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1.
Artigo em Inglês | MEDLINE | ID: mdl-32396611

RESUMO

We aimed to examine the relationship between APOE*4 carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow up duration ranging between 1.2 and 10.7 years. Two-step individual participant data (IPD) meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (i.e., 62 years) and older (i.e., 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32398779

RESUMO

The mechanisms by which neighborhood environmental exposures influence health are poorly understood, although immune system dysregulation represents a potential biological pathway. While many neighborhood exposures have been investigated, there is little research on residential proximity to brownfield waste. Using biomarker data from 262 participants in the Detroit Neighborhood Health Study, we estimated the association between proximity to brownfields and heavy traffic and signal joint T-cell receptor excision circles (sjTRECs, a measure of naive T-cell production), C-reactive protein (CRP, a measure of systemic inflammation), and interleukin-6 (IL-6, a pro-inflammatory cytokine). We assessed residential proximity ≤200 m from brownfields and highways on all three biomarkers using multivariate regression. We demonstrated that living ≤200 m from a brownfield site was associated with a 0.30 (95% CI = 0.59, 0.02, p = 0.04) loge-unit decrease in sjTRECs per million whole blood cells, as well as non-significantly elevated levels of CRP and IL-6. Heavy traffic was not associated with any biomarker. Persons living in close proximity to brownfield sites had significantly lower naive T-cell production, suggesting accelerated immune aging. Decreased T-cell production associated with brownfield proximity may be caused by toxicant exposure in brownfield sites, or may serve as a marker of other neighborhood stressors.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32380512

RESUMO

Post-traumatic stress disorder (PTSD) is a debilitating disorder that develops in some people following trauma exposure. Trauma and PTSD have been associated with accelerated cellular aging. This study evaluated the effect of trauma and PTSD on accelerated GrimAge, an epigenetic predictor of lifespan, in traumatized civilians. This study included 218 individuals with current PTSD, 427 trauma-exposed controls without any history of PTSD and 209 subjects with lifetime PTSD history who are not categorized as current PTSD cases. The Traumatic Events Inventory (TEI) and Clinician-Administered PTSD Scale (CAPS) were used to measure lifetime trauma burden and PTSD, respectively. DNA from whole blood was interrogated using the MethylationEPIC or HumanMethylation450 BeadChips. GrimAge estimates were calculated using the methylation age calculator. Cortical thickness of 69 female subjects was assessed by using T1-weighted structural MRI images. Associations between trauma exposure, PTSD, cortical thickness, and GrimAge acceleration were tested with multiple regression models. Lifetime trauma burden (p = 0.03), current PTSD (p = 0.02) and lifetime PTSD (p = 0.005) were associated with GrimAge acceleration, indicative of a shorter predicted lifespan. The association with lifetime PTSD was replicated in an independent cohort (p = 0.04). In the MRI sub sample, GrimAge acceleration also associated with cortical atrophy in the right lateral orbitofrontal cortex (padj = 0.03) and right posterior cingulate (padj = 0.04), brain areas associated with emotion-regulation and threat-regulation. Our findings suggest that lifetime trauma and PTSD may contribute to a higher epigenetic-based mortality risk. We also demonstrate a relationship between cortical atrophy in PTSD-relevant brain regions and shorter predicted lifespan.

4.
Science ; 368(6493)2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32439765

RESUMO

The social environment, both in early life and adulthood, is one of the strongest predictors of morbidity and mortality risk in humans. Evidence from long-term studies of other social mammals indicates that this relationship is similar across many species. In addition, experimental studies show that social interactions can causally alter animal physiology, disease risk, and life span itself. These findings highlight the importance of the social environment to health and mortality as well as Darwinian fitness-outcomes of interest to social scientists and biologists alike. They thus emphasize the utility of cross-species analysis for understanding the predictors of, and mechanisms underlying, social gradients in health.

