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OBJECTIVE: Whether genetic susceptibility to disease and dietary cholesterol (DC) absorption contribute to inconsistent associations of DC consumption with diabetes and cardiovascular disease (CVD) remains unclear. RESEARCH DESIGN AND METHODS: DC consumption was assessed by repeated 24-h dietary recalls in the UK Biobank. A polygenetic risk score (PRS) for DC absorption was constructed using genetic variants in the Niemann-Pick C1-Like 1 and ATP Binding Cassettes G5 and G8 genes. PRSs for diabetes, coronary artery disease, and stroke were also created. The associations of DC consumption with incident diabetes (n = 96,826) and CVD (n = 94,536) in the overall sample and by PRS subgroups were evaluated using adjusted Cox models. RESULTS: Each additional 300 mg/day of DC consumption was associated with incident diabetes (hazard ratio [HR], 1.17 [95% CI, 1.07–1.27]) and CVD (HR, 1.09 [95% CI, 1.03–1.17]), but further adjusting for BMI nullified these associations (HR for diabetes, 0.99 [95% CI, 0.90–1.09]; HR for CVD, 1.04 [95% CI, 0.98–1.12]). Genetic susceptibility to the diseases did not modify these associations (P for interaction ≥0.06). The DC-CVD association appeared to be stronger in people with greater genetic susceptibility to cholesterol absorption assessed by the non-high-density lipoprotein cholesterol-related PRS (P for interaction = 0.04), but the stratum-level association estimates were not statistically significant. CONCLUSIONS: DC consumption was not associated with incident diabetes and CVD, after adjusting for BMI, in the overall sample and in subgroups stratified by genetic predisposition to cholesterol absorption and the diseases. Nevertheless, whether genetic predisposition to cholesterol absorption modifies the DC-CVD association requires further investigation. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare race- and ethnicity-specific BMI cutoffs for the three classes of obesity based on equivalent risk of type 2 diabetes (T2D)., Methods: Participants without T2D were included from the UK Biobank, the China Health and Nutrition Survey, and the Singapore Chinese Health Study. Poisson regressions with restricted cubic splines were applied to determine BMI cutoffs for each non-White race and ethnicity for equivalent incidence rates of T2D at BMI values of 30.0, 35.0, and 40.0 kg/m 2 in White adults., Results: During a median follow-up of 13.8 years among 507,763 individuals, 5.2% developed T2D. In women, BMI cutoffs for an equivalent incidence rate of T2D as observed at 40.0 kg/m 2 in White adults were 31.6 kg/m 2 in Black, 29.2 kg/m 2 in British Chinese, 27.3 kg/m 2 in South Asian, 26.9 kg/m 2 in Native Chinese, and 25.1 kg/m 2 in Singapore Chinese adults. In men, the corresponding BMI cutoffs were 31.9 kg/m 2 in Black, 30.6 kg/m 2 in British Chinese, 29.0 kg/m 2 in South Asian, 29.6 kg/m 2 in Native Chinese, and 27.6 kg/m 2 in Singapore Chinese adults. The race and ethnicity order was consistent when equivalent BMI cutoffs were estimated for class I and II obesity., Conclusions: Establishing a race- and ethnicity-tailored classification of the three classes of obesity is urgently needed., (© 2024 The Obesity Society.)

Background: Although previous studies have identified specific circulating inflammatory markers associated with the risk of mortality, they have often overlooked the broader impact of a comprehensive inflammatory response on health outcomes. This study aims to assess the association between circulating systemic inflammation and age-related hospitalization and premature death, as well as explore the potential mediating effects of various dietary patterns on these associations., Methods: A total of 448,574 participants enrolled in the UK Biobank study were included. Circulating C-reactive protein(CRP), white blood cell count(WBC), platelet count(Plt), and neutrophil/lymphocyte ratio(NLR) were measured, which were used to establish a weighted systemic inflammatory index of inflammation index(INFLA-Score). Dietary intake information was documented through 24-hour dietary recalls, and dietary pattern scores including Dietary Approaches to Stop Hypertension(DASH), Mediterranean(MED), and Healthy Eating Index-2020(HEI-2020) were calculated. Cox proportional hazards regression models were performed to assess the associations between INFLA-Score and age-related disease hospitalization, cause-specific and all-cause premature death., Results: During a median follow-up of 12.65 years, 23,784 premature deaths were documented. After adjusting for multiple covariates, higher levels of CRP, WBC, NLR, and INFLA-Score were significantly associated with increased risks of age-related disease hospitalization(HR CRP =1.19; 95%:1.17-1.21; HR WBC =1.17; 95%:1.15-1.19; HR NLR =1.18; 95%:1.16-1.20; HR INFLA-Score =1.19; 95%:1.17-1.21) and premature death(HR CRP =1.68; 95%:1.61-1.75; HR WBC =1.23; 95%:1.18-1.27; HR NLR =1.45; 95%:1.40-1.50; HR INFLA-Score =1.58; 95%:1.52-1.64). Compared to the lowest INFLA-Score group, the highest INFLA-Score group was associated with increased values of whole-body and organ-specific biological age, and had a shortened life expectancy of 2.96 (95% CI 2.53-3.41) and 4.14 (95% CI 3.75-4.56) years at the age of 60 years in women and men, respectively. Additionally, we observed no significant association of the INFLA-Score with aging-related hospitalization and premature death among participants who were more adhering to the Mediterranean (MED) dietary pattern(HR Aging-related hospitalization =1.07; 95%:0.99-1.16;HR Premature death =1.19; 95%:0.96-1.47)., Conclusion: A higher INFLA-Score was correlated with an increased risk of age-related hospitalization and premature death. Nevertheless, adherence to a Mediterranean (MED) diet may mitigate these associations., (© 2024. The Author(s).)