Capturing metabolic syndrome: new thresholds for insulin resistance and novel body composition indices.

IR definitions previously validated against the hyperinsulinemic-euglycemic clamp displayed the highest level of agreement with each other.

• Concordance of IR definitions was assessed using Cohen's κ in a sample of 515 patients
• Patients were adults with BMI ≥25 kg/m², White European, without diabetes mellitus
• The study population was 80.9% female with a MetS prevalence of 40%
• Overall agreement was highest among indices validated against the gold-standard hyperinsulinemic-euglycemic clamp method

ROC curve analysis identified a novel cut point of ISI-Matsuda <3.33 for identifying insulin resistance based on metabolic syndrome presence.

• AUROC = 0.675, p < 0.001
• Analysis used 5-fold cross-validation
• Cut point was derived from a cross-sectional study of 515 patients with overweight or obesity
• The analysis was specific to White European adults with BMI ≥25 kg/m² without diabetes

ROC curve analysis identified a novel cut point of HOMA-IR >2.93 for identifying insulin resistance based on metabolic syndrome presence.

• AUROC = 0.663, p < 0.001
• Analysis used 5-fold cross-validation
• Cut point was derived from the same cross-sectional study of 515 patients
• MetS prevalence in the study sample was 40%

ROC curve analysis identified a novel cut point of HOMA2-IR >1.67 for identifying insulin resistance based on metabolic syndrome presence.

• AUROC = 0.651, p < 0.001
• Analysis used 5-fold cross-validation
• This was the lowest AUROC among the three newly proposed IR thresholds
• Cut point was derived from a cross-sectional study of 515 patients with overweight or obesity

The appendicular lean soft tissue-to-visceral fat area ratio (ALST:VFA) significantly predicted MetS status independent of age, whereas fat mass-to-fat-free mass ratio (FM:FFM) did not.

• Mediation analysis was employed to test whether IR mediates the relationship between body composition indices and MetS
• ALST:VFA reflects reduced appendicular muscularity combined with increased visceral adiposity
• FM:FFM did not significantly predict MetS status in this analysis
• The relationship between ALST:VFA and MetS was assessed while controlling for age

Insulin resistance indices mediated the relationship between ALST:VFA and metabolic syndrome status.

• ISI-Matsuda, HOMA-IR, and HOMA2-IR all demonstrated a mediating role in the relationship between ALST:VFA and MetS
• Mediation analysis indicated that IR mediates the effect of altered body composition (reduced appendicular muscularity and increased visceral adiposity) on MetS
• FM:FFM did not show a significant mediated pathway through IR to MetS
• This finding suggests that body composition influences MetS risk partly through its effect on insulin resistance

The study enrolled 515 patients out of 665 assessed for eligibility using a cross-sectional design.

• Inclusion criteria: age ≥18 years, BMI ≥25 kg/m², White European ethnicity, no fulfilled criterion for diabetes mellitus, no current pregnancy
• Final sample: 515 patients (females: 80.9%; MetS prevalence: 40%)
• 150 patients assessed were excluded from the final analysis
• Patients were assessed at a single time point given the cross-sectional design