Longitudinal Associations Between MicroRNAs and Weight in the Diabetes Prevention Program.

OBJECTIVE: Circulating microRNAs show cross-sectional associations with overweight and obesity. Few studies provided data to differentiate between a snapshot perspective on these associations versus how microRNAs characterize prodromal risk from disease pathology and complications. This study assessed longitudinal relationships between circulating microRNAs and weight at multiple time-points in the Diabetes Prevention Program trial. RESEARCH DESIGN AND METHODS: A subset of participants (n=150) from the Diabetes Prevention Program were included. MicroRNAs were measured from banked plasma using a Fireplex Assay. We used generalized linear mixed models to evaluate relationships between microRNAs and changes in weight at baseline, year-1, and year-2. Logistic regression was used to evaluate whether microRNAs at baseline were associated with weight change after 2 years. RESULTS: In fully adjusted models that included relevant covariates, seven miRs (i.e., miR-126, miR-15a, miR-192, miR-23a, and miR-27a) were statistically associated with weight over 2 years. MiR-197 and miR-320a remained significant after adjustment for multiple comparisons. Baseline levels of let-7f, miR-17, and miR-320c were significantly associated with 3% weight loss after 2 years in fully adjusted models. DISCUSSION: This study provided evidence for longitudinal relationships between circulating microRNAs and weight. Because microRNAs characterize the combined effects of genetic determinants and responses to behavioral determinants, they may provide insights about the etiology of overweight and obesity in the context or risk for common, complex diseases. Additional studies are needed to validate the potential genes and biological pathways that might be targeted by these microRNA biomarkers and have mechanistic implications for weight loss and disease prevention.

Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden. Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days. Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Metabolite profiles of plant-based diets and cardiometabolic risk in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

BACKGROUND: Healthy plant-based diets have been associated with lower risk of type 2 diabetes (T2D). Metabolomics can be leveraged to identify potential pathways through which diet influences disease risk. OBJECTIVE: To identify profiles of serum metabolites reflective of plant-based diets of varying quality and examine associations with cardiometabolic risk and T2D. METHODS: We included data from 687 participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort. An overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthful PDI (uPDI) were estimated from food frequency questionnaires. Serum metabolites were assayed using ultra-performance liquid chromatography mass spectrometry. Elastic net regression was used to identify sets of metabolites predictive of each diet index and metabolite profile scores were calculated as the weighted sum of the selected metabolites. Cross-sectional associations between metabolite profile scores and cardiometabolic measures and prospective associations with incident T2D were evaluated with multivariable adjusted linear and logistic regressions. RESULTS: Metabolite profiles for PDI, hPDI, and uPDI consisted of n=51, 55, and 45 metabolites, respectively. Metabolites strongly positively correlated with diet indices included phosphatidylcholine (16:0/18:3) for PDI, phosphatidylethanolamine (20:1/20:4) and pantothenate for hPDI, and lysophosphatidylglycerol (18:2/0:0), proline, and lauric acid for uPDI. Higher metabolite profile scores for PDI and hPDI were associated with lower glycemia and lipids measures, whereas a higher uPDI metabolite score was associated with higher triglycerides and lower LDL-C and HDL-C. A higher metabolite score for hPDI was additionally associated with lower adiposity measures, higher liver fat attenuation, higher adiponectin), lower odds of overweight and obesity (OR 0.64 [95% CI: 0.51-0.81] and 0.59 [95% CI: 0.48-0.74], respectively) and lower odds of incident T2D (OR 0.66 [95% CI: 0.45-0.97]). CONCLUSION: Metabolite profiles of different plant-based diets were identified. Metabolite profiles of overall and healthy plant-based diets were associated with favorable cardiometabolic risk profiles.

Pubertal Timing Across Asian American, Native Hawaiian, and Pacific Islander Subgroups.

