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Objective: To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates., Research Design and Methods: Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011-2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%)., Results: T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and their characteristics resembled those of individuals with T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low-risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low GRS 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001., Conclusions: Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble those of people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates., (© 2024 by the American Diabetes Association.)

Purpose: This study aimed to validate the factor structure of the 12-item Short-Form (SF-12) health-related quality of life (HRQOL) survey for Indian adults and assess the impact of lifestyle modification on the SF-12 of Indian adults with prediabetes., Methods: To validate the context-specific construct of the SF-12, two-factor confirmatory factor analysis (CFA) was performed using data from 1285 adults residing in Chennai, India, who screened for the Diabetes Community Lifestyle Improvement Program (D-CLIP). D-CLIP was a randomized controlled trial of 578 participants with prediabetes (283 treatment, 293 control), focusing on the effect of lifestyle modifications on the prevention of diabetes. Physical and mental component scores (PCS and MCS) were computed by using CFA standardized factor loadings. Multiple linear regression was subsequently conducted to estimate the effect of lifestyle modification on post-study changes of PCS and MCS among D-CLIP participants., Results: Cronbach's alpha and CFA fit indices demonstrated acceptable reliability and model fit of the SF-12 for Indian adults. The intervention group showed greater mean change in PCS after study participation compared to the controls (1.63 ± 0.82, p = 0.046); no significant difference was observed for MCS between two groups (1.00 ± 0.85, p = 0.242)., Conclusion: The study confirmed that the SF-12 is suitable for assessing the physical and mental health dimensions of HRQOL for Indian adults. Our findings suggest that the benefits of diabetes prevention lifestyle modification strategies may primarily enhance the physical well-being of adults with prediabetes. Further studies validating the SF-12 in a broader Asian Indian population are needed., Trial Registration: Clinicaltrials.gov, NCT01283308., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To describe the natural history of diabetes in Indians., Research Design and Methods: Data are from participants older than 20 years in the Centre for Cardiometabolic Risk Reduction in South Asia longitudinal study. Glycemic states were defined per American Diabetes Association criteria. Markov models were used to estimate annual transition probabilities and sojourn time through states., Results: Among 2,714 diabetes-free participants, 641 had isolated impaired fasting glucose (iIFG), and 341 had impaired glucose tolerance (IGT). The annual transition to diabetes for those with IGT was 13.9% (95% CI 12.0, 15.9) versus 8.6% (7.3, 9.8) for iIFG. In the normoglycemia ↔ iIFG → diabetes model, mean sojourn time in normoglycemia was 40.3 (34.6, 48.2) years, and sojourn time in iIFG was 9.7 (8.4, 11.4) years. For the normoglycemia ↔ IGT → diabetes model, mean sojourn time in normoglycemia was 34.5 (29.5, 40.8) years, and sojourn time in IGT was 6.1 (5.3, 7.1) years., Conclusions: Individuals reside in normoglycemia for 35-40 years; however, progression from prediabetes to diabetes is rapid., (© 2024 by the American Diabetes Association.)

The Asian Indian Beta Cell function (ABCs) in Infants Study examined the associations of maternal weight on infant pancreatic beta cell function across 7 months postpartum. Pregnant women aged 18-35 years were recruited in Hyderabad, India. Women were classified by first trimester weight as underweight (UW), BMI < 18.5 kg/m 2 ; normal weight (NW), BMI 18.5-22.9 kg/m 2 ; or overweight (OW), BMI 23.0 through <28.5 kg/m 2 . At age > 7 months, infants had an oral glucose tolerance test (OGTT, 1.75 g glucose/kg bodyweight) following a 3 h fast. Infant blood samples were assayed for C-peptide and glucose. Infant beta cell function (HOMA2-B; disposition index, DI) and insulin resistance (HOMA2-IR) were compared across maternal weight groups. Mothers (UW n = 63; NW n = 43; OW n = 29) had similar age at delivery and second trimester 50 g glucose challenge test results. Cord HOMA2-B values were 51% greater for I UW (83.5, SD 55.2) and 44% greater for I OW (79.9, SD 60.8) vs. I NW (55.4, SD 51.5), forming a U-shaped relationship between maternal weight and HOMA2-B. No qualitative differences in HOMA2-IR were found at birth. However, at 7 months postpartum, HOMA2-IR changed most within I UW (-64% median reduction) and changed the least in I OW (-7% median reduction). At seven months postpartum, DI was higher in I UW vs. the other groups (geometric mean I UW 1.9 SD 2.5; I NW 1.3 SD 2.6 or vs. I OW mean 1.2 SD 3.7), reflecting a +49% difference in DI. Evidence from this study illustrates adaptations in the pancreatic functional response of infants associated with the maternal nutritional environment.

Aims: To examine associations between perceived stress and cardiometabolic risk factors in South Asians with prediabetes and assess whether a diabetes prevention program mitigates the impact of stress on cardiometabolic health., Methods: We conducted a secondary analysis of the Diabetes Community Lifestyle Improvement Program, a lifestyle modification trial for diabetes prevention in India (n = 564). Indicators for cardiometabolic health (weight, waist circumference, blood pressure, glucose, HbA1c, and lipids) were measured at each visit while perceived stress was assessed via questionnaire at baseline. Multivariable linear regression assessed associations between stress and cardiometabolic parameters at baseline and 3-year follow up., Results: At baseline, perceived stress was associated with higher weight (b=0.16; 95% CI: 0.04, 0.29) and waist circumference (b=0.11; 95% CI: 0.01, 0.21) but lower 30-minute postload glucose (b=-0.44; 95% CI: -0.76, -0.14) and LDL cholesterol (b=-0.40; 95% CI: -0.76, -0.03). Over the study period, perceived stress was associated with weight gain (b=0.20; 95% CI: 0.07, 0.33) and increased waist circumference (b=0.14; 95% CI: 0.04, 0.24). Additionally, higher perceived stress was associated with lower HDL cholesterol among the control arm (p interaction = 0.02)., Conclusions: Baseline stress was associated with negative cardiometabolic risk factor outcomes over time in those with prediabetes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Women's Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the pooled EWASs, 1,265 CpG sites were associated with BMI (p < 1E-7) and 1,238 replicated in the WHI (FDR < 0.05). We performed several stratified analyses to examine whether these associations differed between individuals of European and African descent, as defined by self-reported race/ethnicity. We found that five CpG sites had a significant interaction with BMI by race/ethnicity. To examine the utility of the significant CpG sites in predicting BMI, we used elastic net regression to predict log-normalized BMI in the WHI (80% training/20% testing). This model found that 397 sites could explain 32% of the variance in BMI in the WHI test set. Individuals whose methylome-predicted BMI overestimated their BMI (high epigenetic BMI) had significantly higher glucose and triglycerides and lower HDL cholesterol and LDL cholesterol compared to accurately predicted BMI. Individuals whose methylome-predicted BMI underestimated their BMI (low epigenetic BMI) had significantly higher HDL cholesterol and lower glucose and triglycerides. This study confirmed 553 and identified 685 CpG sites associated with BMI. Participants with high epigenetic BMI had poorer metabolic health, suggesting that the overestimation may be driven in part by cardiometabolic derangements characteristic of metabolic syndrome., Competing Interests: Declaration of interests K.M.J. is an employee of Bristol Myers Squibb., (Copyright © 2022 American Society of Human Genetics. All rights reserved.)

