1. HDL Cholesterol and Risk of Type 2 Diabetes: A Mendelian Randomization Study.
- Author
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Haase CL, Tybjærg-Hansen A, Nordestgaard BG, and Frikke-Schmidt R
- Subjects
- ATP Binding Cassette Transporter 1 genetics, Apolipoprotein A-I genetics, Cholesterol Ester Transfer Proteins genetics, Cohort Studies, Dyslipidemias blood, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Lipase genetics, Male, Middle Aged, Phosphatidylcholine-Sterol O-Acyltransferase genetics, Proportional Hazards Models, Prospective Studies, Taq Polymerase genetics, Cholesterol, HDL blood, Diabetes Mellitus, Type 2 genetics, Dyslipidemias genetics, Mendelian Randomization Analysis
- Abstract
Observationally, low levels of HDL cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce the risk of type 2 diabetes. Whether levels of HDL cholesterol are causally associated with type 2 diabetes is unknown. In a prospective study of the general population (n = 47,627), we tested whether HDL cholesterol-related genetic variants were associated with low HDL cholesterol levels and, in turn, with an increased risk of type 2 diabetes. HDL cholesterol-decreasing gene scores and allele numbers associated with up to -13 and -20% reductions in HDL cholesterol levels. The corresponding theoretically predicted hazard ratios for type 2 diabetes were 1.44 (95% CI 1.38-1.52) and 1.77 (1.61-1.95), whereas the genetic estimates were nonsignificant. Genetic risk ratios for type 2 diabetes for a 0.2 mmol/L reduction in HDL cholesterol were 0.91 (0.75-1.09) and 0.93 (0.78-1.11) for HDL cholesterol-decreasing gene scores and allele numbers, respectively, compared with the corresponding observational hazard ratio of 1.37 (1.32-1.42). In conclusion, genetically reduced HDL cholesterol does not associate with increased risk of type 2 diabetes, suggesting that the corresponding observational association is due to confounding and/or reverse causation., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
- Published
- 2015
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