Explore the vast range of titles available.

The rising prevalence of diabetes in South Asians has significant health and economic implications. South Asians are predisposed to the development of diabetes due to biologic causes which are exacerbated by lifestyle and environmental factors. Furthermore, they experience significant morbidity and mortality from complications of diabetes, most notably coronary artery disease, cerebrovascular disease, and chronic kidney disease. Therefore, understanding the pathophysiology and genetics of diabetes risk factors and its associated complications in South Asians is paramount to curbing the diabetes epidemic. With this understanding, the appropriate screening, preventative and therapeutic strategies can be implemented and further developed. In this review, we discuss in detail the biologic and lifestyle factors that predispose South Asians to diabetes and review the epidemiology and pathophysiology of microvascular and macrovascular complications of diabetes in South Asians. We also review the ongoing and completed diabetes prevention and management studies in South Asians.

The Pooled Cohort Equations (PCEs) do not accurately estimate atherosclerotic cardiovascular disease (ASCVD) risk in certain populations. The 2018 AHA/ACC cholesterol guideline identified risk-enhancing factors as a supplement to PCEs-based risk assessment. However, the role of each risk-enhancing factor in ASCVD risk assessment has not been well quantified. Further, social determinants of health (SDOH) are not included in the PCEs nor considered as risk-enhancing factors in the US cholesterol guideline. We sought to evaluate ASCVD risk associated with each risk-enhancing factor and commonly collected SDOH including education, income, and employment status, and to assess if adding risk-enhancing factors and SDOH to the PCEs improve ASCVD risk prediction. We included individuals aged 40 to 75 years, without ASCVD or diabetes at baseline, and with low-density lipoprotein cholesterol 70-189 mg/dL from two contemporary prospective cohort studies (MESA and REGARDS) and from Kaiser Permanente Southern California (KPSC). The primary endpoint was incident ASCVD defined as nonfatal myocardial infarction, fatal coronary heart disease, or fatal or nonfatal stroke over a 10-year period (median follow-up 10 years). We used Cox proportional hazards models to estimate associations between risk-enhancing factors and SDOH with ASCVD. We also assessed changes in model performance after adding risk-enhancing factors and SDOH to the PCEs. We included 13,863 adults (mean age 60.7 years) from the prospective cohorts and 307,931 adults (mean age 54.8 years) from KPSC. Risk-enhancing factors including hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and chronic kidney disease were associated with a higher ASCVD risk, independent of 10-year risk estimated by the PCEs. Low education, low income, and unemployment were also associated with higher ASCVD risk. While adding individual risk-enhancing factors or SDOH to the PCEs had limited impact on model performance, adding multiple risk-enhancing factors and SDOH simultaneously led to modest improvements in discrimination (C-index increased by up to 0.07), calibration (integrated Brier score reduced by up to 2.3%), and net reclassification improvement up to 41.4%. These findings suggest including SDOH and risk-enhancing factors may improve ASCVD risk assessment.

We sought to report the distribution of Lp(a) levels in the Mediators of Atherosclerosis among South Asians Living in America cohort of participants who were free from clinical atherosclerotic cardiovascular disease (ASCVD) at baseline and to evaluate the cross-sectional association with atherosclerosis measured by coronary artery calcification (CAC) and carotid intima media thickness. Among 886 participants (mean [SD] age: 55.4 [9.4] years, 54% male), median lipoprotein (a) level was 17 (9, 33) mg/dl. Compared with the lowest quartile (9 mg/dl), subjects in the highest Lp(a) quartile (33 to 178 mg/dl) were more likely to be women (51% vs 37%, p <0.01) and had a higher mean (SD) total cholesterol (193 [37] mg/dl vs 181 [35] mg/dl, p <0.01). CAC was present in 42% and both the presence and degree of CAC was similar across Lp(a) quartiles (p = 0.58). Median Interquartile range (IQR) common and internal carotid intima-media thickness (IMT) thicknesses were 0.84 (0.73, 0.98) mm and 1.12 (0.95, 1.34) mm, respectively, and were also similar across Lp(a) quartiles. After adjustment for cardiovascular risk factors, Lp(a) quartile had no association with prevalent CAC (p = 0.98), internal carotid IMT (p = 0.46), or common carotid IMT (p = 0.97). Among South Asian Americans, mean Lp(a) levels were higher than previous reports among Whites, Hispanic/Latino, and Chinese-Americans but lower than in Blacks. Unlike findings from other race/ethnic groups, Lp(a) levels were not associated with atherosclerosis among South Asian Americans.

