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
-
Sinhareeb Sabih Wajdi
,
Matin Mohyadini
,
Mohamadhudifa Abdlwhab Hasanain
,
Walaa E Jassim
,
S. Zahra Bathaie
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.
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.
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5. den Hartigh LJ, May KS, Zhang XS, Chait A, Blaser MJ. Serum amyloid A and metabolic disease: evidence for a critical role in chronic inflammatory conditions. Front Cardiovasc Med. 2023;10:1197432. https://doi.org/10.3389/fcvm.2023.1197432.
6. Liu Q, Sun J, Xu T, Bian G, Yang F. Associations of serum amyloid A and 25-hydroxyvitamin D with diabetic nephropathy: A cross-sectional study. J Clin Lab Anal. 2022;36(3):e24283. https://doi.org/10.1002/jcla.24283.
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8. Iglesias-Fortes S, Gonzalez-Blanco C, Garcia-Carrasco A, Izquierdo-Lahuerta A, Garcia G, Garcia-Aguilar A, et al. The overexpression of human amylin in pancreatic beta cells facilitate the appearance of amylin aggregates in the kidney contributing to diabetic nephropathy. Sci Rep. 2024;14(1):24729. https://doi.org/10.1038/s41598-024-77063-9.
9. Aladag T, Mogulkoc R, Baltaci AK. Irisin and Energy Metabolism and the Role of Irisin on Metabolic Syndrome. Mini Rev Med Chem. 2023;23(20):1942-58. https://doi.org/10.2174/1389557523666230411105506.
10. Ding L, Li ZL, Zhou Y, Liu NC, Liu SS, Zhang XJ, et al. Loss of Sirt1 promotes exosome secretion from podocytes by inhibiting lysosomal acidification in diabetic nephropathy. Mol Cell Endocrinol. 2023;568-569:111913. https://doi.org/10.1016/j.mce.2023.111913.
11. Huang HY, Lin TW, Hong ZX, Lim LM. Vitamin D and Diabetic Kidney Disease. Int J Mol Sci. 2023;24(4):3751. https://doi.org/10.3390/ijms24043751.
12. Liu J, Qin L, Zheng J, Tong L, Lu W, Lu C, et al. Research progress on the relationship between vitamins and diabetes: systematic review. Int J Mol Sci. 2023;24(22):16371. https://doi.org/10.3390/ijms242216371
13. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-8. https://doi.org/10.1038/nature10777
14. Gizaw M, Anandakumar P, Debela T. A Review on the Role of Irisin in Insulin Resistance and Type 2 Diabetes Mellitus. J Pharmacopuncture. 2017;20(4):235-42. https://doi.org/10.3831/KPI.2017.20.029.
15. Yacoub R, Lee K, He JC. The Role of SIRT1 in Diabetic Kidney Disease. Front Endocrinol (Lausanne). 2014;5:166. https://doi.org/10.3389/fendo.2014.00166.
16. Ma F, Wu J, Jiang Z, Huang W, Jia Y, Sun W, Wu H. P53/NRF2 mediates SIRT1's protective effect on diabetic nephropathy. Biochim Biophys Acta Mol Cell Res. 2019;1866(8):1272-81. https://doi.org/10.1016/j.bbamcr.2019.04.006.
17. Hong Q, Zhang L, Das B, Li Z, Liu B, Cai G, et al. Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury. Kidney Int. 2018;93(6):1330-43. https://doi.org/10.1016/j.kint.2017.12.008.
18. Elesawy BH, El Askary A, Mehanna OM, Elmorsy EA, Khalifa MM, Ali SE, Abd El Hafez A. High Serum Levels of Irisin, Visfatin and Adiponectin as Potential Independent Risk Factors for Diabetic Nephropathy Progression in Patients With Type 2 Diabetes Mellitus. In Vivo. 2025;39(3):1615-24. https://doi.org/10.21873/invivo.13962
19. Ma L, Fu R, Duan Z, Lu J, Gao J, Tian L, et al. Sirt1 is essential for resveratrol enhancement of hypoxia-induced autophagy in the type 2 diabetic nephropathy rat. Pathol-Res Pract. 2016;212(4):310-8. https://doi.org/10.1016/j.prp.2016.02.001
20. Liu TY, Shi CX, Gao R, Sun HJ, Xiong XQ, Ding L, et al. Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes. Clin Sci (Lond). 2015;129(10):839-50. https://doi.org/10.1042/CS20150009.
