Alterations and Correlation of Metabolic Hormones (Irisin, Amylin, SIRT1), Inflammatory Marker, and Vitamins D3 and B3 in Type 2 Diabetes patients with or without Diabetic Nephropathy

Abstract

Objectives: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in patients with type 2 diabetes mellitus (T2DM), involving complex metabolic, inflammatory, and hormonal dysregulation. This study investigated the circulating levels and interrelationships between Irisin, Amylin, SIRT1, vitamin D3 (Vit-D3), vitamin B3 (Vit-B3), and serum amyloid A (SAA) among healthy controls, patients withT2DM, and DN patients.

Methods: In this case-control study, 150 male participants (50 per group; aged 40–65 years) were enrolled and matched for age and BMI. Fasting samples were used to measure routine biochemical parameters, HOMA-IR, HbA1c, and specific markers (Irisin, Amylin, SIRT1, SAA, Vit-B3 via ELISA; Vit-D3 via CLIA).

Results: Both diabetic groups had elevated FBS, HbA1c, insulin, HOMA-IR, and BMI versus controls. DN group exhibited marked renal impairment (higher urea, creatinine, microalbumin; lower eGFR). Vit-D3 and Vit-B3 were significantly lower in patients with T2DM and DN, with a further reduction in Vit-B3 in DN. Serum amyloid A levels were unexpectedly lower in diabetic groups. The order of amylin levels was: control > T2DM > DN, while Irisin and SIRT1 were in the opposite order. The association between Irisin and SIRT1 was weak in DN group. Amylin-SIRT1 was negative in T2DM and positive in DN groups. Vit-B3 correlated positively with SIRT1 only in DN group. Serum amyloid A was negatively correlated with SIRT1 in diabetic groups. This parameter correlated with HbA1c in DN group.

Conclusion: These findings highlight potential compensatory roles of Irisin-SIRT1, niacin-NAD+ dependency, and atypical serum amyloid A regulation, suggesting novel biomarkers and therapeutic avenues (e.g., NAD+ precursors, SIRT1 modulation) for diabetic kidney disease.