Highest Quintile Research Articles

Maternal Vitamin D Levels During Pregnancy and Offspring Autism Spectrum Disorder

BackgroundFindings from previous studies on maternal 25-hydroxyvitamin D [25(OH)D] levels during pregnancy and autism spectrum disorder (ASD) in offspring are inconsistent. MethodsThe association between maternal 25(OH)D levels during pregnancy and offspring ASD was examined using data from a nationwide population-based register with a nested case-control study design. The ASD cases (n = 1558) were born between 1987 and 2004 and received a diagnosis of ASD by 2015; cases were matched with an equal number of controls. Maternal 25(OH)D levels during pregnancy were measured using quantitative immunoassay from maternal sera collected during the first and early second trimesters and archived in the national biobank of the Finnish Maternity Cohort. Conditional logistic regression examined the association between maternal 25(OH)D levels and offspring ASD. ResultsIn the adjusted model, there was a significant association between increasing log-transformed maternal 25(OH)D levels and decreasing risk of offspring ASD (adjusted odds ratio [aOR] 0.75, 95% confidence interval [CI] 0.62–0.92, p = .005). Analyses by quintiles of maternal 25(OH)D levels revealed increased odds for ASD in the 2 lowest quintiles, <20 (aOR 1.36, 95% CI 1.03–1.79, p = .02) and 20–39 (aOR 1.31, 95% CI 1.01–1.70, p = .04), compared with the highest quintile. The increased risk of ASD was observed in association with deficient (<30 nmol/L) (aOR 1.44, 95% CI 1.15–1.81, p = .001) and insufficient (30–49.9 nmol/L) maternal 25(OH)D levels (aOR 1.26, 95% CI 1.04–1.52, p = .01) compared with sufficient levels. ConclusionsThis finding has implications for understanding the role of maternal vitamin D during fetal brain development and increased risk of ASD.

Time Trends in Colorectal Cancer Incidence Rates by Income and Age at Diagnosis in Canada From 1992 to 2016

Colorectal cancer (CRC) incidence rates among individuals younger than 50 years have been increasing in many countries, including Canada. Whether changes in CRC incidence rates over time are uniform across income and age groups remains unknown. To examine time trends in CRC incidence rates in Canada by area-level average household income by age group from 1992 to 2016. A population-based, retrospective cohort study was conducted including individuals aged 20 years or older diagnosed with CRC in Canada (excluding Québec) from 1992 to 2016. Data analysis was performed from February 27 to September 28, 2020. Average household income was determined by linking an individual's postal code at diagnosis from the Canadian Cancer Registry to Canadian Census data. Average household income was then categorized into quintiles from Q1, the lowest income group, to Q5, the highest income group. Canadian Cancer Registry data were used to determine CRC incidence rates from 1992 to 2016. There were 340 790 cases of CRC diagnosed from 1992 to 2016; 11 790 cases (3.5%) were diagnosed in individuals aged 20 to 44 years. Colorectal cancer incidence rates for individuals aged 20 to 44 years increased for all income quintiles, with higher incidence rates in the lower income quintiles. The ratio between the maximum and minimum CRC incidence rates was highest among the 20- to 29-year age group from 1992 to 1996 (ratio, 2.67; 95% CI, 1.47-4.83) and 2012 to 2016 (ratio, 2.00; 95% CI, 1.29-3.10). For individuals aged 45 to 49 years, CRC incidence rates increased only for individuals in the lower income quintiles (eg, incidence in Q1, 1992-1996 vs 2012-2016: 4.54 per 100 000 [95% CI, 4.05-5.03] vs 5.37 per 100 000 [95% CI, 4.91-5.83]), with higher incidence rates in the high income quintiles (eg, incidence rate for Q5 in 1992-1996: 5.92 per 100 000 [95% CI, 5.36-6.48]). For those aged 50 to 54 years, CRC incidence rates were stable for all income quintiles, with less variability between income quintiles. For individuals aged 55 to 74 years, CRC incidence rates were stable or decreased for all income quintiles (eg, incidence rate for age 55-59 years in Q5, 1992-1992 vs 2012-2016: 17.97 per 100 000 [95% CI, 16.76-19.18] vs 14.56 per 100 000 [95% CI, 13.80-15.32]), and there was less variability in the rates by income quintile, particularly from 2012 to 2016. After age 75 years, CRC incidence rates were stable or decreased (eg, incidence rate for age 75-79 years, 1992-1996 vs 2012-2016: 66.43 per 100 000 [65.00-67.87] vs 57.34 per 100 000 [56.24-58.45]), were highest for the lower income quintiles, and variability between income quintiles increased relative to younger age groups. In this cohort study, trends in CRC incidence rates in Canada differed by age group and income quintile. These results suggest that, although population-based screening can reduce income disparities, targeted interventions and further research are needed to address the increasing CRC incidence rate among younger individuals in Canada, particularly in the lower income quintiles.

