Association between serum Sestrin2 level and diabetic peripheral neuropathy in type 2 diabetic patients

Abstract

BACKGROUND Diabetic peripheral neuropathy (DPN) is a chronic and serious microvascular complication of diabetes linked to redox imbalance. Sestrin2, a novel induciblestress protein, participates in glucose metabolic regulation and redox homeostasis.However, the association between serum Sestrin2 and DPN is unknown.AIMTo explore the association between serum Sestrin2 and DPN in patients with type2 diabetes mellitus (T2DM).METHODSA total of 96 T2DM patients and 39 healthy volunteers, matched by age and sex,participated in this cross-sectional study. Clinical features and metabolic indiceswere identified. Serum Sestrin2 was measured by ELISA. The association betweenSestrin2 and DPN was studied. Correlation and logistic regression analyses wereused to evaluate the associations of different metabolic indices with Sestrin2 andDPN.RESULTSThe 96 patients with T2DM were divided into DPN (n = 47) and patients withoutDPN (n = 49). Serum Sestrin2 was significantly lower in healthy volunteers thanin all T2DM patients combined [9.10 (5.41-13.53) ng/mL vs 12.75 (7.44-23.80)ng/mL, P < 0.01]. T2DM patients without DPN also had significantly higher levels of Sestrin2 than healthy volunteers [14.58 (7.93-26.62) ng/mL vs 9.10 (5.41-13.53) ng/mL, P < 0.01]. However, T2DM patients with DPN had lower circulatingSestrin2 levels compared to T2DM patients without DPN [9.86 (6.72-21.71) ng/mL vs 14.58 (7.93-26.62) ng/mL, respectively, P < 0.01]. Bivariatecorrelation analysis revealed that serum Sestrin2 was positively correlated withbody mass index (r = 0.672, P = 0.000), hemoglobin A1c (HbA1c) (r = 0.292, P =0.000), serum creatinine (r = 0.206, P = 0.016), triglycerides (r = 0.731, P = 0.000),and fasting glucose (r = 0.202, P = 0.040), and negatively associated with estimatedglomerular filtration rate (r = -0.230, P = 0.007). After adjustment for sex, age,HbA1c, and diabetes duration, multiple regression analysis revealed that Sestrin2was independently correlated with body mass index and triglyceride levels (P =0.000). Logistic regression analyses indicated that Sestrin2, diabetes duration, andhigh-density lipoprotein were strongly associated with DPN (odds ratio = 0.855,1.411, and 0.041, respectively).CONCLUSIONOur results show Sestrin2 is decreased in T2DM patients with DNP. As lowerSestrin2 is independently associated with DPN, Sestrin2 may contribute toprogression of DPN in T2DM patients