Subgingival Microbiota and Longitudinal Glucose Change: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS).

Microbial communities along mucosal surfaces throughout the digestive tract are hypothesized as risk factors for impaired glucose regulation and the development of clinical cardiometabolic disease. We investigated whether baseline measures of subgingival microbiota predicted fasting plasma glucose (FPG) longitudinally. The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 230 diabetes-free adults (77% female) aged 20 to 55 y (mean ± SD, 34 ± 10 y) from whom baseline subgingival plaque and longitudinal FPG were measured. DNA was extracted from subgingival plaque, and V3 to V4 regions of the 16S rRNA gene were sequenced. FPG was measured at baseline and again at 2 y; glucose change was defined as follow-up minus baseline. Multivariable linear models regressed 2-y glucose change onto baseline measures of community diversity and abundances of 369 individual taxa. A microbial dysbiosis index (MDI) summarizing top individual taxa associated with glucose change was calculated and used in regression models. Models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and baseline glucose levels. Statistical significance was based on the false discovery rate (FDR; <0.05) or a Bonferroni-corrected P value of 1 × 10-4, derived from the initial 369 hypothesis tests for specific taxa. Mean 2-y FPG change was 1.5 ± 8 mg/dL. Baseline levels of 9 taxa predicted FPG change (all FDR <0.05), among which Stomatobaculum sp oral taxon 097 and Atopobium spp predicted greater FPG change, while Leptotrichia sp oral taxon 498 predicted lesser FPG change (all 3 P values, Bonferroni significant). The MDI explained 6% of variation in longitudinal glucose change (P < 0.001), and baseline glucose levels explained 10% of variation (P < 0.0001). FPG change values ± SE in the third versus first tertile of the MDI were 4.5 ± 0.9 versus 1.6 ± 0.9 (P < 1 × 10-4). Subgingival microbiota predict 2-y glucose change among diabetes-free men and women.

White Matter Lesion Penumbra Shows Abnormalities on Structural and Physiologic MRIs in the Coronary Artery Risk Development in Young Adults Cohort.

BACKGROUND AND PURPOSE: White matter lesions are 1 age-related manifestation of cerebrovascular disease, but subthreshold abnormalities have been identified in nonlesional WM. We hypothesized that structural and physiologic MR imaging findings of early cerebrovascular disease can be measured in middle-aged subjects in tissue adjacent to WM lesions, termed "penumbra." MATERIALS AND METHODS: WM lesions were defined using automated segmentation in 463 subjects, 43-56 years of age, from the Coronary Artery Risk Development in Young Adults (CARDIA) longitudinal observational cohort study. We described 0- to 2-mm and 2- to 4-mm-thick spatially defined penumbral WM tissue ROIs as rings surrounding WM lesions. The remaining WM was defined as distant normal-appearing WM. Mean signal intensities were measured for FLAIR, T1-, and T2-weighted images, and from fractional anisotropy, mean diffusivity, CBF, and vascular reactivity maps. Group comparisons were made using Kruskal-Wallis and pair-wise t tests. RESULTS: Lesion volumes averaged 0.738 ± 0.842 cm3 (range, 0.005-7.27 cm3). Mean signal intensity for FLAIR, T2, and mean diffusivity was increased, while T1, fractional anisotropy, and CBF were decreased in white matter lesions versus distant normal-appearing WM, with penumbral tissues showing graded intermediate values (corrected P < .001 for all group/parameter comparisons). Vascular reactivity was significantly elevated in white matter lesions and penumbral tissue compared with distant normal-appearing white matter (corrected P ≤ .001). CONCLUSIONS: Even in relatively healthy 43- to 56-year-old subjects with small white matter lesion burden, structural and functional MR imaging in penumbral tissue reveals significant signal abnormalities versus white matter lesions and other normal WM. Findings suggest that the onset of WM injury starts by middle age and involves substantially more tissue than evident from focal white matter lesions visualized on structural imaging.

