Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 2026 4 2026 06 20 71 79 Sinhareeb Wajdi Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Matin Mohyadini Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Mohamadhudifa Hasanain Ministry of Health, Salah Aldeen Health Department, Balad General Hospital, Iraq. Walaa E Jassim Department of Medical Laboratory Techniques, Faculty of Health and Medical Technologies, Central Medical University, Baghdad, Iraq. S. Zahra Bathaie Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 2026 04 13 2026 04 27 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. Conclusions: 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. https://abi.tums.ac.ir/index.php/abi/article/view/185 https://abi.tums.ac.ir/index.php/abi/article/download/185/138