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Aims We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease ( CVD) in a cohort of European and South Asian origin. Methods For 682 European and 520 South Asian men and women, aged 58-85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. Results Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist-hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c-defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c-defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P = 0.04]. Conclusions Prediabetes appeared to be less associated with cardiovascular disease in the South Asian than in the European group. These findings have implications for screening, and early cardiovascular prevention strategies in South Asian populations. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this study was to compare exercise capacity, strength and skeletal muscle perfusion during exercise, and oxidative capacity between South Asians, African Caribbeans and Europeans, and determine what effect ethnic differences in the prevalence of type 2 diabetes has on these functional outcomes., Methods: In total, 708 participants (aged [mean±SD] 73 ± 7 years, 56% male) were recruited from the Southall and Brent Revisited (SABRE) study, a UK population-based cohort comprised of Europeans (n = 311) and South Asian (n = 232) and African Caribbean (n = 165) migrants. Measurements of exercise capacity using a 6 min stepper test (6MST), including measurement of oxygen consumption ([Formula: see text]) and grip strength, were performed. Skeletal muscle was assessed using near infrared spectroscopy (NIRS); measures included changes in tissue saturation index (∆TSI%) with exercise and oxidative capacity (muscle oxygen consumption recovery, represented by a time constant [τ]). Analysis was by multiple linear regression., Results: When adjusted for age and sex, in South Asians and African Caribbeans, exercise capacity was reduced compared with Europeans ([Formula: see text] [ml min -1  kg -1 ]: β = -1.2 [95% CI -1.9, -0.4], p = 0.002, and β -1.7 [95% CI -2.5, -0.8], p < 0.001, respectively). South Asians had lower and African Caribbeans had higher strength compared with Europeans (strength [kPa]: β = -9 [95% CI -12, -6), p < 0.001, and β = 6 [95% CI 3, 9], p < 0.001, respectively). South Asians had greater decreases in TSI% and longer τ compared with Europeans (∆TSI% [%]: β = -0.9 [95% CI -1.7, -0.1), p = 0.024; τ [s]: β = 11 [95% CI 3, 18], p = 0.006). Ethnic differences in [Formula: see text] and grip strength remained despite adjustment for type 2 diabetes or HbA 1c (and fat-free mass for grip strength). However, the differences between Europeans and South Asians were no longer statistically significant after adjustment for other possible mediators or confounders (including physical activity, waist-to-hip ratio, cardiovascular disease or hypertension, smoking, haemoglobin levels or β-blocker use). The difference in ∆TSI% between Europeans and South Asians was marginally attenuated after adjustment for type 2 diabetes or HbA 1c and was also no longer statistically significant after adjusting for other confounders; however, τ remained significantly longer in South Asians vs Europeans despite adjustment for all confounders., Conclusions/interpretation: Reduced exercise capacity in South Asians and African Caribbeans is unexplained by higher rates of type 2 diabetes. Poorer exercise tolerance in these populations, and impaired muscle function and perfusion in South Asians, may contribute to the higher morbidity burden of UK ethnic minority groups in older age.

Background: Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause., Methods and Findings: A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40-44 (early), 45-49, 50-51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures. Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73-2.44) (p < 0.001) and early menopause (1.80; 1.66-1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04-1.23; p = 0.006) and 1.15 (1.05-1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45-49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15-20 years, the risk was markedly higher for premature (15.58; 11.29-19.86; p < 0.001) and early (6.55; 5.04-8.52; p < 0.001) menopause. Also, current smokers with 11-15 pack-years had over 4-fold (4.35; 2.78-5.92; p < 0.001) and 3-fold (3.01; 2.15-4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98-1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias., Conclusions: The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: JEC is a director of Dietary Assessment Ltd, a University of Leeds spin out company to support measurement of dietary intake. All other authors have declared that no competing interests exist.

Background: South Asians have a 1.5-fold increased stroke mortality compared with Europeans, despite similar blood pressures (BP). We hypothesized that it is the greater hyperglycaemia in South Asians that increases stroke risk, by adversely affecting cerebrovascular haemodynamics., Methods: A population-based sample of 149 Europeans and 151 South Asians underwent metabolic profiling and concurrent measurement of finger BP using a Finapres and middle cerebral artery (MCA) blood flow velocity using transcranial Doppler ultrasound. Cerebrovascular autoregulation, cerebrovascular resistance [resistive index (RI) and pulsatility index (PI)] were calculated. Means of cerebrovascular haemodynamic measures were compared by ethnicity, with the introduction of explanatory variables to a regression model to determine which variable could best account for ethnic differences., Results: Cerebrovascular resistance (RI) was 12.9 × 10(3) (0.9-24.8, P = 0.04) greater in South Asians than Europeans. Systolic, diastolic and mean MCA velocities were also higher in South Asians (mean velocity 41.4 ± 8.0 cm/s vs 38.0 ± 8.0 cm/s, respectively, P = 0.001). Low frequency gain, a measure of autoregulation, was worse in South Asians compared with Europeans (0.50 ± 0.01 cm/s mm/Hg vs 0.45 ± 0.01 cm/s mm/Hg, P = 0.01). RI positively correlated with HbA(1c) (r = 0.184; P < 0.01). Adjustment for BP could not explain the higher RI in South Asians, but adjustment for HbA(1c) abolished the ethnic difference in RI (5.8 × 10(3) (-6.5 to 18.1, P = 0.4)., Conclusions: Cerebrovascular resistance and autoregulation are worse in South Asians than in Europeans, despite equivalent resting BP. The greater hyperglycaemia in South Asians accounts for their adverse cerebrovascular resistance. This could explain excess stroke in South Asians but requires testing in longitudinal studies.

Aims/hypothesis: People of African origin have increased risk of stroke and retinal microvascular disease compared with populations of European origin. We compared quantitative measures of retinal microvasculature in British white Europeans and African Caribbeans., Methods: Population-based study of 215 (45% male) British African-Caribbean migrants and 323 (48% male) white Europeans aged 40-69 years. Digitised retinal images were analysed using a validated semi-automated system., Results: Arteriolar optimality deviation, an indicator of endothelial dysfunction, was greater in African Caribbeans (age- and sex-adjusted means [95% CIs]: 0.06 [0.05-0.06] vs 0.04 [0.04-0.05], p = 0.004); this was unexplained by conventional risk factors. Arteriolar diameters were narrower in African Caribbeans (age- and sex-adjusted means [95% CIs]: 18.4 [18.1-18.6] vs 17.9 [17.6-18.2], p = 0.011). These ethnic differences in diameters were attenuated on adjustment for systolic BP (SBP) (adjusted means: 18.2 vs 18.1, p = 0.31). However, there was a significant interaction (p = 0.011) between diabetes and SBP, such that SBP was strongly associated with arteriolar diameter in people without diabetes, but not in those with diabetes (adjusted beta-coefficients for SBP: Europeans: -0.42, p = 0.002 vs 0.17, p = 0.69, African Caribbeans: -0.35, p = 0.023 vs 0.01, p = 0.96). Other measures of retinal vasculature did not differ by ethnicity., Conclusions/interpretation: British African Caribbeans appear to have poorer retinal arteriolar endothelial function than white Europeans. Higher BPs explained the narrower arterioles in African Caribbeans; however, patterns of association between arteriolar narrowing and BP suggest the possibility that cerebral autoregulation and/or remodelling might be adversely affected by diabetes in both ethnic groups.