Efficacy of Aspirin for primary prevention among adults with high-risk type 2 diabetes in the ACCORD trial.

AIM: To assess the  of aspirin use for primary prevention of cardiovascular disease (CVD) with incident atherosclerotic CVD and mortality in high-risk type 2 diabetes. METHODS: In this post hoc analysis, we included participants in the ACCORD trial without CVD at baseline. The association between aspirin use and the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke or cardiovascular [CV] death) and all-cause mortality was evaluated using Cox proportional hazard analysis adjusting for demographics, CV risk factors and comorbidities. RESULTS: Eligible participants (n = 6330) were aged 62.8 ± 5.9 years at baseline, 43.8% of the participants were female, and 3026 (47.8%) used aspirin. Over a median (interquartile range) follow-up of 4.9 (4.1-5.7) years, the number (%) of primary outcome and all-cause mortality events in those who used aspirin (vs. those who did not), was 196 (6.5) versus 229 (6.9) and 146 (4.8) versus 147 (4.5), respectively. The adjusted hazard ratios (95% confidence interval) associated with aspirin use for the primary outcome and all-cause mortality were 0.94 (0.77-1.14) and 1.08 (0.85-1.36), respectively. CONCLUSION: In high-risk individuals with type 2 diabetes, the use of aspirin for primary prevention was not associated with a decreased risk of incident CVD or all-cause mortality.

Associations of cannabis use and body mass index-The Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND: With increasing use of cannabis, we need to know if cannabis use and Body Mass Index (BMI) are associated. METHODS: The Coronary Artery Risk Development in Young Adults Study followed Black and White adults over 30 years with assessments every 2 to 5 years in four centers in the USA. We assessed self-reported current and computed cumulative cannabis exposure at every visit, and studied associations with BMI, adjusted for relevant covariables in mixed longitudinal models. We also applied marginal structural models (MSM) accounting for the probability of having stopped cannabis over the last 5 years. RESULTS: At the Year 30 visit, 1,912 (58 %) identified as women and 1,600 (48 %) as Black, mean age was 56 (SD 2) years. While 2,849 (85 %) had ever used cannabis, 479 (14 %) currently used cannabis. Overall, participants contributed to 35,882 individual visits over 30 years. In multivariable adjusted models, mean BMI was significantly lower in daily cannabis users (26.6 kg/m2, 95 %CI 26.3 to 27.0) than in participants without current use (27.7 kg/m2, 95 %CI 27.5 to 27.9, p < 0.001). Cumulative cannabis use was not associated with BMI. The MSM showed no change in BMI when stopping cannabis use over a 5-year period (ß=0.2 kg/m2 total, 95 %CI -0.2 to 0.6). CONCLUSIONS: Current cannabis use was associated with lower BMI, but cumulative cannabis use and cessation were not. This suggests that recreational cannabis use may not lead to clinically relevant changes in BMI and that the association between current cannabis use and lower BMI is likely due to residual confounding.

Cross-sectional and longitudinal associations among healthcare costs and deficit accumulation.

BACKGROUND: Type 2 diabetes mellitus and overweight/obesity increase healthcare costs. Both are also associated with accelerated aging. However, the contributions of this accelerated aging to increased healthcare costs are unknown. METHODS: We use data from a 8-year longitudinal cohort followed at 16 U.S. clinical research sites. Participants were adults aged 45-76 years with established type 2 diabetes and overweight or obesity who had enrolled in the Action for Health in Diabetes clinical trial. They were randomly (1:1) assigned to either an intensive lifestyle intervention focused on weight loss versus a comparator of diabetes support and education. A validated deficit accumulation frailty index (FI) was used to characterize biological aging. Discounted annual healthcare costs were estimated using national databases in 2012 dollars. Descriptive characteristics were collected by trained and certified staff. RESULTS: Compared with participants in the lowest tertile (least frail) of baseline FI, those in the highest tertile (most frail) at Year 1 averaged $714 (42%) higher medication costs, $244 (22%) higher outpatient costs, and $800 (134%) higher hospitalization costs (p < 0.001). At Years 4 and 8, relatively greater increases in FI (third vs. first tertile) were associated with an approximate doubling of total healthcare costs (p < 0.001). Mean (95% confidence interval) relative annual savings in healthcare costs associated with randomization to the intensive lifestyle intervention were $437 ($195, $579) per year during Years 1-4 and $461 ($232, $690) per year during Years 1-8. These were attenuated and the 95% confidence interval no longer excluded $0 after adjustment for the annual FI differences from baseline. CONCLUSIONS: Deficit accumulation frailty tracks well with healthcare costs among adults with type 2 diabetes and overweight or obesity. It may serve as a useful marker to project healthcare needs and as an intermediate outcome in clinical trials.