Association of plasma phospholipid polyunsaturated and trans fatty acids with body mass index: results from the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND/OBJECTIVE: Previous research has focused on associations between dietary fat and body mass index (BMI), but the contributions of different types of fat to BMI remain unclear. The purpose of this study is to estimate whether plasma phospholipid omega-3 (n-3), omega-6 (n-6) or trans fatty acids are associated with BMI at baseline and with subsequent BMI changes over time; and whether total phospholipid n-6 or trans fatty acids modify any association between phospholipid n-3 and BMI. METHODS: Cross-sectional and longitudinal linear mixed models include 6243 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Participants were 45-84 years old, had no history of cardiovascular disease at baseline (2000-2002) and were followed for up to 10 years. Plasma phospholipid fatty acids were measured using fasting plasma samples at baseline. Fully adjusted models include demographics, health behaviors and other fatty acids (n-3, n-6 and trans) as appropriate. RESULTS: In fully adjusted models, phospholipid n-3 fatty acid levels were inversely associated with baseline BMI (Ptrend <0.001). Baseline BMI was 1.14 (95% confidence interval (CI): 0.71, 1.57) kg m-2 lower among participants with total n-3 values in the highest vs the lowest quartiles, but was not associated with changes in BMI. Total phospholipid n-6 was positively associated with baseline BMI in partially adjusted but not fully adjusted models. No overall association was observed between fatty acid levels and changes in BMI. No clear association was observed between trans fatty acids and baseline BMI or BMI change. No effect modification in the association between phospholipid n-3 and baseline BMI or BMI change was observed by either phospholipid n-6 or trans fatty acids. CONCLUSIONS: Phospholipid total and specific n-3 fatty acid levels were inversely associated with BMI at baseline, whereas associations tended to be positive for total n-6 fatty acids. Significant associations between fatty acid levels and BMI changes were not observed.

Persistent organic pollutants in adipose tissue should be considered in obesity research.

Although low doses of persistent organic pollutants (POPs), strong lipophilic chemicals with long half-lives, have been linked to various endocrine, immune, nervous and reproductive system diseases, few obesity studies have considered adipose tissue as an important POPs exposure source. Because the toxicodynamics of POPs relate directly to the dynamics of adiposity, POPs might explain puzzling findings in obesity research. In two people exposed to the same amounts of environmental POPs, the one having more adipose tissue may be advantaged because POPs storage in adipose tissue can reduce burden on other critical organs. Therefore, adipose tissue can play a protective role against the POPs effects. However, two situations increase the POPs release from adipose tissue into the circulation, thereby increasing the risk that they will reach critical organs: (i) weight loss and (ii) insulin resistance. In contrast, weight gain reduces this possibility. Therefore, avoiding harmful health effects of POPs may mostly contradict conventional judgments about obesity and weight change. These contradictory situations can explain the obesity paradox, the adverse effects of intensive intentional weight loss and the protective effects of obesity against dementia. Future studies should consider that adipose tissue is widely contaminated with POPs in modern society.

Oxidative stress, anti-oxidants and the cross-sectional and longitudinal association with depressive symptoms: results from the CARDIA study.

Depression may be accompanied by increased oxidative stress and decreased circulating anti-oxidants. This study examines the association between depressive symptoms, F2-isoprostanes and carotenoids in a US community sample. The study includes 3009 participants (mean age 40.3, 54.2% female) from CARDIA (Coronary Artery Risk Development in Young Adults). Cross-sectional analyses were performed on data from the year 15 examination (2000-2001) including subjects whose depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) and had measurements of plasma F2-isoprostanes (gas chromatography/mass spectrometry) or serum carotenoids (high-performance liquid chromatography). Carotenoids zeaxanthin/lutein, ß-cryptoxanthin, lycopene, α-carotene, ß-carotene were standardized and summed. Longitudinal analyses were conducted using the data from other examinations at 5-year intervals. Cross-lagged analyses investigated whether CES-D predicted F2-isoprostanes or carotenoids at the following exam, and vice versa. Regression analyses were controlled for sociodemographics, health and lifestyle factors. F2-isoprostanes were higher in subjects with depressive symptoms (CES-D ⩾ 16) after adjustment for sociodemographics (55.7 vs 52.0 pg ml(-1); Cohen's d = 0.14, P < 0.001). There was no difference in F2-isoprostanes after further adjustment for health and lifestyle factors. Carotenoids were lower in those with CES-D scores ⩾ 16, even after adjustment for health and lifestyle factors (standardized sum 238.7 vs 244.0, Cohen's d = -0.16, P < 0.001). Longitudinal analyses confirmed that depression predicts subsequent F2-isoprostane and carotenoid levels. Neither F2-isoprostanes nor carotenoids predicted subsequent depression. In conclusion, depressive symptoms were cross-sectionally and longitudinally associated with increased F2-isoprostanes and decreased carotenoids. The association with F2-isoprostanes can largely be explained by lifestyle factors, but lower carotenoids were independently associated with depressive symptoms.

