scholarly journals Serum Urate, PUFAs and Abdominal Obesity in Hispanic Children: The Viva La Familia Study

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1268-1268
Author(s):  
Chinmayee Panda ◽  
Shelley A Cole ◽  
Karin Haack ◽  
Nitesh R Mehta ◽  
Anthony G Comuzzie ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Waist Circumference ◽  
Abdominal Obesity ◽  
Disease Risk ◽  
Genetic Correlations ◽  
Elevated Serum ◽  
Serum Urate ◽  
Inverse Association ◽  
Hispanic Children ◽  
Docosadienoic Acid

Abstract Objectives Elevated serum urate is known to increase chronic kidney and cardiovascular disease risk. Studies in adults have shown inverse association between serum urate and n-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA). Here, we aimed to determine the relationship between serum levels of PUFAs and urate in overweight/obese Hispanic children of the Viva La Familia Study (VFS) and then test whether it is mediated by obesity and insulin resistance. Methods VFS was designed to determine the genetic and environmental effects on childhood obesity. n-3 (EPA, alpha-linolenic acid (ALA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA)) and n-6 (arachidonic acid (AA), linoleic acid (LA), eicosadienoic and docosadienoic acid) PUFAs were measured as part of metabolomic profiling (N = 782). Quantitative genetic and phenotypic analyses were conducted using SOLAR. Mediation analysis was conducted using Baron and Kenny approach with waist circumference (WC), BMIZ and HOMA (measures of obesity and insulin resistance) as mediators. Results Phenotypic correlations showed that serum urate was positively associated with LA (β = 0.08 (0.02), P < 0.0001), ALA (β = 0.03 (0.01), P < 0.05), eicosadienoic (β = 0.09 (0.02), P < 0.0001) and docosadienoic acid (β = 0.04 (0.007), P < 0.0001). Further analysis showed inverse genetic correlations between serum urate and EPA (rhog = −0.30 (0.14), P < 0.05), BMIZ (rhog = 0.45 (0.12), P < 0.005) and waist circumference (rhog = 0.42 (0.11), P < 0.005). The genetic correlation between serum urate and EPA remained significant after adjustment for BMIZ (rhog = −0.27 (0.13), P < 0.05) and HOMA (rhog = −0.23 (0.13), P < 0.05). However, it was no longer significant after adjustment for WC (rhog = −0.21 (0.13), P = 0.10). No statistical significance was observed for other PUFAs. Conclusions Our genetic analysis suggests pleiotropic relationship between EPA and serum urate levels as observed in adults. This relationship seems to be mediated by WC, a surrogate measure for abdominal obesity, but not by BMIZ or HOMA. Further investigations are warranted to determine the role of EPA in reducing serum urate and its implications for associated diseases. Funding Sources NIDDK.

Differential DNA Methylation and Cardiometabolic Risk in African American Mother-Adolescent Dyads

2021 ◽  
pp. 109980042110390
Author(s):  
Amanda Elswick Gentry ◽  
Jo Robins ◽  
Mat Makowski ◽  
Wendy Kliewer
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
African American ◽  
African Americans ◽  
Waist Circumference ◽  
Low Income ◽  
Cardiometabolic Risk ◽  
Disease Risk ◽  
Cardiovascular Disease Risk

Background: Cardiovascular disease disproportionately affects African Americans as the leading cause of morbidity and mortality. Among African Americans, compared to other racial groups, cardiovascular disease onset occurs at an earlier age due to a higher prevalence of cardiometabolic risk factors, particularly obesity, hypertension and type 2 diabetes. Emerging evidence suggests that heritable epigenetic processes are related to increased cardiovascular disease risk, but this is largely unexplored in adolescents or across generations. Materials and Methods: In a cross-sectional descriptive pilot study in low-income African American mother-adolescent dyads, we examined associations between DNA methylation and the cardiometabolic indicators of body mass index, waist circumference, and insulin resistance. Results: Four adjacent cytosine and guanine nucleotides (CpG) sites were significantly differentially methylated and associated with C-reactive protein (CRP), 62 with waist circumference, and none to insulin resistance in models for both mothers and adolescents. Conclusion: Further study of the relations among psychological and environmental stressors, indicators of cardiovascular disease, risk, and epigenetic factors will improve understanding of cardiovascular disease risk so that preventive measures can be instituted earlier and more effectively. To our knowledge this work is the first to examine DNA methylation and cardiometabolic risk outcomes in mother-adolescent dyads.

