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 β-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.

South Asian individuals have ancestral origins from Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka, represent nearly one-quarter of the world’s population, and are the fastest growing subgroup of immigrants to the U.S., currently with over 5.4 million U.S. residents (1). India, the most populous country, had an estimated 101 million people with diabetes and 136 million with prediabetes in 2021 (2). Investigators of several older studies conducted in diaspora countries where South Asians settled generations ago (e.g., Fiji, the U.K., Singapore, and South Africa) reported that South Asian immigrants had higher type 2 diabetes prevalence compared with other local population groups (37) and that diabetes developed at younger ages among the South Asian immigrants (810). Mirroring these observations for diabetes, findings of studies also showed that South Asians have a higher prevalence and earlier age of onset for coronary heart disease compared with other population groups (6,11,12). However, up until 2010, a majority of studies among South Asian populations were of cross-sectional or case-control study designs, with no longitudinal cohorts for investigating the natural history, risk factors, or novel causes for this high burden of cardiometabolic disease.

Studying South Asian populations in the U.S. has more challenges, since all Asian American subgroups, representing individuals with origins from 23 different Asian countries, have been aggregated together in one race category in most surveys and data sets or have been excluded completely (13). The tremendous heterogeneity in ancestral backgrounds, immigration histories, and socioeconomic, linguistic, and cultural factors all have important influences on disease risks, which remain poorly measured in most national, regional, and health systems data. Additionally, when data from 23 diverse communities are aggregated into one larger “Asian American” category, most smaller population groups are rendered invisible, and important differences in disease profiles among specific Asian subgroups are obscured (14,15). Indeed, there is growing traction for more granular data collection, disaggregation, and enhanced visibility for individual Asian American subgroups (14,16,17).

With the growing numbers of several Asian population groups in the U.S., in 2011 the National Health and Nutrition Examination Survey (NHANES) began to oversample Asian Americans in the 2-year survey cycles. Cheng et al. (18) examined data from the non-Hispanic Asian sample combining three waves of NHANES data (2011–2016) and clustered the relatively small but diverse Asian American sample into three geographic origin regions: East Asian (i.e., Chinese, Japanese, and Korean), South Asian, and Southeast Asian (i.e., Filipino, Cambodian, Indonesian, Laotian, Thai, and Vietnamese). In this nationally representative survey of U.S. adults, the prevalence of diabetes (defined according to prior diagnosis, HbA1c ≥6.5%, fasting plasma glucose ≥126 mg/dL, or 2-h postchallenge glucose ≥200 mg/dL) was 23.3% for South Asian, 22.4% for Southeast Asian, and 14.0% for East Asian subgroups compared with 24.6% for Mexican, 20.4% for non-Hispanic Black, and 12.1% for non-Hispanic White adults (18). A high prevalence and incidence of diabetes among U.S. South Asians was also observed from health systems data in California (15,19) and regional surveys in New York City (20). The high and rising prevalence of diabetes among South Asians, in both native and diaspora settings, sounds alarms for better understanding the heterogeneity in the causes of diabetes and additional methods for prevention among South Asians.

Studying high-risk populations can reveal novel clues to the pathophysiology and risk factors for diseases that can inform new prevention and treatment methods, and is critical to stem the rising burden of diabetes and cardiovascular diseases globally (21,22). To better understand the causes for diabetes and atherosclerotic cardiovascular diseases (ASCVD) in U.S. South Asians, our team launched the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study in 2010 at two clinical sites in the San Francisco Bay area (at the University of California, San Francisco) and the greater Chicago area (at Northwestern University). The goals of this National Heart, Lung, and Blood Institute (NHLBI)-funded study were to create a community-based longitudinal cohort of U.S. South Asian adults, aged 40 to 84 years, using methods and measures identical to those of the ongoing Multi-Ethnic Study of Atherosclerosis (MESA) to facilitate comparisons of the South Asian sample with the White, Black, Latino, and Chinese American race and ethnic group samples in MESA (23,24). To be eligible for the MASALA study, individuals had to have at least three grandparents born in any South Asian country, have no existing cardiovascular disease (or any past procedures or surgeries on their heart or arteries), and speak English, Hindi, or Urdu (23). We completed the baseline clinical exam enrolling 906 participants from 2010–2013, conducted the second clinical exam between 2015 and 2018, and are currently in the middle of the third clinical exam (2021–2024). This original cohort was recruited using surname-based sampling frames from both geographic regions, with a 60.8% enrollment rate of those who were reached and eligible for participation (23). We expanded the cohort in 2017–2018 by adding another 258 participants (25) and are currently recruiting another 1,150 participants who identify with Bangladeshi or Pakistani origin to increase the numbers and diversity of specific South Asian subgroups represented within the MASALA study. For the newer waves of recruitment since 2017 we have used primarily community-engaged methods with population-based demographic characteristics guiding the sex, age, and educational attainment strata goals. The final cohort size will be 2,300 as of 2024. In this review, I present both published data and new analyses from our earlier recruitment waves and follow-up (from 2010–2018) focusing on diabetes.