Fatherhood and Cardiovascular Health, Disease, and Mortality: Associations From the Multi-Ethnic Study of Atherosclerosis.

Introduction: Emerging literature links fatherhood to men's health but lacks comprehensive assessment of health outcomes, especially among multiethnic populations. This study's objective was to evaluate the associations of fatherhood (age at onset and status) with cardiovascular health scores, incident cardiovascular disease, cardiovascular disease death, and all-cause mortality, examining differences by race/ethnicity. Methods: The study sample included men from Multi-Ethnic Study of Atherosclerosis, prospective cohort study that enrolled adults aged 45-84 years without known cardiovascular disease at baseline. Cardiovascular health was defined using the American Heart Association's Life's Essential 8 scores (0-100), excluding sleep (cardiovascular health score). Results: In this sample of 2,814 men, mean age at cardiovascular health assessment was 62.2 years, 82% were fathers, 24% self-identified as Black, 13% self-identified Chinese, 22% self-identified Hispanic, and 41% self-identified White. Fathers who were aged <20 years and 20-24 years at their oldest child's birth had worse overall cardiovascular health than fathers who were aged >35 years (adjusted mean score of 61.1 vs 64.7 [p=0.01] and 61.0 vs 64.7 [p<0.001], respectively). Fathers had worse overall cardiovascular health (adjusted mean score of 63.2 vs 64.7, p=0.03) and more nicotine exposure (63.1 vs 66.6, p=0.04) than nonfathers. In age-adjusted models, fathers overall (hazard ratio=0.82; 95% CI=0.69, 0.98) and Black fathers (hazard ratio=0.73; 95% CI=0.53, 0.999) had a lower rate of all-cause mortality rate than nonfathers, but these associations were no longer significant in fully adjusted models. Conclusions: Fatherhood is a social determinant of health, and understanding its influence may provide opportunities to improve men's health, particularly among men of color.

LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes.

BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.METHODSMonocyte mRNA expression of 11 CMTN genes was quantified among 934 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of prediabetes/T2D; cellular cholesterol was measured in a subset of 24 monocyte samples.RESULTSDuring a median 6-year follow-up, lower expression of 3 highly correlated LXR target genes - ABCG1 and ABCA1 (cholesterol efflux) and MYLIP (cholesterol uptake suppression) - and not other CMTN genes, was significantly associated with higher risk of incident prediabetes/T2D. Lower expression of the LXR target genes correlated with higher cellular cholesterol levels (e.g., 47% of variance in cellular total cholesterol explained by ABCG1 expression). Further, adding the LXR target genes to overweight/obesity and other known predictors significantly improved prediction of incident prediabetes/T2D.CONCLUSIONThese data suggest that the aberrant LXR/ABCG1-ABCA1-MYLIP pathway (LAAMP) is a major T2D risk factor and support a potential role for aberrant LAAMP and cellular cholesterol accumulation in diabetogenesis.FUNDINGThe MESA Epigenomics and Transcriptomics Studies were funded by NIH grants 1R01HL101250, 1RF1AG054474, R01HL126477, R01DK101921, and R01HL135009. This work was supported by funding from NIDDK R01DK103531 and NHLBI R01HL119962.

The longitudinal association of adipose-to-lean ratio with incident cardiometabolic morbidity: The CARDIA study.