scholarly journals Sex Differences in Urate Handling

2020 ◽  
Vol 21 (12) ◽  
pp. 4269 ◽  
Author(s):  
Victoria L. Halperin Kuhns ◽  
Owen M. Woodward
Keyword(s):  
Sex Differences ◽  
Disease Risk ◽  
Association Studies ◽  
Elevated Serum ◽  
Serum Urate ◽  
Genome Wide Association Studies ◽  
Renal Handling ◽  
Physiological Regulation ◽  
Genome Wide

Hyperuricemia, or elevated serum urate, causes urate kidney stones and gout and also increases the incidence of many other conditions including renal disease, cardiovascular disease, and metabolic syndrome. As we gain mechanistic insight into how urate contributes to human disease, a clear sex difference has emerged in the physiological regulation of urate homeostasis. This review summarizes our current understanding of urate as a disease risk factor and how being of the female sex appears protective. Further, we review the mechanisms of renal handling of urate and the significant contributions from powerful genome-wide association studies of serum urate. We also explore the role of sex in the regulation of specific renal urate transporters and the power of new animal models of hyperuricemia to inform on the role of sex and hyperuricemia in disease pathogenesis. Finally, we advocate the use of sex differences in urate handling as a potent tool in gaining a further understanding of physiological regulation of urate homeostasis and for presenting new avenues for treating the constellation of urate related pathologies.

Abstract P130: Association Between PFOA, PFOS and Obesity Among Children in a Nationally Representative Sample

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sarah D Geiger ◽  
Ping Yao ◽  
Elizabeth Rogers ◽  
Michael Vaughn ◽  
Zhengmin Qian
Keyword(s):  
Risk Factor ◽  
Waist Circumference ◽  
Abdominal Obesity ◽  
Representative Sample ◽  
Mexican American ◽  
Cross Sectional Study ◽  
Consumer Products ◽  
Inverse Association ◽  
Annual Household Income ◽  
Cross Sectional

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are two types of perfluoroalkyl substances (PFASs) commonly used in the manufacturing process of many consumer products. Both have been detected in the blood of the majority of Americans. PFASs have been shown to be associated with intermediate cardiovascular disease (CVD) outcomes such as hypertension, hyperuricemia and dyslipidemia, but their relationship with obesity, a risk factor for intermediate and advanced CVD, remains largely unexplored. In this context, we examined the associations between PFOA and PFOS levels, and Body Mass Index (BMI) and waist circumference (WC) in a representative sample (N = 5,180) of US children. Our cross-sectional sample included participants aged 12-19 years from CDC’s National Health and Nutrition Examination Survey 1999-2000, 2003-2012. PFOA and PFOS were measured in ng/mL and modeled as quartiles of exposure, where quartile 1 is the referent group across models. Overweight/obesity was defined as age-, sex-specific BMI ≥85 th percentile; abdominal obesity was defined as age-, sex-specific waist circumference ≥90 th percentile. A multivariable model adjusting for age (years), sex (male, female), race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American, other), and annual household income category (<$25,000, $25,500-$54,999, $55,000 and over), revealed an inverse association between PFOS and overweight/obesity. Odds ratios (ORs) for overweight/obesity were 0.81 (95% Confidence Interval [CI] 0.14-0.58) for exposure quartile 2, 0.28 (0.11-0.58) for quartile 3, and 0.26 (0.15-1.05) for quartile 4 (p-trend=0.001). Results were similar for abdominal obesity where, for example, children in quartile 2 of PFOS exposure experienced a multivariable-adjusted OR of 0.42 (0.25-0.72; p-trend=0.023). PFOA was not found to be significantly associated with either outcome. Results are paradoxical in that PFASs may be protective against a risk factor for conditions with which PFASs are positively associated. Because we could not identify any temporal relationships between exposure and outcomes in this cross-sectional study, more studies with improved study design (such as a cohort study) are warranted to confirm the association.