Heterogeneity and threshold effects of environmental regulation on health expenditure: Considering the mediating role of environmental pollution

A comprehensive understanding of the heterogeneity and threshold effects of environmental regulation on health expenditure is essential for policy design and decision-making. This case study seeks to analyze the heterogeneity and threshold effects using panel data, which covers 30 Chinese provinces from 2007 to 2017. We examine the linear and nonlinear impacts of environmental regulation on health expenditure by using the Bayesian quantile regression and panel threshold regression, respectively. The empirical research results indicate a significant heterogeneous effect of environmental regulation on health expenditure in provinces where health expenditure falls in different quintiles. It shows mainly two effects: a positive effect of environmental regulation on health expenditure in provinces in the low quintiles and high quintiles of health expenditure; and a negative interrelationship between environmental regulation and health expenditure for provinces in the medium quintiles of health expenditure. A single threshold effect of environmental regulation on health expenditure is found to be different among three regions: the eastern, central and western regions. Specifically, in eastern and western China, the environmental regulations are stricter, and this helps reduce the health expenditures relating to environmental pollution. However, it was found that stricter environmental regulations do not reduce health expenditures in central China.

Carbon footprint of Canadian self-selected diets: Comparing intake of foods, nutrients, and diet quality between low- and high-greenhouse gas emission diets

Individuals' dietary choices are critical determinants of human and planetary health. Although the carbon footprint of animal-based foods typically exceeds that of plants, trade-offs among nutritional outcomes and environmental sustainability in the context of regional self-selected diets are less understood. The objectives were to estimate the carbon footprint of Canadian self-selected diets and to compare intake of food groups, nutrients, and diet quality between low- and high-greenhouse gas emission (GHGE) diets. Dietary intake was assessed using 24-h recalls from the 2015 Canadian Community Health Survey (CCHS) – Nutrition for adults ≥19 y (n = 13,612). Estimates from the database of Food Impacts on the Environment for Linking to Diets were used to link foods and beverages reported in the CCHS to their GHGE. Boundaries for GHGE estimates were mostly cradle-to-farm gate and for certain processed products, cradle-to-processing gate. Data from Statistics Canada were used to account for food loss at the retail and consumer levels in our calculation of GHGE. The Alternative Healthy Eating Index-2010 was used to calculate diet quality. The study sample was divided into quintiles based on their diet-related GHGE expressed per 1,000 kcal; low- and high-GHGE diets were those of respondents in the lowest and highest quintiles, respectively. Dietary GHGE (mean ± SE) was 3.98 ± 0.06 kg carbon dioxide-equivalents (CO2-eq) per person per d or 2.15 ± 0.03 kg CO2-eq per 1,000 kcal. Animal-based foods contributed three-quarters of Canadians' total diet-related GHGE, with red and processed meat alone accounting for 47.05 ± 0.82%. High-GHGE diets contained more animal-based foods, vegetables and fruit, and miscellaneous foods and beverages, whereas low-GHGE diets contained more cereals, grains, and breads. Moreover, high-GHGE diet respondents had higher intakes of nutrients of public health concern (calcium, vitamin D, iron, and potassium), but also higher intakes of saturated fat and sodium, and a lower overall diet quality compared to low-GHGE diet respondents (47.27 ± 0.46 vs. 55.31 ± 0.49 points). These nutritional and environmental trade-offs warrant attention in shaping future food policy and dietary guidance in Canada aimed at meeting global targets for climate change.

Global, Regional, and National Burden of Diabetes-Related Chronic Kidney Disease From 1990 to 2019.

BackgroundChronic kidney disease (CKD) is a public health problem largely caused by diabetes. The epidemiology of diabetes mellitus–related CKD (CKD-DM) could provide specific support to lessen global, regional, and national CKD burden.MethodsData were derived from the GBD 2019 study, including four measures and age-standardized rates (ASRs). Estimated annual percentage changes and 95% CIs were calculated to evaluate the variation trend of ASRs.ResultsDiabetes caused the majority of new cases and patients with CKD in all regions. All ASRs for type 2 diabetes–related CKD increased over 30 years. Asia and Middle socio-demographic index (SDI) quintile always carried the heaviest burden of CKD-DM. Diabetes type 2 became the second leading cause of CKD and CKD-related death and the third leading cause of CKD-related DALYs in 2019. Type 2 diabetes–related CKD accounted for most of the CKD-DM disease burden. There were 2.62 million incident cases, 134.58 million patients, 405.99 thousand deaths, and 13.09 million disability-adjusted life-years (DALYs) of CKD-DM worldwide in 2019. Age-standardized incidence (ASIR) and prevalence rate (ASPR) of type 1 diabetes–related CKD increased, whereas age-standardized death rate (ASDR) and DALY rate decreased for females and increased for males. In high SDI quintile, ASIR and ASPR of type 1 diabetes–related CKD remained the highest, with the slowest increase, whereas the ASDR and age-standardized DALY rate remained the lowest there. In high SDI quintile, ASIR of type 2 diabetes–related CKD was the highest, with the lowest increasing rate. In addition, type 2 diabetes–related CKD occurred most in people aged 80-plus years worldwide. The main age of type 2 diabetes–related CKD patients was 55–64 years in Asia and Africa. The prevalence, mortality, and DALY rate of type 2 diabetes–related CKD increased with age. As for incidence, there was a peak at 80 years, and after age of 80, the incidence declined. CKD-DM-related anemia was mainly in mild to moderate grade.ConclusionsIncreasing burden of CKD-DM varied among regions and countries. Prevention and treatment measures should be strengthened according to CKD-DM epidemiology, especially in middle SDI quintile and Asia.

