South Asians in the United States have disproportionately high burden of cardiovascular disease compared to other race/ethnic groups but are a heterogenous population, so we evaluated differences in prevalence and adjusted odds of cardiovascular risk factors including diabetes, hypertension, dyslipidemia, and obesity between North Indian, South Indian, and Pakistani immigrants in the United States in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Given cultural differences among residents of Indian regions, for example in dietary patterns, we categorized Indian participants as North or South Indian. In 1,018 participants (728 North Indian [47% women], 223 South Indian [43% women], 67 Pakistani [52% women]), unadjusted diabetes and obesity prevalence was highest in Pakistani participants (33% and 48%, respectively); hypertension prevalence was highest in North Indian participants (54%); dyslipidemia prevalence was highest in South Indian and Pakistani participants (55%); and South Indian participants had a higher odds of dyslipidemia (OR 1.77, 95% CI 1.27, 2.47) compared with North Indian participants in fully adjusted models. As differences in cardiovascular risk factors were observed across South Asian American subgroups, identifying the determinants of suboptimal cardiovascular health within South Asian American subgroups may help to better tailor cardiovascular disease prevention strategies.

Aims/hypothesis: South Asians have a two- to fivefold higher risk of developing type 2 diabetes than those of white European descent. Greater central adiposity and storage of fat in deeper or ectopic depots are potential contributing mechanisms. We collated existing and new data on the amount of subcutaneous (SAT), visceral (VAT) and liver fat in adults of South Asian and white European descent to provide a robust assessment of potential ethnic differences in these factors. Methods: We performed a systematic review of the Embase and PubMed databases from inception to August 2021. Unpublished imaging data were also included. The weighted standardised mean difference (SMD) for each adiposity measure was estimated using random-effects models. The quality of the studies was assessed using the ROBINS-E tool for risk of bias and overall certainty of the evidence was assessed using the GRADE approach. The study was pre-registered with the OSF Registries (https://osf.io/w5bf9). Results: We summarised imaging data on SAT, VAT and liver fat from eight published and three previously unpublished datasets, including a total of 1156 South Asian and 2891 white European men, and 697 South Asian and 2271 white European women. Despite South Asian men having a mean BMI approximately 0.5–0.7 kg/m2 lower than white European men (depending on the comparison), nine studies showed 0.34 SMD (95% CI 0.12, 0.55; I2=83%) more SAT and seven studies showed 0.56 SMD (95% CI 0.14, 0.98; I2=93%) more liver fat, but nine studies had similar VAT (−0.03 SMD; 95% CI −0.24, 0.19; I2=85%) compared with their white European counterparts. South Asian women had an approximately 0.9 kg/m2 lower BMI but 0.31 SMD (95% CI 0.14, 0.48; I2=53%) more liver fat than their white European counterparts in five studies. Subcutaneous fat levels (0.03 SMD; 95% CI −0.17, 0.23; I2=72%) and VAT levels (0.04 SMD; 95% CI −0.16, 0.24; I2=71%) did not differ significantly between ethnic groups in eight studies of women. Conclusions/interpretation: South Asian men and women appear to store more ectopic fat in the liver compared with their white European counterparts with similar BMI levels. Given the emerging understanding of the importance of liver fat in diabetes pathogenesis, these findings help explain the greater diabetes risks in South Asians. Funding: There was no primary direct funding for undertaking the systematic review and meta-analysis. Graphical abstract: [Figure not available: see fulltext.]

