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{Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol
Tuesday,2022-03-01 18:07 America/Los_Angeles — ecterry
| Title | {Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol |
| Publication Type | Journal Article |
| Year of Publication | 2022 |
| Authors | Wu, P, Moon, JY, Daghlas, I, Franco, G, Porneala, BC, Ahmadizar, F, Richardson, TG, Isaksen, JL, Hindy, G, Yao, J, Sitlani, CM, Raffield, LM, Yanek, LR, Feitosa, MF, Cuadrat, RRC, Qi, Q, M. Ikram, A, Ellervik, C, Ericson, U, Goodarzi, MO, Brody, JA, Lange, L, Mercader, JM, Vaidya, D, An, P, Schulze, MB, Masana, L, Ghanbari, M, Olesen, MS, Cai, J, Guo, X, Floyd, JS, Jäger, S, Province, MA, Kalyani, RR, Psaty, BM, Orho-Melander, M, Ridker, PM, Kanters, JK, Uitterlinden, A, G. Smith, D, Gill, D, Kaplan, RC, Kavousi, M, Raghavan, S, Chasman, DI, Rotter, JI, Meigs, JB, Florez, JC, Dupuis, J, Liu, CT, Merino, J |
| Journal | Diabetes Care |
| Volume | 45 |
| Pagination | 232–240 |
| Date Published | Jan |
| Abstract | 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.\ 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.\ 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).\ 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. |
ePub date:
22/01