Abstract 2628: Racial differences in the impact of socioeconomic status on cancer-specific survival in multiple myeloma

Abstract Background: Multiple myeloma (MM) incidence and outcomes differ across racial/ethnic groups in the United States. Interactions between socioeconomic status (SES) with ethnicity in MM incidence and survival outcomes are not well understood. Our objective was to evaluate disparities in cancer-specific survival of patients diagnosed with MM by race/ethnicity. Methods: We conducted a population-based retrospective cohort study of patients ages 20+ years diagnosed with MM between 2000 and 2015 using Surveillance, Epidemiology and End Results, Census Tract-level SES and Rurality Database. SES was defined using the National Cancer Institute's time-dependent composite score developed by Yost et al. (2001). Yost index quintiles were where the 1st and 5th quintiles representing the lowest and highest SES categories respectively. Cumulative incidence functions were used to analyze cancer-specific survival across strata racial/ethnic and SES and equality of functions was determined using Gray's test. Subdistribution hazard ratios (SHR) and 95% confidence intervals (CI) were calculated using the Fine and Gray regression models adjusted for age, sex, year of diagnosis, marital status, insurance status, and treatment with chemotherapy. Race-specific risk estimates were stratified by age (&amp;lt;65 and 65+ years). Results: Overall, 58,095 MM patients were included in our analysis among whom 63.0% were non-Hispanic White, 19.5% were Black, 0.3% were American Indian/Alaskan Native, 5.8% were Asian/Pacific Islander and 11.4% were Hispanic. Compared to White MM patients (median age 69 years), Black (64 years), American Indian/Alaskan Native (64 years), Asian/Pacific Islander (67 years) and Hispanic (64 years) patients were younger on average. A higher proportion of Black (42.8%) and Hispanic (27.9%) MM patients were in the lowest SES quintile compared to White (10.6%), American Indian/Alaskan Native (15.2%), and Asian/Pacific Islander (8.9%) MM patients. Cumulative incidence functions for cancer-specific survival were significantly different across SES quintiles (P &amp;lt; 0.0001) and racial/ethnic groups (P &amp;lt; 0.0001). Overall, MM patients in the lowest SES quintile had a significantly increased risk of MM-specific mortality (SHR: 1.28, 95% CI 1.21-1.36) compared to patients in the highest quintile. Risk estimates comparing the lowest to the highest quintile of SES were higher among Black (SHR 1.39, 95% CI 1.08-1.77), Hispanic (SHR: 1.78, 95% CI 1.21-2.63), and White (SHR 1.44, 95% CI 1.23-1.69) MM patients ages &amp;lt;65 years at diagnosis. Conclusion: Low SES level is independently associated with poor MM-specific survival. However, the impacts of SES on MM-specific survival differ by race/ethnicity and age with the greatest increased risk observed in younger Black, Hispanic, and White patients. Citation Format: Huiwen Deng, Ashwini Zolekar, Hsiao-Ching Huang, Mary H. Smart, Colin C. Hubbard, Brian C. Chiu, Pritesh R. Patel, Karen Sweiss, Gregory S. Calip. Racial differences in the impact of socioeconomic status on cancer-specific survival in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2628.

Gestational Phthalate Exposure and Preschool Attention Deficit Hyperactivity Disorder in Norway.

Prenatal phthalate exposure has been linked to altered neurobehavioral development in both animal models and epidemiologic studies, but whether or not these associations translate to increased risk of neurodevelopmental disorders is unclear. We used a nested case-cohort study design to assess whether maternal urinary concentrations of 12 phthalate metabolites at 17 weeks gestation were associated with criteria for Attention Deficit Hyperactivity Disorder (ADHD) classified among 3-year-old children in the Norwegian Mother, Father and Child Cohort Study (MoBa). Between 2007 and 2011, 260 children in this substudy were classified with ADHD using a standardized, on-site clinical assessment; they were compared with 549 population-based controls. We modeled phthalate levels both linearly and by quintiles in logistic regression models adjusted for relevant covariates and tested for interaction by child sex. Children of mothers in the highest quintile of di-iso-nonyl phthalate (∑DiNP) metabolite levels had 1.70 times the odds of being classified with ADHD compared with those in the lowest quintile (95% confidence interval [CI] = 1.03 to 2.82). In linear models, there was a trend with the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP); each natural log-unit increase in concentration was associated with 1.22 times the odds of ADHD (95% CI = 0.99 to 1.52). In boys, but not girls, mono-n-butyl phthalate exposure was associated with increased odds of ADHD (odds ratio [OR] 1.42; 95% CI = 1.07 to 1.88). Additional adjustment for correlated phthalate metabolites attenuated estimates. These results suggest gestational phthalate exposure may impact the behavior of children as young as 3 years.

Association Between Visceral Fat and Brain Cortical Thickness in the Elderly: A Neuroimaging Study.

