Exploring the association between 5 different alternative indicators of insulin resistance and the risk of multiple cardiovascular and metabolic diseases: A cross-sectional NHANES study from 2005 to 2018.

All five insulin resistance surrogates were significantly associated with increased cardiometabolic multimorbidity (CMM) risk.

• The study included 15,537 participants from NHANES 2005 to 2018, of whom 2,881 developed CMM.
• IR markers assessed included the TyG index, TyG-BMI index, METS-IR, TG/HDL-C ratio, and HOMA-IR.
• Logistic regression, the Boruta algorithm, trend tests, restricted cubic spline analysis, subgroup analysis, Brier scores, and ROC curve analysis were applied.
• Trend analysis showed a dose-response association for all markers (P for trend < .05).

The TyG index and ln[HOMA-IR] exhibited a J-shaped nonlinear relationship with CMM risk.

• Restricted cubic spline analysis indicated a J-shaped nonlinear relationship for TyG index and ln[HOMA-IR] with CMM.
• P for overall < .001 and P for nonlinear < .05 for both TyG index and ln[HOMA-IR].
• This nonlinear pattern suggests that CMM risk increases more steeply at higher levels of these markers.

ln[TyG-BMI], ln[METS-IR], and ln[TG/HDL-C] exhibited linear relationships with CMM risk.

• Restricted cubic spline analysis showed linear relationships for ln[TyG-BMI], ln[METS-IR], and ln[TG/HDL-C] with CMM.
• P for overall < .001 for all three markers.
• P for nonlinear > .05 for ln[TyG-BMI], ln[METS-IR], and ln[TG/HDL-C], confirming linearity.

HOMA-IR demonstrated the highest predictive performance for CMM risk among the five IR surrogates.

• HOMA-IR showed the highest area under the curve (AUC) of 0.699 for predicting CMM risk.
• Brier scores were used alongside ROC curve analysis to assess predictive performance.
• HOMA-IR also demonstrated a J-shaped nonlinear relationship with CMM risk.

The study identified an absence of prior research exploring the correlation between insulin resistance surrogates and cardiometabolic multimorbidity risk.

• CMM is defined as the coexistence of multiple cardiovascular and metabolic diseases.
• Five alternative IR surrogates were compared: TyG index, TyG-BMI index, METS-IR, TG/HDL-C ratio, and HOMA-IR.
• The study used cross-sectional NHANES data spanning 2005 to 2018 to fill this research gap.