5.
Am J Epidemiol ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32440686

RESUMO

US Latinos, a growing, aging population, are disproportionately burdened by cognitive decline and dementia. Modifiable risk factors are needed for interventions aimed at reducing risk. Broad sociocultural context may illuminate complex etiology among culturally diverse Latinos. Among N=1,418 older, predominately Mexican-descent, low-socioeconomic Latinos in Sacramento, CA, we examined whether US acculturation was associated with cognitive performance, decline, and dementia/cognitive impairment, no dementia over 10 years, and whether education modified associations (Sacramento Area Latino Study on Aging, 1998-2008). Analyses used linear mixed models, competing risk regression, and inverse-probability-censoring weights for attrition. High US acculturation participants had better cognitive performance (0.21 fewer cognitive errors at grand-mean-centered age 70) than low acculturation, adjusting for sociodemographic factors, practice effects, and survey language. Results may be driven by cultural language use rather identity factors (e.g. ethnic identity, interactions). Rate of cognitive decline and dementia/cognitive impairment, no dementia risk did not differ by acculturation, regardless of education (ß [standard error]: 0.00 [0.00] and (hazard ratio [95% confidence interval]: 0.81 [0.49, 1.35], respectively). High US acculturation was associated with better cognitive performance among older, low socioeconomic Latinos. Acculturation may benefit cognition when socioeconomic position is low. Future studies should incorporate extended longitudinal assessments among more diverse groups.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32421783

RESUMO

Emerging links between gut microbiota and diseases of aging point to possible shared immune, metabolic, and cellular damage mechanisms, operating long before diseases manifest. We conducted 16S rRNA sequencing of fecal samples collected from a subsample (n=668) of Add Health Wave V, a nationally representative longitudinal study of adults aged 32-42. An overlapping subsample (n=345) included whole blood RNA-seq. We examined associations between fecal taxonomic abundances and dried blood spot-based markers of lipid and glucose homeostasis and C-reactive protein (measured in Wave IV), as well as gene expression markers of inflammation, cellular damage, immune cell composition, and transcriptomic age (measured in Wave V), using Bayesian hierarchical models adjusted for potential confounders. We additionally estimated a co-abundance network between inflammation-related genes and bacterial taxa using penalized Gaussian graphical models. Strong and consistent microbiota associations emerged for HbA1c, glucose, C-reactive protein, and principal components of genes upregulated in inflammation, DNA repair, and reactive oxygen species, with Streptococcus infantis, Pseudomonas spp., and Peptoniphilus as major players for each. This pattern was largely echoed (though attenuated) for immunologic cell composition gene sets, and only Serratia varied meaningfully by transcriptomic age. Network co-abundance indicated relationships between Prevotella sp., Bacteroides sp., and Ruminococcus sp. and gut immune/metabolic regulatory activity, and Ruminococcussp, Dialister, and Butyrivibriocrossotus with balance between Th1 and Th2 inflammation. In conclusion, many common associations between microbiota and major physiologic aging mechanisms are evident in early-mid adulthood, and suggest avenues for early detection and prevention of accelerated aging.

7.
J Am Heart Assoc ; 9(6): e014868, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32157957

RESUMO

Background Changes in white matter microstructural integrity are detectable before appearance of white matter lesions on magnetic resonance imaging as a manifestation of cerebral small-vessel disease. The information relating poor white matter microstructural integrity to aortic stiffness, a hallmark of aging, is limited. We aimed to examine the association between aortic stiffness and white matter microstructural integrity among older adults. Methods and Results We conducted a cross-sectional study to examine the association between aortic stiffness and white matter microstructural integrity among 1484 men and women (mean age, 76 years) at the 2011 to 2013 examination of the ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). Aortic stiffness was measured as carotid-femoral pulse wave velocity. Cerebral white matter microstructural integrity was measured as fractional anisotropy and mean diffusivity using diffusion tensor imaging. Multivariable linear regression was used to examine the associations of carotid-femoral pulse wave velocity with fractional anisotropy and mean diffusivity of the overall cerebrum and at regions of interest. Each 1-m/s higher carotid-femoral pulse wave velocity was associated with lower overall fractional anisotropy (ß=-0.03; 95% CI, -0.05 to -0.02) and higher overall mean diffusivity (ß=0.03; 95% CI, 0.02-0.04). High carotid-femoral pulse wave velocity (upper 25th percentile) was associated with lower fractional anisotropy (ß=-0.40; 95% CI, -0.61 to -0.20) and higher overall mean diffusivity (ß=0.27; 95% CI, 0.10-0.43). Similar associations were observed at individual regions of interest. Conclusions High aortic stiffness is associated with low cerebral white matter microstructural integrity among older adults. Aortic stiffness may serve as a target for the prevention of poor cerebral white matter microstructural integrity.