AIM: To assess the association of adipose-to-lean ratio (ALR) with incident type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia in middle adulthood. METHOD: Black and White Coronary Artery Risk Development in Young Adults participants without T2DM, hypertension, or dyslipidemia in 2005-06 (baseline) were included. Baseline adipose and lean mass were assessed via dual-energy X-ray absorptiometry. ALR was calculated as adipose divided by lean mass and then standardized within sex strata. Single time-point incident morbidity was assessed every five years from baseline through 2016. Cox proportional hazards regression was used to estimate hazard ratios (HR) for morbidity over 10 years per 1-SD increment in ALR adjusted for cardiovascular risk factors. RESULT: The cumulative incidence of T2DM was 7.9 % (129 events/N = 1643; 16,301 person-years), 26.7 % (485 events/N = 1819; 17,895 person-years) for hypertension, and 49.1 % (435 events/N = 855, 8089 person-years) for dyslipidemia. In the adjusted models, ALR was positively associated with a risk of T2DM (HR [95 % CI]; 1.69 [1.31, 2.19]) and hypertension (1.23 [1.08, 1.40]). There was no significant interaction between ALR and sex for any morbidity. CONCLUSION: ALR in middle adulthood is associated with incident T2DM and hypertension. The extent to which localized body composition measures might inform morbidity risk merits further investigation.

Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study.

BACKGROUND: Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes. METHODS: Haptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration. RESULTS: 1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated hemoglobin (%HbA1c) to < 6.5% in either phenotype, with a peak significant difference between treatment arms of 0.5% [non-Hp2-2] and 0.6% [Hp2-2]. The cumulative CAD incidence was 13.4% and 13.8% in the DSE arm and 12.2% and 13.6% in the ILI arm for non-Hp2-2 and Hp2-2 groups, respectively. Compared to DSE, the ILI was not associated with CAD among participants without (HR = 0.95, 95% CI 0.78-1.17) or with (0.89, 0.68-1.19) the Hp2-2 phenotype (p-interaction between Hp phenotype and ILI = 0.58). After Bonferroni correction, there were no significant results among any subgroups. CONCLUSIONS: Hp phenotype did not modify the effect of the weight loss ILI on risk of CAD in Look AHEAD, potentially because it did not substantially impact glycemic control among participants with or without the Hp2-2 phenotype. Further research is needed to determine if these results are conclusive.

Social and psychosocial determinants of racial and ethnic differences in cardiovascular health: The MASALA and MESA studies.

Background: Social and psychosocial determinants are associated with cardiovascular health (CVH). Objectives: To quantify the contributions of social and psychosocial factors to racial/ethnic differences in CVH. Methods: In the Multi-Ethnic Study of Atherosclerosis and Mediators of Atherosclerosis in South Asians Living in America cohorts, Kitagawa-Blinder-Oaxaca decomposition quantified the contributions of social and psychosocial factors to differences in mean CVH score (range 0-14) in Black, Chinese, Hispanic, or South Asian compared with White participants. Results: Among 7,978 adults (mean age 61 [SD 10] years, 52 % female), there were 1,892 Black (mean CVH score for decomposition analysis 7.96 [SD 2.1]), 804 Chinese (CVH 9.69 [1.8]), 1,496 Hispanic (CVH 8.00 [2.1]), 1,164 South Asian (CVH 9.16 [2.0]), and 2,622 White (CVH 8.91 [2.1]) participants. The factors that were associated with the largest magnitude of explained differences in mean CVH score were income for Black participants (if mean income in Black participants were equal to White participants, Black participants' mean CVH score would be 0.14 [SE 0.05] points higher); place of birth for Chinese participants (if proportion of US-born and foreign-born individuals among Chinese adults were equivalent to White participants, Chinese participants' mean CVH score would be 0.22 [0.10] points lower); and education for Hispanic and South Asian participants (if educational attainment were equivalent to White participants, Hispanic and South Asian participants' mean CVH score would be 0.55 [0.11] points higher and 0.37 [0.11] points lower, respectively). Conclusions: In these multiethnic US cohorts, social and psychosocial factors were associated with racial/ethnic differences in CVH.

Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study.

