tbuckley/cabot-search huggingface dataset:
Abstract P430: Waist Circumference is a Key Predictor of Beta-Cell Function in Lean Rwandans With New-Onset Type 2 Diabetes Mellitus
Authors: REGINE MUGENI, Aurore Nishimwe, Gordon I Smith, Anne Sumner, William T Cade, Marcus Bushaku, Dominic N Reeds
Journal: Circulation (2024)

Introduction: Type 2 diabetes mellitus (T2D) is common in Rwanda and other middle and low-income countries. Unlike high-income countries, T2D is prevalent in lean people; the reasons for this are unclear but may relate to abdominal obesity. Therefore, we examined the impact of waist circumference (WC) on insulin-resistance (IR) and insulin secretion rate (ISR) in lean, (BMI &lt;25kg/m 2 ) Rwandan adults with and without new-onset (&lt;1yr) T2D. Hypothesis: We hypothesized that Rwandans with T2D and normal WC would have a lower ISR than both people with T2D and elevated WC and healthy people but that ISR would not be different between Rwandans with T2D and elevated WC and healthy people. Methods: BMI, WC, and a 3-hour frequently-sampled oral-glucose tolerance-test (fsOGTT) were performed in 23 Rwandans; 15 with T2D and 8 healthy people. Normal WC was defined as &lt;85cm for women and &lt;90cm for men (&gt;75 th %ile of group). ISR was determined by mathematical-modeling. Groups were compared by Student’s t-test and ANOVA. Results: Groups were well matched; glucose area under the curve (AUC) was greater and insulinogenic-index was lower in T2D overall than healthy people (Table 1). ISR area under the curve (ISR-AUC) was not different between T2D and healthy people. In contrast, Rwandans with T2D and normal WC had an ISR-AUC ~2.5 fold lower than Rwandans with T2D and elevated WC (P&lt;0.001). Matsuda index and HOMA were greater in Rwandans with T2D and elevated WC than healthy people (P=0.09, P=0.07 respectively). Conclusions: In lean Rwandan people with new-onset T2D but normal WC, alterations in insulin secretion rather than insulin-resistance are key drivers of hyperglycemia. In T2D with elevated WC, IR rather than insulin secretion may be a major factor. This suggests that the pathogenesis of T2D differs based on WC in Rwanda with implications for prevention and therapy. Table 1. Subject Characteristics * P&lt;0.05 vs corresponding value in other groupA, P&lt;0.05 and B, P=0.07 vs corresponding value in other group when comparing on basis of WC.
Abstract P107: The DASH Diet Reduces Markers of Subclinical Cardiac Injury Over an 8-week Period: Results From an Individual Level Meta-Analysis
Authors: Ben Grobman, Michael Liu, Carol Mita, Lawrence J Appel, Lara Kovell, Edgar R Miller, Mingyu Zhang, Ken J Mukamal, Stephen P Juraschek
Journal: Circulation (2024)

Introduction: The Dietary Approaches to Stop Hypertension (DASH) diet has previously been shown to reduce blood pressure and low-density lipoprotein (LDL) cholesterol as compared to the typical American diet. However, direct evidence linking the DASH diet with clinical markers of cardiovascular disease (CVD) is limited. Objectives: To perform a systematic review of trials examining the DASH diet and sensitive markers implicated in CVD: high-sensitivity cardiac troponin (hs-cTnl), N-terminal pro-brain natriuretic peptide (NT-proBNP), and high-sensitivity c-reactive protein (hs-CRP) to determine the effects of the DASH diet on subclinical cardiac injury. Methods: We systematically reviewed 1122 abstracts from PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials (date range 1997 to 2022). We retrieved data from two trials (DASH and DASH-Sodium, using 8-week biomarker measurements), and combined data from the trials to determine subgroup effects. We used mixed effects tobit models to determine the effects of the DASH diet (versus an isocaloric typical American diet) on hs-cTnl, NT-proBNP, and hs-CRP. Effects were determined overall and in subgroups of age, sex, race, hypertension status, obesity, and smoking status. Results: Of the 632 participants included, mean age (SD) was 47 (10.5); 54% were female and 55% were Black. Compared to an isocaloric control diet, the DASH diet reduced hs-cTnl (β = -17.7%, 95% CI: -26.3, -8.1), NT-proBNP (β = -8.6%, 95% CI: -16.8, 0.4), and hs-CRP (β = -11.1%, 95% CI: -20.7, 0.2). Effects were consistent across demographic groups, although the DASH diet had a larger effect on hs-CRP among men ( P -interaction = 0.016) ( Figure ). Conclusion: The DASH diet reduced subclinical cardiac damage and inflammation over an 8-week period. These data provide evidence of the direct benefits of the DASH diet on cardiac health.
Abstract P462: A Novel Framework for the Extraction and Modeling of Meal-Related Glucose Excursions Detected via Continuous Glucose Monitoring (CGM)
Authors: Joseph Sartini, Michael Fang, Mary R Rooney, Elizabeth Selvin, Scott Zeger
Journal: Circulation (2024)