Higher pericardial adiposity is associated with prevalent diabetes: The Coronary Artery Risk Development in Young Adults study.

BACKGROUND AND AIMS: Pericardial adipose tissue (PAT) is located on both sides of the pericardium. We tested whether PAT was associated with prevalent diabetes at the year 25 exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study. METHODS AND RESULTS: The CARDIA Year 25 exam (2010-2011) included complete data for all covariates on 3107 participants. Prevalent diabetes (n = 436) was defined as high fasting (≥126 mg/dl) or 2-h postload glucose (≥200 mg/dl) or HbA1c (≥6.5%) or use of diabetes medications. Volume of PAT was measured from computed tomographic scans. Logistic regression was performed to examine the relationship between quartiles of PAT and diabetes. In regression models adjusted for field center, sex, race, age, systolic blood pressure, total cholesterol, log triglycerides, and treatment with blood pressure and cholesterol lowering medication, PAT volume in the 4th quartile was significantly associated with diabetes status after adjustment for BMI (OR 2.57, 95% CI 1.66, 3.98) or visceral adipose tissue (OR 2.08, 95% CI 1.32, 3.29). PAT volume in the 2nd and 3rd quartiles was not significantly associated with diabetes status relative to the first quartile. CONCLUSIONS: Metabolically active pericardial adipose tissue is associated with prevalent diabetes only at higher volumes independent of overall obesity.

Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat.

BACKGROUND: To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR). SUBJECTS AND METHODS: Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available. RESULTS: A total of 52 single-nucleotide polymorphisms (SNPs) encompassing 7 loci showed suggestive evidence of association (P<1.0 × 10(-6)) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near BBS9 gene and VAT (rs12374818; P=1.10 × 10(-7)), an association that was replicated (P=0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near CYCSP30 and VAT-BMI (rs10506943; P=2.42 × 10(-7)). Our sex-specific analyses identified one genome-wide significant (P<5.0 × 10(-8)) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P=3.97 × 10(-8) to 1.13 × 10(-8)). The THNSL2 gene previously associated with VAT in women was also replicated (P=0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were ADCY8 and KCNK9, respectively. CONCLUSIONS: Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2) previously reported to be associated with abdominal fat in women.

Healthy eating and survival among elderly men with and without cardiovascular-metabolic diseases.

BACKGROUND AND AIMS: The strength of the associations of dietary scores with cardiovascular disease (CVD) and all-cause mortality in elderly vary considerably between a priori scores. To assess whether healthy eating lowers the risk of CVD and all-cause mortality among elderly men. METHODS AND RESULTS: The Zutphen Elderly Study (age 65-84 years) was divided into men with (n = 210) and without (n = 616) cardiovascular-metabolic diseases at baseline in 1985. Diet was assessed with the cross-check dietary history method. We created the "Dutch Healthy Nutrient and Food Score" (DHNaFS) and the "Dutch Undesirable Nutrient and Food Score" (DUNaFS). Associations of the scores with CVD and all-cause mortality were assessed using multivariable Cox regression models. Associations of scores with life years gained used general linear models. During a median follow-up of 10.6 years (IQR 5.8-15.9) 806 participants died, of whom 359 from CVD. In all men, diet scores did not predict death. Among men with cardiovascular-metabolic diseases, DHNaFS was associated with lower CVD (HR: 0.57; 95% CI: 0.35-0.93) and all-cause mortality risk (HR: 0.64; 95% CI: 0.44-0.94) comparing the highest vs. the lowest score tertiles. Men with cardiovascular-metabolic diseases in the highest vs. the lowest tertile of the DHNaFS lived approximately 2.5 years longer. The DHNaFS was not associated with CVD and all-cause mortality in men without cardiovascular-metabolic diseases. The DUNaFS was not associated with any of the outcomes. CONCLUSION: A high quality diet was associated with a 40% lower mortality risk and 2.5 years longer life expectancy in elderly men with, but not without, cardiovascular-metabolic diseases.