BackgroundDespite emerging evidence suggesting that visceral fat may play a major role in obesity-induced neurodegeneration, little evidence exists on the association between visceral fat and brain cortical thickness in the elderly.PurposeWe aimed to examine the association between abdominal fat and brain cortical thickness in a Korean elderly population.MethodsThis cross-sectional study included elderly individuals without dementia (n = 316). Areas of visceral fat and subcutaneous fat (cm2) were estimated from computed tomography scans. Regional cortical thicknesses (mm) were obtained by analyzing brain magnetic resonance images. Given the inverted U-shaped relationship between visceral fat area and global cortical thickness (examined using a generalized additive model), visceral fat area was categorized into quintiles, with the middle quintile being the reference group. A generalized linear model was built to explore brain regions associated with visceral fat. The same approach was used for subcutaneous fat.ResultsThe mean (standard deviation) age was 67.6 (5.0) years. The highest quintile (vs. the middle quintile) group of visceral fat area had reduced cortical thicknesses in the global [β = –0.04 mm, standard error (SE) = 0.02 mm, p = 0.004], parietal (β = –0.04 mm, SE = 0.02 mm, p = 0.01), temporal (β = –0.05 mm, SE = 0.02 mm, p = 0.002), cingulate (β = –0.06 mm, SE = 0.02 mm, p = 0.01), and insula lobes (β = –0.06 mm, SE = 0.03 mm, p = 0.02). None of the regional cortical thicknesses significantly differed between the highest and the middle quintile groups of subcutaneous fat area.ConclusionThe findings suggest that a high level of visceral fat, but not subcutaneous fat, is associated with a reduced cortical thickness in the elderly.

The association between length of stay in the emergency department and short-term mortality

The detrimental effects of increased length of stay at the emergency department (ED-LOS) for patient outcome have been sparsely studied in the Swedish setting. Our aim was to further explore the association between ED-LOS and short-term mortality in patients admitted to the EDs of two large University hospitals in Sweden. All adult patients (> 18 years) visiting the ED at the Karolinska University Hospital, Sweden, from 1/1/2010 to 1/1/2015 (n = 639,385) were retrospectively included. Logistic regression analysis was used to determine association between ED-LOS and 7- and 30-day mortality rates. All patients were triaged according to the RETTS-A into different levels of medical urgency and subsequently separated into five quintiles of ED-LOS. Mortality rate was highest in highest triage priority level (7-day mortality 5.24%, and 30-day mortality 9.44%), and decreased by lower triage priority group. For patients with triage priority levels 2–4, prolonged ED-LOS was associated with increased mortality, especially for lowest priority level, OR for priority level 4 and highest quintile of ED-LOS 30-day mortality 1.49 (CI 95% 1.20–1.85). For patients with highest triage priority level the opposite was at hand, with decreasing mortality risk with increasing quintile of ED-LOS for 7-day mortality, and lower mortality for the two highest quintile of ED-LOS for 30-day mortality. In patients not admitted to in-hospital care higher ED-LOS was associated with higher mortality. Our data suggest that increased ED-LOS could be associated with slightly increased short-term mortality in patients with lower clinical urgency and dismissed from the ED.

Low Healthy Eating Index-2015 Is Associated With Sarcopenia Among US Adult Population

Abstract Objectives The Healthy Eating Index-2015 (HEI-2015), which is designed to reflect the 2015–2020 Dietary Guidelines for Americans (DGA), and its association with muscle function decline (i.e., sarcopenia) is less known in the U.S. Our study aim was to examine the associations between HEI-2015 component and total scores with sarcopenia in a nationally representative sample of the U.S. adult population. Methods This cross-sectional study used data from the National Health and Nutrition Examination Surveys of 2011–2014. Sarcopenia was assessed by handgrip strength measure using an average score of six trails (&amp;lt;35.5kg for males, &amp;lt;20.0kg for females). HEI-2015 was computed from data of two 24-hour dietary recalls and comprised 13 components (e.g., vegetables, greens and beans, fruits, dairy, protein foods, whole grains, fatty acid ratio, refined grains, sodium, saturated fats, and added sugars). Each component was scored on density out of 1000 calories and summed to a total score divided into quintiles. Weighted logistic regressions examined the study aim while controlling for associated covariates: age, sex, race/ethnicity, education, body mass index (BMI), physical activity, comorbidity, medication use, smoking status, and alcohol use. Results The sample included 9006 eligible participants aged 20–80 years, of those, 14.4% had sarcopenia, where males had higher sarcopenia prevalence than females (18.4 vs. 10.7%, P &amp;lt; 0.001), and participants with sarcopenia were older (p &amp;lt; 0.001). Scores for HEI-2015 were total: 54.2 ± 13.6 (mean ± SD), and in the lowest and highest quintiles: 35.9 ± 4.8 and 73.9 ± 5.95, respectively. In the multivariable model, participants in the highest HEI-2015 quintile had 28% lower odds of having sarcopenia (Odds Ratio(OR) = 0.72, 95%CI: 0.55–0.94) compared with those in the lowest quintile. Among the HEI-2015 components; consuming adequate amount of protein foods, greens and beans, vegetables, and whole fruits reduced the odd of having sarcopenia by 18–23%. Conclusions The findings suggest that higher compliance to the 2015–2020 DGA might reduce sarcopenia among U.S. adults, particularly adequate intakes of protein foods, greens and beans, vegetables, and whole fruits. Funding Sources Department of Veterans Affairs (VA) Advanced Special Fellowship in Geriatrics, Baltimore Geriatric Research, Education and Clinical Center.