Size at birth is associated with blood pressure but not insulin resistance in 6–8 year old children in rural Nepal

2010 ◽  
Vol 1 (2) ◽  
pp. 114-122 ◽  
Author(s):  
C. P. Stewart ◽  
P. Christian ◽  
K. J. Schulze ◽  
U. S. Shah ◽  
G. Subedi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Birth Weight ◽  
Waist Circumference ◽  
Inverse Association ◽  
High Waist Circumference ◽  
Increased Risk ◽  
High Prevalence ◽  
Rural Nepal ◽  
Size At Birth

Earlier, we reported that antenatal micronutrient supplementation reduced the risk of metabolic syndrome and microalbuminuria among offspring at 6–8 years of age in rural Nepal. In the same birth cohort, we examined associations of size at birth (weight, length and ponderal index), and gestational age, with cardiometabolic risk factors in childhood across all antenatal micronutrient interventions. There was an inverse association between birth weight and systolic blood pressure (SBP,β= −1.20 mm Hg/kg; 95% confidence interval (CI): −1.93, −0.46) and diastolic blood pressure (DBP,β= −1.24 mm Hg/kg; 95% CI: −2.00, −0.49). Current child body mass index was positively associated with SBP but not with DBP. Birth weight was unassociated with insulin resistance, but each kilogram of increase was associated with a reduced risk of high triglycerides (odds ratio (OR) = 0.64/kg; 95% CI: 0.41, 0.97) and an increased risk of high waist circumference (OR = 3.16/kg; 95% CI: 2.47, 4.41). In this rural Nepalese population of children 6–8 years of age with a high prevalence of undernutrition, size at birth was inversely associated with blood pressure and triglycerides and positively associated with waist circumference.

scholarly journals Hypoadiponectinemia is associated with increased insulin resistance, dyslipidemia and presence of type 2 diabetes in non obese central Indian population

2018 ◽  
Vol 7 (1) ◽  
pp. 106
Author(s):  
Anil B. Choudhury ◽  
Shankar M. Pawar ◽  
Purnima Dey Sarkar ◽  
Keerti Gopi
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Waist Circumference ◽  
Adiponectin Level ◽  
Diabetic Group ◽  
Diabetic Patients ◽  
Inverse Association ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Background: Accumulating evidence suggests that adiponectin, a major adipocyte secretory protein, has insulin-sensitizing and anti-atherogenic properties and protects against later development of type 2 diabetes. We investigated the association of adiponectin with insulin resistance, blood lipids and type 2 diabetes in non obese central Indian population.Methods: Anthropometric and biochemical parameters were measured in 149 (81 male and 68 female) newly diagnosed non obese type 2 diabetic patients and 157 (85 male and 72 female) age and body mass index (BMI) matched controls.Results: Adiponectin level (p<0.0001) was significantly lower in the diabetic group than in non diabetic control. In an age, gender and BMI adjusted model, adiponectin level was significantly negatively correlated with waist circumference, waist to hip ratio, systolic blood pressure, fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) (p= 0.0034), HbA1C, total cholesterol, LDL-cholesterol, and triglycerides (p<0.0001) and positively correlated with HDL-cholesterol (p =0.0014) in non obese type 2 diabetic group. However, there was no significant correlation between adiponectin and glucose in this study. In stepwise linear regression analysis, adjusted for potential confounder, significant inverse association was observed between serum adiponectin level and HOMA-IR (p = 0.0001). In multivariate logistic regression model, adjusted for age, gender, BMI, waist circumference, and waist-hip ratio, lower adiponectin was independently associated with the presence of type 2 diabetes (p<0.0001).Conclusions: Lower adiponectin levels in non obese type 2 diabetic patients were significantly related to the increased insulin resistance, dyslipidemia, and presence of type 2 diabetes, independently of overall and abdominal adiposity, thereby suggesting a direct link between adiponectin and carbohydrate and lipid metabolism in human.

scholarly journals ASSOCIATIONS OF IRS-1 POLYMORPHISM WITH VARIOUS COMPONENTS OF THE METABOLIC SYNDROME IN HYPERTENSIVE PATIENTS