Periodontal Bacteria and Prediabetes Prevalence in ORIGINS: The Oral Infections, Glucose Intolerance, and Insulin Resistance Study.

Periodontitis and type 2 diabetes mellitus are known to be associated. The relationship between periodontal microbiota and early diabetes risk has not been studied. We investigated the association between periodontal bacteria and prediabetes prevalence among diabetes-free adults. ORIGINS (the Oral Infections, Glucose Intolerance and Insulin Resistance Study) cross sectionally enrolled 300 diabetes-free adults aged 20 to 55 y (mean ± SD, 34 ± 10 y; 77% female). Prediabetes was defined as follows: 1) hemoglobin A1c values ranging from 5.7% to 6.4% or 2) fasting plasma glucose ranging from 100 to 125 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species were assessed at baseline, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Actinomyces naeslundii. Full-mouth clinical periodontal examinations were performed, and participants were defined as having no/mild periodontitis vs. moderate/severe periodontitis per the definition of the Centers for Disease Control and Prevention / American Academy of Periodontology. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Prevalence ratios and 95% confidence intervals for third vs. first tertiles are presented. All analyses were adjusted for cardiometabolic risk factors. All results presented currently arise from the baseline cross section. Prediabetes prevalence was 18%, and 58% of participants had moderate/severe periodontitis. Prevalence ratios (95% confidence intervals) summarizing associations between bacterial levels and prediabetes were as follows: A. actinomycetemcomitans, 2.48 (1.34, 4.58), P = 0.004; P. gingivalis, 3.41 (1.78, 6.58), P = 0.0003; T. denticola, 1.99 (0.992, 4.00), P = 0.052; T. forsythia, 1.95 (1.0, 3.84), P = 0.05; A. naeslundii, 0.46 (0.25, 0.85), P = 0.01. The prevalence ratio for prediabetes among participants with moderate/severe vs. no/mild periodontitis was 1.47 (0.78, 2.74), P = 0.23. Higher colonization levels of specific periodontal microbiota are associated with higher prediabetes prevalence among diabetes-free adults.

Changes in N-terminal pro-B-type natriuretic peptide and incidence of diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA).

AIMS: This study looked at whether the inverse association of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes is modified by changes in NT-proBNP (ΔNT-proBNP) levels. METHODS: Plasma NT-proBNP was assayed at baseline and 3.2 years later (visit 3) in the Multi-Ethnic Study of Atherosclerosis (MESA). ΔNT-proBNP was calculated as NT-proBNP visit3-NT-proBNP baseline. A Poisson distribution was fitted to determine the incidence density of diabetes, adjusted for age, race, gender, educational attainment, antihypertensive medication, total intentional exercise and plasma IL-6 levels. In the primary analysis (n=3236 without diabetes up to visit 3, followed for a mean of 6.3 years), incidence density was regressed for the following categories of baseline NT-proBNP: (1)<54.4 pg/mL; (2) 54.4-85.9 pg/mL; and (3) 86-54.2 pg/mL. This was crossed with categories of ΔNT-proBNP as medians (ranges): (1) -6.2 (-131-11.7) pg/mL; (2) 19.8 (11.8-30.1) pg/mL; (3) 44.0 (30.2-67.9) pg/mL; and (4) 111.2 (68.0-3749.9) pg/mL. RESULTS: The incidence density of diabetes followed a U-shaped association across categories of ΔNT-proBNP within categories of baseline NT-proBNP after adjusting for other covariates (P=0.02). At each level of baseline NT-proBNP, the incidence density of diabetes was lowest for small-to-moderate increases in NT-proBNP. CONCLUSION: This analysis suggests that NT-proBNP has a biphasic association with diabetes in which the risk of incident diabetes decreases within a 'physiological range' of ΔNT-proBNP, and plateaus or increases as NT-proBNP concentrations increase, probably in response to pathophysiological conditions leading to high levels of NT-proBNP.

Cognitive function in a middle aged cohort is related to higher quality dietary pattern 5 and 25 years earlier: the CARDIA study.

