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Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol.
- Source :
-
Diabetes care [Diabetes Care] 2022 Jan 01; Vol. 45 (1), pp. 232-240. - Publication Year :
- 2022
-
Abstract
- Objective: LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown.<br />Research Design and Methods: We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,908 participants to investigate the effect of lowering LDLc on type 2 diabetes risk and the proportion of this effect mediated through BMI. We used data from 92,532 participants from 14 observational studies to replicate findings in individual-level MR analyses.<br />Results: A 1-SD decrease in genetically predicted LDLc was associated with increased type 2 diabetes odds (odds ratio [OR] 1.12 [95% CI 1.01, 1.24]) and BMI (β = 0.07 SD units [95% CI 0.02, 0.12]) in univariable MR analyses. The multivariable MR analysis showed evidence of an indirect effect of lowering LDLc on type 2 diabetes through BMI (OR 1.04 [95% CI 1.01, 1.08]) with a proportion mediated of 38% of the total effect (P = 0.03). Total and indirect effect estimates were similar across a number of sensitivity analyses. Individual-level MR analyses confirmed the indirect effect of lowering LDLc on type 2 diabetes through BMI with an estimated proportion mediated of 8% (P = 0.04).<br />Conclusions: These findings suggest that the diabetogenic effect attributed to lowering LDLc is partially mediated through increased BMI. Our results could help advance understanding of adipose tissue and lipids in type 2 diabetes pathophysiology and inform strategies to reduce diabetes risk among individuals taking LDLc-lowering medications.<br /> (© 2021 by the American Diabetes Association.)
Details
- Language :
- English
- ISSN :
- 1935-5548
- Volume :
- 45
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Diabetes care
- Publication Type :
- Academic Journal
- Accession number :
- 34789503
- Full Text :
- https://doi.org/10.2337/dc21-1284