8.
9.
Clin Epigenetics ; 12(1): 44, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160902

RESUMO

BACKGROUND: Neighborhood characteristics are robust predictors of overall health and mortality risk for residents. Though there has been some investigation of the role that molecular indicators may play in mediating neighborhood exposures, there has been little effort to incorporate newly developed epigenetic biomarkers into our understanding of neighborhood characteristics and health outcomes. METHODS: Using 157 participants of the Detroit Neighborhood Health Study with detailed assessments of neighborhood characteristics and genome-wide DNA methylation profiling via the Illumina 450K methylation array, we assessed the relationship between objective neighborhood characteristics and a validated DNA methylation-based epigenetic mortality risk score (eMRS). Associations were adjusted for age, race, sex, ever smoking, ever alcohol usage, education, years spent in neighborhood, and employment. A secondary model additionally adjusted for personal neighborhood perception. We summarized 19 neighborhood quality indicators assessed for participants into 9 principal components which explained over 90% of the variance in the data and served as metrics of objective neighborhood quality exposures. RESULTS: Of the nine principal components utilized for this study, one was strongly associated with the eMRS (ß = 0.15; 95% confidence interval = 0.06-0.24; P = 0.002). This principal component (PC7) was most strongly driven by the presence of abandoned cars, poor streets, and non-art graffiti. Models including both PC7 and individual indicators of neighborhood perception indicated that only PC7 and not neighborhood perception impacted the eMRS. When stratified on neighborhood indicators of greenspace, we observed a potentially protective effect of large mature trees as this feature substantially attenuated the observed association. CONCLUSION: Objective measures of neighborhood disadvantage are significantly associated with an epigenetic predictor of mortality risk, presenting a potential novel avenue by which neighborhood-level exposures may impact health. Associations were independent of an individual's perception of their neighborhood and attenuated by neighborhood greenspace features. More work should be done to determine molecular risk factors associated with neighborhoods, and potentially protective neighborhood features against adverse molecular effects.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32049631

RESUMO

INTRODUCTION: Individuals with type 1 diabetes (T1D) present with diverse body weight status and degrees of glycemic control, which may warrant different treatment approaches. We sought to identify subgroups sharing phenotypes based on both weight and glycemia and compare characteristics across subgroups. RESEARCH DESIGN AND METHODS: Participants with T1D in the SEARCH study cohort (n=1817, 6.0-30.4 years) were seen at a follow-up visit >5 years after diagnosis. Hierarchical agglomerative clustering was used to group participants based on five measures summarizing the joint distribution of body mass index z-score (BMIz) and hemoglobin A1c (HbA1c) which were estimated by reinforcement learning tree predictions from 28 covariates. Interpretation of cluster weight status and glycemic control was based on mean BMIz and HbA1c, respectively. RESULTS: The sample was 49.5% female and 55.5% non-Hispanic white (NHW); mean±SD age=17.6±4.5 years, T1D duration=7.8±1.9 years, BMIz=0.61±0.94, and HbA1c=76±21 mmol/mol (9.1±1.9)%. Six weight-glycemia clusters were identified, including four normal weight, one overweight, and one subgroup with obesity. No cluster had a mean HbA1c <58 mmol/mol (7.5%). Cluster 1 (34.0%) was normal weight with the lowest HbA1c and comprised 85% NHW participants with the highest socioeconomic position, insulin pump use, dietary quality, and physical activity. Subgroups with very poor glycemic control (ie, ≥108 mmol/mol (≥12.0%); cluster 4, 4.4%, and cluster 5, 7.5%) and obesity (cluster 6, 15.4%) had a lower proportion of NHW youth, lower socioeconomic position, and reported decreased pump use and poorer health behaviors (overall p<0.01). The overweight subgroup with very poor glycemic control (cluster 5) showed the highest lipids and blood pressure (p<0.01). CONCLUSIONS: There are distinct subgroups of youth and young adults with T1D that share weight-glycemia phenotypes. Subgroups may benefit from tailored interventions addressing differences in clinical care, health behaviors, and underlying health inequity.