24-hour blood pressure variability and treatment effect of intravenous alteplase in acute ischaemic stroke.

To assess the association between 24 h blood pressure variability (BPV) on functional outcome and treatment effect of intravenous alteplase in acute ischaemic stroke. In all patients with acute ischaemic stroke of unknown onset randomised in the WAKE-UP (Efficacy and Safety of magnetic resonance imaging [MRI]-based Thrombolysis in Wake-Up Stroke) trial, blood pressure (BP) was measured before randomisation and after initiation of treatment at regular intervals up to 24 hours. Individual BPV was measured by coefficient of variation (CV) of all BP values. Primary outcome measure was favourable outcome defined by a modified Rankin Scale (mRS) score 0 or 1 at 90 days after stroke. BP measurements were available for 498 of 503 patients randomised (177 women [35.5%], mean age [SD] of 65.2 [11.5] years). Systolic BPV was not associated with the treatment effect of thrombolysis (test for interaction, p = 0.46). The adjusted odds ratio (aOR) for favourable outcome with alteplase, adjusted for age, stroke severity and baseline BP on admission, did not show an association across the quintiles of increasing systolic BPV with an aOR 1.89 (95% confidence interval [CI], 0.76-4.70) in the lowest quintile to aOR 1.05 (95% CI, 0.43-2.56) in the highest quintile. Higher mean systolic BP was associated with a smaller treatment effect of thrombolysis with a significant interaction (p = 0.033). The aOR for favourable outcome with alteplase decreased with quintiles of increasing mean systolic BP from aOR 3.16 (95% CI, 1.26-7.93) in the lowest quintile to aOR 0.84 (95% CI, 0.34-2.10) in in the highest quintile. There was a significant interaction between mean systolic BP and treatment effect of thrombolysis with higher mean systolic BP being associated with poorer outcome. BPV was not associated with outcome after thrombolysis.ClinicalTrials.gov identifier NCT01525290.

Food Insecurity Among Farmers in Rural Sri Lanka and the Perceived Impacts of COVID-19

ObjectivesLittle is known about how the COVID-19 pandemic (C19) has affected food security and farmers’ livelihoods in Sri Lanka. In this study, we assessed food security, perceived impacts of C19 and coping mechanisms to deal with these impacts.MethodsAs part of a baseline survey for an evaluation of the World Food Programme's Nutrition-Sensitive Food Assistance for Assets Program in Sri Lanka, we conducted ∼1300 quantitative household phone surveys across five districts between December 2020 and February 2021. Food insecurity was assessed using the 8-item Food Insecurity Experience Scale and categorized as moderate or severe using the Rasch model. Perceived impacts of C19 and the coping mechanisms used to deal with these shocks were assessed via questionnaire. Additionally, we explored how these experiences varied by wealth quintile, highest attained education level in the household, and district.ResultsDespite having had a relatively low burden of C19 cases in Sri Lanka compared to other countries, 85% of respondents in our sample reported being affected in some way by C19 or its associated control measures. Reported impacts include those on income (77% overall, 89% in lowest quintile, 62% in highest quintile) and agriculture activities (76% overall, 65% in lowest quintile, 87% in highest quintile), among others. Normal crop cultivation and harvesting was adversely impacted due to being advised to stay home (42%), being unable to purchase inputs (33%) and poor demand in the market (56%). In response to COVID shocks, about 30% of respondents in the lowest two wealth quintiles reported selling their livestock and about 20% of respondents across all wealth quintiles reported selling other assets. Half of the households interviewed were either moderately (36%) or severely (14%) food insecure. The proportion of households experiencing food insecurity varied by wealth quintile (mod: 55%-21%; sev: 27%-5%) and district (mod: 46%-29%; sev: 21%-10%).ConclusionsHigh levels of food insecurity and disruptions across domains such as income, asset ownership, and agriculture could have short- and long-term effects on people's health, nutrition and well-being. Control measures enacted in Sri Lanka should consider the potentially devastating effects on smallholder farmers and introduce measures to mitigate these issues in those most affected.Funding SourcesA4NH and WFP