To study the relationship between body mass index (BMI) and central obesity and mortality in elderly patients with coronary artery disease (CAD). We identified 7057 patients 65 years or older from 5 cohort studies assessing mortality risk using either waist circumference (WC) or waist-hip ratio (WHR) in patients with CAD from January 1, 1980, to December 31, 2008. Normal weight, overweight, and obesity were defined using standard BMI cutoffs. High WHR was defined as 0.85 or more for women and 0.90 or more for men. High WC was defined as 88 cm or more for women and 102 cm or more for men. Separate models examined WC or WHR in combination with BMI (6 categories each) as the primary predictor (referent = normal BMI and normal WC or WHR). Cox proportional hazards models investigated the relationship between these obesity categories and mortality. Patients' mean age was 73.0±6.0 years (3741 [53%] women). The median censor time was 7.1 years. A normal BMI with central obesity (high WHR or high WC) demonstrated highest mortality risk (hazard ratio [HR], 1.29; 95% CI, 1.14-1.46; HR, 1.29; 95% CI, 1.12-1.50, respectively). High WHR was also predictive of mortality in the overall (HR, 2.14; 95% CI, 1.93-2.38) as well as in the sex-specific cohort. In the overall cohort, high WC was not predictive of mortality (HR, 1.04; 95% CI, 0.97-1.12); however, it predicted higher risk in men (HR, 1.12; 95% CI, 1.01-1.24). In older adults with CAD, normal-weight central obesity defined using either WHR or WC is associated with high mortality risk, highlighting a need to combine measures in adiposity-related risk assessment.

We examined whether abuse in childhood and/or adolescence was associated with shorter telomere length in a pooled analysis of 3,232 participants from five diverse cohorts. We also assessed whether religion or spirituality (R/S) could buffer deleterious effects of abuse. Physical and sexual abuse in childhood (age <12) and adolescence (age 12-18) was assessed using the Revised Conflict Tactics Scale and questions from a 1995 Gallup survey. We measured relative leukocyte telomere lengths (RTL) using quantitative real time polymerase chain reaction. We used generalized estimating equations to assess associations of physical and sexual abuse with log-transformed RTL z-scores. Analyses were conducted in each cohort, overall, and stratified by extent of religiosity or spirituality and religious coping in adulthood. We pooled study-specific estimates using random-effects models and assessed between-study heterogeneity. Compared to no abuse, severe sexual abuse was associated with lower RTL z-scores, in childhood: -15.6%, 95% CI: -25.9, -4.9; p-trend = 0.04; p-heterogeneity = 0.58 and in adolescence: -16.5%, 95% CI: -28.1, -3.0; p-trend = 0.08; p-heterogeneity = 0.68. Sexual abuse experienced in both childhood and adolescence was associated with 11.3% lower RTL z-scores after adjustment for childhood and demographic covariates (95% CI: -20.5%, -2.0%; p-trend = 0.03; p-heterogeneity = 0.62). There was no evidence of effect modification by R/S. Physical abuse was not associated with telomere length. Sexual abuse in childhood or adolescence was associated with a marker of accelerated biological aging, decreased telomere length. The lack of moderation by R/S may be due to inability to capture the appropriate time period for those beliefs and practices.

MicroRNAs (miRNAs) may be considered important regulators of risk for type 2 diabetes (T2D). The aim of the present study was to identify novel sets of miRNAs associated with T2D risk, as well as their gene and pathway targets. Circulating miRNAs (n=59) were measured in plasma from participants in a previously completed clinical trial (n=82). An agnostic statistical approach was applied to identify novel sets of miRNAs with optimal co-expression patterns. In silico analyses were used to identify the messenger RNA and biological pathway targets of the miRNAs within each factor. A total of three factors of miRNAs were identified, containing 18, seven and two miRNAs each. Eight biological pathways were revealed to contain genes targeted by the miRNAs in all three factors, 38 pathways contained genes targeted by the miRNAs in two factors, and 55, 18 and two pathways were targeted by the miRNAs in a single factor, respectively (all q<0.05). The pathways containing genes targeted by miRNAs in the largest factor shared a common theme of biological processes related to metabolism and inflammation. By contrast, the pathways containing genes targeted by miRNAs in the second largest factor were related to endocrine function and hormone activity. The present study focused on the pathways uniquely targeted by each factor of miRNAs in order to identify unique mechanisms that may be associated with a subset of individuals. Further exploration of the genes and pathways related to these biological themes may provide insights about the subtypes of T2D and lead to the identification of novel therapeutic targets.

South Asians have a high prevalence of type 2 diabetes, even at a lower BMI. This review sets out our perspective and hypothesis on the reasons for this. Emerging data from epidemiological studies indicate that South Asians may have a lower ability to secrete insulin, and thus may have less compensatory reserves when challenged with unhealthy lifestyles. Thus, insulin resistance may not be the primary driver of type 2 diabetes in this population. Furthermore, data also suggest that South Asians, on average, have lower muscle mass, and may have a specific propensity to ectopic hepatic fat accumulation and for intramyocellular fat deposition, which cause further disruption in insulin action. We hypothesise that the high diabetes susceptibility in South Asians is evolutionarily set through dual parallel and/or interacting mechanisms: reduced beta cell function and impaired insulin action owing to low lean mass, which is further accentuated by ectopic fat deposition in the liver and muscle. These areas warrant further research.

