Associations of Dietary Cholesterol Consumption With Incident Diabetes and Cardiovascular Disease: The Role of Genetic Variability in Cholesterol Absorption and Disease Predisposition

• Published in: Diabetes care Vol. 47; no. 6; pp. 1092 - 1098
• Main Authors: Shi, Shuxiao, Dong, Ying, Wang, Sujing, Du, Xihao, Feng, Nannan, Xu, Lan, Zhong, Victor W
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.06.2024
• Subjects: Absorption; Adult; Aged; ATP Binding Cassette Transporter, Subfamily G, Member 5 - genetics; ATP Binding Cassette Transporter, Subfamily G, Member 8 - genetics; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Cholesterol; Cholesterol, Dietary - administration & dosage; Cholesterol, Dietary - adverse effects; Consumption; Coronary artery disease; Diabetes; Diabetes mellitus; Diabetes Mellitus - epidemiology; Diabetes Mellitus - genetics; Diet; Female; Genetic diversity; Genetic Predisposition to Disease; Genetic variability; Genetic variance; Heart diseases; High density lipoprotein; Humans; Male; Membrane Transport Proteins - genetics; Middle Aged; Niemann-Pick disease; Research design; Statistical analysis; Subgroups
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc23-2336

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. 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. 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. 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.