Abstract
Introduction: Insulin resistance among young adults is influenced by modifiable behaviors. Irisin, an exercise-responsive myokine, and adropin, a nutrient-regulated hepatokine, may connect lifestyle with glucose homeostasis. We investigated whether a composite lifestyle score was associated with insulin resistance in university students and whether irisin and adropin mediated this association.
Methods: This cross-sectional study enrolled 180 apparently healthy students aged 18–25 years (90 men and 90 women) from the University of Samarra, Iraq, who were selected by stratified random sampling between November 2025 and March 2026. Physical activity (IPAQ-short), sleep quality (PSQI), adherence to the Mediterranean diet (MEDAS), recreational screen time and smoking were combined into a lifestyle score ranging from 0 to 5. Fasting serum irisin, adropin and insulin concentrations were quantified by ELISA, and insulin resistance was estimated using HOMA-IR and the triglyceride–glucose (TyG) index. Multivariable regression, covariate-adjusted parallel bootstrap mediation (exploratory and hypothesis-generating) and internally validated ROC analyses were performed.
Results: Insulin resistance (HOMA-IR≥2.5) was identified in 54 students (30.0%; 95% CI 23.8–37.1%), and its prevalence increased from 8.0% in the healthy lifestyle group to 30.5% in the intermediate group and 52.1% in the unhealthy group. Relative to a healthy lifestyle, the adjusted odds of insulin resistance were 4.69 (95% CI 1.48–14.87) for an intermediate lifestyle and 11.25 (95% CI 3.39–37.32) for an unhealthy lifestyle. Irisin (P=0.007) and adropin (P=0.008) concentrations rose progressively from the unhealthy to the healthy group. In multivariable regression, the lifestyle score (β=−0.26), adropin (β=−0.24), waist circumference (β=0.30), family history of diabetes (β=0.22) and male sex (β=0.15) were independently associated with HOMA-IR, whereas irisin, although lower in insulin-resistant students and inversely correlated with HOMA-IR in univariate analysis, was not significant (β=−0.08; P=0.182). In a cross-sectional exploratory mediation model, which cannot establish temporal order or causality, the two peptides statistically accounted for 29% of the lifestyle–HOMA-IR association (total indirect effect −0.050; 95% CI −0.080 to −0.024), almost entirely through adropin (−0.041; 95% CI −0.069 to −0.019), whereas the indirect effect through irisin was not significant. A model combining irisin, adropin and waist circumference identified insulin resistance with a modest optimism-corrected AUC of 0.739.
Conclusion: Almost one in three Iraqi students showed insulin resistance, and a healthier lifestyle was strongly associated with a lower risk. Adropin, but not irisin, was independently associated with HOMA-IR and accounted statistically, in an exploratory cross-sectional model, for part of this association; this is hypothesis-generating and compatible with, but does not demonstrate, a diet- and sleep-sensitive hepatic pathway. These findings warrant further study of multicomponent campus programs addressing diet, sleep and physical activity, and longitudinal and interventional studies are required to establish temporal order and causality.