Aims: Various cardiovascular risk prediction models have been developed for patients with type 2 diabetes mellitus. Yet few models have been validated externally. We perform a comprehensive validation of existing risk models on a heterogeneous population of patients with type 2 diabetes using secondary analysis of electronic health record data., Methods: Electronic health records of 47,988 patients with type 2 diabetes between 2013 and 2017 were used to validate 16 cardiovascular risk models, including 5 that had not been compared previously, to estimate the 1-year risk of various cardiovascular outcomes. Discrimination and calibration were assessed by the c-statistic and the Hosmer-Lemeshow goodness-of-fit statistic, respectively. Each model was also evaluated based on the missing measurement rate. Sub-analysis was performed to determine the impact of race on discrimination performance., Results: There was limited discrimination (c-statistics ranged from 0.51 to 0.67) across the cardiovascular risk models. Discrimination generally improved when the model was tailored towards the individual outcome. After recalibration of the models, the Hosmer-Lemeshow statistic yielded p-values above 0.05. However, several of the models with the best discrimination relied on measurements that were often imputed (up to 39% missing)., Conclusion: No single prediction model achieved the best performance on a full range of cardiovascular endpoints. Moreover, several of the highest-scoring models relied on variables with high missingness frequencies such as HbA1c and cholesterol that necessitated data imputation and may not be as useful in practice. An open-source version of our developed Python package, cvdm, is available for comparisons using other data sources.

Aims: To assess the prevalence and clinical implications of "mismatches" between HbA1c and glucose levels in the United States across the life course., Methods: Participants ages 12-79 years from U.S. National Health and Nutrition Examination Survey (NHANES) 2005-2016 without known diagnosis of diabetes and who had a 75 g oral glucose tolerance test were included. Previously undiagnosed diabetes (DM), prediabetes, and normal glucose metabolism (NGM) were defined using American Diabetes Association cut-points. Mismatches were defined by the hemoglobin glycation index (HGI)., Results: In 10,361 participants, 5% and 41% had diabetes and prediabetes, respectively, by fasting or 2-hour glucose criteria. By HbA1c criteria, the high HGI tertile consisted of mostly abnormal classification (3% DM, 52% prediabetes) and the low HGI tertile contained mostly normal classification (78% NGM). Across all ages, 15% (weighted: 30 million individuals) had clinically significant mismatches of HGI magnitude ≥+0.5% (i.e., high mismatch) or ≤-0.5% (low mismatch). Mismatch was most common in older adults and non-Hispanic Black participants., Conclusions: Mismatches of clinically significant magnitude could lead to HbA1c-related misdiagnosis or inappropriate management in up to 30 million Americans. Older adults, non-Hispanic Black individuals, and others with high mismatches may benefit from complementing HbA1c with additional diagnostic and management strategies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Family history is considered as an important predictor of cardiovascular diseases (CVDs) and diabetes. Available research findings suggest that family history of chronic diseases is associated with perceived risk of disease and adoption of healthy behaviours. We examined the association between family history of cardio-metabolic diseases (CMDs) and healthy behaviours among adults without self-reported CMDs., Methods: Cross-sectional data of 12,484 adults, without self-reported CMDs, from the baseline survey of Centre for cArdiometabolic Risk Reduction in South-Asia (CARRS) cohort study were analysed., Results: Family history was positively associated with non-smoking and high fruits & vegetables consumption in the age group of 45-64 years and moderate to high physical activity in the age group ≥65 years after adjusting for sex, education, wealth index, city and body mass index., Conclusions: Understanding perceived risks and cultural or psychological factors related to family history through ethnographic studies may deepen understanding of these associations., Competing Interests: Declaration of conflicting interest The Authors declare that there is no conflict of interest., (Copyright © 2022 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Competing Interests: We declare no competing interests. KMVN and LRS were partly supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (award number P30DK111024) and Rapid Acceleration of Diagnostics (award number P30KD11024–05S1). LRS was also partly supported by Georgia Clinical and Translational Science Awards UL1 (UL1TR002378) and KL2 (KL2TR002381). The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health.

As blood-derived miRNAs (c-miRNAs) are modulated by exercise and nutrition, we postulated that they might be used to monitor the effects of a lifestyle intervention (LI) to prevent diabetes development. To challenge this hypothesis, obese Asian Indian pre-diabetic patients were submitted to diet modifications and physical activity for 4 months (LI group) and compared to a control group which was given recommendations only. We have considered 2 periods of time to analyze the data, i.e.; a first one to study the response to the intervention (4 months), and a second one post-intervention (8 months). At basal, 4 months and 8 months post-intervention the levels of 17 c-miRNAs were quantified, selected either for their relevance to the pathology or because they are known to be modulated by physical activity or diet. Their variations were correlated with variations of 25 metabolic and anthropometric parameters and cytokines. As expected, fasting-glycaemia, insulin-sensitivity, levels of exercise- and obesity-induced cytokines were ameliorated after 4 months. In addition, the levels of 4 miRNAs (i.e.; miR-128-3p, miR-374a-5p, miR-221-3p, and miR-133a-3p) were changed only in the LI group and were correlated with metabolic improvement (insulin sensitivity, cytokine levels, waist circumference and systolic blood pressure). However, 8 months post-intervention almost all ameliorated metabolic parameters declined indicating that the volunteers did not continue the protocol on their own. Surprisingly, the LI positive effects on c-miRNA levels were still detected, and were even more pronounced 8 months post-intervention. In parallel, MCP-1, involved in tissue infiltration by immune cells, and Il-6, adiponectin and irisin, which have anti-inflammatory effects, continued to be significantly and positively modified, 8 months post-intervention. These data demonstrated for the first time, that c-miRNA correlations with metabolic parameters and insulin sensitivity are in fact only indirect and likely associated with the level systemic inflammation. More generally speaking, this important result explains the high variability between the previous studies designed to identify specific c-miRNAs associated with the severity of insulin-resistance. The results of all these studies should take into account the level of inflammation of the patients. In addition, this finding could also explain why, whatever the pathology considered (i.e.; cancers, diabetes, neurodegenerative disorders, inflammatory diseases) the same subset of miRNAs is always found altered in the blood of patients vs healthy subjects, as these pathologies are all associated with the development of inflammation., Competing Interests: The authors have declared that no competing interests exist.