Introduction: Several interventions have been found to be effective for reversing prediabetes in adults. This systematic review and meta-analysis aims to compare the effectiveness of such interventions. Methods: MEDLINE, Embase, and Cochrane Library databases were searched for articles published between January 1, 2000 and June 27, 2018. RCTs in adults with prediabetes, testing nonsurgical interventions lasting for ≥3 months, and reporting the number of participants achieving normal glucose levels at intervention end were eligible. The pooled risk difference and number needed to treat for achieving normoglycemia were estimated using a random-effects, arm-based network meta-analysis. The strength of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. Data were obtained in 2018 and analyzed in 2019 and 2021. Results: Of 54 studies included in the systematic review, 47 were meta-analyzed (n=26,460, mean age=53 years, 46% male, 31% White). Studies included 27 arms testing lifestyle modification interventions, 25 testing medications, 5 testing dietary supplements, and 10 testing Chinese medicine. There were 35 control/placebo arms. At a median follow-up of 1.6 years, more participants in the lifestyle modification groups achieved normoglycemia than those in the control (risk difference=0.18, number needed to treat=6). The strength of the evidence was strong for lifestyle modification. Over a median follow-up of 2.7 years, more participants receiving glucagon-like peptide-1 receptor agonists (risk difference=0.47, number needed to treat=2), α-glucosidase inhibitors (risk difference=0.29, number needed to treat=4), and insulin sensitizers (risk difference=0.23, number needed to treat=4) achieved normoglycemia than control. The strength of evidence was moderate for these medications. Discussion: Although several pharmacological approaches can reverse prediabetes, lifestyle modification provides the strongest evidence of effectiveness and should remain the recommended approach to address this condition.

Aims: To determine whether obesity-associated metabolites are associated with type 2 diabetes (T2DM) risk among South Asians. Materials and Methods: Serum-based nuclear magnetic resonance imaging metabolomics data were generated from two South Asian population-based prospective cohorts from Karachi, Pakistan: CARRS1 (N = 4017) and CARRS2 (N = 4802). Participants in both cohorts were followed up for 5 years and incident T2DM was ascertained. A nested case-control study approach was developed to select participants from CARRS1 (Ncases = 197 and Ncontrols = 195) and CARRS2 (Ncases = 194 and Ncontrols = 200), respectively. First, we investigated the association of 224 metabolites with general obesity based on body mass index and with central obesity based on waist-hip ratio, and then the top obesity-associated metabolites were studied in relation to incident T2DM. Results: In a combined sample of the CARRS1 and CARRS2 cohorts, out of 224 metabolites, 12 were associated with general obesity and, of these, one was associated with incident T2DM. Fifteen out of 224 metabolites were associated with central obesity and, of these, 10 were associated with incident T2DM. The higher level of total cholesterol in high-density lipoprotein (HDL) was associated with reduced T2DM risk (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.53, 0.86; P = 1.2 × 10−3), while higher cholesterol esters in large very-low-density lipoprotein (VLDL) particles were associated with increased T2DM risk (OR 1.90, 95% CI 1.40, 2.58; P = 3.5 × 10−5). Conclusion: Total cholesterol in HDL and cholesterol esters in large VLDL particles may be an important biomarker in the identification of early development of obesity-associated T2DM risk among South Asian adults.

Aim: To assess the level of glycemic, blood pressure, and cholesterol control (the ‘ABCs’) nationally amongst adults with diabetes living in Kuwait. Materials and Methods: Using data from two national cross-sectional surveys, the levels of risk factor control were assessed in 1,801 adults with diabetes, aged 18–82 years. Glycemic control was defined as HbA1c < 7%, blood pressure control as systolic and diastolic blood pressures of <140/90 mmHg, and non-HDL cholesterol control as <3.4 mmol/L. Results: The percentage of adults with diabetes achieving control was 39.2% (95% CI, 37.0–41.5) for glycemia, 58.4% (95% CI, 56.0–60.7) for blood pressure, and 28.3% (95% CI, 26.3–30.4) for non-HDL cholesterol. The percentage of adults who were non-smokers was 77.6% (95%, CI 75.6–79.4). The percentage of adults with diabetes achieving control on all three risk factors was 7.4% (95% CI, 6.3–8.8), and only 5.8% (95% CI, 4.8–7.0) achieved ABC control and were nonsmokers. ABC control was 30% higher in women compared with men. Non-Kuwaitis were almost twice as likely to have uncontrolled ABC factors compared with Kuwaitis. Conclusions: Only 1 in 13 people with diabetes in Kuwait achieved good control of glycemia, blood pressure, and cholesterol. Only 2 in 5 achieved glycemic control, 6 in 10 blood pressure control, and 2 in 7 cholesterol control. A national diabetes quality improvement program is urgently needed to improve the quality of care and to prevent long-term complications.

