0777 Association of Chronotype with the Gene Expression of SLC2A3 and SLC2A5: Relationships with Energy Metabolism and Risk of Insulin Resistance

Abstract Introduction The circadian rhythm, which follows an approximately 24-hour cycle, plays a fundamental role in glucose metabolism and the regulation of insulin sensitivity. It is known that the human circadian rhythm presents phenotypically as three chronotypes: morning, evening, and intermediate. This circadian preference distinguishes individuals who become more active early in the day—sleeping and waking earlier—from those who sleep, wake, and reach peak performance later. When the sleep–wake pattern deviates from an individual’s circadian preference, metabolic alterations such as decreased insulin sensitivity may be observed. Furthermore, sleep disorders are known to affect the expression of genes involved in energy metabolism, such as SLC2A3 and SLC2A5. In this sense, this study aimed to investigate the association between circadian preference, sleep patterns, and the gene expression of SLC2A3 and SLC2A5. Methods A prospective cross-sectional assessment was conducted with participants aged 30 to 40 years, who underwent blood collection at a standardized time for measurement of these genetic markers and completed questionnaires assessing sleep and circadian preference. Results Results indicated that the evening chronotype was associated with a higher frequency of insulin resistance (χ²= 16.343; df= 8; p= 0.038), higher fasting insulin levels (β= 2.127; CI95% = 0.182 – 4.070, p=0.032), poorer subjective sleep quality (χ²= 9.563, df= 3; p= 0.042), and greater severity of insomnia symptoms (β= 0.257; CI95%= 0.053 – 0.462, p= 0.013). Expression of SLC2A5 correlated negatively with insulin (ρ= –0.489; p = 0.039) and HOMA-IR (ρ= –0.478; p= 0.045), suggesting a protective effect against insulin resistance. We also found that the association between chronotype and fasting insulin levels was significantly mediated by SLC2A5 expression (β= −2.684; 95% CI = −5.112 to −0.255; p=0.030). Conclusion In conclusion, the evening chronotype was associated with worse metabolic and sleep outcomes, indicating a risk profile that may be related to the expression of genes involved in energy metabolism. Support (if any) This work was supported by Associação Fundo de Incentivo à Pesquisa (AFIP) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 24/08022-8 to BCRR).