Abstract Background Previous research has made use of the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index to explore the association between shiftwork (SW) and insulin resistance (IR). However, the limitations of the HOMA-IR index restrict its use. This study aimed to investigate the relationship between SW and IR in professional drivers using four alternative non-insulin-based IR surrogate measures (NIRS), and to determine the predictors of elevated NIRS. Methods A comparative cross-sectional study was conducted on professional drivers at four Egyptian companies, where 187 SW were compared to 193 dayworkers (DW). Measurements included: sociodemographic, work, and clinical characteristics. Laboratory and NIRS data included: triglyceride glucose (TyG), triglyceride glucose-body mass index (TyG-BMI), triglyceride to high density lipoprotein cholesterol (TG/HDL-C), and metabolic score of insulin resistance (METS-IR). Further assessments included insomnia severity index (ISI), and perceived stress scale (PSS-10). Results Shiftwork-drivers showed significantly higher levels of NIRS compared to DW-drivers. Shiftwork was significantly associated with elevated TyG (OR: 5.04, 95% CI: 1.98–12.84), TyG-BMI (OR: 4.50, 95% CI: 2.45–8.26), and METS-IR (OR: 6.30, 95% CI: 2.72–14.58). Significant interactions between SW and insomnia or meal-timing habits existed, where SW-drivers with clinically significant insomnia had 11 times higher odds of elevated TyG compared to DW drivers without insomnia. Likewise, SW-drivers experiencing poor meal timing habits had 5.5- and 6.8-times higher odds of elevated TG/HDL-C and METS-IR, respectively, compared to DW divers without poor meal timing habits. Other significant predictors for elevated NIRS included: age, income, stress, overweight/obesity, and poor meal timing habits. Conclusions This study demonstrates a significant association between shiftwork and elevated insulin resistance in professional drivers. Insomnia and poor meal timing habits significantly increases the odds of insulin resistance among professional drivers, suggesting interventions targeting sleep quality, meal timing, and stress management.
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