Background: Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health., Results: The discovery study population was derived from three Women's Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation β values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm β value, the risk of incident CHD increased by 9% in one site and decreased by 6-10% in two sites over 25 years., Conclusions: Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health., (© 2021. The Author(s).)

Background: Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women's Health Initiative (WHI) and the TwinsUK cohort., Design: The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction., Results: Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P = 2.7x10-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L)., Conclusions: Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Introduction: We conducted a systematic review and meta-analysis to evaluate the updated evidence regarding prediabetes for predicting mortality, macrovascular and microvascular outcomes., Research Design and Methods: We identified English language studies from MEDLINE, PubMed, OVID and Cochrane database indexed from inception to January 31, 2020. Paired reviewers independently identified 106 prospective studies, comprising nearly 1.85 million people, from 27 countries. Primary outcomes were all-cause mortality (ACM), cardiovascular mortality (CVDM), cardiovascular disease (CVD), coronary heart disease (CHD) and stroke. Secondary outcomes were heart failure, chronic kidney disease (CKD) and retinopathy., Results: Impaired glucose tolerance was associated with ACM; HR 1.19, 95% CI (1.15 to 1.24), CVDM; HR 1.21, 95% CI (1.10 to 1.32), CVD; HR 1.18, 95% CI (1.11 to 1.26), CHD; HR; 1.13, 95% CI (1.05 to 1.21) and stroke; HR 1.24, 95% CI (1.06 to 1.45). Impaired fasting glucose (IFG) 110-125 mg/dL was associated with ACM; HR 1.17, 95% CI (1.13 to 1.22), CVDM; HR 1.20, 95% CI (1.09 to 1.33), CVD; HR 1.21, 95% CI (1.09 to 1.33), CHD; HR; 1.14, 95% CI (1.06 to 1.22) and stroke; HR 1.22, 95% CI (1.07 to 1.40). IFG 100-125 mg/dL was associated with ACM; HR 1.11, 95% CI (1.04 to 1.19), CVDM; HR 1.14, 95% CI (1.03 to 1.25), CVD; HR 1.15, 95% CI (1.05 to 1.25), CHD HR; 1.10, 95% CI (1.02 to 1.19) and CKD; HR; 1.09, 95% CI (1.01 to 1.18). Glycosylated hemoglobin A1c (HbA1c) 6.0%-6.4% was associated with ACM; HR 1.30, 95% CI (1.03 to 1.66), CVD; HR 1.32, 95% CI (1.00 to 1.73) and CKD; HR 1.50, 95% CI (1.32 to 1.70). HbA1c 5.7%-6.4% was associated with CVD HR 1.15, 95% CI (1.02 to 1.30), CHD; HR 1.28, 95% CI (1.13 to 1.46), stroke; HR 1.23, 95% CI (1.04 to 1.46) and CKD; HR 1.32, 95% CI (1.16 to 1.50)., Conclusion: Prediabetes is an elevated risk state for macrovascular and microvascular outcomes. The prevention and management of prediabetes should be considered., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: South Asians (SA) and Pima Indians have high prevalence of diabetes but differ markedly in body size. We hypothesize that young SA will have higher diabetes incidence than Pima Indians at comparable body mass index (BMI) levels., Research Design and Methods: We used prospective cohort data to estimate age-specific, sex, and BMI-specific diabetes incidence in SA aged 20-44 years living in India and Pakistan from the Center for Cardiometabolic Risk Reduction in South Asia Study (n=6676), and compared with Pima Indians, from Pima Indian Study (n=1852)., Results: At baseline, SA were considerably less obese than Pima Indians (BMI (kg/m 2 ): 24.4 vs 33.8; waist circumference (cm): 82.5 vs 107.0). Age-standardized diabetes incidence (cases/1000 person-years, 95% CI) was lower in SA than in Pima Indians (men: 14.2, 12.2-16.2 vs 37.3, 31.8-42.8; women: 14.8, 13.0-16.5 vs 46.1, 41.2-51.1). Risk of incident diabetes among 20-24-year-old Pima men and women was six times (relative risk (RR), 95% CI: 6.04, 3.30 to 12.0) and seven times (RR, 95% CI: 7.64, 3.73 to 18.2) higher as compared with SA men and women, respectively. In those with BMI <25 kg/m 2 , however, the risk of diabetes was over five times in SA men than in Pima Indian men. Among those with BMI ≥30 kg/m 2 , diabetes incidence in SA men was nearly as high as in Pima men. SA and Pima Indians had similar magnitude of association between age, sex, BMI, and insulin secretion with diabetes. The effect of family history was larger in SA, whereas that of insulin resistance was larger in Pima Indians CONCLUSIONS: In the background of relatively low insulin resistance, higher diabetes incidence in SA is driven by poor insulin secretion in SA men. The findings call for research to improve insulin secretion in early natural history of diabetes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We compared diabetes incidence in South Asians aged ≥45 years in urban India (Chennai and Delhi) and Pakistan (Karachi), two low-income and middle-income countries undergoing rapid transition, with blacks and whites in the US, a high-income country., Research Design and Methods: We computed age-specific, sex-specific and body mass index (BMI)-specific diabetes incidence from the prospective Center for Cardiometabolic Risk Reduction in South Asia Study (n=3136) and the Atherosclerosis Risk in Communities Study (blacks, n=3059; whites, n=9924). We assessed factors associated with incident diabetes using Cox proportional hazards regression., Results: South Asians have lower BMI and waist circumference than blacks and whites (median BMI, kg/m 2 : 24.9 vs 28.2 vs 26.0; median waist circumference, cm 87.5 vs 96.0 vs 95.0). South Asians were less insulin resistant than blacks and whites (age-BMI-adjusted homeostatic model assessment of insulin resistance, µIU/mL/mmol/L: 2.30 vs 3.45 vs 2.59), and more insulin deficient than blacks but not whites (age-BMI-adjusted homeostasis model assessment of β-cell dysfunction, µIU/mL/mmol/L: 103.7 vs 140.6 vs 103.9). Age-standardized diabetes incidence (cases/1000 person-years (95% CI)) in South Asian men was similar to black men and 1.6 times higher (1.37 to 1.92) than white men (26.0 (22.2 to 29.8) vs 26.2 (22.7 to 29.7) vs 16.1 (14.8 to 17.4)). In South Asian women, incidence was slightly higher than black women and 3 times (2.61 to 3.66) the rate in white women (31.9 (27.5 to 36.2) vs 28.6 (25.7 to 31.6) vs 11.3 (10.2 to 12.3)). In normal weight (BMI <25 kg/m 2 ), diabetes incidence adjusted for age was 2.9 times higher (2.09 to 4.28) in South Asian men, and 5.3 times (3.64 to 7.54) in South Asian women than in white women., Conclusions: South Asian adults have lower BMI and are less insulin resistant than US blacks and whites, but have higher diabetes incidence than US whites, especially in subgroups without obesity. Factors other than insulin resistance (ie, insulin secretion) may play an important role in the natural history of diabetes in South Asians., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: A stepwise approach that includes screening and lifestyle modification followed by the addition of metformin for individuals with high risk of diabetes is recommended to delay progression to diabetes; however, there is scant evidence regarding whether this approach is cost-effective., Objective: To estimate the cost-effectiveness of a stepwise approach in the Diabetes Community Lifestyle Improvement Program., Design, Setting, and Participants: This economic evaluation study included 578 adults with impaired glucose tolerance, impaired fasting glucose, or both. Participants were enrolled in the Diabetes Community Lifestyle Improvement Program, a randomized clinical trial with 3-year follow-up conducted at a diabetes care and research center in Chennai, India., Interventions: The intervention group underwent a 6-month lifestyle modification curriculum plus stepwise addition of metformin; the control group received standard lifestyle advice., Main Outcomes and Measures: Cost, health benefits, and incremental cost-effectiveness ratios (ICERs) were estimated from multipayer (including direct medical costs) and societal (including direct medical and nonmedical costs) perspectives. Costs and ICERs were reported in 2019 Indian rupees (INR) and purchasing power parity-adjusted international dollars (INT $)., Results: The mean (SD) age of the 578 participants was 44.4 (9.3) years, and 364 (63.2%) were men. Mean (SD) body mass index was 27.9 (3.7), and the mean (SD) glycated hemoglobin level was 6.0% (0.5). Implementing lifestyle modification and metformin was associated with INR 10 549 (95% CI, INR 10 134-10 964) (INT $803 [95% CI, INT $771-834]) higher direct costs; INR 5194 (95% CI, INR 3187-INR 7201) (INT $395; 95% CI, INT $65-147) higher direct nonmedical costs, an absolute diabetes risk reduction of 10.2% (95% CI, 1.9% to 18.5%), and an incremental gain of 0.099 (95% CI, 0.018 to 0.179) quality-adjusted life-years per participant. From a multipayer perspective (including screening costs), mean ICERs were INR 1912 (INT $145) per 1 percentage point diabetes risk reduction, INR 191 090 (INT $14 539) per diabetes case prevented and/or delayed, and INR 196 960 (INT $14 986) per quality-adjusted life-year gained. In the scenario of a 50% increase or decrease in screening and intervention costs, the mean ICERs varied from INR 855 (INT $65) to INR 2968 (INT $226) per 1 percentage point diabetes risk reduction, from INR 85 495 (INT $6505) to INR 296 681 (INT $22 574) per diabetes case prevented, and from INR 88 121 (INT $6705) to INR 305 798 (INT $23 267) per quality-adjusted life-year gained., Conclusions and Relevance: The findings of this study suggest that a stepwise approach for diabetes prevention is likely to be cost-effective, even if screening costs for identifying high-risk individuals are added.

