Background: Despite being a defining feature of metabolic syndrome (MetS), clinical assessment of IR remains challenging, due to the costs of reference methods and the numerosity of IR indices. Furthermore, to which extent IR contributes to MetS, while controlling for altered body composition, is still largely unexplored. Objectives: The present work aims at proposing new cut points for IR among people with overweight and obesity, assessing the concordance of different IR definitions and investigating how IR interacts with body composition in predicting MetS status. Subjects: 665 patients were assessed for potential enrolment, using a cross-sectional design. The following inclusion criteria were applied: age ≥18 years, body mass index ≥25 kg/m2, White European, no fulfilled criterion for diabetes mellitus, no current pregnancy. Methods: Concordance of previously validated IR definitions was assessed by Cohen’s κ. ROC curve analysis with 5-fold cross-validation was used to determine novel cut points for IR indices based on MetS presence. Finally, mediation analysis was employed to test whether IR mediates the relationship between body composition indices (i.e., fat mass-to-fat-free mass ratio, FM:FFM and appendicular lean soft tissue-to-visceral fat area ratio, ALST:VFA) and MetS. Results: A total of 515 patients were included in the final analysis (females: 80.9%; MetS prevalence: 40%). Overall, IR definitions which previously validated against the hyperinsulinemic-euglycemic clamp displayed the highest level of agreement. The following cut-points were identified from ROC curve analysis: ISI-Matsuda<3.33 (AUROC = 0.675, p < 0.001), HOMA-IR > 2.93 (AUROC = 0.663 p < 0.001), HOMA2-IR > 1.67 (AUROC = 0.651 p < 0.001). Finally, ALST:VFA but not FM:FFM significantly predicted MetS status independent of age, with the mediating role of ISI-Matsuda, HOMA-IR and HOMA2-IR. Conclusions: IR indices mediated the effect of altered body composition (i.e., reduced appendicular muscularity and increased visceral adiposity) on MetS. Newly proposed diagnostic thresholds can aid in the identification of IR among patients at increased cardio-metabolic risk.
Capturing metabolic syndrome: new thresholds for insulin resistance and novel body composition indices
Frigerio, Francesco;Caprio, Massimiliano;
2026-01-01
Abstract
Background: Despite being a defining feature of metabolic syndrome (MetS), clinical assessment of IR remains challenging, due to the costs of reference methods and the numerosity of IR indices. Furthermore, to which extent IR contributes to MetS, while controlling for altered body composition, is still largely unexplored. Objectives: The present work aims at proposing new cut points for IR among people with overweight and obesity, assessing the concordance of different IR definitions and investigating how IR interacts with body composition in predicting MetS status. Subjects: 665 patients were assessed for potential enrolment, using a cross-sectional design. The following inclusion criteria were applied: age ≥18 years, body mass index ≥25 kg/m2, White European, no fulfilled criterion for diabetes mellitus, no current pregnancy. Methods: Concordance of previously validated IR definitions was assessed by Cohen’s κ. ROC curve analysis with 5-fold cross-validation was used to determine novel cut points for IR indices based on MetS presence. Finally, mediation analysis was employed to test whether IR mediates the relationship between body composition indices (i.e., fat mass-to-fat-free mass ratio, FM:FFM and appendicular lean soft tissue-to-visceral fat area ratio, ALST:VFA) and MetS. Results: A total of 515 patients were included in the final analysis (females: 80.9%; MetS prevalence: 40%). Overall, IR definitions which previously validated against the hyperinsulinemic-euglycemic clamp displayed the highest level of agreement. The following cut-points were identified from ROC curve analysis: ISI-Matsuda<3.33 (AUROC = 0.675, p < 0.001), HOMA-IR > 2.93 (AUROC = 0.663 p < 0.001), HOMA2-IR > 1.67 (AUROC = 0.651 p < 0.001). Finally, ALST:VFA but not FM:FFM significantly predicted MetS status independent of age, with the mediating role of ISI-Matsuda, HOMA-IR and HOMA2-IR. Conclusions: IR indices mediated the effect of altered body composition (i.e., reduced appendicular muscularity and increased visceral adiposity) on MetS. Newly proposed diagnostic thresholds can aid in the identification of IR among patients at increased cardio-metabolic risk.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