Cumulative Consumption of Sulfur Amino Acids Intake and Incidence of Diabetes

ObjectivesIncreasing evidence in animal models and humans suggests that diets high in sulfur-containing amino acids (SAA) could be associated a greater risk for type 2 diabetes (T2D). However, data from longitudinal human studies linking dietary SAA intake with T2D is lacking. The present study aimed to examine the association between long-term dietary intake of SAA including total SAAs, methionine, and cysteine and incident T2D in participants of the Framingham Heart Study (FHS). MethodsAdult participants were selected from two prospective FHS cohorts: The Offspring Cohort (followed from 1991 to 2015, n = 3799) and the Third Generation Cohort (followed from 2002 to 2011, n = 4096). Individuals identified as diabetes patients before baseline, having missing diet or covariates data, or reported extreme daily energy intake were excluded. Energy-adjusted intake of dietary SAAs was calculated from responses to a 131-item food frequency questionnaire. Cox proportional hazards models were used to evaluate associations between intakes of SAAs (in quintiles) and risk of T2D in each cohort. A combined analysis was also performed pooling subjects from both cohorts. ResultsOverall, we documented 471 T2D events during 9–23 years of follow-up. In both cohorts, higher SAA intake was associated with a higher risk of T2D after adjustment for demographics, traditional risk factors and related nutrients. Comparing participants in the highest quintile with those in the lowest quintile of intake, adjusted hazard ratios (95% CI) were 1.98 (1.15–3.41) for total intake (P for trend = 0.04) in the Offspring cohort, and 4.37 (1.40–13.67) (P for trend = 0.01) in the Third Generation cohort. In the combination analysis of two cohorts, adjusted hazard ratios (95% CI) were 1.98 (1.23–3.21) for total intake, 2.21 (1.38–3.53) for methionine, and 1.79 (1.12–2.87) for cysteine (P for trends < 0.03). ConclusionsHigher long-term SAA intake was associated with higher risk for T2D in humans, suggesting that dietary patterns emphasizing low SAA intake are protective against development of T2D. Funding SourcesNo funding.

Identification of Branched-Chain Fatty Acid Producing Phenotypes in Holstein Cows

Abstract Objectives Branched chain fatty acids (BCFA) are rumen-derived fatty acids comprising about 2% of bovine milk fatty acids. BCFA possess anti-inflammatory properties and enriching the BCFA content of bovine milk may provide human health benefits of milk consumption. In this work, we determined whether high vs low forage diets impact the BCFA content of milk from Holstein cows and identified fatty acid phenotypes in high vs low BCFA-containing milks. Methods In this study, 62 Holstein cows were fed for 70 days, in a cross-over design fashion, either a high forage: concentrate (HF: C) diet or a low forage: concentrate (LF: C) diet. At the end of the 70-day feeding period, cows were switched to the alternate feeding arm. Milk samples were collected prior to the start of the first feeding period and at the end of each treatment period. Milk fatty acid content was determined by fatty acid methyl ester analysis. Paired t-tests, one-way ANOVA, and sparse partial least squares discriminant analysis (sPLSDA) were used to analyze the data. Results The total milk fatty acid concentration at the end of HF: C diet period was greater than that of the LF: C diet (4.2 ± 0.9 g/100 mL vs 3.95 ± 0.9 g/100 mL). sPLSDA demonstrated clear separation of the dietary treatments, with BCFA and odd-chain fatty acids as primary determinants. Total BCFA content was elevated by HF: C intake (1.86 ± 0.13%) vs LF: C intake (1.77 ± 0.14%). Quintile separation of high vs low BCFA milks resulted in 4 groups (n = 12) HF: C/low BCFA, HF: C/high BCFA; LF: C/low BCFA, and LF: C/high BCFA. The total BCFA contents of the low BCFA milks were not different regardless of forage content (1.70 ± 0.06% and 1.61 ± 0.04%) and were lower than the high BFCA milks (2.04 ± 0.11% and 1.98 ± 0.11%). Milks from the high BCFA quintiles had lower saturated fatty acid (SFA) content but higher oleic acid content than milks from the low BCFA quintiles. Of the 62 cows, 5 cows were identified as high BCFA producers and 6 cows as low BCFA producers regardless of the LF: C or HF: C diets. Conclusions The data demonstrate that the BCFA content of milk is diet-sensitive but variation in cow responses suggest factors such as genotype or rumen microbiome composition may play significant roles. The potential to produce milk with high BCFA content and lower SFA content needs further study. Funding Sources USDA-ARS Projects 3062–53000-001–00D, 5090–31000-025–00D, 80–8040-05–01-0000–0000.

325-OR: Genetic and Socioeconomic Factors Are Independently Associated with Type 2 Diabetes

Genetics and socioeconomic status (SES) are key drivers of increased type 2 diabetes (T2D) risk, but the extent to which they impact disease in an additive or non-additive manner is unknown. We examined T2D prevalence using cross-sectional electronic health record (EHR) data from 27,771 participants of European ancestry in the Mass General Brigham Biobank. A polygenic score for T2D was derived using a previously published globally expanded score (gePS). Multiple area-based socioeconomic risk estimates were evaluated (including deprivation indices and a machine learning model incorporating hundreds of census variables) with similar impact on T2D risk; here, an individual’s estimated SES risk was defined as the percent of residents in their census tract with less than high school education. T2D status was derived using a machine-learning algorithm validated by expert chart review to have 90% positive predictive value. The age and sex-adjusted odds of T2D was 1.72 (95% CI 1.63-1.81, p&amp;lt;0.001) per SD increase of T2D gePS and 1.36 (95% CI 1.31-1.42, p&amp;lt;0.001) per SD increase in socioeconomic risk. In a combined model of gePS and socioeconomic risk, these associations persisted, with no evidence of interaction. Persons in the highest quintile of both genetic and socioeconomic risk had an almost 3-fold risk of T2D compared to those of middle quintile risk for both (OR 2.67, 95% CI 2.08-3.44, p&amp;lt;0.001). Notably, the T2D risk of individuals in the highest quintile of genetic risk but lowest quintile of socioeconomic risk was indistinguishable from that of those in the middle quintile for both risk factors (OR 1.13, 95% CI 0.85-1.51). These data provide evidence for the independent associations of genetic risk and SES with T2D and suggest that living in a community with high SES is associated with reduced T2D risk, even among those at increased genetic risk. Our findings raise the hypothesis that interventions targeted at specific elements of SES, such as education, may reduce risk of T2D in those with high genetic risk. Disclosure S. Cromer: Employee; Spouse/Partner; Johnson &amp; Johnson Medical Devices Companies. C. M. Lakhani: Consultant; Self; xy. ai. J. M. Mercader: None. T. Majarian: None. J. C. Florez: Consultant; Self; Goldfinch Bio, Inc., Other Relationship; Self; Novo Nordisk. A. Manning: Employee; Spouse/Partner; Emulate, Inc, Stock/Shareholder; Spouse/Partner; Invitae. J. Merino: None. M. Udler: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007028)