Aims: To examine the association of HbA 1c and glucose levels with incident diabetic retinopathy according to black African or white European ancestry., Methods: In this retrospective cohort study of 202 500 US Veterans with diabetes (2000-2014), measures included HbA 1c , outpatient random serum/plasma glucose, and incident retinopathy [conversion from negative to ≥2 positive evaluations (ICD-9 codes), without a subsequent negative]., Results: At baseline, the study population had a mean age of 59.3 years, their mean BMI was 31.9 kg/m 2 , HbA 1c level was 57 mmol/mol (7.4%) and glucose level was 8.8 mmol/l, and 77% were of white European ancestry (white individuals) and 21% of black African ancestry (black individuals). HbA 1c was 0.3% higher in black vs white individuals (P < 0.001), adjusting for baseline age, sex, BMI, estimated glomerular filtration rate (eGFR), haemoglobin, and average systolic blood pressure and glucose. Over 11 years, incident retinopathy occurred in 9% of black and 7% of white individuals, but black individuals had higher HbA 1c , glucose, and systolic blood pressure (all P < 0.001); adjusted for these factors, incident retinopathy was reduced in black vs white individuals (P < 0.001). The population incidence of retinopathy (7%) was associated with higher mean baseline HbA 1c in individuals with black vs white ancestry [63 mmol/mol (7.9%) vs 58 mmol/mol (7.5%); P < 0.001)], but with similar baseline glucose levels (9.0 vs 9.0 mmol/l; P = 0.660, all adjusted for baseline age, sex and BMI)., Conclusions: Since retinopathy occurs at higher HbA 1c levels in black people for a given level of average plasma glucose, strategies may be needed to individualize the interpretation of HbA 1c measurements., (© 2020 Diabetes UK.)