2019 ◽  
Vol 72 (8) ◽  
pp. 1494-1498
Author(s):  
Maryna Kochuieva ◽  
Valentyna Psarova ◽  
Larysa Ruban ◽  
Nataliia Kyrychenko ◽  
Olena Alypova ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Glucose Tolerance ◽  
Arterial Hypertension ◽  
Abdominal Obesity ◽  
Healthy Individuals ◽  
Hypertensive Patients ◽  
The Metabolic Syndrome

Introduction: The metabolic syndrome is one of the most discussed cross-disciplinary problems of modern medicine. Now there are various definitions and criteria of diagnostics of metabolic syndrome. The abdominal obesity is considered the main component of the metabolic syndrome, as a reflection of visceral obesity which degree is offered to be estimated on an indirect indicator – a waist circumference. Alongside with abdominal obesity, a number of classifications distinguish insulin resistance (IR) as a diagnostic criterion of metabolic syndrome. It is proved that IR is one of the pathophysiological mechanisms influencing the development and the course of arterial hypertension (AH), type 2 DM and obesity. There are two components in the development of IR: genetic (hereditary) and acquired. In spite of the fact that IR has the accurate genetic predisposition, exact genetic disorders of its appearance have not been identified yet, thus demonstrating its polygenic nature. The aim: To establish possible associations of the insulin receptor substrate-1 (IRS-1) gene polymorphism with the severity of the metabolic syndrome components in patients with arterial hypertension (AH). Materials and methods: 187 patients with AH aged 45-55 years and 30 healthy individuals. Methods: anthropometry, reactive hyperemia, color Doppler mapping, biochemical blood analysis, HOMA-insulin resistance (IR), glucose tolerance test, enzyme immunoassay, molecular genetic method. Results: Among hypertensive patients, 103 had abdominal obesity, 43 - type 2 diabetes, 131 - increased blood triglycerides, 19 - decreased high density lipoproteins, 59 -prediabetes (33 - fasting hyperglycemia and 26 - impaired glucose tolerance), 126 had IR. At the same time, hypertensive patients had the following distribution of IRS-1 genotypes: Gly/Gly - 47.9%, Gly/Arg - 42.2% and Arg/Arg - 10.7%, whereas in healthy individuals the distribution of genotypes was significantly different: Gly/Gly - 86.8% (p<0.01), Gly/ Arg - 9.9% (p<0.01) and Arg/Arg - 3.3% (p<0.05). Hypertensive patients with Arg/Arg and Gly/Arg genotypes had significantly higher HOMA-IR (p<0.01), glucose, insulin and triglycerides levels (p<0.05), than in Gly/Gly genotype. At the same time, body mass index, waist circumference, blood pressure, adiponectin, HDL, interleukin-6, C-reactive protein, degree of endothelium-dependent vasodilation, as well as the frequency of occurrence of impaired glucose tolerance did not significantly differ in IRS-1 genotypes. Conclusions: in hypertensive patients, the genetic polymorphism of IRS-1 gene is associated with such components of the metabolic syndrome as hypertriglyceridemia and fasting hyperglycemia; it is not associated with proinflammatory state, endothelial dysfunction, dysglycemia, an increase in waist circumference and decrease in HDL.

scholarly journals Physical Activity and Insulin Resistance in 6,500 NHANES Adults: The Role of Abdominal Obesity

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
James R. Fowler ◽  
Larry A. Tucker ◽  
Bruce W. Bailey ◽  
James D. LeCheminant
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Waist Circumference ◽  
Abdominal Obesity ◽  
Total Activity ◽  
Effect Modification ◽  
Activity Level ◽  
The Other ◽  
Model Assessment ◽  
The Relationship