Importance: Earlier puberty is associated with adverse health outcomes, such as mental health issues in adolescence and cardiometabolic diseases in adulthood. Despite rapid growth of the Asian American, Native Hawaiian, and Pacific Islander populations in the US, limited research exists on their pubertal timing, potentially masking health disparities. Objective: To examine pubertal timing among Asian American, Native Hawaiian, and Pacific Islander children and adolescents by disaggregating ethnic subgroups. Design, Setting, and Participants: This retrospective cohort study included Asian American, Native Hawaiian, and Pacific Islander youths aged 5 to 18 years assessed for pubertal development at Kaiser Permanente Northern California, a large, integrated health care delivery system. Follow-up occurred from March 2005, through December 31, 2019. Data were analyzed in October 2023. Exposure: Race and ethnicity, categorized into 11 ethnic subgroups: Asian Indian, Chinese, Filipino, Japanese, Korean, Native Hawaiian and Pacific Islander, Other South Asian, Other Southeast Asian, Vietnamese, multiethnic, and multiracial. Main Outcomes and Measures: Pubertal timing was determined using physician-assessed sexual maturity ratings (SMRs). Outcomes included the median age at transition from SMR 1 (prepubertal) to SMR 2 or higher (pubertal) for onset of genital development (gonadarche) in boys, breast development (thelarche) in girls, and pubic hair development (pubarche) in both boys and girls. Results: In this cohort of 107 325 Asian American, Native Hawaiian, and Pacific Islander children and adolescents (54.61% boys; 12.96% Asian Indian, 22.24% Chinese, 26.46% Filipino, 1.80% Japanese, 1.66% Korean, 1.96% Native Hawaiian and Pacific Islander, 0.86% Other South Asian, 3.26% Other Southeast Asian, 5.99% Vietnamese, 0.74% multiethnic, and 22.05% multiracial), the overall median ages for girls' pubarche and thelarche were 10.98 years (95% CI, 10.96-11.01 years) and 10.13 years (95% CI, 10.11-10.15 years), respectively. For boys' pubarche and gonadarche, median ages were 12.08 years (95% CI, 12.06-12.10 years) and 11.54 years (95% CI, 11.52-11.56 years), respectively. Differences between subgroups with earliest and latest median age at onset were 14 months for girls' pubarche, 8 months for thelarche, 8 months for boys' pubarche, and 4 months for gonadarche. In general, Asian Indian, Native Hawaiian and Pacific Islander, and Other South Asian subgroups had the earliest ages at onset across pubertal markers, while East Asian youths exhibited the latest onset. Restricting to those with healthy body mass index did not substantially change the findings. Conclusions and Relevance: In this cohort study of Asian American, Native Hawaiian, and Pacific Islander children and adolescents, pubertal timing varied considerably across ethnic subgroups. Further investigation is warranted to assess whether these differences contribute to observed health disparities in adulthood, such as type 2 diabetes and cardiovascular diseases.

Association of cardiovascular health with subclinical coronary atherosclerosis progression among five racial and ethnic groups: The MASALA and MESA studies.

BACKGROUND AND AIMS: South Asian adults (SA) are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared with other racial/ethnic groups. Life's Simple 7 (LS7) is a guideline-recommended, cardiovascular health (CVH) construct to guide optimization of cardiovascular risk factors. We sought to assess if the LS7 metrics predict coronary artery calcium (CAC) incidence and progression in asymptomatic SA compared with four other racial/ethnic groups. METHODS: We assessed the distribution of CVH metrics (inadequate: score 0-8, average: 9-10, optimal: 11-14, and per 1-unit higher score) and its association with incidence and progression of CAC among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study compared with other race/ethnic groups from the Multiethnic Study of Atherosclerosis (MESA). RESULTS: We included 810 SA, 2622 Non-Hispanic White (NHW), and 4192 Other adults (collectively 1893 Black, 1496 Hispanic and 803 Chinese American participants, respectively). SA and White participants compared to Other race/ethnicity groups were more likely to have optimal CVH metrics (26% SA vs 28% White participants vs 21% Other, respectively, p < 0.001). Similar to NHW and the Other race/ethnic group, SA participants with optimal baseline CVH were less likely to develop incident CAC on follow-up evaluation compared to participants with inadequate CVH metrics, optimal CVH/CAC = 0: 24% SA, 28% NHW, and 15% Other (p < 0.01). In multivariable linear and logistic regression models, there was no difference in annualized CAC incidence or progression between each race/ethnic group (pinteraction = 0.85 and pinteraction = 0.17, respectively). Optimal blood pressure control was associated with lower CAC incidence among SA participants [OR (95% CI): 0.30 (0.14-0.63), p < 0.01] and Other race and ethnicity participants [0.32 (0.19-0.53), p < 0.01]. CONCLUSIONS: Optimal CVH metrics are associated with lower incident CAC and CAC progression among South Asians, similar to other racial groups/ethnicities. These findings underscore the importance of optimizing and maintaining CVH to mitigate the future risk of subclinical atherosclerosis in this higher risk population.