Aims: To determine whether HbA 1c mismatches (HbA 1c levels that are higher or lower than expected for the average glucose levels in different individuals) could lead to errors if diagnostic classification is based only on HbA 1c levels., Methods: In a cross-sectional study, 3106 participants without known diabetes underwent a 75-g oral glucose tolerance test (fasting glucose and 2-h glucose) and a 50-g glucose challenge test (1-h glucose) on separate days. They were classified by oral glucose tolerance test results as having: normal glucose metabolism; prediabetes; or diabetes. Predicted HbA 1c was determined from the linear regression modelling the relationship between observed HbA 1c and average glucose (mean of fasting glucose and 2-h glucose from the oral glucose tolerance test, and 1-h glucose from the glucose challenge test) within oral glucose tolerance test groups. The haemoglobin glycation index was calculated as [observed - predicted HbA 1c ], and divided into low, intermediate and high haemoglobin glycation index mismatch tertiles., Results: Those participants with higher mismatches were more likely to be black, to be men, to be older, and to have higher BMI (all P<0.001). Using oral glucose tolerance test criteria, the distribution of normal glucose metabolism, prediabetes and diabetes was similar across mismatch tertiles; however, using HbA 1c criteria, the participants with low mismatches were classified as 97% normal glucose metabolism, 3% prediabetes and 0% diabetes, i.e. mostly normal, while those with high mismatches were classified as 13% normal glucose metabolism, 77% prediabetes and 10% diabetes, i.e. mostly abnormal (P<0.001)., Conclusions: Measuring only HbA 1c could lead to under-diagnosis in people with low mismatches and over-diagnosis in those with high mismatches. Additional oral glucose tolerance tests and/or fasting glucose testing to complement HbA 1c in diagnostic classification should be performed in most individuals., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Aims: To examine the clinical utility of 30-min plasma glucose (30-min-PG) measurement during an oral glucose tolerance (OGTT) in predicting type 2 diabetes (T2DM)., Research Design and Methods: Data from a 3-year, randomized, controlled, primary prevention trial among 548 Asian Indians with prediabetes were analyzed. Participants underwent OGTT with PG measurements at fasting, 30-min, and 2-h at baseline and annually until the end of the study. Multivariable Cox regression models were constructed to calculate the risk of developing diabetes based on 30-min-PG levels. Improvement in prediction performance gained by adding an elevated level of 30-min-PG over prediabetic categories was calculated using the area-under-curve (AUC), net-reclassification (NRI), and integrated discrimination improvement (IDI) statistics., Results: At the end of follow-up, 30.4% of individuals had been diagnosed with T2DM by ADA criteria. Based on the maximally selected log-rank statistics, the optimal 30-min-PG cut point for predicting incident T2DM was >182 mg/dl. Multivariable-adjusted Cox regression models showed an independent association between elevated 30-min-PG (>182 mg/dl) and incident diabetes (hazard ratio (95% CI): 1.85 [1.32, 2.59]; D xy  = 0.353, c-statistic = 0.676). The addition of an elevated 30-min-PG (>182 mg/dl) model significantly improved the prediction of diabetes (Δdeviance: -15.4; ΔAUC: 0.11; NRI continuous : 0.51; IDI: 0.08) compared with IFG model alone) in individuals with prediabetes., Conclusion: In prediabetic individuals, baseline 30-min-PG independently predicted T2DM and significantly improved reclassification and discrimination. Therefore, 30-min-PG should be considered as part of the routine testing in addition to FPG and 2-h-PG for better risk stratification., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Type 2 diabetes is a heterogeneous disease and may manifest from multiple disease pathways. We examined insulin secretion and insulin resistance across two ethnicities with particularly high risk for diabetes yet with widely different distributions of weight class., Materials and Methods: In this population-based, cross-sectional study, Pima Indians from Southwestern United States (n = 865) and Asian Indians from Chennai, India (n = 2374) had a 75-g oral glucose tolerance test. We analysed differences in plasma glucose, plasma insulin, insulin resistance (HOMA-IR), and insulin secretion (ΔI 0-30 /ΔG 0-30 ) across categories of body mass index (BMI) and glycemic status per American Diabetes Association criteria., Results: Pima Indians were younger (mean 27.4 ± SD 6.6, Asian: 33.9 ± 6.7 years) and had higher BMI (33.6 ± 8.1, Asian: 25.7 ± 4.9 kg/m 2 ). Among normal weight participants (mean BMI: Pima 22.4 SE 0.2; Asian 22.2 SE 0.06 kg/m 2 ), fasting glucose was higher in Asian Indians (5.2 vs Pima: 4.8 mmol/L, P = .003), adjusted for age and sex. Pima Indians were three times as insulin resistant as Asian Indians (HOMA-IR: 7.7 SE 0.1, Asian: 2.5 SE 0.07), while Asian Indians had three times less insulin secretion (Pima: 2.8 SE 1.0 vs Asian: 0.9 SE 1.0 pmol/mmol), a pattern evident across age, BMI, and glycemic strata., Conclusions: Metabolic differences between Pima and Asian Indians suggest heterogeneous pathways of type 2 diabetes in the early natural history of disease, with emphasis of insulin resistance in Pima Indians and emphasis of poor insulin secretion in Asian Indians., (© 2019 John Wiley & Sons, Ltd.)

Aim: To characterize differences between black and white people in optimal HbA 1c thresholds for diagnoses of diabetes and prediabetes., Methods: Data were included from the National Health and Nutrition Examination Survey, 2005-2014. Black and white adults (age 18-70 years) who underwent an oral glucose tolerance test and had available fasting plasma glucose, 2-h plasma glucose and HbA 1c measurements were eligible for inclusion. Diabetes or prediabetes status was defined by fasting plasma glucose and 2-h plasma glucose using American Diabetes Association criteria. Classification of diabetes, prediabetes and dysglycaemia by HbA 1c was evaluated for a range of HbA 1c thresholds, with optimal thresholds defined as those values that maximized the sum of sensitivity and specificity (Youden's index)., Results: In 5324 black (32.3%) and white (67.7%) individuals, Youden's index (optimal) thresholds for HbA 1c were ≥42 mmol/mol (6.0%) and ≥39 mmol/mol (5.7%) for discriminating diabetes vs non-diabetes, ≥ 44 mmol/mol (6.2%) and ≥39 mmol/mol (5.7%) for discriminating diabetes vs prediabetes (excluding normoglycaemia), ≥39 mmol/mol (5.7%) and ≥37 mmol/mol (5.5%) for discriminating dysglycaemia vs normoglycaemia, and ≥39 mmol/mol (5.7%) and ≥37 mmol/mol (5.5%) for discriminating prediabetes vs normoglycaemia (excluding diabetes), in black and white people, respectively., Conclusions: Consistently higher optimal HbA 1c thresholds in black people than in white people suggest a need to individualize HbA 1c relative to glucose levels if HbA 1c is used to diagnose diabetes and prediabetes., (© 2019 Diabetes UK.)

Aims/hypothesis: Early recognition of those at high risk for diabetes as well as diabetes itself can permit preventive management, but many Americans with diabetes are undiagnosed. We sought to determine whether routinely available outpatient random plasma glucose (RPG) would be useful to facilitate the diagnosis of diabetes., Methods: Retrospective cohort study of 942,446 U.S. Veterans without diagnosed diabetes, ≥3 RPG in a baseline year, and ≥1 primary care visit/year during 5-year follow-up. The primary outcome was incident diabetes (defined by diagnostic codes and outpatient prescription of a diabetes drug)., Results: Over 5 years, 94,599 were diagnosed with diabetes [DIAB] while 847,847 were not [NONDIAB]. Baseline demographics of DIAB and NONDIAB were clinically similar, except DIAB had higher BMI (32 vs. 28 kg/m2) and RPG (150 vs. 107 mg/dl), and were more likely to have Black race (18% vs. 15%), all p<0.001. ROC area for prediction of DIAB diagnosis within 1 year by demographic factors was 0.701, and 0.708 with addition of SBP, non-HDL cholesterol, and smoking. These were significantly less than that for prediction by baseline RPG alone (≥2 RPGs at/above a given level, ROC 0.878, p<0.001), which improved slightly when other factors were added (ROC 0.900, p<0.001). Having ≥2 RPGs ≥115 mg/dl had specificity 77% and sensitivity 87%, and ≥2 RPGs ≥130 mg/dl had specificity 93% and sensitivity 59%. For predicting diagnosis within 3 and 5 years by RPG alone, ROC was reduced but remained substantial (ROC 0.839 and 0.803, respectively)., Conclusions: RPG levels below the diabetes "diagnostic" range (≥200 mg/dl) provide good discrimination for follow-up diagnosis. Use of such levels-obtained opportunistically, during outpatient visits-could signal the need for further testing, allow preventive intervention in high risk individuals before onset of disease, and lead to earlier identification of diabetes., Competing Interests: The authors read the journal’s policy, and the authors of this manuscript have the following competing interests: MKR, PWFW and LSP declare the competing interests of receiving funding from the NIH and the VA. LRS, CNF, and SR declare the competing interests of receiving funding from the NIH. LSP declares the following competing interests: he has served on Scientific Advisory Boards for Janssen, and the Profil Institute for Clinical Research; has/had research support from the NIH, the VA, Merck, Amylin, Eli Lilly, Novo Nordisk, Sanofi, PhaseBio, Roche, Abbvie, Vascular Pharmaceuticals, Janssen, Glaxo SmithKline, Pfizer, and the Cystic Fibrosis Foundation; and is co-founder, Officer, Board member, and stockholder of DIASYST, Inc. YH, SR, JLV, KC, and DG have declared that no competing interests exist. There are no patents, products in development, or marketed products to declare. Though there are ethical and legal restrictions imposed on sharing the data underlying this study, the reported competing interests do not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.