Introduction: Understanding factors that influence glycemic response to meals can inform strategies for diabetes management. Continuous glucose monitoring (CGM) facilitates analyzing glycemic regulation, but concurrent meal timing, required to study meal-induced excursions, is rarely collected. Objective: We develop a framework for extracting meal-related glucose excursions from CGM time series, modeling the excursions using interpretable features, and estimating feature variability explained by patient characteristics and instance-specific patterns. Methods: We used CGM data (Abbott Freestyle Pro) from N = 175 clinical trial participants with type 2 diabetes not using insulin (HYPNOS Trial: mean age 60; 49% female; 36% Black adults). To find excursions, we marked local maxima points in the CGM time series. We discarded points with glucose increases &lt;50 mg/dL in a symmetric window around the point. Remaining point-windows became excursions ( Fig. 1A) . We summarized excursions using relevant features: baseline, height, and shape quantified by splines ( Fig. 1B ).We then assumed each feature could be modelled as the sum of patient-specific effects, both measured as covariates and unmeasured, and instance-specific effects ( Fig. 1C ). Covariates included demographic, biometric, and lifestyle characteristics. Using linear mixed-effects models, we estimated the effects and corresponding variance explained for each feature. Results: For baseline glucose, measured covariate effects notably explain 61.2% of variability. For both height and shape, the summed patient-specific effects explain negligible variation, 17.8% and 10% respectively ( Fig. 1D ). Conclusion: Using our novel framework, we found that instance-specific information explains most variability in glucose excursions. As diet and adjacent physical activity are the instance-specific features primarily impacting glucose metabolism, it follows that healthy lifestyle choices impact postprandial glucose patterns more than inherent traits.
Abstract P505: Investigating Sudden Death in a Large North Carolina County: Methods and Findings of a Population-Based Registry
Authors: Gabriella Day, Thibaut Davy-Mendez, Rebecca E Beyer, Susan Keen, Golsa Joodi, Andrew Cesmat, Alia Capone, Jefferson Williams, Ross J Simpson
Journal: Circulation (2024)

Introduction: Evidence on drivers of sudden death (SD) is needed to understand its persistently high incidence and inform prevention interventions. SD studies have been hampered by data limitations and restrictive SD criteria. We conducted a population-based study of all-cause, out-of-hospital SD using Emergency Medical Services (EMS) data from Wake County, a large North Carolina county with &gt;1 million residents. Methods: We screened EMS records of out-of-hospital deaths between 2013-2015 among persons aged 18-64 years, collected medical and death records, and adjudicated 399 SD cases according to a standardized protocol. Deaths occurring in hospices or nursing homes were excluded, as were those due to unnatural death or cancer. Deaths were not excluded by time last seen or coronary artery disease (CAD) criteria. Frequency matched living controls were identified from the same county and time. We compiled and summarized findings based on peer-reviewed papers and published abstracts in Table 1. Results: Cardiovascular disease risk factors were common among decedents, including hypertension (60.4%, 244 of 371), though only 14.8% (55 of 371) had documented CAD. SD cases had lower adjusted mean total cholesterol, low-density lipoprotein and high-density lipoprotein levels compared to controls. Furthermore, left ventricular hypertrophy and inflammation suggested nodes on a common causal pathway. Poor health care management was frequent as well as mental health and substance use problems. Environmental factors such as poverty, air pollution and absence of nearby greenways were associated with SD. Conclusions: Conducting a population-based registry of adjudicated SD cases was feasible and provided high quality data for study. Our findings suggest that SD is not only tied to CAD but a syndrome with potentially different environmental and inflammatory etiologies. Future studies should investigate modifiable risk factors for interventions to prevent SD.
Abstract P397: Choline Metabolites Are Associated With Non-Alcoholic Fatty Liver Disease: A Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Jessica K Sprinkles, Susan U McRitchie, Blake U Rushing, James G Terry, Xiuxia U Du, Yuankai Z Huo, Christy L Avery, Kari E North, Penny Z Gordon-Larsen, Lisa B VanWagner, Donald M Lloyd-Jones, J. Jeffery Z Carr, Susan U Sumner, Katie A Meyer
Journal: Circulation (2024)

