ArticleDiabetes2024
Genetic Evidence for Distinct Biological Mechanisms That Link Adiposity to Type 2 Diabetes: Toward Precision Medicine.
Article in Diabetes, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 12 citations in OpenAlex.
- Genetic and molecular signatures highlight diverse pathways linking obesity to type 2 diabetes.Nature communications · 2026Article
- Genetics of MASLD: a diabetes perspective.Diabetologia · 2026Review
- Specific Fat Depots and Cardiometabolic Risk and Insulin Resistance in Children With Obesity.Pediatric obesity · 2026Article
- Social, psychosocial, and lifestyle determinants of diabetes and prediabetes in US adults before and after COVID-19: a cross-sectional NHANES analysis.Diabetology & metabolic syndrome · 2026Article
- Distinct genetic profiles of obesity have different effects on breast cancer risk: leveraging Mendelian randomisation to interrogate causal pathways and identify mediating proteins.Breast cancer research : BCR · 2026Article
- Visceral fat area and visceral-to-subcutaneous fat ratio are more strongly associated with residual cholesterol than conventional anthropometric indices in adults with type 2 diabetes.Frontiers in endocrinology · 2026Article
- Emodin Enhances Rosiglitazone's Therapeutic Profile by Dual Modulation of SREBP1-Mediated Adipogenesis and PPARγ-Driven Thermogenesis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Genetic subtyping of obesity reveals biological insights into the uncoupling of adiposity from its cardiometabolic comorbidities.Nature medicine · 2025Article
- Crosstalk Between Skeletal Muscle and Proximal Connective Tissues in Lipid Dysregulation in Obesity and Type 2 Diabetes.Metabolites · 2025Review
- Article
- Disentangling the divergent causal pathways underlying the association between body mass index and bone mineral density: a comprehensive Mendelian randomization study.BMC medicine · 2025Article
- Genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal MRI.Frontiers in genetics · 2025Article
- Monolayer whole adherent islets: A novel tool for studying drug-induced diabetic phenotypes in vitro.PloS one · 2025Article
- Use of Cross-Sectional Imaging Body Composition Assessment to Predict Pancreas Transplant Outcomes.Transplant international : official journal of the European Society for Organ Transplantation · 2025Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
Abstract
We aimed to unravel the mechanisms connecting adiposity to type 2 diabetes. We used MR-Clust to cluster independent genetic variants associated with body fat percentage (388 variants) and BMI (540 variants) based on their impact on type 2 diabetes. We identified five clusters of adiposity-increasing alleles associated with higher type 2 diabetes risk (unfavorable adiposity) and three clusters associated with lower risk (favorable adiposity). We then characterized each cluster based on various biomarkers, metabolites, and MRI-based measures of fat distribution and muscle quality. Analyzing the metabolic signatures of these clusters revealed two primary mechanisms connecting higher adiposity to reduced type 2 diabetes risk. The first involves higher adiposity in subcutaneous tissues (abdomen and thigh), lower liver fat, improved insulin sensitivity, and decreased risk of cardiometabolic diseases and diabetes complications. The second mechanism is characterized by increased body size and enhanced muscle quality, with no impact on cardiometabolic outcomes. Furthermore, our findings unveil diverse mechanisms linking higher adiposity to higher disease risk, such as cholesterol pathways or inflammation. These results reinforce the existence of adiposity-related mechanisms that may act as protective factors against type 2 diabetes and its complications, especially when accompanied by reduced ectopic liver fat. ARTICLE HIGHLIGHTS:
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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 Socratic graph.