ArticleDiabetes care2022
Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol.
Open access · bronzeAbstract read
In one paragraph
Article in Diabetes care, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- The Central Role of Lipid Metabolism Disorders in Diabetes Mellitus: Mechanisms, Clinical Manifestations, and Emerging Therapeutic Strategies.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Glucose metabolism in heterozygous familial hypercholesterolemia with a founder effect and a high diabetes prevalence: a cross-sectional study.Cardiovascular diabetology · 2025Article
- Exploring the shared genetic landscape of diabetes and cardiovascular disease: findings and future implications.Diabetologia · 2025Review
- Metformin for Treating Gestational Diabetes: What Have We Learned During the Last Two Decades? A Systematic Review.Life (Basel, Switzerland) · 2025Review
- The Diabetogenic Effect of Statin Use May Interact With Polygenic Risk Scores for Type 2 Diabetes: Evidence From the UK Biobank.Journal of preventive medicine and public health = Yebang Uihakhoe chi · 2025Article
- Body mass index impacts the lipid-lowing effects of statins in patients with type 2 diabetes.Frontiers in cardiovascular medicine · 2025Article
- Effects of ACLY Inhibition on Body Weight Distribution: A Drug Target Mendelian Randomization Study.Genes · 2024Article
- Efficacy and safety of metformin during pregnancy: an update.Endocrine · 2024Review
- Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes.Cardiovascular diabetology · 2024Article
- Article
- Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges.Diabetologia · 2023Review
- Linear and nonlinear analyses of the association between low-density lipoprotein cholesterol and diabetes: The spurious U-curve in observational study.Frontiers in endocrinology · 2022Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
52 authors at 20 institutions in 8 countries.
Peitao Wu1Department of Biostatistics, Boston University School of Public Health, Boston, MA.
Jee-Young Moon2Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
Iyas Daghlas3Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.
Giulianini Franco5Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Bianca C Porneala6Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA.
Fariba Ahmadizar7Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0002-6261-9445
Tom G Richardson8MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, U.K.
Jonas L Isaksen10Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Georgy Hindy11Department of Clinical Sciences, Skåne University Hospital Malmo Clinical Research Center, Lund University, Malmo, Sweden.
Jie Yao12Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
Colleen M Sitlani13Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA.
Laura M Raffield14Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC.
Lisa R Yanek15Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Mary F Feitosa16Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO.
Rafael R C Cuadrat17Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
Qibin Qi2Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.ORCID 0000-0002-2687-1758
M Arfan Ikram7Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Christina Ellervik19Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Ulrika Ericson11Department of Clinical Sciences, Skåne University Hospital Malmo Clinical Research Center, Lund University, Malmo, Sweden.
Mark O Goodarzi21Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.ORCID 0000-0001-6364-5103
Jennifer A Brody13Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA.
Leslie Lange22Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
Josep M Mercader4Programs in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0001-8494-3660
Dhananjay Vaidya15Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Ping An16Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO.
Matthias B Schulze17Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.ORCID 0000-0002-0830-5277
Lluis Masana26Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Rovira i Virgil University, IISPV, Reus, Spain.ORCID 0000-0002-0789-4954
Mohsen Ghanbari7Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Morten S Olesen28Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark.
Jianwen Cai30Collaborative Studies Coordinating Center, Department of Biostatistics, The University of North Carolina at Chapel Hill, NC.
Xiuqing Guo12Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
James S Floyd13Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA.
Susanne Jäger17Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.ORCID 0000-0001-6619-0861
Michael A Province16Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO.
Rita R Kalyani15Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-1530-6884
Bruce M Psaty13Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA.
Marju Orho-Melander11Department of Clinical Sciences, Skåne University Hospital Malmo Clinical Research Center, Lund University, Malmo, Sweden.
Paul M Ridker5Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Jørgen K Kanters10Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Andre Uitterlinden7Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
George Davey Smith8MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, U.K.