Background: Non-alcoholic fatty liver disease (NAFLD), a common cause of chronic liver disease, has become increasingly prevalent. Choline deficiency has long been a model for the study of accelerated NAFLD, in preclinical and small-scale human studies. More recently, NAFLD has been associated with choline metabolites betaine (inversely) and trimethylamine N-oxide (TMAO) (positively). There has been a paucity of research on circulating choline metabolites and NAFLD in diverse and population-based cohort studies. Methods: We used data from 2,413 CARDIA participants who did not self-report liver disease or heavy alcohol intake at Y15, had stored plasma available from Y15, and chest computed tomography (CT) measures from Y25. NAFLD was defined as a mean CT-derived liver attenuation score &lt;51 Hounsfield units; severe NAFLD was &lt;40 Hounsfield units. Liquid chromatography mass spectrometry was used to quantify choline, betaine, and TMAO concentrations from stored plasma samples. Plasma metabolite concentrations were standardized for analysis. Plasma TMAO was natural log transformed for normality. Multivariable-adjusted logistic regression models quantified associations between plasma choline metabolites and NAFLD. Results (Table): In fully adjusted models, plasma betaine was inversely associated with NAFLD, and plasma TMAO was positively associated with NAFLD. Plasma choline was not associated with NAFLD in fully adjusted models. Conclusions: Our findings support an inverse association between plasma betaine and NAFLD in a diverse, population-based US cohort, and a positive association between plasma TMAO and NAFLD. Circulating betaine reflects dietary intake of betaine, as well as conversion from choline. TMAO reflects an alternative fate of choline, through metabolism by the gut microbiota. These results contribute to a growing literature on choline metabolism and cardiometabolic risk.
Abstract P341: Physical Activity and Dual Energy X-ray Absorptiometry Measured Body Composition in Global Multi-Ethnic Cohorts
Authors: Jennifer L Carter
Journal: Circulation (2024)

