Articles producció científica> Medicina i Cirurgia

Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol

  • Dades identificatives

    Identificador: imarina:9243519
    Autors:
    Wu PMoon JYDaghlas IFranco GPorneala BCAhmadizar FRichardson TGIsaksen JLHindy GYao JSitlani CMRaffield LMYanek LRFeitosa MFCuadrat RRCQi QIkram MAEllervik CEricson UGoodarzi MOBrody JALange LMercader JMVaidya DAn PSchulze MBMasana LGhanbari MOlesen MSCai JGuo XFloyd JSJager SProvince MAKalyani RRPsaty BMOrho-Melander MRidker PMKanters JKUitterlinden ASmith GDGill DKaplan RCKavousi MRaghavan SChasman DIRotter JIMeigs JBFlorez JCDupuis JLiu CTMerino J
    Resum:
    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. 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. 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 (b 5 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 5 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 5 0.04). 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.
  • Altres:

    Autor segons l'article: 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; Ikram MA; 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; Jager S; Province MA; Kalyani RR; Psaty BM; Orho-Melander M; Ridker PM; Kanters JK; Uitterlinden A; Smith GD; Gill D; Kaplan RC; Kavousi M; Raghavan S; Chasman DI; Rotter JI; Meigs JB; Florez JC; Dupuis J; Liu CT; Merino J
    Departament: Medicina i Cirurgia
    Autor/s de la URV: Masana Marín, Luis / MERINO RIBAS, JORDI
    Paraules clau: Density-lipoprotein cholesterol risk pcsk9 mendelian randomization instruments genome-wide association genetic-variants bias
    Resum: 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. 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. 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 (b 5 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 5 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 5 0.04). 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.
    Àrees temàtiques: Saúde coletiva Odontología Nutrição Medicina iii Medicina ii Medicina i Internal medicine Interdisciplinar General medicine Engenharias iv Enfermagem Endocrinology, diabetes and metabolism Endocrinology & metabolism Ciências biológicas ii Ciências biológicas i Biotecnología Antropologia / arqueologia Advanced and specialized nursing
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    Adreça de correu electrònic de l'autor: luis.masana@urv.cat
    Identificador de l'autor: 0000-0002-0789-4954
    Data d'alta del registre: 2024-09-07
    Versió de l'article dipositat: info:eu-repo/semantics/acceptedVersion
    Enllaç font original: https://diabetesjournals.org/care/article-abstract/45/1/232/138981/Obesity-Partially-Mediates-the-Diabetogenic-Effect?redirectedFrom=fulltext
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Diabetes Care. 45 (1): 232-240
    Referència de l'ítem segons les normes APA: 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 (2022). Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol. Diabetes Care, 45(1), 232-240. DOI: 10.2337/dc21-1284
    DOI de l'article: 10.2337/dc21-1284
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2022
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Advanced and Specialized Nursing,Endocrinology & Metabolism,Endocrinology, Diabetes and Metabolism,Internal Medicine
    Density-lipoprotein cholesterol
    risk
    pcsk9
    mendelian randomization
    instruments
    genome-wide association
    genetic-variants
    bias
    Saúde coletiva
    Odontología
    Nutrição
    Medicina iii
    Medicina ii
    Medicina i
    Internal medicine
    Interdisciplinar
    General medicine
    Engenharias iv
    Enfermagem
    Endocrinology, diabetes and metabolism
    Endocrinology & metabolism
    Ciências biológicas ii
    Ciências biológicas i
    Biotecnología
    Antropologia / arqueologia
    Advanced and specialized nursing
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