BACKGROUND: Preserving cognitive function is an important public health issue. We investigated whether dietary pattern associates with cognitive function in middle-age. METHODS: We studied 2435 participants in the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study of black and white men and women aged 18-30 in 1985-86 (year 0, Y0). We hypothesized that a higher A Priori Diet Quality Score, measured at Y0 and Y20, is associated with better cognitive function measured at Y25. The diet score incorporated 46 food groups (each in servings/day) as the sum of quintile ranks of food groups rated beneficial, 0 for food groups rated neutral, and reversed quintile ranks for food groups rated adverse; higher score indicated better diet quality. Y25 cognitive testing included verbal memory (Rey Auditory-Verbal Learning Test (RAVLT)), psychomotor speed (Digit Symbol Substitution Test (DSST)) and executive function (Stroop). RESULTS: Per 10-unit higher diet score at Y20, the RAVLT was 0.32 words recalled higher, the DSST was 1.76 digits higher, and the Stroop was 1.00 seconds+errors lower (better performance) after adjusting for race, sex, age, clinic, and energy intake. Further adjustment for physical activity, smoking, education, and body mass index attenuated the association slightly. Diet score at Y0 and increase in diet score over 20 years were also positively associated with each cognitive test. CONCLUSIONS: A higher quality dietary pattern was associated with better cognitive function 5 years and even 25 years later in apparently healthy middle-aged adults.

Diet quality and markers of endothelial function: the CARDIA study.

BACKGROUND AND AIM: Dietary patterns are associated cross-sectionally with cellular adhesion molecules (CAMs). We studied prospective associations of three dietary patterns with CAMs. METHODS AND RESULTS: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, diet was assessed at years 0 (1985-86) and 7 (1992-93) examinations. Four circulating CAMs (E-selectin, P-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), and vascular cellular adhesion molecule (VCAM)) were assayed at years 7 and 15 (2000-01). We created one index score "A Priori Diet Quality Score" and derived dietary patterns using principal components analysis (PCA). Multivariable linear regression models predicted year 15 CAMs from averaged (year 0/7) dietary patterns. The A Priori Diet Quality Score rated 46 food groups beneficial, neutral or adverse based on hypothesized health effects. We derived two PCA dietary patterns: "fruit and vegetables (FV)" (high intakes of fruit, vegetables, and whole grains) and "meat" (high intakes of red meat, refined grain, and butter). All dietary patterns were related to E-selectin and sICAM-1. P-selectin was not related to the FV dietary pattern. VCAM was only related to the A Priori Diet Quality Score. Strongest associations were for the meat dietary pattern with E-selectin (effect size 28% of an SD (+3.9/13.7 ng/mL)) and P-selectin (effect size 37% of an SD (+4.1/11.2 ng/mL)) and the A Priori Diet Quality Score with sICAM-1 (effect size 34% of an SD (-15.1/44.7 ng/mL)) and VCAM (effect size of 26% of an SD (-45.1/170.3 ng/mL)). CONCLUSION: This prospective analysis suggests that dietary patterns are associated with CAMs.

Longitudinal association between serum urate and subclinical atherosclerosis: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

OBJECTIVE: The aim of the present study was to determine whether serum urate (sUA) concentration is positively associated with subclinical atherosclerosis, independent of body mass index (BMI), amongst generally healthy adults. DESIGN AND SETTING: The CARDIA study followed 5115 Black and White individuals aged 18-30 years in 1985-1986 (year 0). Subclinical atherosclerosis comprised coronary artery calcified plaque (CAC; years 15, 20 and 25), and maximum common carotid intima-media thickness (IMT; year 20). sUA (years 0, 10, 15 and 20) was modelled as gender-specific quartiles that were pooled. Discrete-time hazard regressions and generalized linear regressions were used for analyses. RESULTS: Mean sUA concentration was lower in women than in men and increased with age. Adjusting for demographic and lifestyle factors, the highest versus lowest quartile of sUA at year 0 was associated with a 44% [95% confidence interval (CI) 20%, 73%] greater risk of CAC progression from years 15 to 25 (Ptrend  < 0.001), which was attenuated by adjustment for BMI at year 0 (Ptrend  = 0.45). A stronger association was found between sUA at year 15 and CAC progression at year 20 or 25 (hazard ratio 2.07, 95% CI 1.66, 2.58 for the highest versus lowest sUA quartile Ptrend  < 0.001), which was attenuated, but remained significant with additional adjustment for BMI at year 15 (Ptrend  = 0.01). A greater increment in sUA concentration from year 0 to year 15, independent of change in BMI, was related to a higher risk of CAC progression (Ptrend  < 0.001). Similar associations were found between sUA and IMT, but only in men. CONCLUSION: sUA may be an early biomarker for subclinical atherosclerosis in young adults; starting in early middle age, sUA predicts subclinical atherosclerosis independently of BMI.