Background: Obesity is an important risk factor for the development of heart disease, and unfortunately rates of obesity have been growing worldwide. Obesity is often defined by body mass index (BMI) ≥30kg/m 2 , however, BMI cannot distinguish between fat or lean mass nor differences in fat distribution. Dual energy x-ray absorptiometry (DXA) provides more detailed measurements of body composition, but research assessing the association between physical activity and detailed body composition measures in diverse populations is lacking. This study therefore examined associations between physical activity and DXA-derived measures of adiposity in Chinese, Malay, Indian and White European adults from two large-scale prospective cohort studies. Methods: From 2006-2010, adults from the general population were recruited to both The Malaysian Cohort (TMC) study (N=119 555) and the UK Biobank (N=502 487). Physical activity was self-reported by questionnaire at baseline assessment and approximately 5-yearly resurveys in both cohorts. Between 2020-2023, 5489 participants underwent a DXA scan in TMC; while between 2014-2023, 60 280 participants had DXA scans in UK Biobank. Analyses excluded participants with missing data and prior diseases that may impact body composition. Multivariable linear regression (adjusted for demographic and lifestyle confounders) was used to examine associations between physical activity and body composition measures across ethnic groups, and estimates were corrected for regression dilution bias by using estimates of ‘usual physical activity’ derived from repeat measurements. Results: After exclusions, 1723 Chinese, 1245 Malay and 609 Indian participants were included in the TMC analyses and 56 758 White Europeans in the UK Biobank (mean age 57.1 years, 41.2% male in TMC and 54.7 years, 47.7% male in UK). In TMC, physical activity was not associated with BMI, however it was inversely associated with DXA adiposity measures and positively associated with lean mass. Comparing the highest quintile of physical activity to the lowest, total fat mass was 0.7 kg lower (95%CI: -1.1- -0.3) and total lean mass was 0.6 kg higher (0.3-0.9). There was no evidence of effect modification by ethnicity in TMC, but results in White Europeans were stronger: total fat mass was 3.9 kg lower (-4.1- -3.6) and lean mass was 1.2 kg higher (1.1-1.4) comparing the highest to lowest quintiles of physical activity. Interpretation: This is the first large-scale study to examine associations between physical activity and DXA-derived measures of body composition in multi-ethnic cohorts from Malaysia and the UK. The findings support physical activity interventions to reduce obesity-related disease across diverse populations and highlight the value of using detailed body composition measures.
Abstract P335: Predictors of Cognitive Resilience in Those With and Without High White Matter Hyperintensity Burden: A Post-Hoc Analysis of Systolic Blood Pressure Intervention Trial Memory &amp; Cognition in Decreased Hypertension (SPRINT MIND)
Authors: Eric Stulberg, Alexander Zheutlin, Adam H de Havenon
Journal: Circulation (2024)

Introduction: Little is known if predictors of cognitive resilience (CR) differ between adults with or without large white matter hyperintensity burdens. In the current analysis of cross-sectional baseline SPRINT MIND data, we a) determined bivariate associations of sociodemographic, vascular-metabolic, and neurodegenerative biomarkers with CR and b) delineated variables that maximized predictive fit of CR among participants with the highest and lowest white matter hyperintensity volumes (WMHv). Methods: We included SPRINT MIND participants with baseline available plasma biomarker concentrations &amp; Montreal Cognitive Assessment (MoCA) scores. We then created two analytic samples: those with the highest tertile of WMHv (N = 186) and those with the lowest tertile (N=134). We defined CR two ways: as a MoCA score a) &gt;25 or b) &gt;22. We determined the association between sociodemographic, vascular-metabolic, and serum neurodegenerative variables, as well as WMHv with CR using logistic regressions to generate unadjusted odds ratios (OR) &amp; 95% confidence intervals (CI). Multivariate lasso regressions were then used to determine which variables optimized predictive fit of CR, and R 2 values were calculated. Results: In participants with the lowest tertile of WMHv , the median age was 66 years, 45.5% were female and 63% were Non-Hispanic white. In participants with the highest tertile of WMHv, the median age was 73 years, 45.7% were female and 66% were Non-Hispanic white. . CR defined as MoCA scores &gt; 25 &amp; &gt;22 was present in 37.3% and 64.9% in those with the lowest tertile of WMHv and 28.5% &amp; 56.5% in those with the highest tertile, respectively. Higher education and self-reported race generally had the strongest ORs in all analyses (Table 1 excerpt). Only age and education level were included in all four predictive models after lasso shrinkage. The R 2 values for all lasso regressions were &lt;0.25. Conclusion: Education level may be associated with CR irrespective of WMHv. However, a large variation of CR remains unaccounted for.
Abstract P423: Individual and Combined Effects of Diet, Exercise, and Metformin on Risk of Microvascular Complications in Older Type 2 Diabetes Patients: Post-Hoc Analysis of Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial Data
Authors: Kaustubh Parab, Xiaotian Gao, Neha Gothe, Kenneth Wilund, Chelsea R Singleton
Journal: Circulation (2024)

