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

**Authors:** Muhammad Ammar Zahid, Shahenda Salah Abdelsalam, Hicham Raïq, Hanan H. Abunada, Aijaz Parray, Abdelali Agouni

PMC · DOI: 10.3389/fendo.2025.1518388 · Frontiers in Endocrinology · 2025-05-13

## TL;DR

This study explores how Sestrin2, an antioxidant protein, is linked to metabolic health in healthy and diabetic individuals from Qatar.

## Contribution

The study reveals a context-dependent role of Sestrin2 in metabolic regulation, differing between healthy and diabetic populations.

## Key findings

- Sestrin2 levels were significantly lower in diabetic individuals compared to healthy controls.
- Higher Sestrin2 levels in healthy individuals were associated with better metabolic profiles.
- In diabetics, higher Sestrin2 levels were linked to worse metabolic indicators like increased triglycerides and body fat.

## Abstract

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.

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.

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).

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.

## Linked entities

- **Proteins:** SESN2 (sestrin 2)
- **Diseases:** diabetes (MONDO:0005015), metabolic syndrome (MONDO:0000816)

## Full-text entities

- **Genes:** SESN2 (sestrin 2) [NCBI Gene 83667] {aka HI95, SES2, SEST2}
- **Diseases:** atherogenic (MESH:D050197), metabolic syndrome (MESH:D024821), diabetes (MESH:D003920), visceral adiposity (MESH:D007418), metabolic dysfunction (MESH:D008659), adiposity (MESH:D018205), Insulin Resistance (MESH:D007333)
- **Chemicals:** triglycerides (MESH:D014280), lipid (MESH:D008055), triglyceride glucose (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12106026/full.md

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Source: https://tomesphere.com/paper/PMC12106026