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Table 1_Insulin resistance, metabolic phenotypes, and the obesity paradox: a triglyceride glucose-body mass index framework in partial kidney diseases.docx Xiangzhe Sun (25097128) Lu Bai (343118) Changchang Liang (23090237) Shuai Guo (1353816) Yongliang Chen (3567410) Maodong Liu (363285) Cell Metabolism CKM syndrome insulin resistance kidney disease obesity paradox TyG-BMI Background<p>Insulin resistance(IR) is a key driver of cardiorenal-metabolic diseases. The Triglyceride Glucose-Body Mass Index (TyG-BMI), a composite marker of lipid-glucose metabolism and overall adiposity, has gained traction as a predictive tool. Its clinical application, however, is complicated by non-linear and sometimes paradoxical associations with clinical outcomes, a phenomenon reminiscent of the”obesity paradox”. This review critically evaluates the performance of TyG-BMI across the spectrum of kidney disease, aiming to reconcile these divergent findings through a metabolic-endocrine framework.</p>Methods<p>We performed a narrative synthesis of observational studies and secondary analyses of large-scale public databases such as National Health and Nutrition Examination Survey(NHANES), China Health and Retirement Longitudinal Study(CHARLS), UK Biobank, Medical Information Mart for Intensive Care IV(MIMIC-IV), identified through PubMed and Google Scholar, to evaluate the association of TyG-BMI with the incidence, progression, and prognosis of acute kidney injury (AKI), diabetic kidney disease (DKD), chronic kidney disease (CKD), and Cardiovascular-Kidney-Metabolic syndrome(CKM).</p>Results<p>TyG-BMI shows significant, context-dependent predictive value. In early-stage or metabolically heterogeneous populations, elevated TyG-BMI consistently predicts higher disease risk. Conversely, in advanced stages (e.g., end-stage renal disease, stage 4 CKM), the association frequently becomes U-shaped, with low TyG-BMI paradoxically linked to excess mortality. This reflects its dual nature: the TyG component captures ‘metabolic toxicity’, while BMI proxies ‘nutritional reserve’. Thus, the ‘obesity paradox’ may represent a metabolic phenotype spectrum—from metabolically healthy obesity (MHO) to metabolically unhealthy lean (MUL)—that the combination of its TyG and BMI components helps differentiate. For disease incidence prediction, TyG-BMI is often outperformed by indices of central obesity (e.g., Triglyceride-Glucose-Waist Circumference Index(TyG-WC), Triglyceride-Glucose–Waist-to-Height Ratio(TyG-WHtR); for mortality in advanced illness, the standalone TyG index may be superior.</p>Conclusion<p>TyG-BMI is a valuable tool for metabolic phenotyping and risk stratification in kidney disease, with its paradoxical associations highlighting the complex interplay between metabolic health and nutritional reserve. Future research must establish context-specific clinical thresholds. TyG-BMI is preferentially useful in settings where waist circumference is unavailable, in early CKD screening, and in select type 2 diabetes mellitus (T2DM) subgroups. In advanced CKD, dialysis, critical illness, and CKM stage 4, alternative indices such as TyG index, TyG-WC, or TyG-WHtR should be prioritized due to the confounding effects of fluid overload and catabolic state.</p> 2026-09-23T11:58:24Z Dataset Dataset 10.3389/fendo.2026.1915011.s001 https://figshare.com/articles/dataset/Table_1_Insulin_resistance_metabolic_phenotypes_and_the_obesity_paradox_a_triglyceride_glucose-body_mass_index_framework_in_partial_kidney_diseases_docx/33973030 CC BY 4.0