Relation of chemokines to BMI and insulin resistance at ages 18-21.

OBJECTIVE: In obesity, adipose tissue becomes a significant source of chemokines and inflammatory cytokines that are associated with chronic systemic low-grade inflammation and may lead to insulin resistance. Studies in children have mainly focused on inflammatory cytokines and there are limited data for chemokines in adolescents and young adults. We studied the relation of chemokines to cardiovascular (CV)-risk factors, insulin resistance and adipocytokines in 18-21-year-old individuals. SUBJECTS AND DESIGN: Cross-sectional data collected in a cohort originally enrolled at mean age 13, with data for the present study obtained from 252 examined at age 18.7±0.1 years. METHODS: Multiple linear regression models were used to analyze the associations among chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein-1ß (MIP-1ß), visfatin and interleukin-8 (IL-8)) and between chemokines and body mass index (BMI), glucose, lipids, blood pressure (BP), insulin resistance (euglycemic hyperinsulinemic clamp) and adipocytokines (IL-6, TNF-α and adiponectin). RESULTS: Chemokine levels were significantly intercorrelated. Significant associations (P<0.05) with adjustment for age, race and sex included: MIP-1ß with waist circumference and IL-6, IL-8 with systolic BP and visfatin with IL-6. No other significant relations were found between the chemokines and the other variables. Further adjustment for BMI did not alter these conclusions. CONCLUSION: Considered in the context of prior studies in children and adults, these results suggest that in large part, the association between chemokines and CV risk or inflammatory factors does not appear to develop until adult life.

Development of associations among central adiposity, adiponectin and insulin sensitivity from adolescence to young adulthood.

OBJECTIVE: To examine associations of central adiposity, serum adiponectin and clamp-derived insulin sensitivity in a single longitudinal cohort from early adolescence to young adulthood. METHODS: The cohort was examined three times at mean ages 15 years (n = 308), 19 years (n = 218) and 22 years (n = 163). Insulin sensitivity was measured with the euglycaemic hyperinsulinaemic clamp. Circulating adiponectin was measured by enzyme-linked immunosorbent assay. Computed tomography scans were used at mean age 22 to compute subcutaneous and visceral abdominal fat volume. Partial Pearson correlations and linear regression were used to examine cross-sectional associations at each examination. RESULTS: The moderate negative correlation between waist circumference and adiponectin was significant and essentially unchanged from mean age 15 (-0.32, P < 0.0001) to mean age 22 (-0.29, P < 0.002), whereas the negative correlation between waist circumference and insulin sensitivity and the positive correlation between adiponectin and insulin sensitivity increased steadily in magnitude to mean age 22 (-0.29, P = 0.0002; and 0.32, P < 0.0001, respectively). In regression models including both visceral and subcutaneous fat, only visceral fat was significantly associated with insulin sensitivity, while only subcutaneous fat was nearly significantly associated with adiponectin. CONCLUSIONS: This study shows that the significant negative relationship between waist circumference and adiponectin predated the development of significant relationships between insulin sensitivity and both waist circumference and adiponectin. It also shows that adiponectin is more closely related to subcutaneous fat and insulin sensitivity is more closely related to visceral fat in young adults.

The association between obesity and mortality in the elderly differs by serum concentrations of persistent organic pollutants: a possible explanation for the obesity paradox.