AIMS/HYPOTHESIS: We examined the association of attainment of diabetes remission in the context of a 12 year intensive lifestyle intervention with subsequent incidence of chronic kidney disease (CKD) and CVD. METHODS: The Look AHEAD study was a multi-centre RCT comparing the effect of a 12 year intensive lifestyle intervention with that of diabetes support and education on CVD and other long-term health conditions. We compared the incidence of CVD and CKD among 4402 and 4132 participants, respectively, based on achievement and duration of diabetes remission. Participants were 58% female, and had a mean age of 59 years, a duration of diabetes of 6 year and BMI of 35.8 kg/m2. We applied an epidemiological definition of remission: taking no diabetes medications and having HbA1c <48 mmol/mol (6.5%) at a single point in time. We defined high-risk or very high-risk CKD based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, and CVD incidence as any occurrence of non-fatal acute myocardial infarction, stroke, admission for angina or CVD death. RESULTS: Participants with evidence of any remission during follow-up had a 33% lower rate of CKD (HR 0.67; 95% CI 0.52, 0.87) and a 40% lower rate of the composite CVD measure (HR 0.60; 95% CI 0.47, 0.79) in multivariate analyses adjusting for HbA1c, BP, lipid levels, CVD history, diabetes duration and intervention arm, compared with participants without remission. The magnitude of risk reduction was greatest for participants with evidence of longer-term remission. CONCLUSIONS/INTERPRETATION: Participants with type 2 diabetes with evidence of remission had a substantially lower incidence of CKD and CVD, respectively, compared with participants who did not achieve remission. This association may be affected by post-baseline improvements in weight, fitness, HbA1c and LDL-cholesterol. TRIAL REGISTRATION: ClinicalTrials.gov NCT00017953 DATA AVAILABILITY: https://repository.niddk.nih.gov/studies/look-ahead/.

Universal Risk Prediction for Individuals With and Without Atherosclerotic Cardiovascular Disease.

BACKGROUND: American College of Cardiology/American Heart Association guidelines recommend distinct risk classification systems for primary and secondary cardiovascular disease prevention. However, both systems rely on similar predictors (eg, age and diabetes), indicating the possibility of a universal risk prediction approach for major adverse cardiovascular events (MACEs). OBJECTIVES: The authors examined the performance of predictors in persons with and without atherosclerotic cardiovascular disease (ASCVD) and developed and validated a universal risk prediction model. METHODS: Among 9,138 ARIC (Atherosclerosis Risk In Communities) participants with (n = 609) and without (n = 8,529) ASCVD at baseline (1996-1998), we examined established predictors in the risk classification systems and other predictors, such as body mass index and cardiac biomarkers (troponin and natriuretic peptide), using Cox models with MACEs (myocardial infarction, stroke, and heart failure). We also evaluated model performance. RESULTS: Over a follow-up of approximately 20 years, there were 3,209 MACEs (2,797 for no prior ASCVD). Most predictors showed similar associations with MACE regardless of baseline ASCVD status. A universal risk prediction model with the predictors (eg, established predictors, cardiac biomarkers) identified by least absolute shrinkage and selection operator regression and bootstrapping showed good discrimination for both groups (c-statistics of 0.747 and 0.691, respectively), and risk classification and showed excellent calibration, irrespective of ASCVD status. This universal prediction approach identified individuals without ASCVD who had a higher risk than some individuals with ASCVD and was validated externally in 5,322 participants in the MESA (Multi-Ethnic Study of Atherosclerosis). CONCLUSIONS: A universal risk prediction approach performed well in persons with and without ASCVD. This approach could facilitate the transition from primary to secondary prevention by streamlining risk classification and discussion between clinicians and patients.

Association of Lifestyle Intervention With Risk for Cardiovascular Events Differs by Level of Glycated Hemoglobin.