OBJECTIVES: Latent Tuberculosis infection (LTBI) is marked by dynamic host-pathogen interactions with persistent low-grade inflammation and is associated with increased risk of cardiovascular diseases (CVD) including acute coronary syndrome, myocardial infarction, and stroke. However, few studies assess the relationship between LTBI and hypertension, an intermediate of CVD. We sought to determine the association between LTBI and hypertension using data representative of the adult US population. METHODS: We performed cross-sectional analyses using data from the 2011-2012 US National Health and Nutrition Examination Survey (NHANES). Eligible participants included adults with valid QuantiFERON-TB Gold In-Tube (QFT-GIT) test results who also had blood pressure measures and no history of TB disease. LTBI was defined by a positive QFT-GIT. We defined hypertension by either elevated measured blood pressure levels (i.e., systolic ≥130mmHg or diastolic ≥80mmHg) or known hypertension indications (i.e., self-reported previous diagnosis or use of antihypertensive medications). Analyses were performed using robust quasi-Poisson regressions and accounted for the stratified probability sampling design of NHANES. RESULTS: The overall prevalence of LTBI was 5.7% (95%CI 4.7-6.7) and hypertension was present among 48.9% (95%CI 45.2-52.7) of participants. The prevalence of hypertension was higher among those with LTBI (58.5%, 95%CI 52.4-64.5) than those without LTBI (48.3%, 95%CI 44.5-52.1) (prevalence ratio [PR]=1.2, 95%CI 1.1-1.3). However, after adjusting for confounders, the prevalence of hypertension was similar for those with and without LTBI (adjusted PR=1.0, 95%CI 0.9 -1.1). Among individuals without CVD risk factors of elevated BMI (PRnormal BMI=1.6, 95%CI 1.2-2.0), hyperglycemia (PReuglycemia=1.3, 95%CI 1.1-1.5), or cigarette smoking (PRnon-smokers=1.2, 95%CI 1.1-1.4), the unadjusted prevalence of hypertension was higher among those with LTBI vs. no LTBI. CONCLUSIONS: More than half of adults with LTBI in the US had hypertension. Importantly, we observed a relationship between LTBI and hypertension among those without established CVD risk factors.

South Asian individuals in the United States are at an increased risk of type 2 diabetes (T2DM); however, the mechanisms behind this are not well understood. The Mediators of Atherosclerosis in South Asians Living in America (MASALA) study is the only longitudinal cohort of South Asians in the United States and provides key insights as to the epidemiology of T2DM in South Asians. Evidence from the MASALA study suggests that South Asians experience a disproportionately high burden of prevalent and incident T2DM compared with members of other race/ethnic groups. Higher insulin resistance in South Asians, even with low body mass index (BMI), more impairment in insulin secretion, and greater deposition of ectopic fat likely play a role in T2DM etiology. Furthermore, South Asian migrants to the United States experience a range of factors related to acculturation, social networks, and religious beliefs, which may impact physical activity and dietary practices. Interventions to prevent T2DM in South Asians should include a focus on cultural factors related to health and should consider the complete mechanistic pathway and the relative contributions of insulin resistance, β cell dysfunction, and ectopic fat deposition on T2DM development in South Asians, particularly in those with lower BMI.

OBJECTIVE: Many patients with hyperglycemic crises present with combined features of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). The implications of concomitant acidosis and hyperosmolality are not well known. We investigated hospital outcomes in patients with isolated or combined hyperglycemic crises. RESEARCH DESIGN AND METHODS: We analyzed admissions data listing DKA or HHS at two academic hospitals. We determined 1) the frequency distributions of HHS, DKA, and combined DKA-HHS (DKA criteria plus elevated effective osmolality); 2) the relationship of markers of severity of illness and clinical comorbidities with 30-day all-cause mortality; and 3) the relationship of hospital complications associated with insulin therapy (hypoglycemia and hypokalemia) with mortality. RESULTS: There were 1,211 patients who had a first admission with confirmed hyperglycemic crises criteria, 465 (38%) who had isolated DKA, 421 (35%) who had isolated HHS, and 325 (27%) who had combined features of DKA-HHS. After adjustment for age, sex, BMI, race, and Charlson Comorbidity Index score, subjects with combined DKA-HHS had higher in-hospital mortality compared with subjects with isolated hyperglycemic crises (adjusted odds ratio [aOR] 2.7; 95% CI 1.4, 4.9; P = 0.0019). In all groups, hypoglycemia (<40 mg/dL) during treatment was associated with a 4.8fold increase in mortality (aOR 4.8; 95% CI 1.4, 16.8). Hypokalemia ≤3.5 mEq/L was frequent (55%). Severe hypokalemia (≤2.5 mEq/L) was associated with increased inpatient mortality (aOR 4.9; 95% CI 1.3, 18.8; P = 0.02). CONCLUSIONS: Combined DKA-HHS is associated with higher mortality compared with isolated DKA or HHS. Severe hypokalemia and severe hypoglycemia are associated with higher hospital mortality in patients with hyperglycemic crises.

