ArticlePLoS genetics2020
The causal effect of obesity on prediabetes and insulin resistance reveals the important role of adipose tissue in insulin resistance.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 70 citations in OpenAlex.
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- Efficacy and safety of Obex® in overweight and obese subjects: a randomised, double-blind, placebo-controlled clinical trial.BMC complementary medicine and therapies · 2023Trial
- Current Trends in the Epidemiology of Obesity and the Association Between Obesity and Metabolic Liver Disease (MASLD/MASH).Diabetes, obesity & metabolism · 2026Review
- Lessons from single cell omics: admixed American ancestry and sex confer cardiometabolic disease risk in Mexicans.Genome medicine · 2026Article
- Insulin resistance in obese children and adolescents: from mechanisms to screening and exercise intervention.Frontiers in pediatrics · 2026Review
- A predictive study of glycaemic reversal in Chinese individuals with prediabetes based on machine learning: a 5-year cohort study.Frontiers in endocrinology · 2026Article
- Predictive effect of the triglyceride glucose index on abnormal blood glucose metabolism events in populations with sarcopenia: a cross-sectional study.BMC endocrine disorders · 2025Article
- Prevalence and associated factors of prediabetes among primary health care attendees in the West bank of Palestine: a cross-sectional study.BMC public health · 2025Article
- Oil spill cleanup related exposures to benzene, toluene, ethylbenzene, xylenes, and n-hexane and incident diabetes mellitus.Environmental research · 2025Article
- Exploring the genetic intersection between obesity-associated genetic variants and insulin sensitivity indices.Scientific reports · 2025Article
- Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM.Cell genomics · 2025Article
- Identification of genetic loci enriched in obese or lean T2D cases in the Korean population.Genes & genomics · 2025Article
- Article
- The Clínica Universidad de Navarra-Body Adiposity Estimator index is a reliable tool for prediabetes: a multi-center retrospective cohort study.Frontiers in nutrition · 2025Article
- The impact of butyrate on glycemic control in animals and humans: a comprehensive semi-systemic review.Frontiers in nutrition · 2025Review
- Higher neighborhood disadvantage is associated with weaker interactions among cardiometabolic drivers.International journal of cardiology. Cardiovascular risk and prevention · 2024Article
- An abdominal obesity missense variant in the adipocyte thermogenesis gene TBX15 is implicated in adaptation to cold in Finns.American journal of human genetics · 2024Article
- Higher serum myostatin levels are associated with lower insulin sensitivity in adults with overweight/obesity.Physiological reports · 2024Article
- 5-Methoxy-2-aminoindane Reverses Diet-Induced Obesity and Improves Metabolic Parameters in Mice: A Potential New Class of Antiobesity Therapeutics.ACS pharmacology & translational science · 2024Article
- Transcriptomic profiling of sciatic nerves and dorsal root ganglia reveals site-specific effects of prediabetic neuropathy.Translational research : the journal of laboratory and clinical medicine · 2024Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Reverse causality has made it difficult to establish the causal directions between obesity and prediabetes and obesity and insulin resistance. To disentangle whether obesity causally drives prediabetes and insulin resistance already in non-diabetic individuals, we utilized the UK Biobank and METSIM cohort to perform a Mendelian randomization (MR) analyses in the non-diabetic individuals. Our results suggest that both prediabetes and systemic insulin resistance are caused by obesity (p = 1.2×10-3 and p = 3.1×10-24). As obesity reflects the amount of body fat, we next studied how adipose tissue affects insulin resistance. We performed both bulk RNA-sequencing and single nucleus RNA sequencing on frozen human subcutaneous adipose biopsies to assess adipose cell-type heterogeneity and mitochondrial (MT) gene expression in insulin resistance. We discovered that the adipose MT gene expression and body fat percent are both independently associated with insulin resistance (p≤0.05 for each) when adjusting for the decomposed adipose cell-type proportions. Next, we showed that these 3 factors, adipose MT gene expression, body fat percent, and adipose cell types, explain a substantial amount (44.39%) of variance in insulin resistance and can be used to predict it (p≤2.64×10-5 in 3 independent human cohorts). In summary, we demonstrated that obesity is a strong determinant of both prediabetes and insulin resistance, and discovered that individuals' adipose cell-type composition, adipose MT gene expression, and body fat percent predict their insulin resistance, emphasizing the critical role of adipose tissue in systemic insulin resistance.
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