PURPOSE: We reevaluated the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) to assess whether the effect of ILI on cardiovascular disease (CVD) prevention differed by baseline glycated hemoglobin (HbA1c). METHODS: Look AHEAD randomized 5145 adults, aged 45 to 76 years with type 2 diabetes and overweight/obesity to ILI or a diabetes support and education (DSE) control group for a median of 9.6 years. ILI focused on achieving weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial's primary composite CVD outcome. We evaluated additive and multiplicative heterogeneity of the intervention on CVD risk by baseline HbA1c. RESULTS: Mean baseline HbA1c was 7.3% (SD 1.2) and ranged from 4.4% (quintile 1) to 14.5% (quintile 5). We observed additive and multiplicative heterogeneity of the association between ILI and CVD (all P < .001) by baseline HbA1c. Randomization to ILI was associated with lower CVD risk for HbA1c quintiles 1 [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.53, 0.88] and 2 (HR: 0.80, 95% CI: 0.66, 0.96) and associated with higher CVD risk for HbA1c quintile 5 (HR: 1.27, 95% CI: 1.02, 1.58), compared to DSE. CONCLUSION: Among adults with type 2 diabetes and overweight/obesity, randomization to a lifestyle intervention was differentially associated with CVD risk by baseline HbA1c such that it was associated with lower risk at lower HbA1c levels and higher risk at higher HbA1c levels. There is a critical need to develop and tailor lifestyle interventions to be successful for individuals with type 2 diabetes and high HbA1c.

Trajectory modeling of cannabis use over 30 years identifies five unique longitudinal patterns.

Cannabis is the most prevalently used psychoactive substance in the United States. Cannabis has conflicting federal and state legal status in the US, however medical and recreational cannabis use are increasing. When assessing health outcomes, cannabis use classification has been modeled largely as current use status (never/former/current) or cumulative use (joint-years). These methods do not describe longitudinal patterns of use which may have unique relationships with health outcomes. We used cannabis use data spanning 30 years from the Coronary Artery Risk Development in Young Adults Cohort (CARDIA) to create trajectories of current cannabis use during young and middle adulthood. We identified 5 unique patterns of the probability of cannabis use during young and middle adulthood in the CARDIA Cohort. To support the cannabis probability trajectories, we qualitatively examined cumulative cannabis use as joint-years for each trajectory group. Trajectory group 5 had high probability of consistent cannabis use (0.8-0.9% probability of use) and had the highest number of joint-years (0.6 +/- 0.4). Trajectory group 1 who had a lower probability of cannabis use (0.05-0% probability of use) with the lowest number of joint-years (0.1 +/- 0.1).

A National Survey of Physicians' Views on the Importance and Implementation of Deintensifying Diabetes Medications.

BACKGROUND: Guidelines recommend deintensifying hypoglycemia-causing medications for older adults with diabetes whose hemoglobin A1c is below their individualized target, but this rarely occurs in practice. OBJECTIVE: To understand physicians' decision-making around deintensifying diabetes treatment. DESIGN: National physician survey. PARTICIPANTS: US physicians in general medicine, geriatrics, or endocrinology providing outpatient diabetes care. MAIN MEASURES: Physicians rated the importance of deintensifying diabetes medications for older adults with type 2 diabetes, and of switching medication classes, on 5-point Likert scales. They reported the frequency of these actions for their patients, and listed important barriers and facilitators. We evaluated the independent association between physicians' professional and practice characteristics and the importance of deintensifying and switching diabetes medications using multivariable ordered logistic regression models. KEY RESULTS: There were 445 eligible respondents (response rate 37.5%). The majority of physicians viewed deintensifying (80%) and switching (92%) diabetes medications as important or very important to the care of older adults. Despite this, one-third of physicians reported deintensifying diabetes medications rarely or never. While most physicians recognized multiple reasons to deintensify, two-thirds of physicians reported barriers of short-term hyperglycemia and patient reluctance to change medications or allow higher glucose levels. In multivariable models, geriatricians rated deintensification as more important compared to other specialties (p=0.027), and endocrinologists rated switching as more important compared to other specialties (p<0.006). Physicians with fewer years in practice rated higher importance of deintensification (p<0.001) and switching (p=0.003). CONCLUSIONS: While most US physicians viewed deintensifying and switching diabetes medications as important for the care of older adults, they deintensified infrequently. Physicians had ambivalence about the relative benefits and harms of deintensification and viewed it as a potential source of conflict with their patients. These factors likely contribute to clinical inertia, and studies focused on improving shared decision-making around deintensifying diabetes medications are needed.

Association of Intensive Lifestyle Intervention for Type 2 Diabetes With Labor Market Outcomes.