Insulin-Like Growth Factor-II and Ischemic Stroke-A Prospective Observational Study.

Insulin-like growth factor-II (IGF-II) regulates prenatal brain development, but the role in adult brain function and injury is unclear. Here, we determined whether serum levels of IGF-II (s-IGF-II) are associated with mortality and functional outcome after ischemic stroke (IS). The study population comprised ischemic stroke cases (n = 492) and controls (n = 514) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months and 2 years using the modified Rankin Scale (mRS), and additionally, survival was followed at a minimum of 7 years or until death. S-IGF-II levels were higher in IS cases both in the acute phase and at 3-month follow-up compared to controls (p < 0.05 and p < 0.01, respectively). The lowest quintile of acute s-IGF-II was, compared to the four higher quintiles, associated with an increased risk of post-stroke mortality (median follow-up 10.6 years, crude hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.56–3.49, and fully adjusted HR 1.64, 95% CI 1.02–2.61). In contrast, crude associations with poor functional outcome (mRS 3–6) lost significance after full adjustment for covariates. In conclusion, s-IGF-II was higher in IS cases than in controls, and low acute s-IGF-II was an independent risk marker of increased mortality.

Socioeconomic Inequality in Respiratory Health in the US From 1959 to 2018

Air quality has improved and smoking rates have declined over the past half-century in the US. It is unknown whether such secular improvements, and other policies, have helped close socioeconomic gaps in respiratory health. To describe long-term trends in socioeconomic disparities in respiratory disease prevalence, pulmonary symptoms, and pulmonary function. This repeated cross-sectional analysis of the nationally representative National Health and Nutrition Examination Surveys (NHANES) and predecessor surveys, conducted from 1959 to 2018. included 160 495 participants aged 6 to 74 years. Family income quintile defined using year-specific thresholds; educational attainment. Trends in socioeconomic disparities in prevalence of current/former smoking among adults aged 25 to 74 years; 3 respiratory symptoms (dyspnea on exertion, cough, and wheezing) among adults aged 40 to 74 years; asthma stratified by age (6-11, 12-17, and 18-74 years); chronic obstructive pulmonary disease ([COPD] adults aged 40-74 years); and 3 measures of pulmonary function (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and FEV1/FVC<0.70) among adults aged 24 to 74 years. Our sample included 160 495 individuals surveyed between 1959 and 2018: 27 948 children aged 6 to 11 years; 26 956 children aged 12 to 17 years; and 105 591 adults aged 18 to 74 years. Income- and education-based disparities in smoking prevalence widened from 1971 to 2018. Socioeconomic disparities in respiratory symptoms persisted or worsened from 1959 to 2018. For instance, from 1971 to 1975, 44.5% of those in the lowest income quintile reported dyspnea on exertion vs 26.4% of those in the highest quintile, whereas from 2017 to 2018 the corresponding proportions were 48.3% and 27.9%. Disparities in cough and wheezing rose over time. Asthma prevalence rose for all children after 1980, but more sharply among poorer children. Income-based disparities in diagnosed COPD also widened over time, from 4.5 percentage points (age- and sex-adjusted) in 1971 to 11.3 percentage points from 2013 to 2018. Socioeconomic disparities in FEV1 and FVC also increased. For instance, from 1971 to 1975, the age- and height-adjusted FEV1 of men in the lowest income quintile was 203.6 mL lower than men in the highest quintile, a difference that widened to 248.5 mL from 2007 to 2012 (95% CI, -328.0 to -169.0). However, disparities in rates of FEV1/FVC lower than 0.70 changed little. Socioeconomic disparities in pulmonary health persisted and potentially worsened over the past 6 decades, suggesting that the benefits of improved air quality and smoking reductions have not been equally distributed. Socioeconomic position may function as an independent determinant of pulmonary health.

