Incidence and pathophysiology of diabetes in south Asian adults living in India and Pakistan compared with US blacks and whites

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/m2: 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 \u3c25 kg/m2), 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

Association between varying cut-points of intermediate hyperglycemia and risk of mortality, cardiovascular events and chronic kidney disease: a systematic review and meta-analysis

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

Association of family history of cardiometabolic diseases (CMDs) and individual health behaviours: Analysis of CARRS study from South Asia

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

Incidence of diabetes in South Asian young adults compared to Pima Indians

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/m2): 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/m2, however, the risk of diabetes was over five times in SA men than in Pima Indian men. Among those with BMI ≥30 kg/m2, 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 IndiansConclusions 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

Incidence of diabetes in south Asian young adults compared to Pima Indians

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/m2): 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 \u3c25 kg/m2, however, the risk of diabetes was over five times in SA men than in Pima Indian men. Among those with BMI ≥30 kg/m2, 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

Random plasma glucose predicts the diagnosis of diabetes.

Aims/hypothesisEarly 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.MethodsRetrospective 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).ResultsOver 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 pConclusionsRPG 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

Natural History of Type 2 Diabetes in Indians: Time to Progression

Objective: To describe the natural history of diabetes in Indians.Research Design and Methods: Data are from CARRS longitudinal study participants aged ≥20 years. Glycemic states were defined per ADA criteria. Markov models estimated annual transition probabilities, and sojourn time through states.Results: Among 2714 diabetes-free participants, 641 had isolated impaired fasting glucose (iIFG), and 341 had impaired glucose tolerance (IGT). The annual transition to diabetes for IGT was 13.9% (12.0%, 15.9%) vs 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) while 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) while sojourn time in IGT was (6.1;5.3, 7.1 years).Conclusion: Individuals reside in normoglycemia for 35-40 years, however, progression from prediabetes to diabetes is rapid. </p

Epigenome-wide association study of diet quality in the Women's Health Initiative and TwinsUK cohort

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