Predictors of weight and waist gain in US South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

Background: Weight and waist gain are significant concerns in adulthood. Both weight and waist gain are particularly important among South Asians, a high-risk group known to develop chronic cardiometabolic complications at any body mass index compared to other racial and ethnic groups. Objective: The aim of this study was to investigate factors predicting weight and waist gain in a longitudinal cohort of US South Asians, a high-risk group for developing obesity-related complications. Methods: We used data from Mediators of Atherosclerosis in South Asians Living in America study (MASALA) exam 1 (2010-2013) and exam 2 (2015-2018), with a mean 4.8 years of follow-up. Results: Of 634 participants studied (42.7% women, mean age 55 years, BMI 25.7 kg/m2, weight 70.4 kg at exam 1), 34.7% had gained ≥5% weight and 32.3% gained ≥5% waist at exam 2. In the adjusted models, older age, higher number of years of US residence, and having diabetes were associated with lower odds of weight gain; being female and having higher adiponectin were associated with higher odds of weight gain. Being female, employed full or part time, or retired were associated with lower odds of waist gain. Being single, separated/divorced, having a higher leptin and a higher C-reactive protein level were associated with higher odds of waist gain. Conclusions: South Asian subgroups with higher risk of weight and/or waist gain may benefit from targeted interventions to improve health outcomes.

Do Religion and Spirituality Buffer the Effect of Childhood Trauma on Depressive Symptoms? Examination of a South Asian Cohort from the USA.

Asian Americans have been identified as a racial group that is disproportionately affected by childhood trauma. The goal of this study was  to assess if religion/spirituality moderate the effects of childhood trauma on adult depressive symptoms among a sample of South Asians in the USA. Our analysis drew from the study on stress, spirituality, and health (SSSH) questionnaire fielded in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study (n = 990) during 2016-2018. A series of regression models with multiplicative interaction terms were conducted. Emotional neglect, emotional abuse, and physical neglect were associated with higher depressive symptoms. Higher religious attendance and negative religious coping techniques were found to exacerbate this relationship. There were two findings conditional on gender. Among men, gratitude and positive religious coping also exacerbated the relationship between childhood trauma and depressive symptoms. Negative religious coping also exacerbated the association between childhood trauma and depressive symptoms for women. This is the first community-based study of US South Asians to consider the association between various forms of childhood trauma and depressive symptom outcomes. South Asians remain an understudied group in the religion and health literature, and this study sheds light on the important differences in the function and effectiveness of religion/spirituality for those faced with early life trauma.

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.

Inverse association between total bilirubin and type 2 diabetes in U.S. South Asian males but not females.