Body shape is a known risk factor for diabetes and mortality, but the methods estimating body shape, BMI and waist circumference are crude. We determined whether a novel body shape measure, trunk to leg volume ratio, was independently associated with diabetes and mortality. Data from the National Health and Nutritional Examination Survey 1999-2004, a study representative of the US population, were used to generate dual-energy X-ray absorptiometry-derived trunk to leg volume ratio and determine its associations to diabetes, metabolic covariates, and mortality by BMI category, gender, and race/ethnicity group. The prevalence of pre-diabetes and diabetes increased with age, BMI, triglycerides, blood pressure, and decreased HDL level. After adjusting for covariates, the corresponding fourth to first quartile trunk to leg volume ratio odds ratios (OR) were 6.8 (95% confidence interval [CI], 4.9-9.6) for diabetes, 3.9 (95% CI, 3.0-5.2) for high triglycerides, 1.8 (95% CI, 1.6-2.1) for high blood pressure, 3.0 (95% CI, 2.4-3.8) for low HDL, 3.6 (95% CI, 2.8-4.7) for metabolic syndrome, and 1.76 (95% CI, 1.20-2.60) for mortality. Additionally, trunk to leg volume ratio was the strongest independent measure associated with diabetes (P<0.001), even after adjusting for BMI and waist circumference. Even among those with normal BMI, those in the highest quartile of trunk to leg volume ratio had a higher likelihood of death (5.5%) than those in the lowest quartile (0.2%). Overall, trunk to leg volume ratio is driven by competing mechanisms of changing adiposity and lean mass. A high ratio of trunk to leg volume showed a strong association to diabetes and mortality that was independent of total and regional fat distributions. This novel body shape measure provides additional information regarding central adiposity and appendicular wasting to better stratify individuals at risk for diabetes and mortality, even among those with normal BMI.

Background Psychosocial stressors increase the risks for cardiovascular disease across diverse populations. However, neighborhood level resilience resources may protect against poor cardiovascular health (CVH). This study used data from three CVH cohorts to examine longitudinally the associations of a resilience resource, perceived neighborhood social cohesion (hereafter referred to as neighborhood social cohesion), with the American Heart Association’s Life’s Simple 7 (LS7), and whether psychosocial stressors modify observed relationships. Methods We examined neighborhood social cohesion (measured in tertiles) and LS7 in the Jackson Heart Study, Multi-Ethnic Study of Atherosclerosis, and Mediators of Atherosclerosis in South Asians Living in America study. We used repeated-measures, modified Poisson regression models to estimate the relationship between neighborhood social cohesion and LS7 (primary analysis, n = 6,086) and four biological metrics (body mass index, blood pressure, cholesterol, blood glucose; secondary analysis, n = 7,291). We assessed effect measure modification by each psychosocial stressor (e.g., low educational attainment, discrimination). Results In primary analyses, adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) for ideal/intermediate versus poor CVH among high or medium (versus low) neighborhood social cohesion were 1.01 (0.97–1.05) and 1.02 (0.98–1.06), respectively. The psychosocial stressors, low education and discrimination, functioned as effect modifiers. Secondary analyses showed similar findings. Also, in the secondary analyses, there was evidence for effect modification by income. Conclusion We did not find much support for an association between neighborhood social cohesion and LS7, but did find evidence of effect modification. Some of the effect modification results operated in unexpected directions. Future studies should examine neighborhood social cohesion more comprehensively and assess for effect modification by psychosocial stressors.

Blood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to assess the potential influence of religiosity/spirituality (R/S) on significant protein-CVD associations, in South Asians from the MASALA Study. We used a nested case–control design of 50 participants with incident CVD and 50 sex- and age-matched controls. Plasma samples were analyzed by SOMAscan for expression of 1305 proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates, with further effect modification analyses conducted to assess the influence of R/S measures on significant associations between proteins and incident CVD events. We identified 36 proteins that were significantly expressed differentially among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5 [CNTN5], Low affinity immunoglobulin gamma Fc region receptor II-a [FCGR2A], and Complement factor B [CFB]) associated with incident CVD after adjustment for diabetes (AUC = 0.82). Religious struggles that exacerbate the adverse impact of stressful life events, significantly modified the effect of Contactin-5 and Complement factor B on risk of CVD. Our research is this first assessment of the relationship between protein concentrations and risk of CVD in a South Asian sample. Further research is needed to understand patterns of proteomic profiles across diverse ethnic communities, and the influence of resources for resiliency on proteomic signatures and ultimately, risk of CVD.