21. de Almeida DC, Agudelo JSH. Irisin and the kidney: Key points to know? Nefrología. 2025:501443. https://doi.org/10.1016/j.nefro.2025.501443
22. Makimattila S, Fineman MS, Yki-Jarvinen H. Deficiency of total and nonglycosylated amylin in plasma characterizes subjects with impaired glucose tolerance and type 2 diabetes. J Clin Endocrinol Metab. 2000;85(8):2822-7. https://doi.org/10.1210/jcem.85.8.6721.
23. Qiu WQ, Li H, Zhu H, Scott T, Mwamburi M, Rosenberg I, Rosenzweig J. Plasma Amylin and Cognition in Diabetes in the Absence and the Presence of Insulin Treatment. J Diabetes Metab. 2014;5(11):458. https://doi.org/10.4172/2155-6156.1000458.
24. Walker CS, Aitken JF, Vazhoor Amarsingh G, Zhang S, Cooper GJS. Amylin: emergent therapeutic opportunities in overweight, obesity and diabetes mellitus. Nat Rev Endocrinol. 2025;21(8):482-94. https://doi.org/10.1038/s41574-025-01125-9.
25. Verma N, Despa F. The association between renal accumulation of pancreatic amyloid-forming amylin and renal hypoxia. Front Endocrinol. 2023;14:1104662. https://doi.org/10.3389/fendo.2023.1104662
26. Diabetes Prevention Program Research G. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-75. https://doi.org/10.1016/S2213-8587(15)00291-0.
27. Dean YE, Elawady SS, Shi W, Salem AA, Chotwatanapong A, Ashraf H, et al. Progression of diabetic nephropathy and vitamin D serum levels: A pooled analysis of 7722 patients. Endocrinol Diabetes Metab. 2023;6(6):e453. https://doi.org/10.1002/edm2.453.
28. Herwana E, Yenny, Alvina, Kurniasari, Febinia CA, Pusparini. Sirtuin, irisin, and vitamin D as predictors of diabetes mellitus with uncontrolled glycemia in Indonesian patients. Endocr Metab Sci. 2025;17:100214. https://doi.org/10.1016/j.endmts.2024.100214.
29. Hong SH, Kim YB, Choi HS, Jeong TD, Kim JT, Sung YA. Association of Vitamin D Deficiency with Diabetic Nephropathy. Endocrinol Metab (Seoul). 2021;36(1):106-13. https://doi.org/10.3803/EnM.2020.826.
30. Safarpour P, Daneshi-Maskooni M, Vafa M, Nourbakhsh M, Janani L, Maddah M, et al. Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial. BMC Fam Pract. 2020;21(1):26. https://doi.org/10.1186/s12875-020-1096-3.
31. Huwaimel B, Alqarni S, Abouzied AS, Alghubayshi A, Alotaibi T, Elshafei A, et al. Dysregulation of Niacin-Derived NAD(+) Salvage Pathway Markers (CD38, NAMPT, SIRT1) Across Albuminuria Stages in Type 2 Diabetes. Medicina (Kaunas). 2025;61(12):2089. https://doi.org/10.3390/medicina61122089.
32. Hu C, Tang T. Association between niacin intake and chronic kidney disease in male participants—a cross-sectional study from the NHANES (2005–2018). Front nutr. 2025;12:1578118. https://doi.org/10.3389/fnut.2025.1578118
33. Morevati M, Fang EF, Mace ML, Kanbay M, Gravesen E, Nordholm A, et al. Roles of NAD(+) in Acute and Chronic Kidney Diseases. Int J Mol Sci. 2022;24(1):137. https://doi.org/10.3390/ijms24010137.
34. Ji A, Meredith LW, Shridas P. Serum Amyloid A: A Double-Edged Sword in Health and Disease. Int J Mol Sci. 2025;26(10). https://doi.org/10.3390/ijms26104528.
35. Salminen A, Ojala J, Huuskonen J, Kauppinen A, Suuronen T, Kaarniranta K. Interaction of aging-associated signaling cascades: inhibition of NF-kappaB signaling by longevity factors FoxOs and SIRT1. Cell Mol Life Sci. 2008;65(7-8):1049-58. https://doi.org/10.1007/s00018-008-7461-3.
2. Mohyadini M, Fahimi A, Bathaie SZ, Yaghooti H. Ranolazine as a therapeutic agent for diabetic cardiomyopathy: reducing endoplasmic reticulum stress and inflammation in type 2 diabetic rat model. BMC Pharmacol Toxicol. 2025;26(1):111. https://doi.org/10.1186/s40360-025-00945-9
3. Maringhini S, Zoccali C. Chronic Kidney Disease Progression-A Challenge. Biomedicines. 2024;12(10):2203. https://doi.org/10.3390/biomedicines12102203.