OBJECTIVE: Numerous studies have documented an obesity paradox in which the overweight and obese elderly have a better prognosis than those with ideal body weight. Good prognosis among the overweight or obese elderly may reflect the relative safety of storing the harmful lipophilic chemicals, known as persistent organic pollutants (POPs), in adipose tissue rather than in other critical organs. Therefore, we hypothesized lower mortality among the obese elderly with a higher body burden of POPs, but this pattern may not exist among the obese elderly with a lower body burden of POPs. PARTICIPANTS: Using the National Health and Nutrition Examination Survey (NHANES) 1999-2004 study with a mean 4.2-year follow-up, we tested whether the association between fat mass and total mortality in 635 (652 for organochlorine pesticides) elderly participants aged ≥70 years differed depending on serum concentrations of 23 POPs. RESULTS: There were statistically significant interactions between fat mass and POPs in predicting total mortality. In those with low POP concentrations, there was no obesity paradox; mortality increased with fat mass (hazard ratios about 2-3 in the highest vs. lowest quintile of fat mass). However, consistent with an obesity paradox, these patterns completely disappeared in those with high POP concentrations. Compared with the lowest quintile of fat mass, statistically significantly lower mortality was observed in the elderly in the third to fifth quintiles of fat mass. In the case of polychlorinated biphenyls, the mortality in the highest quintile of fat mass was only one-fifth of that in the lowest quintile. CONCLUSION: These findings are consistent with our hypothesis that adipose tissue provides relatively safe storage of toxic lipophilic chemicals, a phenomenon that could explain the obesity paradox. Although weight loss may be beneficial among the obese elderly with low POP concentrations, weight loss in the obese elderly with higher serum concentrations of POPs may carry some risk.

Associations of fat mass and lean mass with bone mineral density differ by levels of persistent organic pollutants: National Health and Nutrition Examination Survey 1999-2004.

Persistent organic pollutants (POPs), xenobiotics that accumulate in fat tissue, may impair bone metabolism. We studied (1) the association of bone mineral density (BMD) with POPs and (2) whether associations of fat mass (FM) or lean mass (LM), two components of body composition, with BMD differed depending on levels of POPs. Participants aged ≥ 20 in the National Health and Nutrition Examination Survey 1999-2004 were included (n=2769). Eight POPs with detection rate ≥ 80% and three skeletal subregions (left arm, pelvis, and right leg) were selected. All analyses were stratified by gender and age (cutpoint 50 years or more). POPs at background concentrations were mostly unassociated with BMD. However, the associations of FM and LM with BMD depended on POPs concentrations, in particular with BMD of the left arm (usually not weight-bearing) in postmenopausal women. When POPs concentrations were low, FM showed inverse associations with BMD while LM showed positive associations. However, when POPs levels were high, FM showed positive associations with BMD while the positive associations between LM and BMD weakened. POPs may biologically modify the associations of FM and LM with BMD, especially among postmenopausal women, possibly explaining inconsistent associations between FM and BMD in previous epidemiological studies.

Fish oil, selenium and mercury in relation to incidence of hypertension: a 20-year follow-up study.

OBJECTIVES: Long-chain omega-3 polyunsaturated fatty acids (LCω3PUFAs), selenium (Se) and mercury (Hg) are three important components in fish. The cardioprotective effect of LCω3PUFA intake has been recognized; however, the hypothesis that this benefit may be greatest with high Se and low Hg levels has not been investigated. DESIGN: A cohort of 4508 American adults aged 18-30, without hypertension at baseline in 1985, were enrolled. Six follow-ups were conducted at examinations in 1987, 1990, 1992, 1995, 2000 and 2005. Diet was assessed by a validated interviewer-administered quantitative food frequency questionnaire at exams in 1985, 1992 and 2005. Incident hypertension was defined as first occurrence at any follow-up examination of systolic blood pressure (BP) ≥ 140 mmHg, diastolic BP ≥ 90 mmHg or taking antihypertensive medication. Toenail clippings were collected in 1987, and Se and Hg levels were quantified by instrumental neutron-activation analysis. RESULT: Participants in the highest LCω3PUFA intake quartile had a significantly lower incidence of hypertension (hazard ratio: 0.65; 95% CI: 0.53-0.79; P(trend) < 0.01) compared to those in the lowest quartile after adjustment for potential confounders. Docosahexaenoic acid showed a greater inverse association than eicosapentaenoic acid. The inverse association of LCω3PUFA intake with hypertension appeared more pronounced at higher Se and lower Hg levels, although interaction tests were statistically nonsignificant. CONCLUSIONS: Our findings indicated that LCω3PUFA intake was inversely associated with incidence of hypertension. The prior hypothesis that the potential antihypertensive effect of LCω3PUFA intake varies depending on joint levels of Se and Hg received modest support and cannot be ruled out.