Dipender Gill9Novo Nordisk Research Centre Oxford, Old Road Campus, Oxford, U.K.ORCID 0000-0001-7312-7078
Robert C Kaplan2Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.ORCID 0000-0003-1571-4615
Maryam Kavousi7Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0001-5976-6519
Sridharan Raghavan38Department of Veterans Affairs Medical Center, Eastern Colorado Health Care System, Denver, CO.
Daniel I Chasman3Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.ORCID 0000-0003-3357-0862
Jerome I Rotter12Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
James B Meigs4Programs in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.
Jose C Florez4Programs in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.
Josée Dupuis1Department of Biostatistics, Boston University School of Public Health, Boston, MA.
Ching-Ti Liu1Department of Biostatistics, Boston University School of Public Health, Boston, MA.ORCID 0000-0002-0703-0742
Jordi Merino4Programs in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0001-8312-1438
Broad Institute · USErasmus MC · NLUniversity of Washington · USAlbert Einstein College of Medicine · USBoston University · USJohns Hopkins University · USLund University · SEUCLA Medical Center · USUniversity of Copenhagen · DKBrigham and Women's Hospital · USDeutsches Diabetes-Zentrum e.V. · DEUniversity of Bristol · GBUniversity of North Carolina at Chapel Hill · USCedars-Sinai Medical Center · USCentro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas · ESCopenhagen University Hospital · DKMassachusetts General Hospital · USSt George's, University of London · GBUniversity of Colorado Anschutz Medical Campus · USUniversity of Potsdam · DE
Funding
ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Elizabeth Austen Lawson, Takara Leah Stanley · 1994 to 2026
$31.6MWashington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Dominic N Reeds · 1999 to 2026
$30.2MTranslational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI DONALD K. SCOTT · 2015 to 2026
$27.7MNorth Carolina Translational and Clinical Science Institute (NC TraCS) KL2KL2TR002490 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WEINBERGER, MORRIS · 2018 to 2022
$11.0MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MNew York Regional Center for Diabetes Translation Research - Translational Intervention Methodology CoreP30DK111022 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI JEFFREY GONZALEZ · 2016 to 2026
$7.8MDevelopment of Polygenic Risk Scores for Diabetes and Complications across the Life-Span in Populations of Multiple AncestriesU01HG011723 · NHGRI · BROAD INSTITUTE, INC. · PI Alisa Knodle Manning, Josep Maria Mercader · 2021 to 2026
$5.7MThe Genetic Epidemiology of Heart, Lung, and Blood TraitsTraining Grant (GenHLB)T32HL129982 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christy Leigh Avery, KAREN L. MOHLKE · 2016 to 2026
$3.8MTOPMed Omics of Type 2 Diabetes and Quantitative TraitsUM1DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MANNING, ALISA KNODLE · 2021 to 2025
$3.8MRare Sequence Variation and Diabetes Quantitative TraitsU01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2015 to 2019
$3.6MTOPMed Omics of Cardiovascular Disease in DiabetesR01HL151855 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2020 to 2023
$3.3MThalassemia Clinical Research Network, CanadaU01HL065233 · NHLBI · UNIVERSITY HEALTH NETWORK · PI OLIVIERI, NANCY F · 2000 to 2009
$2.6MBritish Heart Foundation RE/18/4/34215CSRD VA IK2 CX001907Department of Health CL-2020-16-001Medical Research Council MC_UU_00011/1NCATS NIH HHS KL2 TR002490NHGRI NIH HHS U01 HG011723NHLBI NIH HHS K24 HL157960NHLBI NIH HHS N01 HC065233NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL151855NHLBI NIH HHS T32 HL129982NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK040561NIDDK NIH HHS P30 DK056341NIDDK NIH HHS P30 DK111022NIDDK NIH HHS U01 DK078616NIDDK NIH HHS UM1 DK078616
Abstract
objectiveLDL 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
methodsWe 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.
resultsA 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).
conclusionsThese 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.
Indexed as
Diabetes Mellitus, Type 2Cholesterol, LDLGenome-Wide Association StudyHumansMendelian Randomization AnalysisObesityRisk FactorsCholesterol, LDL
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.