Abstract P120: Association Of Carotid Intima-Media Thickness With Brain MRI Markers In The Atherosclerosis Risk In Communities Neurocognitive Study (ARIC-NCS)

Background: Elevated carotid intima-media thickness (cIMT) and presence of carotid plaque are markers of atherosclerosis, which may be linked to structural brain injury. Using data from the ARIC-NCS cohort, we tested the hypotheses that greater cIMT and presence of carotid plaque at late midlife were each associated with presence of infarcts (lacunar and cortical) and cerebral microbleeds (lobar and subcortical), greater white matter hyperintensity (WMH) volume, and smaller regional brain volumes in late life. Methods: We included 1,795 ARIC participants who had carotid ultrasounds in 1990-92 and brain MRI scans in 2011-13. Weighted linear regression was used for continuous (brain volume) outcomes, and weighted logistic regression for dichotomous outcomes (infarcts and cerebral microbleeds). Results: Participants were aged 57±6 years at baseline, 57% were female, and 23% were Black. Mean ± SD follow-up was 21±1 years. After multivariable adjustments, the highest quintile of cIMT in late midlife was associated with smaller deep grey matter volume (β [95% CI]: -0.11 [-0.22, -0.01]) and cortical volume in a temporal-parietal meta region of interest (ROI) (β [95% CI]: -0.10 [-0.20, -0.01]) in late life (Table). At baseline, 473 (26%) participants had carotid plaque present on their carotid ultrasound. Similar to cIMT, those with carotid plaque had smaller regional brain volumes than those without carotid plaque present (βs [95% CIs]: -0.05 [-0.12, 0.03] and -0.06 [-0.13, 0.01] for deep grey matter and temporal-parietal meta ROI volumes, respectively). No significant relations were observed with WMH volume, or the presence of any infarcts or cerebral microbleeds. Conclusion: Greater midlife cIMT and presence of carotid plaque were associated with smaller deep grey matter volume and cortical volume in a temporal-parietal meta ROI in later life. Contrary to our hypothesis, associations between midlife subclinical atherosclerosis and markers of vascular brain injury in later life were null.

Abstract P060: Plasma Osteocalcin And Incident Diabetes Mellitus: The Atherosclerosis Risk In Communities (ARIC) Study

Introduction: Diabetes is a major risk factor for cardiovascular disease. Osteocalcin is a vitamin K-dependent, bone-derived hormone that functions as an endocrine regulator of energy metabolism, male fertility, and cognition. Early studies of endocrine effects of osteocalcin have shown that genomic deletion of osteocalcin in mice resulted in a diabetic phenotype (i.e. glucose intolerance, and insulin resistance). However, results from clinical studies have shown mixed associations between blood levels of osteocalcin and risk of incident type 2 diabetes mellitus. Hypothesis: Lower values of plasma osteocalcin would be associated with an increased risk of diabetes. Methods: A total of 11,557 ARIC participants without diabetes at baseline were followed from ARIC visit 3 (1993-1995) through 2018. Diabetes cases were identified through self-report on annual and semi-annual follow-up phone calls. Plasma osteocalcin data was measured using an aptamer-based proteomic profiling platform (SomaLogic). We used Cox regression to evaluate the association of quintiles of plasma osteocalcin and incident diabetes. The primary model adjusted for age, sex, and race-center. Results: Participants were age 60 ± 5.6 years at visit 3, 56% identified as female, 21% identified as Black. There were 3,031 incident diabetes cases over a median follow-up of 17.9 years. Mean ± SD was 10.053 ± 0.775. When comparing the highest quintile of plasma osteocalcin (values 10.42 to 14.66) to the lowest quintile (values 9.03 to 9.52), there was no association with incident diabetes (HRs [95% CIs]: 0.92 [0.81, 1.02]). There was also no significant trend across the quintiles (p = 0.19). Results were similar when adjusting for additional potential confounders, and when limiting the follow-up time to 10 years. Conclusions: These data do not support the hypothesis that total plasma osteocalcin, as measured by Somalogic proteomic panel, is a biomarker associated with diabetes risk. It is possible that total plasma or serum osteocalcin and/or other isoforms of osteocalcin protein (i.e. gamma carboxylated or uncarboxylated osteocalcin) measured via other validated methodologies may be linked to diabetes.

Abstract P103: Association Of Lipid Variability With Incident Alzheimers Disease And Alzheimers Disease Related Dementias

Background: Prevention strategies for Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRDs) are urgently needed for reducing incidence. Intra-patient variability in lipid levels is a potentially modifiable risk factor for incident AD/ADRD. Although regular lipid measurements are a part of common clinical practice and longitudinal data routinely available in electronic health records (EHR), research examining this association between AD/ADRD and lipid variability across multiple lipid types remains scarce. Methods: All residents living in Olmsted County, MN on 1/1/2006 age ≥60 years without an AD/ADRD diagnosis were identified using Centers for Medicare &amp; Medicaid Services diagnostic codes. Persons with ≥3 lipid measurements (total cholesterol or triglycerides) in the 5 years prior to index date were retained. Lipid variability was quantified using variability independent of the mean (VIM). Models were adjusted for traditional risk factors. Associations between lipid variability quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Multiple imputation was used for missing covariates. Participants were followed through 2018 for incident AD/ADRD. Results: The final analysis included data on 11,551 participants with total cholesterol and 11,502 participants with triglycerides. Participants had a mean age of 71 (range 60-99) years, and were primarily white (96%). Females (54%) were also slightly more frequent than males. Median follow up was 12.9 years (range: 0-13). Participants in the highest quintile of variability for total cholesterol and triglycerides had a 20% increased risk of incident AD/ADRD. Similar results were found in the subset with complete covariate data. Conclusion: In a large EHR derived cohort, persons in the highest quintile of lipid variation had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this risk factor and replication of these results across a more diverse population are needed.