Sestrin-2: a new biomarker for type 2 Diabetes Mellitus and Insulin resistance

Sestrin-2 is a stress-inducible protein involved in metabolic regulation and oxidative stress, and has been suggested to play a role in insulin resistance and type 2 diabetes mellitus (T2DM).

To evaluate circulating Sestrin-2 levels and their association with insulin resistance across the glycemic spectrum.

This cross-sectional study included 300 participants cat isegorized into controls (n = 100), prediabetes (n = 100), and T2DM (n = 100) based on WHO criteria. Fasting blood samples were analyzed for glucose, HbA1c, insulin and Sestrin-2 using standard methods. Insulin resistance was assessed using HOMA-IR. Statistical evaluation was conducted using ANOVA along with Pearson's correlation analysis.

A significant progressive increase was observed in BMI, blood pressure, and glycemic parameters from controls to T2DM (p < 0.001). Sestrin-2 levels were significantly higher in T2DM (9.53 ± 1.46 ng/mL) compared with prediabetes (5.46 ± 0.56 ng/mL) and healthy controls (4.94 ± 0.79 ng/mL) (p < 0.001). Sestrin-2 demonstrated a strong positive correlation with fasting glucose (r = 0.62), HbA1c (r = 0.58), fasting insulin (r = 0.55), and HOMA-IR (r = 0.66), all of which were statistically significant (p < 0.001).

Sestrin-2 levels increase progressively across the glycemic spectrum and are strongly associated with insulin resistance, suggesting its potential as a biomarker of metabolic stress and glycemic dysregulation.