Importance: An intensive lifestyle intervention (ILI) has been shown to improve diabetes management and physical function. These benefits could lead to better labor market outcomes, but this has not been previously studied. Objective: To estimate the association of an ILI for weight loss in type 2 diabetes with employment, earnings, and disability benefit receipt during and after the intervention. Design, Setting, and Participants: This cohort study included participants with type 2 diabetes and overweight or obesity and compared an ILI with a control condition of diabetes support and education. Data for the original trial were accrued from August 22, 2001, to September 14, 2012. Trial data were linked with Social Security Administration records to investigate whether, relative to the control group, the ILI was associated with improvements in labor market outcomes during and after the intervention period. Difference-in-differences models estimating relative changes in employment, earnings, and disability benefit receipt between the ILI and control groups were used, accounting for prerandomization differences in outcomes for linked participants. Outcome data were analyzed from July 13, 2020, to May 17, 2023. Exposure: The ILI consisted of sessions with lifestyle counselors, dieticians, exercise specialists, and behavioral therapists on a weekly basis in the first 6 months, decreasing to a monthly basis by the fourth year, designed to achieve and maintain at least 7% weight loss. The control group received group-based diabetes education sessions 3 times annually during the first 4 years, with 1 annual session thereafter. Main Outcomes and Measures: Employment and receipt of federal disability benefits (Supplemental Security Income and Social Security Disability Insurance), earnings, and disability benefit payments from 1994 through 2018. Results: A total of 3091 trial participants were linked with Social Security Administration data (60.1% of 5145 participants initially randomized and 97.0% of 3188 of participants consenting to linkage). Among the 3091 with fully linked data, 1836 (59.4%) were women, and mean (SD) age was 58.4 (6.5) years. Baseline clinical and demographic characteristics were similar between linked participants in the ILI and control groups. Employment increased by 2.9 (95% CI, 0.3-5.5) percentage points for the ILI group relative to controls (P = .03) with no significant relative change in disability benefit receipt (-0.9 [95% CI, -2.1 to 0.3] percentage points; P = .13). Conclusions and Relevance: The findings of this cohort study suggest that an ILI to prevent the progression and complications of type 2 diabetes was associated with higher levels of employment. Labor market productivity should be considered when evaluating interventions to manage chronic diseases.

Methods for estimating insulin resistance from untargeted metabolomics data.

CONTEXT: Insulin resistance is associated with multiple complex diseases; however, precise measures of insulin resistance are invasive, expensive, and time-consuming. OBJECTIVE: Develop estimation models for measures of insulin resistance, including insulin sensitivity index (SI) and homeostatic model assessment of insulin resistance (HOMA-IR) from metabolomics data. DESIGN: Insulin Resistance Atherosclerosis Family Study (IRASFS). SETTING: Community based. PARTICIPANTS: Mexican Americans (MA) and African Americans (AA). MAIN OUTCOME: Estimation models for measures of insulin resistance, i.e. SI and HOMA-IR. RESULTS: Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net regression were used to build insulin resistance estimation models from 1274 metabolites combined with clinical data, e.g. age, sex, body mass index (BMI). Metabolite data were transformed using three approaches, i.e. inverse normal transformation, standardization, and Box Cox transformation. The analysis was performed in one MA recruitment site (San Luis Valley, Colorado (SLV); N = 450) and tested in another MA recruitment site (San Antonio, Texas (SA); N = 473). In addition, the two MA recruitment sites were combined and estimation models tested in the AA recruitment sample (Los Angeles, California; N = 495). Estimated and empiric SI were correlated in the SA (r2 = 0.77) and AA (r2 = 0.74) testing datasets. Further, estimated and empiric SI were consistently associated with BMI, low-density lipoprotein cholesterol (LDL), and triglycerides. We applied similar approaches to estimate HOMA-IR with similar results. CONCLUSIONS: We have developed a method for estimating insulin resistance with metabolomics data that has the potential for application to a wide range of biomedical studies and conditions.

Visit-to-Visit Glucose Variability, Cognition, and Global Cognitive Decline: The Multi-Ethnic Study of Atherosclerosis.