Aims: Diabetes prevention interventions have been less successful in Asian Indians compared to other populations, which may be due in part to dietary differences. The objective of this study was to determine the impact of a diabetes prevention intervention on diet and risk of diabetes in Asian Indians at high risk., Methods: Data were included from the Diabetes Community Lifestyle Improvement Program (D-CLIP), a randomized control trial to prevent diabetes in overweight/obese Asian Indian adults (20-65 years) with prediabetes. Respondents received standard treatment (control; n = 283) or a 6-month intervention (n = 295) that included education and support to reduce intakes of fat and total calories (kilocalories; kcal). Diet was ascertained using a food frequency questionnaire, and incident diabetes was determined from annual 2-h plasma glucose post-oral glucose tolerance test or biannual fasting plasma glucose., Results: There were 485 (control 240; intervention 245) respondents with complete diet data at baseline. At 6 months, the intervention was associated with decreased intake of total energy (- 185.6 kcal/day; 95% CI - 353.6, - 17.5 kcal/day) and refined cereals (- 7.2 g/1000 kcal; 95% CI - 12.7, - 1.7 g/1000 kcal), and increased intakes of fruits and vegetables (33.4 g/1000 kcal; 95% CI 16.0, 50.8 g/1000 kcal). The intervention group was half (HR 0.49; 95% CI 0.25, 0.94) as likely to develop diabetes at 1 year, and the hazard was significantly attenuated (12.2%; P = 0.015) with adjustment for fruits and vegetable intake., Conclusion: The D-CLIP decreased the total energy intake and increased the intakes of fruits and vegetables, and reduced the 1-year incidence of diabetes by half., Trial Registration: Clinicaltrails.gov # NCT01283308.

Objective: We evaluated the effects of a diabetes prevention itervention on self-efficacy (SE) and the associations between SE and diabetes-related outcomes among overweight Asian Indian adults with pre-diabetes in a randomized controlled translational trial (the Diabetes Community Lifestyle Improvement Program, D-CLIP)., Research Design and Methods: Data were obtained from 550 adults who were randomized to a diabetes prevention program or standard of care. Dietary and exercise-related SEs were measured at baseline, core intervention completion (4  months), and annually until the end of follow-up (3 years or diabetes diagnosis). Mixed-effects regressions described changes in SE over time by treatment group. Among treatment participants, multivariable-adjusted models described associations of SE at baseline and intervention completion with diabetes incidence and other secondary outcomes (weight, waist circumference (WC), exercise, and energy intake)., Results: From baseline to 4  months, dietary (β=10.3, p=0.04) and exercise (β=0.49, p=0.04) SE increased significantly in the treatment arm only; however, this increase from baseline was no longer significant at later time points. Among treatment participants, there was no association of dietary or exercise SE with diabetes incidence, but baseline exercise SE was independently associated with improved weight, WC, and exercise at 4  months (p<0.05). Change in exercise SE from baseline to intervention completion also predicted increased exercise at 4, 12, and 24 months (p<0.05)., Conclusions: Exposure to D-CLIP resulted in improved SE at treatment completion, but this effect was not sustained over longer follow-up. Several short-term and long-term secondary outcomes, but not diabetes risk, were significantly associated with exercise SE, suggesting this psychosocial trait may facilitate success in achieving certain health goals., Trial Registration Number: NCT01283308., Competing Interests: Competing interests: None declared.

Purpose of Review: Overweight and obesity are well-established risk factors for type 2 diabetes. However, a substantial number of individuals develop the disease at underweight or normal weight. In this review, we discuss the epidemiology of type 2 diabetes in non-overweight adults; pose questions about etiology, pathophysiology, diagnosis, and prognosis; and examine implications for prevention and treatment., Recent Findings: In population-based studies, the prevalence of type 2 diabetes ranged from 1.4-10.9%. However, the prevalence of type 2 diabetes in individuals with BMI < 25 kg/m 2 ranged from 1.4-8.8%. In countries from Asia and Africa, the proportion of individuals with diabetes who were underweight or normal weight ranged from 24 to 66%, which is considerably higher than the US proportion of 10%. Impairments in insulin secretion, in utero undernutrition, and epigenetic alterations to the genome may play a role in diabetes development in this subgroup. A substantial number of individuals with type 2 diabetes, particularly those with recent ancestry from Asia or Africa, are underweight or normal weight. Future research should consist of comprehensive studies of the prevalence of type 2 diabetes in non-overweight individuals; studies aimed at understanding gaps in the mechanisms, etiology, and pathophysiology of diabetes development in underweight or normal weight individuals; and trials assessing the effectiveness of interventions in this population.

Aims: Clinical trials show lifestyle change programs are beneficial, yet large-scale, successful translation of these programs is scarce. We investigated the association between participation in the largest U.S. lifestyle change program, MOVE!, and diabetes control outcomes., Methods: This longitudinal, retrospective cohort study used Veterans Health Administration databases of patients with diabetes who participated in MOVE! between 2005 and 2012, or met eligibility criteria (BMI ≥25kg/m 2 ) but did not participate. Main outcomes were diabetic eye disease, renal disease, and medication intensification., Results: There were 400,170 eligible patients with diabetes, including 87,366 (22%) MOVE!, Participants: Included patients were 96% male, 77% white, with mean age 58years and BMI 34kg/m 2 . Controlling for baseline measurements and age, race, sex, BMI, and antidiabetes medications, MOVE! participants had lower body weight (-0.6kg), random plasma glucose (-2.8mg/dL), and HbA1c (-0.1%) at 12months compared to nonparticipants (each p<0.001). In multivariable Cox models, MOVE! participants had lower incidence of eye disease (hazard ratio 0.80, 95% CI 0.75-0.84) and renal disease (HR 0.89, 95% CI 0.86-0.92) and reduced medication intensification (HR 0.82, 95% CI 0.80-0.84)., Conclusions: If able to overcome participation challenges, lifestyle change programs in U.S. health systems may improve health among the growing patient population with diabetes., (Published by Elsevier Inc.)