The MASALA study participants (n = 1,164) comprise roughly equal numbers of male and female individuals; 98% were immigrants to the U.S., of whom a majority (83%) were born in India (6% from Pakistan, 1–2% in other South Asian countries, and 6% in other diaspora countries) (Fig. 1). Recent genetic ancestry analysis of the study population identified the top two axes of variation with a cline of genetic heterogeneity that included mostly individuals of north Indian origin at one end and south Indian origin at the other end, with substantial overlap between the north and south regions. In addition, there was another cluster of individuals that consisted of mostly individuals born in Gujarat (a northwestern state of India), the region with the greatest representation in the MASALA study (23%) (Fig. 1). The mean ± SD age of the study participants was 57 ± 9 years, with mean years of life in the U.S. 28 ± 12 years. The MASALA study participants have high socioeconomic status, with 86% having a bachelor’s degree or higher educational attainment and 71% with a family income ≥$75,000 per year. The data on sociodemographic characteristics of this cohort are similar to the U.S. Census data from 2010 (26) and other national surveys (13,27) showing that Asian Indian immigrants having higher socioeconomic attainment than most other groups, mainly due to the Immigration and Nationality Act of 1965 that gave preference to professionals and individuals with specialized skills (28,29). This is an important demographic characteristic for this cohort, that may provide a source of resilience and better health, and cautions against generalization of the findings to other diaspora or native South Asian populations.

Figure 1

Country of birth and genetic ancestry of MASALA study participants; n = 1,164. PC, principal components.

Figure 1

Country of birth and genetic ancestry of MASALA study participants; n = 1,164. PC, principal components.

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The prevalence of diabetes in MASALA study population was 26% based on fasting plasma glucose ≥126 mg/dL, 2-h postchallenge glucose ≥200 mg/dL, or use of a diabetes medication (30). Using data from both the original participants and the second wave of participant enrollment (2017–2018), the overall diabetes prevalence was 26%, with 32% having prediabetes and 42% had normal glucose tolerance. There were differences in glucose tolerance status by sex, with men having higher diabetes and prediabetes prevalence than women (30% for diabetes in men vs. 21% in women and 35% prediabetes in men vs. 28% in women). MASALA study participants had significantly higher diabetes prevalence compared with each of the four race and ethnic groups represented in MESA (30), which was further accentuated after serial adjustment for sociodemographic, behavioral, and other metabolic risk factors (31). After full covariate adjustment, diabetes prevalence was 27% in the MASALA study versus 7% for White, 10% for Hispanic, 13% for Chinese, and 15% for Black participants in MESA (31). Neither the MASALA study nor MESA included measurement of islet autoantibody status or other genetic markers to distinguish type 1 diabetes, latent autoimmune diabetes in adults, or maturity-onset diabetes of the young. Intriguingly, in comparisons with a contemporaneous cohort of south Indians from urban Chennai, in the southern state of Tamil Nadu, the Indian immigrants in the MASALA study had a lower prevalence of diabetes and a higher prevalence of prediabetes than those in India (32)—the first report of diabetes prevalence in India exceeding that of its emigrants to any diaspora country.