4. Yaghooti H, Mohyadini M, Bathaie SZ, Dinarvand N, Mohammadtaghvaei N. Eplerenone alleviates diabetic cardiomyopathy by modulating ER stress, oxidative stress, and NLRP3 inflammasome activation. J Diabetes Metab Disord. 2025;24(2):169. https://doi.org/10.1007/s40200-025-01677-7.
5. den Hartigh LJ, May KS, Zhang XS, Chait A, Blaser MJ. Serum amyloid A and metabolic disease: evidence for a critical role in chronic inflammatory conditions. Front Cardiovasc Med. 2023;10:1197432. https://doi.org/10.3389/fcvm.2023.1197432.
6. Liu Q, Sun J, Xu T, Bian G, Yang F. Associations of serum amyloid A and 25-hydroxyvitamin D with diabetic nephropathy: A cross-sectional study. J Clin Lab Anal. 2022;36(3):e24283. https://doi.org/10.1002/jcla.24283.
7. Muskiet MHA, Nardone M, Rensen PCN, Cherney DZI, Cooper ME. Amylin and the renin-angiotensin system: risk or opportunity in amylin-based therapy? Lancet. 2026;406(10522):2980-3. https://doi.org/10.1016/S0140-6736(25)01776-3.
8. Iglesias-Fortes S, Gonzalez-Blanco C, Garcia-Carrasco A, Izquierdo-Lahuerta A, Garcia G, Garcia-Aguilar A, et al. The overexpression of human amylin in pancreatic beta cells facilitate the appearance of amylin aggregates in the kidney contributing to diabetic nephropathy. Sci Rep. 2024;14(1):24729. https://doi.org/10.1038/s41598-024-77063-9.
9. Aladag T, Mogulkoc R, Baltaci AK. Irisin and Energy Metabolism and the Role of Irisin on Metabolic Syndrome. Mini Rev Med Chem. 2023;23(20):1942-58. https://doi.org/10.2174/1389557523666230411105506.
10. Ding L, Li ZL, Zhou Y, Liu NC, Liu SS, Zhang XJ, et al. Loss of Sirt1 promotes exosome secretion from podocytes by inhibiting lysosomal acidification in diabetic nephropathy. Mol Cell Endocrinol. 2023;568-569:111913. https://doi.org/10.1016/j.mce.2023.111913.
11. Huang HY, Lin TW, Hong ZX, Lim LM. Vitamin D and Diabetic Kidney Disease. Int J Mol Sci. 2023;24(4):3751. https://doi.org/10.3390/ijms24043751.
12. Liu J, Qin L, Zheng J, Tong L, Lu W, Lu C, et al. Research progress on the relationship between vitamins and diabetes: systematic review. Int J Mol Sci. 2023;24(22):16371. https://doi.org/10.3390/ijms242216371
13. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463-8. https://doi.org/10.1038/nature10777
14. Gizaw M, Anandakumar P, Debela T. A Review on the Role of Irisin in Insulin Resistance and Type 2 Diabetes Mellitus. J Pharmacopuncture. 2017;20(4):235-42. https://doi.org/10.3831/KPI.2017.20.029.
15. Yacoub R, Lee K, He JC. The Role of SIRT1 in Diabetic Kidney Disease. Front Endocrinol (Lausanne). 2014;5:166. https://doi.org/10.3389/fendo.2014.00166.
16. Ma F, Wu J, Jiang Z, Huang W, Jia Y, Sun W, Wu H. P53/NRF2 mediates SIRT1's protective effect on diabetic nephropathy. Biochim Biophys Acta Mol Cell Res. 2019;1866(8):1272-81. https://doi.org/10.1016/j.bbamcr.2019.04.006.
17. Hong Q, Zhang L, Das B, Li Z, Liu B, Cai G, et al. Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury. Kidney Int. 2018;93(6):1330-43. https://doi.org/10.1016/j.kint.2017.12.008.
18. Elesawy BH, El Askary A, Mehanna OM, Elmorsy EA, Khalifa MM, Ali SE, Abd El Hafez A. High Serum Levels of Irisin, Visfatin and Adiponectin as Potential Independent Risk Factors for Diabetic Nephropathy Progression in Patients With Type 2 Diabetes Mellitus. In Vivo. 2025;39(3):1615-24. https://doi.org/10.21873/invivo.13962
19. Ma L, Fu R, Duan Z, Lu J, Gao J, Tian L, et al. Sirt1 is essential for resveratrol enhancement of hypoxia-induced autophagy in the type 2 diabetic nephropathy rat. Pathol-Res Pract. 2016;212(4):310-8. https://doi.org/10.1016/j.prp.2016.02.001
20. Liu TY, Shi CX, Gao R, Sun HJ, Xiong XQ, Ding L, et al. Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes. Clin Sci (Lond). 2015;129(10):839-50. https://doi.org/10.1042/CS20150009.
