Abstract

PurposeUnderstanding the pathogenesis and the molecular mechanisms of diabetic nephropathy (DN) helps its timely detection and prevention. The current work aims tomeasure serum sestrin 2 and betatrophin levels in healthy and type diabetic (T2DM)subjects with/or without diabetic nephropathy (DN) and also to test their correlation with serum neutrophil gelatinase associated lipocalin (sNGAL); indicator of DN.MethodsThis study included 96 subjects; 20 healthy (G1) and 76 T2DM [22 normoalbuminuric (G2), 35 microalbuminuric (G3) and 19 macroalbuminuric (G4)]. Serum sestrin 2, betatrophin and NGAL were measured by their corresponding kits.ResultsSignificant low levels of serum sestrin 2 andhigh levels of serum betatrophin were found in T2DM group when compared to G1 (p = 0.002,p > 0.001, respectively) and this difference is manifested in G4 followed, in order, by G3, G2 then G1 (p= > 0.001 for both). Also, serum sestrin2 levels showed significant negative correlations with sNGAL in G1 (r = −0.497, p = 0.026), G2 (r = −0.784, p > 0.001), G3 (r = −0.894, p > 0.001) and G4 (r = −0.896, pp. > 0.001) while serum betatrophin levels showed significant positive correlations with sNGAL in G2 (r = 0.681, p > 0.001), G3 (r = 0.518, p > 0.001) and G4 (r = 0.727, p > 0.001).ConclusionSerum sestrin 2 levels decrease significantly while betatrophin levels increase significantly in T2DM patients with DN especially those with macroalbuminuria. These levels have significant effect strengths on the indicator of diabetic nephropathy; sNGAL which might indicate theirvaluablerole in the timely detection and prevention of the development of DN.

Highlights

  • Diabetes mellitus is a syndrome with elevated blood glucose along with abnormal carbohydrate, lipid and protein metabolism [1]

  • Significant low levels of serum sestrin 2 were found in Type 2 diabetes mellitus (T2DM) patients when compared to the healthy control group while the levels of serum betatrophin and serum neutrophil gelatinase associated lipocalin (sNGAL) were significantly high (Table 1)

  • The current study found significant low levels of serum sestrin 2 in T2DM patients when compared to the healthy control

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Summary

Introduction

Diabetes mellitus is a syndrome with elevated blood glucose along with abnormal carbohydrate, lipid and protein metabolism [1]. DN is preventable by controlling blood glucose [8] which indicates the importance of understanding the pathogenesis and the timely detection of DN Both T2DM and obesity are considered as inflammatory conditions and the control of their accompanied systemic inflammation may improve the both conditions and minimize their complications [9,10,11]. Sestrin 2 (His 95, 54.5 Kda, 480 aminoacid) belongs to a group of proteins that are induced under stress conditions such as oxidative stress, inflammation and DNA damage. It protects the cell from oxidative damage and helps to maintain normal cell metabolism, homeostasis, growth and survival [12, 13]. The investigation of sestrin 2 levels in obese and/or T2DMpatients revealed controversial results [14, 16, 17]

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