The incidence of diabetes among South Asians in the U.S. was reported to be higher than that of other U.S. race and ethnic groups in a large northern California health system (15). The overall incidence rate of type 2 diabetes from normal or prediabetes glucose tolerance was 18.9 (95% CI 12.9–25.3) per 1,000 person-years in the MASALA study, estimated after a mean 5 years of follow-up (33).

Using data from MASALA study participants without diabetes, in comparison with MESA groups, we compared surrogate measures for insulin resistance with homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β). South Asian individuals had higher levels of HOMA-IR than the four MESA groups between ages 45–65 years, with a sharp decline in HOMA-IR among those ages ≥65 years, but HOMA-β was lowest for South Asians compared with the four MESA groups across the entire age distribution (30) (Fig. 2). Similarly, levels of HOMA-IR were highest among South Asian participants with BMI between 19 and 30 kg/m2 and across the full distribution of waist circumference, while HOMA-β levels were lowest for South Asians across both measures of adiposity in comparisons with the four MESA groups (30). These findings highlight both insulin resistance and β-cell dysfunction as equally important contributors to the high burden of diabetes in South Asians (3436). Preliminary studies in Asian Indian populations suggest a more prominent role of β-cell dysfunction in dysglycemia progression (37,38) and for early-onset type 2 diabetes (39). Longer follow-up of MASALA study participants will allow us to determine relative contributions of these factors for incident diabetes compared with MESA groups.

Figure 2

Insulin resistance and insulin secretion for MASALA study compared with MESA participants. Adapted from Kanaya et al. (30).

Figure 2

Insulin resistance and insulin secretion for MASALA study compared with MESA participants. Adapted from Kanaya et al. (30).

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Bancks et al. (40) analyzed data from 1,293 participants in the MASALA study and MESA who had type 2 diabetes to define the subtypes of diabetes using age, BMI, HbA1c, HOMA-IR, and HOMA-β. Based on cluster analysis, there were five diabetes subtypes: older age at onset (44% of the entire study population), severe hyperglycemia (26%), severe obesity (20%), insulin using (9%), and younger age at onset (1%). While these diabetes subtypes are somewhat similar to what has been reported among Chinese, European, Indian, and U.S. populations (4144), we were able to contrast the distribution of diabetes subtypes in multiple race and ethnic origin groups. Among South Asians, the highest proportion of individuals had severe hyperglycemia (38%), followed by older age at onset (29%) and severe obesity (24%) diabetes subtypes (40) (Fig. 3). These findings differed dramatically from Chinese Americans, with 67% with older age at onset and much lower proportions with severe hyperglycemia and severe obesity subtypes. Those with the severe hyperglycemia subtype had higher HbA1c levels, lower BMI, and lowest HOMA-β levels, and this subtype was associated with the highest incidence of coronary artery calcification (CAC), a measure of subclinical atherosclerosis. Those of the older age at onset subtype had fewer adverse outcomes for chronic kidney disease or atherosclerosis. The severe obesity subtype with the highest BMI and HOMA-IR levels also was associated with fewer adverse outcomes after 5 years of follow-up (40). South Asians with diabetes have more β-cell dysfunction than other race and ethnic groups, but also this most common severe hyperglycemia subtype is characterized by a higher burden of atherosclerosis—not the obesity or insulin resistance subtypes. As the MASALA study population grows and ages, we will be able determine which of these subtypes is most closely linked to both microvascular and macrovascular disease events.

Figure 3

Distribution of diabetes subtypes by race/ethnic group, comparing the MASALA study with MESA. Data are from Bancks et al. (40).

Figure 3

Distribution of diabetes subtypes by race/ethnic group, comparing the MASALA study with MESA. Data are from Bancks et al. (40).