AIMS: United States South Asians constitute a fast-growing ethnic group with high prevalence of type 2 diabetes (T2D) despite lower mean BMI and other traditional risk factors compared to other races/ethnicities. Bilirubin has gained attention as a potential antioxidant, cardio-protective marker. Hence we sought to determine whether total bilirubin was associated with prevalent and incident T2D in U.S. South Asians. METHODS: We conducted a cross-sectional and prospective analysis of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Total bilirubin was categorized into gender-specific quartiles (Men: <0.6, 0.6, 0.7-0.8, >0.8; Women: <0.5, 0.5, 0.6, >0.6 mg/dl). We estimated odds of type 2 diabetes as well as other cardiovascular (CV) risk factors using multivariable logistic regression. RESULTS: Among a total 1,149 participants (48% female, mean [SD] age of 57 [9] years), 38% had metabolic syndrome and 24% had T2D. Men and women in the lowest bilirubin quartile had 0.55% and 0.17% higher HbA1c than the highest quartile. Men, but not women, in the lowest bilirubin quartile had higher odds of T2D compared to the highest quartile (aOR [95% CI]; Men: 3.00 [1.72,5.23], Women: 1.15 [0.57,2.31]). There was no association between bilirubin and other CV risk factors. CONCLUSION: Total bilirubin was inversely associated with T2D in SA men but not women. Longitudinal studies are needed to understand temporality of association.

Demographic and Clinical Factors Associated With SARS-CoV-2 Spike 1 Antibody Response Among Vaccinated US Adults: the C4R Study.

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination.

Adipose tissue-derived metabolite risk scores and risk for type 2 diabetes in South Asians.

BACKGROUND: South Asians are at higher risk for type 2 diabetes (T2D) than many other race/ethnic groups. Ectopic adiposity, specifically hepatic steatosis and visceral fat may partially explain this. Our objective was to derive metabolite risk scores for ectopic adiposity and assess associations with incident T2D in South Asians. METHODS: We examined 550 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort study aged 40-84 years without known cardiovascular disease or T2D and with metabolomic data. Computed tomography scans at baseline assessed hepatic attenuation and visceral fat area, and fasting serum specimens at baseline and after 5 years assessed T2D. LC-MS-based untargeted metabolomic analysis was performed followed by targeted integration and reporting of known signals. Elastic net regularized linear regression analyses was used to derive risk scores for hepatic steatosis and visceral fat using weighted coefficients. Logistic regression models associated metabolite risk score and incident T2D, adjusting for age, gender, study site, BMI, physical activity, diet quality, energy intake and use of cholesterol-lowering medication. RESULTS: Average age of participants was 55 years, 36% women with an average body mass index (BMI) of 25 kg/m2 and 6% prevalence of hepatic steatosis, with 47 cases of incident T2D at 5 years. There were 445 metabolites of known identity. Of these, 313 metabolites were included in the MET-Visc score and 267 in the MET-Liver score. In most fully adjusted models, MET-Liver (OR 2.04 [95% CI 1.38, 3.03]) and MET-Visc (OR 2.80 [1.75, 4.46]) were associated with higher odds of T2D. These associations remained significant after adjustment for measured adiposity. CONCLUSIONS: Metabolite risk scores for intrahepatic fat and visceral fat were strongly related to incident T2D independent of measured adiposity. Use of these biomarkers to target risk stratification may help capture pre-clinical metabolic abnormalities.

Diabetes in South Asians: Uncovering Novel Risk Factors With Longitudinal Epidemiologic Data: Kelly West Award Lecture 2023.

South Asian populations have a higher prevalence and earlier age of onset of type 2 diabetes and atherosclerotic cardiovascular diseases than other race and ethnic groups. To better understand the pathophysiology and multilevel risk factors for diabetes and cardiovascular disease, we established the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study in 2010. The original MASALA study cohort (n = 1,164) included 83% Asian Indian immigrants, with an ongoing expansion of the study to include individuals of Bangladeshi and Pakistani origin. We have found that South Asian Americans in the MASALA study had higher type 2 diabetes prevalence, lower insulin secretion, more insulin resistance, and an adverse body composition with higher liver and intermuscular fat and lower lean muscle mass compared with four other U.S. race and ethnic groups. MASALA study participants with diabetes were more likely to have the severe hyperglycemia subtype, characterized by ß-cell dysfunction and lower body weight, and this subtype was associated with a higher incidence of subclinical atherosclerosis. We have found several modifiable factors for cardiometabolic disease among South Asians including diet and physical activity that can be influenced using specific social network members and with cultural adaptations to the U.S. context. Longitudinal data with repeat cardiometabolic measures that are supplemented with qualitative and mixed-method approaches enable a deeper understanding of disease risk and resilience factors. Studying and contrasting Asian American subgroups can uncover the causes for cardiometabolic disease heterogeneity and reveal novel methods for prevention and treatment.