11.
Annu Rev Public Health ; 41: 101-118, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-31905322

RESUMO

Disease surveillance systems are a cornerstone of public health tracking and prevention. This review addresses the use, promise, perils, and ethics of social media- and Internet-based data collection for public health surveillance. Our review highlights untapped opportunities for integrating digital surveillance in public health and current applications that could be improved through better integration, validation, and clarity on rules surrounding ethical considerations. Promising developments include hybrid systems that couple traditional surveillance data with data from search queries, social media posts, and crowdsourcing. In the future, it will be important to identify opportunities for public and private partnerships, train public health experts in data science, reduce biases related to digital data (gathered from Internet use, wearable devices, etc.), and address privacy. We are on the precipice of an unprecedented opportunity to track, predict, and prevent global disease burdens in the population using digital data.

12.
Cancer Causes Control ; 31(3): 221-230, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31950321

RESUMO

PURPOSE: Understanding breast cancer mortality disparities by race and age is complex due to disease heterogeneity, comorbid disease, and the range of factors influencing access to care. It is important to understand how these factors group together within patients. METHODS: We compared socioeconomic status (SES) and comorbidity factors in the Carolina Breast Cancer Study Phase 3 (CBCS3, 2008-2013) to those for North Carolina using the 2010 Behavioral Risk Factor Surveillance Study. In addition, we used latent class analysis of CBCS3 data to identify covariate patterns by SES/comorbidities, barriers to care, and tumor characteristics and examined their associations with race and age using multinomial logistic regression. RESULTS: Major SES and comorbidity patterns in CBCS3 participants were generally similar to patterns in the state. Latent classes were identified for SES/comorbidities, barriers to care, and tumor characteristics that varied by race and age. Compared to white women, black women had lower SES (odds ratio (OR) 6.3, 95% confidence interval (CI) 5.2, 7.8), more barriers to care (OR 5.6, 95% CI 3.9, 8.1) and several aggregated tumor aggressiveness features. Compared to older women, younger women had higher SES (OR 0.5, 95% CI 0.4, 0.6), more barriers to care (OR 2.1, 95% CI 1.6, 2.9) and aggregated tumor aggressiveness features. CONCLUSIONS: CBCS3 is representative of North Carolina on comparable factors. Patterns of access to care and tumor characteristics are intertwined with race and age, suggesting that interventions to address disparities will need to target both access and biology.

13.
Gerontologist ; 60(2): 239-249, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-31774118

RESUMO

BACKGROUND AND OBJECTIVES: Globally, obesity influences the risk of many major chronic diseases. Our study examines the association between individual nativity and neighborhood level concentration of immigrants with 10-year changes in weight, body mass index (BMI), and waist circumference (WC) among older Latinos. RESEARCH DESIGN AND METHODS: The Sacramento Area Latino Study on Aging (SALSA) is a population-based prospective study of community-dwelling older adults of Mexican origin (baseline ages 58-101 years). The primary outcome was repeated measures of weight over a 10-year period for 1,628 respondents. Nativity was defined by participants' reported place of birth (US-born or Latin American foreign born). Neighborhood immigrant concentration was measured as the percentage of foreign born at census tract level (2000 US Census). We used linear mixed models with repeated measures of weight, height, BMI, and WC as dependent variables (level 1), clustered within individuals (level 2) and neighborhood migrant concentration (level 3). RESULTS: Foreign born (FB) respondents had lower baseline weight than the US-born (mean, 160 vs. 171 lbs, p < .0001). Over time, weight differences between the FB and the US-born decreased by 1.7 lbs/5 years as US-born weight decreased more rapidly. We observed a significant interaction between individual nativity and neighborhood immigrant concentration (p = .012). We found similar patterns for BMI, but did not find statistically significant differences in WC trajectories. DISCUSSION AND IMPLICATIONS: Our study observed significant differences by foreign born vs. US nativity in baseline weight/BMI and in their trajectories over time. Additionally, we found weight/BMI differences in neighborhood immigrant concentration for the FB, but not for the US-born.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31841258