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Asian American populations have lower average body weight, height, and calculated BMI than other U.S. race and ethnic groups (45). In 2002, based on data from Asian countries, an expert panel for the World Health Organization recommended using modified cut points to classify overweight (BMI 23–27.4 kg/m2) and obesity (BMI ≥27.5 kg/m2) for public health action among Asian populations (46). We categorized MASALA study and MESA participants using these World Health Organization–recommended BMI criteria for South Asians and Chinese Americans and the standard BMI categories for other MESA groups. South Asians had intermediate levels of normal weight (25%), overweight (45%), and obesity (30%) compared with MESA participants, with the highest prevalence of normal BMI among Chinese Americans (40%) and of obesity among Black participants (45%) (47). The prevalence of two or more metabolic abnormalities (based on the National Cholesterol Education Panel Adult Treatment Panel III criteria [48]) among those with normal weight was 29% overall but was highest among the South Asian population (44%) vs. 21% in White participants, 32% in Chinese American participants, 31% in Black participants, and 38% in Latino participants (47). In multivariable models adjusted for sociodemographic measures, behavioral factors, and body composition, South Asians had 2.5-fold higher odds of two or more metabolic abnormalities compared with White individuals and 1.5- to 1.8-fold higher odds compared with the other MESA groups (47). Moreover, South Asian participants with a BMI of 19.6 kg/m2 had a prevalence of metabolic abnormalities equivalent to that of the White population, with an average BMI of 25 kg/m2—a lower BMI than that of other MESA subgroups.

The American Diabetes Association (in 2015) and the U.S. Preventive Services Task Force (in 2021) recommended diabetes screening in adults who are overweight, using the lower BMI ≥23 kg/m2 for Asian Americans (49,50). Indeed, the change to lower the BMI criterion for diabetes screening among Asian Americans was enacted after a 2015 review of epidemiologic data from diverse Asian American populations including data from the MASALA study (51,52). However, our findings that 21–44% of individuals with “normal BMI” have two or more metabolic abnormalities, recent reports of a greater increase in prevalence among populations with normal “lean” BMI in comparison with prevalence among those in the overweight or obese range in the U.S. between 2015 and 2020 (53), and well-known limitations of BMI as a surrogate marker for adiposity (5456) should prompt the American Diabetes Association and other organizations to update their guidelines for more universal screening for diabetes in adults, regardless of BMI. Some analyses have shown reasonable cost-effectiveness of opportunistic screening of younger adults (57), but optimal intervals for screening need to be determined (58,59).

Body composition differences between South Asian and White/European populations have been reported in studies over the past few decades (60,61). In earlier studies investigators quantified differences in waist circumference and central obesity with anthropometric tools, finding more central abdominal obesity in South Asian populations even at low or normal body weight and BMI (4). In the MASALA study and MESA, we used computed tomography to quantify and compare regional fat areas (subcutaneous abdominal fat, abdominal visceral fat, abdominal intermuscular fat), fat volumes (pericardial fat), tissue density (hepatic attenuation), and lean muscle mass (sum of abdominal wall muscle groups). After adjustment for sociodemographic factors, behaviors, BMI, and several metabolic risk factors, the MASALA study participants had significantly higher subcutaneous fat area, intermuscular fat area, lower hepatic attenuation (implying more liver fat), and lower lean muscle mass than all four of the MESA groups (62) (Fig. 4). Abdominal visceral fat level was higher in South Asians than in most groups but similar to that of the White population in MESA (62). In a recent meta-analysis of studies with comparison of visceral fat and liver fat between South Asian and European/White populations, investigators also found that liver fat was significantly higher among South Asians, while visceral fat quantities were similar in both population groups (63). Consequently, hormones and proteins made by adipocytes and adipose tissue were more aberrant among South Asian populations in comparison with other population groups as well (62,64). Importantly, we found that both hepatic attenuation and visceral fat were independent predictors of glycemic progression from normal glucose tolerance to impaired glucose tolerance, to impaired fasting glucose, and to diabetes among MASALA study participants (33). Additionally, Gadgil et al. (65) found that circulating levels of ceramides mediated the relationship between hepatic fat and glycemic status after 5 years of follow-up.

Figure 4

Ectopic fat and lean muscle mass in South Asians compared with MESA groups. Adapted with permission from Shah et al. (62).

Figure 4

Ectopic fat and lean muscle mass in South Asians compared with MESA groups. Adapted with permission from Shah et al. (62).

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These differences in body composition, higher levels of insulin resistance, and lower β-cell function have led to newer hypotheses for why South Asians have high diabetes prevalence in comparison with other populations (34). The higher prevalence and stronger association between the severe hyperglycemia diabetes subtype and incident atherosclerosis are important clues suggesting that β-cell dysfunction may be an important precursor for cardiovascular disease, worthy of more in-depth study (66).