Aims: To test the hypothesis that a 50-g oral glucose challenge test with 1-h glucose measurement would have superior performance compared with other opportunistic screening methods., Methods: In this prospective study in a Veterans Health Administration primary care clinic, the following test performances, measured by area under receiver-operating characteristic curves, were compared: 50-g oral glucose challenge test; random glucose; and HbA 1c level, using a 75-g oral glucose tolerance test as the 'gold standard'., Results: The study population was comprised of 1535 people (mean age 56 years, BMI 30.3 kg/m 2 , 94% men, 74% black). By oral glucose tolerance test criteria, diabetes was present in 10% and high-risk prediabetes was present in 22% of participants. The plasma glucose challenge test provided area under receiver-operating characteristic curves of 0.85 (95% CI 0.78-0.91) to detect diabetes and 0.76 (95% CI 0.72-0.80) to detect high-risk dysglycaemia (diabetes or high-risk prediabetes), while area under receiver-operating characteristic curves for the capillary glucose challenge test were 0.82 (95% CI 0.75-0.89) and 0.73 (95% CI 0.69-0.77) for diabetes and high-risk dysglycaemia, respectively. Random glucose performed less well [plasma: 0.76 (95% CI 0.69-0.82) and 0.66 (95% CI 0.62-0.71), respectively; capillary: 0.72 (95% CI 0.65-0.80) and 0.64 (95% CI 0.59-0.68), respectively], and HbA 1c performed even less well [0.67 (95% CI 0.57-0.76) and 0.63 (95% CI 0.58-0.68), respectively]. The cost of identifying one case of high-risk dysglycaemia with a plasma glucose challenge test would be $42 from a Veterans Health Administration perspective, and $55 from a US Medicare perspective., Conclusions: Glucose challenge test screening, followed, if abnormal, by an oral glucose tolerance test, would be convenient and more accurate than other opportunistic tests. Use of glucose challenge test screening could improve management by permitting earlier therapy., (© 2016 Diabetes UK.)

Introduction: Lifestyle change programs implemented within healthcare systems could reach many Americans, but their impact on cardiovascular disease (CVD) remains unclear. The MOVE! program is the largest lifestyle change program implemented in a healthcare setting in the U.S. This study aimed to determine whether MOVE! participation was associated with reduced CVD incidence., Methods: This retrospective cohort study, analyzed in 2013-2015, used national Veterans Health Administration databases to identify MOVE! participants and eligible non-participants for comparison (2005-2012). Patients eligible for MOVE!-obese or overweight with a weight-related health condition, and no baseline CVD-were examined (N=1,463,003). Of these, 169,248 (12%) were MOVE!, Participants: Patients were 92% male, 76% white, with mean age 52 years and BMI of 32. The main outcome was incidence of CVD (ICD-9 and procedure codes for coronary artery disease, cerebrovascular disease, peripheral vascular disease, and heart failure)., Results: Adjusting for age, race, sex, BMI, statin use, and baseline comorbidities, over a mean 4.9 years of follow-up, MOVE! participation was associated with lower incidence of total CVD (hazard ratio [HR]=0.83, 95% CI=0.80, 0.86); coronary artery disease (HR=0.81, 95% CI=0.77, 0.86); cerebrovascular disease (HR=0.87, 95% CI=0.82, 0.92); peripheral vascular disease (HR=0.89, 95% CI=0.83, 0.94); and heart failure (HR=0.78, 95% CI=0.74, 0.83). The association between MOVE! participation and CVD incidence remained significant when examined across categories of race/ethnicity, BMI, diabetes, hypertension, smoking status, and statin use., Conclusions: Although participation was limited, MOVE! was associated with reduced CVD incidence in a nationwide healthcare setting., (Published by Elsevier Inc.)

Background: Cardiometabolic and chronic pulmonary diseases may be associated with modifiable risk factors that can be targeted to prevent multimorbidity., Objectives: (i) Estimate the prevalence of multimorbidity across four cardiometabolic and chronic pulmonary disease groups; (ii) compare the prevalence of multimorbidity to that of one disease and no disease; and (iii) quantify population attributable fractions (PAFs) for modifiable risk factors of multimorbidity., Design: Data from adults aged 18-79 years who participated in the US National Health and Nutrition Examination Survey 2007-2012 were examined. Multimorbidity was defined as ≥2 co-occurring diseases across four common cardiometabolic and chronic pulmonary disease groups. Multivariate-adjusted PAFs for poverty, obesity, smoking, hypertension, and low high-density lipoprotein (HDL) cholesterol were estimated., Results: Among 16,676 adults, the age-standardized prevalence of multimorbidity was 9.3%. The occurrence of multimorbidity was greater with age, from 1.5% to 5.9%, 15.0% and 34.8% for adults aged 18-39, 40-54, 55-64 and 65-79 years, respectively. Multimorbidity was greatest among the poorest versus non-poorest adults and among blacks versus other races/ethnicities. Multimorbidity was also greater in adults with obesity, hypertension, and low HDL cholesterol. Risk factors with greatest PAFs were hypertension (38.8%; 95% confidence interval [CI] 29.4-47.4) and obesity (19.3%; 95% CI 10.2-28.2)., Conclusions: In the USA, 9.3% of adults have multimorbidity across four chronic disease groups, with a disproportionate burden among older, black, and poor adults. Our results suggest that targeting two intermediate modifiable risk factors, hypertension and obesity, might help to reduce the prevalence of multimorbidity in US adults., Competing Interests: No financial, consultant, institutional, or other relationships were reported by the authors of this paper. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Objective: This study tests the effectiveness of expert guidelines for diabetes prevention: lifestyle intervention with addition of metformin, when required, among people with prediabetes., Research Design and Methods: The Diabetes Community Lifestyle Improvement Program (D-CLIP) is a randomized, controlled, translation trial of 578 overweight/obese Asian Indian adults with isolated impaired glucose tolerance (iIGT), isolated impaired fasting glucose (iIFG), or IFG+IGT in Chennai, India. Eligible individuals were identified through community-based recruitment and randomized to standard lifestyle advice (control) or a 6-month, culturally tailored, U.S. Diabetes Prevention Program-based lifestyle curriculum plus stepwise addition of metformin (500 mg, twice daily) for participants at highest risk of conversion to diabetes at ≥4 months of follow-up. The primary outcome, diabetes incidence, was assessed biannually and compared across study arms using an intention-to-treat analysis., Results: During 3 years of follow-up, 34.9% of control and 25.7% of intervention participants developed diabetes (P = 0.014); the relative risk reduction (RRR) was 32% (95% CI 7-50), and the number needed to treat to prevent one case of diabetes was 9.8. The RRR varied by prediabetes type (IFG+IGT, 36%; iIGT, 31%; iIFG, 12%; P = 0.77) and was stronger in participants 50 years or older, male, or obese. Most participants (72.0%) required metformin in addition to lifestyle, although there was variability by prediabetes type (iIFG, 76.5%; IFG+IGT, 83.0%; iIGT, 51.3%)., Conclusions: Stepwise diabetes prevention in people with prediabetes can effectively reduce diabetes incidence by a third in community settings; however, people with iIFG may require different interventions., (© 2016 by the American Diabetes Association.)