Lessons Learned from Immigrant Health Cohorts: A Review of the Evidence and Implications for Policy and Practice in Addressing Health Inequities among Asian Americans, Native Hawaiians, and Pacific Islanders.

The health of Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI) is uniquely impacted by structural and social determinants of health (SSDH) shaped by immigration policies and colonization practices, patterns of settlement, and racism. These SSDH also create vast heterogeneity in disease risks across the AANHPI population, with some ethnic groups having high disease burden, often masked with aggregated data. Longitudinal cohort studies are an invaluable tool to identify risk factors of disease, and epidemiologic cohort studies among AANHPI populations have led to seminal discoveries of disease risk factors. This review summarizes the limited but growing literature, with a focus on SSDH factors, from seven longitudinal cohort studies with substantial AANHPI samples. We also discuss key information gaps and recommendations for the next generation of AANHPI cohorts, including oversampling AANHPI ethnic groups; measuring and innovating on measurements of SSDH; emphasizing the involvement of scholars from diverse disciplines; and, most critically, engaging community members to ensure relevancy for public health, policy, and clinical impact.

Identification and Management of Atherosclerotic Cardiovascular Disease Risk in South Asian Populations in the U.S.

South Asians (SAs, individuals with ancestry from Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka) are among the fastest growing ethnic subgroups in the United States. SAs typically experience a high prevalence of diabetes, abdominal obesity, and hypertension, among other cardiovascular disease risk factors, which are often under recognized and undermanaged. The excess coronary heart disease risk in this growing population must be critically assessed and managed with culturally appropriate preventive services. Accordingly, this scientific document prepared by a multidisciplinary group of clinicians and investigators in cardiology, internal medicine, pharmacy, and SA-centric researchers describes key characteristics of traditional and nontraditional cardiovascular disease risk factors, compares and contrasts available risk assessment tools, discusses the role of blood-based biomarkers and coronary artery calcium to enhance risk assessment and prevention strategies, and provides evidenced-based approaches and interventions that may reduce coronary heart disease disparities in this higher-risk population.

Multi-Tiered Assessment of Gene Expression Provides Evidence for Mechanisms That Underlie Risk for Type 2 Diabetes.

Introduction: Integrated transcriptome and microRNA differential gene expression (DEG) analyses may help to explain type 2 diabetes (T2D) pathogenesis in at-risk populations. The purpose of this study was to characterize DEG in banked biospecimens from underactive adult participants who responded to a randomized clinical trial measuring the effects of lifestyle interventions on T2D risk factors. DEGs were further examined within the context of annotated biological pathways. Methods: Participants (n = 52) in a previously completed clinical trial that assessed a 12-week behavioural intervention for T2D risk reduction were included. Participants who showed >6mg/dL decrease in fasting blood glucose were identified as responders. Gene expression was measured by RNASeq, and overrepresentation analysis within KEGG pathways and weighted gene correlation network analysis (WGCNA) were performed. Results: No genes remained significantly differentially expressed after correction for multiple comparisons. One module derived by WGCNA related to body mass index was identified, which contained genes located in KEGG pathways related to known mechanisms underlying risk for T2D as well as pathways related to neurodegeneration and protein misfolding. A network analysis showed indirect connections between genes in this module and islet amyloid polypeptide (IAPP), which has previously been hypothesized as a mechanism for T2D. Discussion: We validated prior studies that showed pathways related to metabolism, inflammation/immunity, and endocrine/hormone function are related to risk for T2D. We identified evidence for new potential mechanisms that include protein misfolding. Additional studies are needed to determine whether these are potential therapeutic targets to decrease risk for T2D.

"Does Religious Service Attendance Modify the Relationship between Everyday Discrimination and Risk of Obesity? Results from the Study on Stress, Spirituality and Health".