RESUMO

OBJECTIVE: This study examined how neighborhood characteristics were associated with health outcomes among older adults with osteoarthritis. METHODS: We examined in multilevel, cross-sectional and longitudinal analyses if four neighborhood characteristics were a) associated with depressive symptoms and reported knee impact scores and b) interacted with race / ethnicity among older adults with radiographic knee osteoarthritis (n=656 for cross-sectional analyses and n=434 for longitudinal analyses). Data came from the Johnston County Osteoarthritis Project, a prospective cohort study in North Carolina designed to examine risk factors for osteoarthritis. RESULTS: Although few longitudinal associations were found, cross-sectional results suggested that greater perceived neighborhood social cohesion (B= -0.04, p< 0.001) and perceived neighborhood resources for physical activity and walking (B= -0.03, p< 0.001) were associated with fewer depressive symptoms and that greater perceived neighborhood resources for physical activity and walking were associated with higher (better) knee impact scores (B=0.48, p=0.008). We also observed two significant interactions among neighborhood characteristics and race / ethnicity related to depressive symptoms (p<0.01); for Black adults, greater perceived neighborhood resources for physical activity and walking was associated with fewer depressive symptoms (B= -0.03, p<.001), but for White adults, greater perceived neighborhood safety was associated with fewer depressive symptoms (B= -0.04, p=0.003). CONCLUSION: In a sample of older adults with radiographic knee osteoarthritis, neighborhood context matters, but in nuanced ways. Interventions aiming to improve mental and physical functioning of older adults with knee osteoarthritis can look to this study as evidence for the importance of neighborhood characteristics.

15.
Nat Commun ; 10(1): 4558, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594949

RESUMO

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.


Assuntos
Loci Gênicos , Predisposição Genética para Doença , Transtornos de Estresse Pós-Traumáticos/genética , Ubiquitina-Proteína Ligases/genética , Grupo com Ancestrais do Continente Africano/genética , Conjuntos de Dados como Assunto , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Fatores Sexuais , Veteranos/estatística & dados numéricos
16.
PLoS Med ; 16(7): e1002853, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31335910

RESUMO

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.


Assuntos
Cognição , Disfunção Cognitiva/etnologia , Grupos Étnicos/psicologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Comorbidade , Diabetes Mellitus/etnologia , Exercício Físico , Feminino , Educação em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Fumar/etnologia , Acidente Vascular Cerebral/etnologia
17.
J Clin Endocrinol Metab ; 104(12): 6003-6016, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31290977

RESUMO

CONTEXT: Subclinical and clinical complications emerge early in type 1 diabetes (T1D) and may be associated with obesity and hyperglycemia. OBJECTIVE: Test how longitudinal "weight-glycemia" phenotypes increase susceptibility to different patterns of early/subclinical complications among youth with T1D. DESIGN: SEARCH for Diabetes in Youth observational study. SETTING: Population-based cohort. PARTICIPANTS: Youth with T1D (n = 570) diagnosed 2002 to 2006 or 2008. MAIN OUTCOME MEASURES: Participants were clustered based on longitudinal body mass index z score and HbA1c from a baseline visit and 5+ year follow-up visit (mean diabetes duration: 1.4 ± 0.4 years and 8.2 ± 1.9 years, respectively). Logistic regression modeling tested cluster associations with seven early/subclinical diabetes complications at follow-up, adjusting for sex, race/ethnicity, age, and duration. RESULTS: Four longitudinal weight-glycemia clusters were identified: The Referent Cluster (n = 195, 34.3%), the Hyperglycemia Only Cluster (n = 53, 9.3%), the Elevated Weight Only Cluster (n = 206, 36.1%), and the Elevated Weight With Increasing Hyperglycemia (EWH) Cluster (n = 115, 20.2%). Compared with the Referent Cluster, the Hyperglycemia Only Cluster had elevated odds of dyslipidemia [adjusted odds ratio (aOR) 2.22, 95% CI: 1.15 to 4.29], retinopathy (aOR 9.98, 95% CI: 2.49 to 40.0), and diabetic kidney disease (DKD) (aOR 4.16, 95% CI: 1.37 to 12.62). The EWH Cluster had elevated odds of hypertension (aOR 2.18, 95% CI: 1.19 to 4.00), dyslipidemia (aOR 2.36, 95% CI: 1.41 to 3.95), arterial stiffness (aOR 2.46, 95% CI: 1.09 to 5.53), retinopathy (aOR 5.11, 95% CI: 1.34 to 19.46), and DKD (aOR 3.43, 95% CI: 1.29 to 9.11). CONCLUSIONS: Weight-glycemia phenotypes show different patterns of complications, particularly markers of subclinical macrovascular disease, even in the first decade of T1D.

