Analysis of serum Growth Differentiation Factor–15, SMAD7, miRNA-21 & miRNA-181b in pre-diabetics and type 2 diabetics without comorbidities-a case-control study

Abstract

Analysis of serum Growth Differentiation Factor–15, SMAD7, miRNA-21 & miRNA-181b in pre-diabetics and type 2 diabetics without comorbidities-a case-control study Dipayan Roy a, Manoj Khokhar a, Ravindra Kumar Shukla b, Praveen Sharma a, Purvi Purohit a,* a Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Jodhpur, Rajasthan, 342005, India b Department of Endocrinology and Metabolism, All India Institute of Medical Sciences (AIIMS), Jodhpur, Rajasthan, 342005, India A R T I C L E I N F O Handling Editor: Prof A Angelo Azzi Keywords: GDF-15 SMAD7 miR-181b-5p miR-21-5p Type 2 diabetes mellitus A B S T R A C T Background: Growth Differentiation Factor-15 (GDF-15) is involved in insulin resistance and diabetes. But its association with mothers against decapentaplegic homolog 7 (Smad7), miR-21, and miR-181b in peripheral blood mononuclear cells (PBMCs) of prediabetes and type 2 diabetes (T2DM) patients without comorbidities is not established. The roles of miR-21 and miR-181b as diagnostic tools in these conditions also need exploration. Methods: One hundred sixteen patients, including diabetics (n = 56), pre-diabetics (n = 30), and non-diabetic controls (n = 30), were recruited. Fasting venous blood samples were collected for biochemical analyses, total RNA isolation, and real-time PCR. Results: Serum GDF-15 showed an increasing trend from healthy controls to pre-diabetic and T2DM patients. Our study also showed upregulated miR-21 and miR-181b and downregulated Smad7 expressions in prediabetes and T2DM groups. Serum GDF-15 was positively associated with miR-21 (ρ = 0.345, p < 0.001) and miR-181b (ρ = 0.398, p < 0.001), and negatively associated with Smad7 (ρ = 􀀀 0.196, p = 0.035). Both miR-21 and miR-181b were positively associated with HbA1c, fasting blood sugar, and each other. In T2DM, miR-21 showed a significant discriminatory power (area under the curve 0.806, p < 0.05) compared to healthy controls. Conclusion: Our findings suggest that GDF-15 and miR-21 can be used as non-invasive and rapid tools for delineating prediabetes and T2DM states, which can be validated in larger prospective cohorts. The significant association of serum GDF-15 with miR-21, miR-181b, and Smad7 suggest possible regulatory roles of these molecules in prediabetes and T2DM. Further studies are necessary to explore these molecules as potential therapeutic targets.