and environmental exposures likely underlie the previously reported excess burden of WMH in AAs.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 05/2012;