We measured CAC, a marker of subclinical atherosclerosis, in all MASALA study participants at the baseline the second exam (23). CAC has been shown to be an independent predictor of ASCVD and is recommended for risk stratification (67,68). South Asian men in the MASALA study had a high CAC burden at baseline and the fastest CAC progression compared with all MESA population groups. After adjustment for traditional risk factors, both CAC burden and progression was similar for South Asian and White men, but greater than the other MESA participants; there was no significant difference in CAC burden or progression among women of all backgrounds (69,70). Diabetes is a strong independent risk factor for CAC (69). Both South Asian and White men with diabetes had higher CAC burden compared with their counterparts with normal glucose or prediabetes. Diabetes was more strongly associated with a high CAC burden (CAC >100) among both South Asian and Chinese men (approximately twice the odds) in comparison with the other MESA groups (71). Additionally, as discussed above, the most common diabetes subtype for South Asians, severe hyperglycemia, was associated with the highest risk of incident CAC (40).

Unfortunately, the proportional mortality for ischemic heart disease has been climbing among U.S. Asian Indians, from 2018 to 2020, while rates have been steadily decreasing in most other race and ethnic groups (17,22). South Asian populations have not only high prevalence and incidence of diabetes but also more rapid progression from prediabetes to diabetes (33,72) and lower β-cell function at all ages in comparison with other population groups. Therefore, measures of glycemia across the glycemic spectrum and β-cell function, not just a known diabetes diagnosis, may be more important for ASCVD risk prognostication among South Asian individuals (66). Our long-term goal in the MASALA study is to improve ASCVD risk stratification with risk models that are derived from and validated from data from South Asian populations (73).

We have measured individual-level, interpersonal level, and societal/structural-level factors in the MASALA study repeatedly over time, with the goal of better understanding which factors may be causally associated with disease, which factors may explain differences between South Asian subgroups, and those that may be modifiable for disease prevention (74). Individual-level factors that we have collected can be categorized into demographic, socioeconomic, behavioral, psychological, and biological factors. Interpersonal factors include home and family structures, social networks, discrimination, and cultural factors. Societal and structural measures include neighborhood characteristics, environmental exposures, and health care access.

Diet has been suggested as a major modifiable factor for cardiometabolic risk among South Asians (75,76). Given that the MASALA study participants are mostly first-generation immigrants to the U.S., it was important to measure the frequency and quantity of consumption of both South Asian and American food items. We used a 163-item food-frequency questionnaire that was created and validated among South Asians in Canada (77). Data from this food-frequency questionnaire have been analyzed with several different techniques to derive dietary patterns, diet scores, and other indices. Using principal components analyses, Gadgil et al. (78) found that there were three major dietary patterns that MASALA study participants consumed: 1) an animal protein pattern; 2) a fried snacks, sweets, and high-fat dairy pattern; and 3) a fruits, vegetables, nuts, and legume pattern. The animal protein pattern was associated with higher BMI, waist circumference, and total and LDL cholesterol levels; the fried snacks, sweets, and high-fat dairy pattern was associated with higher HOMA-IR and lower HDL cholesterol; and the fruits, vegetables, nuts, and legumes pattern was associated with lower odds of hypertension and the metabolic syndrome (78). Participants also reported that they perceived dietary patterns of their closest social network members to be similar to their own (79). Approximately 38% of the original MASALA study cohort reported consuming a vegetarian diet (which may include dairy and eggs but not other animal protein) (80). Interestingly, both the fried snacks, sweets, and high-fat dairy dietary pattern and the fruits, vegetables, nuts, and legume dietary pattern have mostly vegetarian major food items, but the cardiometabolic risk associations and metabolite signatures for each diet pattern were completely divergent (78,81). Compared with the four groups in MESA, the overall dietary quality, measured with the Alternative Healthy Eating Index-2010, was higher in South Asian adults, with South Asian participants consuming greater amounts of vegetables, fruit, whole grains, nuts, and legumes and fewer sugary beverages, red meat, and trans fatty acids (82).

