Association of plasma levels of Sestrin2 with adiposity and metabolic function indices in healthy and diabetic subjects from Qatar Biobank

Abdelali Agouni ^1* Muhammad Ammar Zahid ¹ Shahenda Salaheldine Abdelsalam ¹ Hicham Raïq ² Hanan H Abunada ³ Aijaz Parray ⁴

• ¹ Department of Pharmaceutical Sciences, College of Pharmacy, Qatar University, Doha, Qatar
• ² Department of Social Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar
• ³ Office of Vice President for Medical & Health Sciences, QU Health, Qatar University, Doha, Qatar
• ⁴ Neuroscience Institute, Hamad Medical Corporation, Doha, Qatar

Background: Despite the accumulating evidence from cellular and animal studies, the role of circulating Sestrin2, a stress-inducible antioxidant protein, in human cardiometabolic health remains largely unexplored. Hence, the current study aimed to investigate the association between circulating Sestrin2 and cardiometabolic risk factors in healthy and diabetic individuals. Methods: This cross-sectional study leveraging data and plasma samples from the Qatar Biobank investigated the relationship between plasma Sestrin2 levels and various cardiometabolic indices in 326 healthy and 518 diabetic subjects. Results: The study found that Sestrin2 levels were significantly lower in diabetic individuals compared to healthy controls (5.49 ng/mL vs 8.25 ng/mL, p < 0.001). In the healthy cohort, higher Sestrin2 levels were associated with a favorable metabolic profile, indicated by lower odd ratios (OR) of high glycated hemoglobin (OR: 0.33), Homeostatic Model Assessment for Insulin Resistance score (OR: 0.58), visceral adiposity index (OR: 0.46), lipid accumulation product (OR: 0.49), atherogenic index of plasma (OR: 0.42) and metabolic syndrome (OR: 0.23). Conversely, in the diabetic cohort, higher Sestrin2 levels were paradoxically linked to increased triglycerides (OR: 1.57), the product of triglyceride glucose and waist circumference (OR: 1.8), body fat (OR: 1.72), waist circumference (OR: 1.82), waist-to-hip ratio (OR: 1.96) and metabolic syndrome (OR: 1.48). Conclusions: These findings suggest that Sestrin2 may play a complex and context-dependent role in metabolic regulation, potentially serving as a protective factor in healthy individuals but contributing to metabolic dysfunction in the context of established diabetes. Further research is needed to elucidate the underlying mechanisms and implications for targeted interventions.