CONTEXT: Higher visit-to-visit glucose variability (GV) is associated with dysglycemia and type 2 diabetes (T2D), key risk factors for cognitive decline. OBJECTIVE: Evaluate the association of GV with cognitive performance and decline in racially/ethnically diverse older populations with and without T2D. METHODS: We calculated the standard deviation of glucose (SDG), average real variability (ARV), and variability independent of the mean (VIM) among 4367 Multi-Ethnic Study of Atherosclerosis participants over 6 clinical examinations. Participants completed a cognitive assessment at the fifth examination, and a subset completed a second assessment 6 years later. We used multivariable linear regression to estimate the association of intraindividual GV with cognitive test scores after adjustments for cardiovascular risk factors and mean glucose level over the study period. RESULTS: Two-fold increments in the VIM and SDG were associated with worse Cognitive Abilities Screening Instrument (CASI) performance, while two-fold increments in VIM and ARV were associated with worse Digit Symbol Coding test score. GV measures were not associated with change in CASI performance among 1834 participants with repeat CASI data 6 years later. However, among 229 participants with incident T2D, the SDG and VIM were associated with decline in CASI (-1.7 [95% CI: -3.1, -0.3] and -2.1 [-3.7, -0.5] points, respectively). In contrast, single-timepoint glucose and HbA1c were not associated with CASI decline among participants with or without incident T2D. CONCLUSION: Higher visit-to-visit GV over 16 to 18 years is associated with worse cognitive performance in the general population, and with modest global cognitive decline in participants with T2D.

Contribution of social, behavioral, and contextual exposures to Black-White disparities in incident obesity: The CARDIA study.

OBJECTIVE: The aim of this study was to quantify the contributions of socioeconomic, psychosocial, behavioral, reproductive, and neighborhood exposures in young adulthood to Black-White differences in incident obesity. METHODS: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 4488 Black or White adults aged 18 to 30 years without obesity at baseline (1985-1986) were followed over 30 years. Sex-specific Cox proportional hazard models were used to estimate Black-White differences in incident obesity. Models were adjusted for baseline and time-updated indicators. RESULTS: During follow-up, 1777 participants developed obesity. Black women were 1.87 (95% CI: 1.63-2.13) times more likely and Black men were 1.53 (95% CI: 1.32-1.77) times more likely to develop obesity than their White counterparts after adjusting for age, field center, and baseline BMI. Baseline exposures explained 43% of this difference in women and 52% in men. Time-updated exposures explained more of the racial difference in women but less for men, compared with baseline exposures. CONCLUSIONS: Adjusting for these exposures accounted for a substantial but incomplete proportion of racial disparities in incident obesity. Remaining differences may be explained by incomplete capture of the most salient aspects of these exposures or potential variation in the impact of these exposures on obesity by race.

Racial difference in the association between non-alcoholic fatty liver disease and incident type 2 diabetes: findings from the CARDIA study.

AIMS/HYPOTHESIS: Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) are prevalent diseases of metabolic origin. We examined the association between NAFLD and the development of type 2 diabetes among non-Asian adults, and whether the association differs by race. METHODS: We analysed data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based prospective cohort study. Participants underwent non-contrast abdominal computed tomography (CT) at baseline (2010-2011) and assessment of glucose measures at the follow-up exam (2015-2016). NAFLD was defined as liver attenuation ≤51 Hounsfield units on CT images after exclusion for other liver fat causes. Race was self-reported. We used targeted maximum likelihood estimation (TMLE) with machine-learning algorithms to estimate difference in type 2 diabetes risk between the NAFLD and non-NAFLD groups. RESULTS: Of the 1995 participants without type 2 diabetes at baseline (mean age±SD, 50.0±3.6 years; 59% women; 55.0% White and 45.0% Black), 21.7% of White and 16.8% of Black participants had NAFLD at baseline, and 3.7% of White and 8.0% of Black participants developed type 2 diabetes at follow up. After multivariable adjustment, risk difference for type 2 diabetes associated with NAFLD vs no NAFLD was 4.1% (95% CI 0.3%, 7.9%) among White participants and -1.9% (95% CI -5.7%, 2.0%) in Black participants. CONCLUSIONS/INTERPRETATION: NAFLD was associated with a higher risk of type 2 diabetes among White participants but not among Black participants. This finding suggests that the effect of liver fat on impaired glucose metabolism may be smaller in Black than in White individuals.