In a prospective analysis comparing healthy versus unhealthy plant-based diet indices, Bhupathiraju et al. (83) reported that higher scores on the healthy plant-based diet index were associated with lower HbA1c, higher adiponectin levels, lower abdominal visceral fat area, lower likelihood of fatty liver and obesity, and an 18% lower odds of incident type 2 diabetes. Taken collectively, these study findings display unique dietary patterns in South Asian immigrants and that vegetarian diets may vary greatly in quality and metabolic consequences. Clinically, it is important to probe about exact food items and preparation types for a complete diet assessment. While diet is a major modifiable behavior, culturally tailored dietary advice is critical to optimize dietary quality without demonizing traditional foods.

Physical activity level is another modifiable risk factor, often found to be low and difficult to improve in South Asian individuals (76,84,85). Despite having higher socioeconomic attainment, MASALA study participants had the lowest self-reported exercise levels in comparisons with the four MESA groups (30); this was even worse among South Asian individuals with diabetes, who had the lowest levels of exercise compared with those with normal glucose or prediabetes (86). More time spent in sedentary activity such as television viewing was associated with higher total and regional adiposity after adjustment for exercise and other confounders (87). In a prospective analysis, we also found that more minutes of television watching was associated with greater risk of incident diabetes after adjustment for sociodemographic and other behavioral characteristics. Clearly, finding newer methods to promote physical activity, starting earlier in life (88), is critical to improving risk factors for diabetes and other chronic diseases.

Kandula led an ancillary study in the MASALA study to map the social networks of the study participants, both with individuals and organizational affiliations in the networks. We found that South Asian participants had large, dense, and kin-centered social networks (89). Social networks were sources of emotional closeness, perceived as being beneficial to health. Just as dietary pattern was found to be similar among participants’ social networks (79), physical activity was also similar within networks, but there were sex-specific differences. South Asian men who exercised with a nonspousal exercise partner had more minutes of exercise than those without exercise partners; for women, this association was only observed with a spousal exercise partner (90). Using qualitative interviews with participants and a mixed-methods approach, Ram et al. (91) found that adult children of MASALA study participants had influence on parents’ health behaviors including better dietary quality and physical activity. Taken collectively, our findings show how the strong and dense social networks among South Asian immigrants are important for wellness and can be leveraged to promote healthier behaviors (92).

Another construct with both interpersonal and individual-level components is the experience of acculturation among immigrant populations (93). Needham and colleagues used nine survey items in the MASALA study to create three distinct acculturation strategy groups using latent class analysis (9496). In updated analyses including the second wave of MASALA study participants and additional cultural measures, the three main acculturation strategies included the separation class (21% of the study population), who retained preference for mostly South Asian cultural beliefs; the integration class (49%), characterized by similar level of preference for South Asian and U.S. cultures; and the assimilation class (30%), who have relatively high degree of preference for U.S. culture. Individuals in the separation class were more likely to be women and to have fewer years of life in the U.S., lower level of education and family income, lower levels of exercise, and lower tobacco and alcohol use; a higher proportion consumed the fried snacks, sweets, and high-fat dairy dietary pattern than among those in the other two strategies (Fig. 5). In contrast, people in the assimilation class had lived longer in the U.S., had higher socioeconomic attainment, reported higher exercise levels, higher tobacco, and alcohol intake, and consumed more of the animal protein dietary pattern. Those in the separation class had higher depressive symptoms than those in the integration class, while there were no differences between the integration and assimilation classes (97). In cross-sectional analyses, Al-Sofiani et al. (98) reported that women in the assimilation class had lower BMI, waist circumference, and triglycerides and higher HDL cholesterol compared with women in the separation class after accounting for other sociodemographic factors. In preliminary analyses of change in cardiometabolic risk factors over 5 years, those in the separation class had a greater increase in fasting glucose levels, while those in the assimilation class had greater increase in weight and waist circumference, with the integration (bicultural) class having the most favorable risk profile. Future waves of data collection, with the inclusion of more recent Pakistani and Bangladeshi immigrant populations, and including updating acculturation categories with aging in the original MASALA study population, will enable more nuanced analyses of acculturation among and between South Asian subgroups (74).