18.
Brain Behav Immun ; 81: 280-291, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228611

RESUMO

Post-traumatic stress disorder (PTSD) is a debilitating mental disorder precipitated by trauma exposure. However, only some persons exposed to trauma develop PTSD. There are sex differences in risk; twice as many women as men develop a lifetime diagnosis of PTSD. Methylomic profiles derived from peripheral blood are well-suited for investigating PTSD because DNA methylation (DNAm) encodes individual response to trauma and may play a key role in the immune dysregulation characteristic of PTSD pathophysiology. In the current study, we leveraged recent methodological advances to investigate sex-specific differences in DNAm-based leukocyte composition that are associated with lifetime PTSD. We estimated leukocyte composition on a combined methylation array dataset (483 participants, ∼450 k CpG sites) consisting of two civilian cohorts, the Detroit Neighborhood Health Study and Grady Trauma Project. Sex-stratified Mann-Whitney U test and two-way ANCOVA revealed that lifetime PTSD was associated with significantly higher monocyte proportions in males, but not in females (Holm-adjusted p-val < 0.05). No difference in monocyte proportions was observed between current and remitted PTSD cases in males, suggesting that this sex-specific difference may reflect a long-standing trait of lifetime history of PTSD, rather than current state of PTSD. Associations with lifetime PTSD or PTSD status were not observed in any other leukocyte subtype and our finding in monocytes was confirmed using cell estimates based on a different deconvolution algorithm, suggesting that our sex-specific findings are robust across cell estimation approaches. Overall, our main finding of elevated monocyte proportions in males, but not in females with lifetime history of PTSD provides evidence for a sex-specific difference in peripheral blood leukocyte composition that is detectable in methylomic profiles and that may reflect long-standing changes associated with PTSD diagnosis.

19.
Health Place ; 57: 131-138, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31035097

RESUMO

This study investigates the association between neighborhood disadvantage from adolescence to young adulthood and metabolic syndrome using a life course epidemiology framework. Data from the United States-based National Longitudinal Study of Adolescent to Adult Health (n = 9500) and a structural equation modeling approach were used to test neighborhood disadvantage across adolescence, emerging adulthood, and young adulthood in relation to metabolic syndrome. Adolescent neighborhood disadvantage was directly associated with metabolic syndrome in young adulthood. Evidence supporting an indirect association between adolescent neighborhood disadvantage and adult metabolic syndrome was not supported. Efforts to improve cardiometabolic health may benefit from strategies earlier in life.

20.
Pediatr Diabetes ; 20(5): 556-566, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30972889

RESUMO

BACKGROUND/OBJECTIVE: To identify and characterize subgroups of adolescents with type 1 diabetes (T1D) and elevated hemoglobin A1c (HbA1c) who share patterns in their continuous glucose monitoring (CGM) data as "dysglycemia phenotypes." METHODS: Data were analyzed from the Flexible Lifestyles Empowering Change randomized trial. Adolescents with T1D (13-16 years, duration >1 year) and HbA1c 8% to 13% (64-119 mmol/mol) wore blinded CGM at baseline for 7 days. Participants were clustered based on eight CGM metrics measuring hypoglycemia, hyperglycemia, and glycemic variability. Clusters were characterized by their baseline features and 18 months changes in HbA1c using adjusted mixed effects models. For comparison, participants were stratified by baseline HbA1c (≤/>9.0% [75 mmol/mol]). RESULTS: The study sample included 234 adolescents (49.8% female, baseline age 14.8 ± 1.1 years, baseline T1D duration 6.4 ± 3.7 years, baseline HbA1c 9.6% ± 1.2%, [81 ± 13 mmol/mol]). Three Dysglycemia Clusters were identified with significant differences across all CGM metrics (P < .001). Dysglycemia Cluster 3 (n = 40, 17.1%) showed severe hypoglycemia and glycemic variability with moderate hyperglycemia and had a lower baseline HbA1c than Clusters 1 and 2 (P < .001). This cluster showed increases in HbA1c over 18 months (p-for-interaction = 0.006). No other baseline characteristics were associated with Dysglycemia Clusters. High HbA1c was associated with lower pump use, greater insulin doses, more frequent blood glucose monitoring, lower motivation, and lower adherence to diabetes self-management (all P < .05). CONCLUSIONS: There are subgroups of adolescents with T1D for which glycemic control is challenged by different aspects of dysglycemia. Enhanced understanding of demographic, behavioral, and clinical characteristics that contribute to CGM-derived dysglycemia phenotypes may reveal strategies to improve treatment.

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