Background: Over half of the people with diabetes in the world live in Asia. Emerging scientific evidence suggests that diabetes is associated with environmental pollutants, exposures that are also abundant in Asia., Objective: To systematically review the literature concerning the association of persistent organic pollutants (POPs) and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia., Methods: PubMed and Embase were searched to identify studies published up to November 2014. A secondary reference review of all extracted articles and the National Toxicology Program Workshop on the association of POPs with diabetes was also conducted. A total of 19 articles met the inclusion criteria and were evaluated in this review., Results: To date, the evidence relating POPs and non-persistent pesticides with diabetes in Asian populations is equivocal. Positive associations were reported between serum concentrations of polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and several organochlorine pesticides (DDT, DDE, oxychlordane, trans-nonachlor, hexachlorobenzene, hexachlorocyclohexane) with diabetes. PCDD/Fs were also associated with blood glucose and insulin resistance, but not beta-cell function. There were substantial limitations of the literature including: most studies were cross-sectional, few studies addressed selection bias and confounding, and most effect estimates had exceptionally wide confidence intervals. Few studies evaluated the effects of organophosphates., Conclusions: Well-conducted research is urgently needed on these pervasive exposures to inform policies to mitigate the diabetes epidemic in Asia., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The burden of cardiovascular disease (CVD) is disproportionately greater in those with diabetes than in the general population, including higher rates of hospitalization, stroke, myocardial infarction, and mortality. Health-promoting lifestyle factors reduce both diabetes and CVD in healthy individuals; however, the efficacy of these strategies for CVD reduction in people with preexisting diabetes is unclear. In this review, we describe the most recent evidence (2013-2014) surrounding the effects of lifestyle changes on CVD outcomes in those with diabetes, and we contextualize the evidence against a backdrop of earlier key findings. Two major randomized controlled trials were identified, providing opposing conclusions about the role of lifestyle factors on CVD events in those with diabetes. Other recent prospective observational analyses support associations of physical activity and reduced CVD risk in diabetes. Limitations across studies include the use of self-report for measurement of lifestyle or lifestyle change, the length of follow-up needed to measure CVD outcomes, and the role of participants' medications on associations of lifestyle factors and CVD outcomes. Equivocal findings from the two randomized controlled trials support the need for additional research to identify the specific lifestyle factors that reduce CVD mortality and macrovascular complications in populations with diabetes.

Objective: To examine β-cell function across a spectrum of glycemia among Asian Indians, a population experiencing type 2 diabetes development at young ages despite low BMI., Research Design and Methods: One-thousand two-hundred sixty-four individuals without known diabetes in the Diabetes Community Lifestyle Improvement Program in Chennai, India, had a 75-g oral glucose tolerance test, with glucose and insulin measured at 0, 30, and 120 min. Type 2 diabetes, isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), combined impaired fasting glucose and impaired glucose tolerance, and normal glucose tolerance (NGT) were defined by American Diabetes Association guidelines. Measures included insulin resistance and sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], modified Matsuda Index, 1/fasting insulin) and β-cell function (oral disposition index = [Δ insulin0-30/Δ glucose 0-30] × [1/fasting insulin])., Results: Mean age was 44.2 years (SD, 9.3) and BMI 27.4 kg/m(2) (SD, 3.8); 341 individuals had NGT, 672 had iIFG, IGT, or IFG plus IGT, and 251 had diabetes. Patterns of insulin resistance or sensitivity were similar across glycemic categories. With mild dysglycemia, the absolute differences in age- and sex-adjusted oral disposition index (NGT vs. iIFG, 38%; NGT vs. iIGT, 32%) were greater than the differences in HOMA-IR (NGT vs. iIFG, 25%; NGT vs. iIGT, 23%; each P < 0.0001). Compared with NGT and adjusted for age, sex, BMI, waist circumference, and family history, the odds of mild dysglycemia were more significant per SD of oral disposition index (iIFG: odds ratio [OR], 0.36; 95% CI, 0.23-0.55; iIGT: OR, 0.37; 95% CI, 0.24-0.56) than per SD of HOMA-IR (iIFG: OR, 1.69; 95% CI, 1.23-2.33; iIGT: OR, 1.53; 95% CI, 1.11-2.11)., Conclusions: Asian Indians with mild dysglycemia have reduced β-cell function, regardless of age, adiposity, insulin sensitivity, or family history. Strategies in diabetes prevention should minimize loss of β-cell function.

This systematic review synthesizes data published between 1988 and 2009 on mean BMI and prevalence of overweight, obesity, and type 2 diabetes among Asian subgroups in the U.S. We conducted systematic searches in Pub- Med for peer-reviewed, English-language citations that reported mean BMI and percent overweight, obesity, and diabetes among South Asians/Asian Indians, Chinese, Filipinos, Koreans, and Vietnamese. We identified 647 database citations and 23 additional citations from hand-searching. After screening titles, abstracts, and full-text publications, 97 citations remained. None were published between 1988 and 1992, 28 between 1993 and 2003, and 69 between 2004 and 2009. Publications were identified for the following Asian subgroups: South Asian (n=8), Asian Indian (n=20), Chinese (n=44), Filipino (n=22), Korean (n= 8), and Vietnamese (n=3). The observed sample sizes ranged from 32 to 4245 subjects with mean ages from 24 to 78 years. Among samples of men and women, the lowest reported mean BMI was in South Asians (22.1 kg/m(2)), and the highest was in Filipinos (26.8 kg/m(2)). Estimates for overweight (12.8-46.7%) and obesity (2.1-59.0%) were variable. Among men and women, the highest rate of diabetes was reported in Asian Indians with BMI ≥ 30 kg/m(2) (32.9%, age and sex standardized). This review suggests heterogeneity among U.S. Asian populations in cardiometabolic risk factors, yet comparisons are limited due to variability in study populations, methods, and definitions used in published reports. Future efforts should adopt standardized methods to understand overweight, obesity and diabetes in this growing U.S. ethnic population.

This review summarizes the current data on diabetes risk factors, prevalence, and prevention efforts in Asia and Asian migrant populations. Studies indicate that type 2 diabetes mellitus is a large and growing threat to public health in Asian populations. Furthermore, Asian subgroups (e.g., South Asians/Asian Indians, Chinese) have unique risk factor profiles for developing diabetes, which differ from other populations and between Asian ethnic groups. Lifestyle intervention programs are effective in preventing diabetes in Asians, as with other ethnicities. The strength of these findings is lessened by the lack of systematically collected data using objective measurements. Large epidemiologic studies of diabetes prevalence and risk factor profiles and translational trials identifying sustainable and culturally acceptable lifestyle programs for Asian subgroups are needed.