Figure 5

Acculturation strategies among MASALA study participants, 2010–2018. Values show mean prevalence (%) or years lived in the U.S. SA, South Asian; SES, socioeconomic status.

Figure 5

Acculturation strategies among MASALA study participants, 2010–2018. Values show mean prevalence (%) or years lived in the U.S. SA, South Asian; SES, socioeconomic status.

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Neighborhood environments can influence behaviors, mental health, and cardiometabolic risk. Lagisetty et al. (99) found that South Asian women living in neighborhoods with high social cohesion had almost half the odds of hypertension in comparison with those in low cohesion areas. Other geospatial measurements of neighborhood walkability, area-level deprivation, and air pollution are underway.

Levels of a persistent organic pollutant, dichlorodiphenyltrichloroethane (DDT), were 8- to 12-fold higher in the pilot MASALA study participants than in contemporaneous populations in the U.S. and California; higher levels of DDT and related chemicals were associated higher adiposity and insulin levels and greater odds of prevalent diabetes and fatty liver (100). More detailed organic chemical exposure measurements are currently underway for the original cohort in collaboration with the Human Health Exposure Analysis Resource.

The MASALA study established a model for collecting multilevel data in understudied populations to facilitate comparisons with ongoing cohort studies both in the U.S. and globally (32), and included use of mixed-methods approaches to provide deeper insights to answer the why and how questions. The MASALA study is expanding to collect longitudinal data on three South Asian subgroups, with deeper -omics phenotyping and plans to measure cognitive aging. As the study population ages, we will be able to compare and contrast disease outcomes with those of several other groups and provide more granular insights to inform prevention and treatment strategies. We have found that South Asians have higher prevalence and incidence of diabetes, with a higher proportion with severe hyperglycemia subtype characterized by lower β-cell function. South Asian population groups on average also have more adverse body composition, higher levels of insulin resistance, and adverse adipokine levels, contributing to the development of diabetes. Importantly, there are several modifiable behaviors that may be better targeted for change using key social network members, and bicultural beliefs and behaviors may have healthier outcomes than either traditional or assimilating strategies in the U.S. context.

There are several opportunities to contrast several diverse and understudied Asian American and Native Hawaiian and Pacific Islander (NHPI) populations with different ancestral backgrounds, cultural traditions, immigration experiences, and risk factor profiles (14). Recently, the National Institutes of Health introduced new grant opportunities (Notice of Special Interest, NOT-23-001) to remedy prior funding disparities (101), address gaps in knowledge, and harness the scientific potential among these population groups (14). The NHLBI and other institutes have dedicated funding to create a new longitudinal cohort among specific Asian American and NHPI population groups that is expected to launch in 2025. Broader and deeper representation from several Asian and NHPI ancestral groups defines a new path forward for diabetes epidemiology and prevention science. Having a better understanding of the heterogeneity of disease etiology, risk factors, trajectories, and outcomes has the potential to benefit humanity.

This article is featured in a podcast available at diabetesjournals.org/care/pages/diabetes_care_on_air.

The 2023 Kelly West Award Lecture was presented at the American Diabetes Association’s 83rd Scientific Sessions, San Diego, CA, 24 June 2023.

Acknowledgments. A.M.K. thanks the late Dr. Elizabeth Barrett-Connor for inspiring her to pursue this line of research. A.M.K. is also grateful for many influential mentors, including Drs. Deborah Grady, David Herrington, the late Stephen Hulley, Kiang Liu, and Morris Schambelan. A.M.K. thanks her long-term colleagues and collaborators for their continued insights and support including Drs. Namratha Kandula, K.M. Venkat Narayan, M.R. Happy Araneta, and Nadia Islam. A.M.K. thanks Drs. Namratha Kandula, Meghana Gadgil, and the late Teresa Hillier for their valuable input on the content of this talk and Drs. Elad Ziv and Scott Huntsman for their assistance with the genetic ancestry analysis. Finally, the MASALA study would not be possible without the dedication of the MASALA study staff and team and the time and effort of the MASALA study participants.

Funding. The MASALA study was funded by the NHLBI, National Institutes of Health (grants 2R01HL093009 and 2K24HL112827).

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

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