HDL Cholesterol and Risk of Type 2 Diabetes: A Mendelian Randomization Study
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HDL Cholesterol and Risk of Type 2 Diabetes : A Mendelian Randomization Study. / Haase, Christiane L; Tybjærg-Hansen, Anne; Nordestgaard, Børge G; Frikke-Schmidt, Ruth.
In: Diabetes, Vol. 64, No. 9, 09.2015, p. 3328-33.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - HDL Cholesterol and Risk of Type 2 Diabetes
T2 - A Mendelian Randomization Study
AU - Haase, Christiane L
AU - Tybjærg-Hansen, Anne
AU - Nordestgaard, Børge G
AU - Frikke-Schmidt, Ruth
N1 - © 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.
PY - 2015/9
Y1 - 2015/9
N2 - 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.
AB - 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.
KW - ATP Binding Cassette Transporter 1
KW - Apolipoprotein A-I
KW - Cholesterol Ester Transfer Proteins
KW - Cholesterol, HDL
KW - Cohort Studies
KW - Diabetes Mellitus, Type 2
KW - Dyslipidemias
KW - Female
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Humans
KW - Lipase
KW - Male
KW - Mendelian Randomization Analysis
KW - Middle Aged
KW - Phosphatidylcholine-Sterol O-Acyltransferase
KW - Proportional Hazards Models
KW - Prospective Studies
KW - Taq Polymerase
U2 - 10.2337/db14-1603
DO - 10.2337/db14-1603
M3 - Journal article
C2 - 25972569
VL - 64
SP - 3328
EP - 3333
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 9
ER -
ID: 162675374