21. de Almeida DC, Agudelo JSH. Irisin and the kidney: Key points to know? Nefrología. 2025:501443. https://doi.org/10.1016/j.nefro.2025.501443
22. Makimattila S, Fineman MS, Yki-Jarvinen H. Deficiency of total and nonglycosylated amylin in plasma characterizes subjects with impaired glucose tolerance and type 2 diabetes. J Clin Endocrinol Metab. 2000;85(8):2822-7. https://doi.org/10.1210/jcem.85.8.6721.
23. Qiu WQ, Li H, Zhu H, Scott T, Mwamburi M, Rosenberg I, Rosenzweig J. Plasma Amylin and Cognition in Diabetes in the Absence and the Presence of Insulin Treatment. J Diabetes Metab. 2014;5(11):458. https://doi.org/10.4172/2155-6156.1000458.
24. Walker CS, Aitken JF, Vazhoor Amarsingh G, Zhang S, Cooper GJS. Amylin: emergent therapeutic opportunities in overweight, obesity and diabetes mellitus. Nat Rev Endocrinol. 2025;21(8):482-94. https://doi.org/10.1038/s41574-025-01125-9.
25. Verma N, Despa F. The association between renal accumulation of pancreatic amyloid-forming amylin and renal hypoxia. Front Endocrinol. 2023;14:1104662. https://doi.org/10.3389/fendo.2023.1104662
26. Diabetes Prevention Program Research G. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-75. https://doi.org/10.1016/S2213-8587(15)00291-0.
27. Dean YE, Elawady SS, Shi W, Salem AA, Chotwatanapong A, Ashraf H, et al. Progression of diabetic nephropathy and vitamin D serum levels: A pooled analysis of 7722 patients. Endocrinol Diabetes Metab. 2023;6(6):e453. https://doi.org/10.1002/edm2.453.
28. Herwana E, Yenny, Alvina, Kurniasari, Febinia CA, Pusparini. Sirtuin, irisin, and vitamin D as predictors of diabetes mellitus with uncontrolled glycemia in Indonesian patients. Endocr Metab Sci. 2025;17:100214. https://doi.org/10.1016/j.endmts.2024.100214.
29. Hong SH, Kim YB, Choi HS, Jeong TD, Kim JT, Sung YA. Association of Vitamin D Deficiency with Diabetic Nephropathy. Endocrinol Metab (Seoul). 2021;36(1):106-13. https://doi.org/10.3803/EnM.2020.826.
30. Safarpour P, Daneshi-Maskooni M, Vafa M, Nourbakhsh M, Janani L, Maddah M, et al. Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial. BMC Fam Pract. 2020;21(1):26. https://doi.org/10.1186/s12875-020-1096-3.
31. Huwaimel B, Alqarni S, Abouzied AS, Alghubayshi A, Alotaibi T, Elshafei A, et al. Dysregulation of Niacin-Derived NAD(+) Salvage Pathway Markers (CD38, NAMPT, SIRT1) Across Albuminuria Stages in Type 2 Diabetes. Medicina (Kaunas). 2025;61(12):2089. https://doi.org/10.3390/medicina61122089.
32. Hu C, Tang T. Association between niacin intake and chronic kidney disease in male participants—a cross-sectional study from the NHANES (2005–2018). Front nutr. 2025;12:1578118. https://doi.org/10.3389/fnut.2025.1578118
33. Morevati M, Fang EF, Mace ML, Kanbay M, Gravesen E, Nordholm A, et al. Roles of NAD(+) in Acute and Chronic Kidney Diseases. Int J Mol Sci. 2022;24(1):137. https://doi.org/10.3390/ijms24010137.
34. Ji A, Meredith LW, Shridas P. Serum Amyloid A: A Double-Edged Sword in Health and Disease. Int J Mol Sci. 2025;26(10). https://doi.org/10.3390/ijms26104528.
35. Salminen A, Ojala J, Huuskonen J, Kauppinen A, Suuronen T, Kaarniranta K. Interaction of aging-associated signaling cascades: inhibition of NF-kappaB signaling by longevity factors FoxOs and SIRT1. Cell Mol Life Sci. 2008;65(7-8):1049-58. https://doi.org/10.1007/s00018-008-7461-3.
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| Issue | Vol 2026 No 4 (2) | |
| Section | Original Articles | |
| Keywords | ||
| Amylin Diabetic Nephropathy Irisin SIRT1 Type 2 diabetes Vitamins. | ||
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How to Cite
1.
Wajdi S, Mohyadini M, Hasanain M, Jassim WE, Bathaie SZ. 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. ABI. 2026;2026(4):71-79.