This study examined the association of everyday discrimination with risk of obesity and the potential modifying effect of religious service attendance. Participants included Black, South Asian, and white women in three cohort studies that belong to the Study on Stress, Spirituality and Health. Logistic regression models estimated odds of obesity classification (BMI ≥ 30) relative to experiences of everyday discrimination. In initial pooled analyses, high levels of discrimination were related to increased odds of obesity. Race-specific analyses revealed marginal associations for white and South Asian women. Among Black women, high levels of discrimination and religious service attendance were both associated with higher odds of obesity. However, among women who attended religious services frequently, higher levels of everyday discrimination were associated with slightly lower odds of obesity. These findings underline the complex association between obesity and religion/spirituality, suggesting that higher levels of discrimination may uniquely activate religious resources or coping strategies. Findings highlight the need for additional studies to examine the impact of everyday discrimination on risk of obesity across racial/ethnic communities and how religious practices or coping strategies might affect these dynamics.

Association of diabetes with coronary artery calcium in South Asian adults and other race/ethnic groups: The multi-ethnic study of atherosclerosis and the mediators of atherosclerosis in South Asians living in America study.

PURPOSE: South Asian (SA) persons have increased risks for diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). We examined whether the association of DM with subclinical atherosclerosis assessed by coronary artery calcium (CAC) differs in SA versus other ethnic groups. METHODS: We studied adults from the Multi-Ethnic Study of Atherosclerosis and the Mediators of Atherosclerosis in South Asians Living in America studies without ASCVD. CAC was examined among those normoglycemic, pre-DM and DM. Logistic regression examined pre-DM and DM with the odds of any CAC > 0 and CAC ≥ 100. RESULTS: Among 7562 participants, CAC > 0 and CAC ≥ 100 in those with DM was highest in non-Hispanic White (NHW) (80% and 48%) and SA (72% and 41%) persons. Adjusted Ln (CAC + 1) was highest in NHW (3.68 ± 0.21) and SA (3.60 ± 0.23) (p < .01) DM patients. SA and NHW adults with DM (vs normoglycemic) had highest odds of CAC > 0 (2.13 and 2.27, respectively, p < .01). For CAC ≥ 100, SA and Chinese adults had the highest odds (2.28 and 2.27, respectively, p < .01). Fasting glucose and glycated hemoglobin were most strongly associated with CAC among SA. CONCLUSIONS: Diabetes mellitus most strongly relates to any CAC in SA and NHW adults and CAC ≥ 100 in SA and Chinese adults, helping to explain the relation of DM with ASCVD in these populations.

Association of lipoprotein subfractions with incidence of type 2 diabetes among five U.S. Race and Ethnic groups: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multi-Ethnic study of Atherosclerosis (MESA).

AIMS: We examined associations between lipoprotein subfractions and prevalent and incident T2D in two race/ethnically diverse cohort studies. METHODS: Adults self-identifying as White, Black, Chinese, Hispanic and South Asian-American without cardiovascular disease, with fasting serum, demographic, and clinical data at enrollment and after 5 years of follow-up were included. Lipoprotein subfractions were measured at enrollment using NMR spectrometry. LASSO regularized logistic regression models adjusted for age, sex, race/ethnicity, lipid-lowering agent use, and waist circumference assessed odds of incident T2D in pooled analyses. RESULTS: There were 4474 participants with lipoprotein subfraction data at enrollment and 3839 participants without prevalent diabetes, mean age 62 years, 51 % women, with 234 incident T2D cases at 5 years. Triglycerides in small, dense LDL-5 [OR 1.26 (95 % CI 1.11,1.43)], VLDL triglycerides 1.30** [1.16,1.46] and phospholipids in VLDL-1 [OR 1.31 (1.17,1.47)] were associated with higher odds of incident T2D, while free cholesterol in large HDL-1 [OR 0.75 (95 % CI 0.63,0.89)] was inversely associated. The results were similar for prevalent diabetes and did not vary by race/ethnic group. CONCLUSIONS: Composition of lipoprotein subfractions is differentially associated with prevalent and incident T2D without difference by race/ethnic group. Assessment of lipoprotein composition may enhance targeted risk reduction for T2D.