OBJECTIVE: To assess the prevalence of diabetes and prediabetes and the associated risk factors in two Asian Indian populations living in different environments. RESEARCH DESIGN AND METHODS: We performed cross-sectional analyses, using representative samples of 2,305 Asian Indians aged 40-84 years living in Chennai, India, from the Centre for cArdiometabolic Risk Reduction in South-Asia study (CARRS) (2010-2011), and 757 Asian Indians aged 40-84 years living in the greater San Francisco and Chicago areas from the U.S. Mediators of Atherosclerosis in South Asians Living in America (MASALA) study (2010-2013). Diabetes was defined as self-reported use of glucose-lowering medication, fasting glucose ≥126 mg/dL, or 2-h glucose ≥200 mg/dL. Prediabetes was defined as fasting glucose 100-125 mg/dL and/or 2-h glucose 140-199 mg/dL. RESULTS: Age-adjusted diabetes prevalence was higher in India (38% [95% CI 36-40]) than in the U.S. (24% [95% CI 21-27]). Age-adjusted prediabetes prevalence was lower in India (24% [95% CI 22-26]) than in the U.S. (33% [95% CI 30-36]). After adjustment for age, sex, waist circumference, and systolic blood pressure, living in the U.S. was associated with an increased odds for prediabetes (odds ratio 1.2 [95% CI 0.9-1.5]) and a decreased odds for diabetes (odds ratio 0.5 [95% CI 0.4-0.6]). CONCLUSIONS: These findings indicate possible changes in the relationship between migration and diabetes risk and highlight the growing burden of disease in urban India. Additionally, these results call for longitudinal studies to better identify the gene-environment-lifestyle exposures that underlie the elevated risk for type 2 diabetes development in Asian Indians.

Traditionally, fasting and 2-hour post challenge plasma glucose have been used to diagnose diabetes. However, evidence indicates that clinically relevant pathophysiological information can be obtained by adding intermediate time-points to a standard oral glucose tolerance test (OGTT). Methods We studied a population-based sample of 3666 Asian Indians without diabetes from the CARRS-Chennai Study, India. Participants underwent a three-point (fasting, 30-min, and 2-h) OGTT at baseline. Patterns of glycemic response during OGTT were identified using latent class mixed-effects models. After a median follow-up of two years, participants had a second OGTT. Logistic regression adjusted for diabetes risk factors was used to compare risk of incident diabetes among participants in different latent classes. Results We identified four latent classes with different glucose patterns (Classes 1–4). Glucose values for Classes 1, 2, and 4 ranked consistently at all three time-points, but at gradually higher levels. However, Class 3 represented a distinct pattern, characterized by high 30-min (30 minPG), normal fasting (FPG) and 2-h (2hPG) plasma glucose, moderately high insulin sensitivity, and low acute insulin response. Approximately 22% of participants were categorized as Class 3, and had a 10-fold risk of diabetes compared to the group with the most favorable glucose response, despite 92.5% of Class 3 participants having normal glucose tolerance (NGT) at baseline. Conclusions Elevated 30 minPG is associated with high risk of incident diabetes, even in individuals classified as NGT by a traditional OGTT. Assessing 30 minPG may identify a subgroup of high-risk individuals who remained unidentified by traditional measures.