This cross-sectional investigation studied differences in insulin resistance across levels of physical activity in 6,500 US adults who were randomly selected as part of the National Health and Nutrition Examination Survey (NHANES). Another important objective was to determine the influence of abdominal obesity on the physical activity and insulin resistance relationship. MET-minutes were utilized to quantify total activity based on participation in 48 different physical activities. Two strategies were employed to categorize levels of physical activity: one was based on relative MET-minutes (quartiles), and the other approach was based on the US physical activity guidelines. Insulin resistance was indexed using the homeostatic model assessment (HOMA). Abdominal obesity was indexed using waist circumference. Effect modification was tested by dividing waist circumferences into sex-specific quartiles and then evaluating the relationship between physical activity and HOMA-IR within each quartile separately. Results showed that relative physical activity level was associated with HOMA-IR after controlling for demographic and demographic and lifestyle covariates (F = 11.5, P<0.0001 and F = 6.0, P=0.0012, respectively). Adjusting for demographic and demographic and lifestyle covariates also resulted in significant relationships between guideline-based activity and HOMA-IR (F = 8.0, P<0.0001 and F = 4.9, P=0.0017, respectively). However, statistically controlling for differences in waist circumference with the other covariates nullified the relationship between total physical activity and HOMA-IR. Effect modification testing showed that when the sample was delimited to adults with abdominal obesity (Quartile 4), relative (F = 5.6, P=0.0019) and guideline-based physical activity (F = 3.7, P=0.0098) and HOMA-IR were significantly associated. Physical activity and HOMA-IR were not related within the other three quartiles. In conclusion, it appears that differences in physical activity may play a meaningful role in insulin resistance in those with abdominal obesity, but total activity does not seem to account for differences in insulin resistance among US adults with smaller waists.

Abstract P198: Cumulative Abdominal Obese-Years and Arterial Stiffness in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Priya Palta ◽  
Michelle Snyder ◽  
Hirofumi Tanaka ◽  
David Aguilar ◽  
Sunil K Agarwal ◽  
...  
Keyword(s):  
Older Adults ◽  
African American ◽  
Waist Circumference ◽  
Arterial Stiffness ◽  
Abdominal Obesity ◽  
Abdominal Circumference ◽  
Cumulative Exposure ◽  
Inverse Association ◽  
Cross Sectional ◽  
Fat Deposits

Introduction: Arterial stiffness quantifies subclinical cardiovascular disease (CVD) and is predictive of athero-thrombotic events and mortality. Time-cumulative measures of obesity may more accurately estimate the lifetime burden of CVD due to obesity by accounting for both duration and intensity. Compared to generalized obesity, abdominal obesity is more consistently associated with vascular outcomes and, specifically, arterial stiffness. We examined whether 20-year cumulative abdominal obese-years is associated with greater arterial stiffness in older adults. Methods: We analyzed 5,177 participants from the ARIC cohort. Cumulative abdominal obesity was defined as the product of waist circumference units above the conventional cutpoints for obesity, 88 cm for women and 102 cm for men, and the years of exposure to that waist circumference. This accounts for obesity exposure over 20 years from the five ARIC visits. Arterial stiffness was measured by pulse wave velocity (PWV) at the fifth ARIC visit. Measures of PWV obtained include: carotid-femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and segment-specific measures [heart-femoral (hfPWV) and femoral-ankle (faPWV)]. Multivariable linear regression, adjusted for age, sex, race, systolic blood pressure and smoking, was used to quantify the change in PWV (cm/s) per unit increase in cumulative abdominal obese-years. Subsidiary analyses examined visit five waist circumference. Hypertension and diabetes were explored as effect modifiers. Results: Among the 5,177 participants (mean age: 75, 43% male, 21% African-American), 66% had cumulative abdominal obese-years greater than zero (range: 1-1595), while 34% were not abdominally obese across any ARIC visit and thus had zero cumulative abdominal obese-years. Participants with higher cumulative abdominal obese-years were more often male, African-American and had a history of diabetes and hypertension. Cumulative abdominal obese-years were associated with lower baPWV (beta=-0.19, 95% CI: -0.23, -0.14), lower faPWV (beta=-0.12, 95% CI: -0.15, -0.09) and lower hfPWV (beta=-0.06, 95% CI: -0.10, -0.03). There was no significant association with cfPWV (beta=-0.03, 95% CI: -0.08, 0.01). The cross-sectional association between visit five abdominal circumference and PWV were similar in magnitude to cumulative abdominal obese-years. Hypertension and diabetes did not modify these associations. Conclusions: We observed an inverse association between cumulative exposure to abdominal fat and arterial stiffness in older adults. Survivor bias or the role of sarcopenia may explain these findings.The association of fat deposits with subclinical vascular disease in older adults deserves careful evaluation. Estimation of long-term exposure to abdominal obesity did not reveal associations with arterial stiffness beyond a cross-sectional assessment of abdominal obesity.

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