Introduction: Microvascular complications are a major burden on the health of type 2 diabetes (T2D) patients. The literature has yielded mixed results regarding synergistic effects of common diabetes treatments (i.e., metformin, exercise, and diet) on microvascular complication risk. Some trials demonstrated that the combination of metformin and exercise diminished beneficial effects. We aimed to explore this ambiguity in findings by examining the effects of metformin, exercise, and diet on microvascular complication risk over time among T2D patients in the U.S. and Canada. Hypothesis: We hypothesize that the combined effects of metformin, exercise, and diet would be better than their individual effects on microvascular complication risk. Methods: We analyzed data from 923 participants [mean age: 62.6; 39.2% female; mean years with diabetes: 10.7] of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) (2003-2009) trial. Adequate exercise was defined as &gt; 150 mins of moderate-intensity physical activity per week. Metformin use was defined as yes vs. no. An adequate diet score was ≤ 2.4 of the summary fat intake score (range: 0 - 5). We defined composite outcomes for microvascular complications (i.e., nephropathy, retinopathy, and neuropathy) based on several measurements including serum creatinine doubling, decrease in estimated glomerular filtration ratio (≥ 20 ml/min/1.73 m2 decrease), vision loss, Michigan Neuropathy Screening Instrument. We performed longitudinal analysis with synergy factor (SF) approach using multinomial logistic regression models adjusted for sex, diabetes years, education, alcohol, treatment arm, and baseline outcome. Results: Among individuals with poor diet score, those taking metformin but not adequate exercise had an odds ratio of 1.12 (95% CI: 0.65 - 1.94, p = 0.68) for microvascular complication. Those not taking metformin but had adequate exercise had an odds ratio of 2.71 (95% CI: 1.12 - 6.59, p &lt; 0.05). However, taking metformin and having adequate exercise produced an odds ratio of 0.90 (95% CI: 0.49 - 1.67, p = 0.75), which was 0.30 times less than the predicted odds of the joint effect (SF = 0·30, 95% CI: 0 - 0.59, p = 0·05). Individuals with an adequate diet, adequate exercise, and taking metformin had an odds ratio of 0.85 (95% CI: 0.48 - 1.49, p = 0.57). However, we did not find these associations to be statistically significant. A similar pattern holds for individual microvascular complication outcomes. Conclusion: Additional randomized controlled trials are needed to confirm the potential additive beneficial effect of metformin, adequate exercise, and adequate diet combination over their individual effects on odds of microvascular complications.
Abstract P240: Association of Perceived Lifetime Discrimination With COVID-19 Infection, Hospitalization and Death: The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study
Authors: Kellee White Whilby, Yiqun Jin, Pallavi Balte, Debora Kamin Mukaz, Karen Hinckley Stukovsky, Jana Hirsch, Norrina B Allen, Wendy S Post, Mario Sims, Elizabeth Oelsner
Journal: Circulation (2024)

Rationale: Perceived discrimination adversely impacts individual and population health. However, limited studies have examined associations between discrimination and COVID-19 severity in a diverse cohort of adults. We investigated the association between lifetime discrimination and risk of severe COVID-19. Methods: This study included Black, Chinese, Hispanic, and White participants (45-84 years of age) from the Multi-Ethnic Study of Atherosclerosis (MESA). Lifetime discrimination (experiences of unfair treatment in 6 domains) was assessed at baseline (2000-2002). Incident COVID-19 was ascertained by the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) via questionnaires, serosurvey, and medical records in 2020-2023. Hospitalized and fatal cases were defined as severe; all other cases were defined as non-severe. Associations of lifetime discrimination and incident severe and non-severe COVID-19 were examined via Fine-Gray proportional sub-distribution hazards models, adjusting for covariates. Effect modification by sex, race/ethnicity, and educational attainment was tested. Results: Of 3,441 participants (mean age 76 years, 54% female, 13% Chinese, 20% Hispanic, 25% Black, 41% White), there were 248 cases of non-severe COVID-19 and 83 cases of severe COVID-19. Individuals reporting lifetime discrimination in ≥2 domains (vs none) had a two-fold higher hazard of severe COVID-19. Effect modification was observed by sex (P=.003) and educational attainment (P=.072), but not by race/ethnicity (P=.24). In stratified models, associations of lifetime discrimination and severe COVID-19 were stronger in women versus men and in participants with lower versus higher educational attainment ( Table ). Conclusion: Lifetime discrimination was associated with greater risk of severe COVID-19, particularly in women and persons with lower educational attainment. Further research is needed to understand mechanisms underlying these associations and to inform prevention and risk mitigation.