Original Articles

Impact of Procollagen III Amino Terminal Peptide and Laminin on Nephropathy in Pre-Diabetic and Type 2 Diabetic Patients

Abstract

Chronic hyperglycemia is one of the most prevalent causes of the development of type 2 diabetes mellitus (T2DM) worldwide, with diabetic nephropathy (DN) being the principal microvascular complication. Laminin is a major non‑collagenous glycoprotein that is an important component of all basement membranes. Serum PIIINP is a precursor of collagen III associated with several inflammatory disorders and tissue fibrosis, including liver and kidney fibrosis. The aim of this study was to assess and compare the concentrations of Laminin (LM), Procollagen III N‑terminal Peptide (PIIINP), and various biochemical parameters in individuals diagnosed with type 2 diabetes, both with and without nephropathy, alongside control subjects, in order to explore the potential of LM and PIIINP as predictive biomarkers for early detection in these patients. A case‑control study was conducted from March 2024 to October 2024. The study included 180 participants (93 females and 87 males) consisting of four groups: Group 1 (45) healthy participants, Group 2 (45) participants with prediabetes, Group 3 (40) T2DM patients with normoalbuminuria, and Group 4 (50) T2DM patients with nephropathy (microalbuminuria and macroalbuminuria). The study was conducted at Al‑Imamin Al‑Kadhimeen City Hospital. Our study showed that the serum concentration of laminin in patients with type 2 diabetes mellitus with nephropathy (560.60±66.85 pg/ml) was significantly elevated compared with individuals with type 2 diabetes without nephropathy (359.60±29.83 pg/ml), prediabetes (140.00±19.72 pg/ml), and healthy subjects (113.90±29.65 pg/ml) (P<0.001). Additionally, the mean serum PIIINP value was significantly higher in type 2 diabetes patients with nephropathy (660.90±47.67 pg/ml) compared to those without nephropathy (521.60±80.00 pg/ml), prediabetes (437.80±75.00 pg/ml), and controls (360.30±57.50 pg/ml) (P<0.001). There was no correlation between LM and PIIINP in prediabetes; however, there was a substantial positive correlation between laminin and PIIINP in type 2 diabetes with nephropathy (r=0.67, P<0.001) and in type 2 diabetes without nephropathy (r=0.36, P<0.014).

1. Rett K, Gottwald-Hostalek U. Understanding prediabetes: definition, prevalence, burden and treatment options for an emerging disease. Curr Med Res Opin 2019;35:1529-34.
2. Ogurtsova K, Guariguata L, Barengo NC, Ruiz PL-D, Sacre JW, Karuranga S, et al. IDF diabetes Atlas: Global estimates of undiagnosed diabetes in adults for 2021. Diabetes Res Clin Pract 2022;183:109118.
3. Sanyaolu A, Marinkovic A, Prakash S, Williams M, Dixon Y, Okorie C, et al. Diabetes mellitus: An overview of the types, prevalence, comorbidity, complication, genetics, economic implication, and treatment. World J Meta-Anal 2023;11:134-43.
4. Kropp M, Golubnitschaja O, Mazurakova A, Koklesova L, Sargheini N, Vo T-TKS, et al. Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation. EPMA J 2023;14:21-42.
5. Demir S, Nawroth PP, Herzig S, Ekim Üstünel B. Emerging targets in type 2 diabetes and diabetic complications. Adv Sci (Weinh) 2021;8:2100275.
6. Cowan DA, Moncrieffe DA. Procollagen type III amino-terminal propeptide and insulin-like growth factor I as biomarkers of growth hormone administration. Drug Test Anal 2022;14:808-19.
7. Genovese F, Gonçalves I, Nielsen SH, Karsdal MA, Edsfeldt A, Nilsson J, et al. Plasma levels of PRO-C3, a type III collagen synthesis marker, are associated with arterial stiffness and increased risk of cardiovascular death. Atherosclerosis 2024;388:117420.
8. Mi YJ, Zhang Z, Jin SL, Yan HM, Yang XM, Zhao J, et al. The relationship and diagnostic efficacy of N-terminal propeptide type III collagen in pathological changes associated with non-alcoholic steatohepatitis. Eur Rev Med Pharmacol Sci 2024;28:1036-44.
9. Panera N, Braghini MR, Crudele A, Smeriglio A, Bianchi M, Condorelli AG, et al. Combination treatment with hydroxytyrosol and vitamin E improves NAFLD-related fibrosis. Nutrients 2022;14:3791.
10. Santanasto AJ, Cvejkus RK, Wojczynski MK, Marron MM, Schupf N, Christensen K, et al. Circulating procollagen type III N-terminal peptide and physical function in adults from the long life family study. J Gerontol A Biol Sci Med Sci 2021;76:1273-9.
11. Chu YH, Pang BY, Yang M, Meng Q, Leng Y. The intervention of curcumin on rodent models of hepatic fibrosis: A systematic review and meta-analysis. PLoS One 2024;19:e0304176.
12. Shin HE, Kim M, Won CW. Association between plasma procollagen type III N-terminal peptide (P3NP) levels and physical performance in elderly men: The Korean Frailty and Aging Cohort Study (KFACS). Exp Gerontol 2021;154:111523.
13. Akter L, Flechsig H, Marchesi A, Franz CM. Observing dynamic conformational changes within the coiled-coil domain of different laminin isoforms using high-speed atomic force microscopy. Int J Mol Sci 2024;25:1951.
14. Barros D, Amaral IF, Pego AP. Laminin-inspired cell-instructive microenvironments for neural stem cells. Biomacromolecules 2020;21:276-93.
15. Xie L, Zhou Z, Chen HX, Yan XY, Ye JQ, Jiang Y, et al. Correlations between serum laminin level and severity of heart failure in patients with chronic heart failure. Front Cardiovasc Med 2023;10:1089304.
16. Yurchenco PD, Kulczyk AW. Polymerizing laminins in development, health and disease. J Biol Chem 2024;300:107429.
17. Altun O, Arman Y, Yoldemir SA, Pala AS, Gümüşkaya PÖ, Özcan M, et al. The association of laminin levels with insulin resistance and non-alcoholic hepatosteatosis. Diabetol Metab Syndr 2021;13:1-7.
18. Goddi A, Schroedl L, Brey EM, Cohen RN. Laminins in metabolic tissues. Metabolism 2021;120:154775.
19. Jian G, Lin W, Wang N, Wu J, Wu X. Urine albumin/creatinine ratio and microvascular disease in elderly hypertensive patients without comorbidities. Biomed Res Int 2021;2021:5560135.
20. Bland M. An introduction to medical statistics. 4th ed. Oxford: Oxford University Press; 2015.
21. World Health Organization. Global report on hypertension: the race against a silent killer. Geneva: World Health Organization; 2023.
22. Ionin VA, Baranova EI, Zaslavskaya EL, Petrishcheva EY, Morozov AN, Shlyakhto EV. Galectin 3, N terminal propeptides of type I and III procollagen in patients with atrial fibrillation and metabolic syndrome. Int J Mol Sci 2020;21:5689.
Files
IssueVol 64 No 4 (2026) QRcode
SectionOriginal Articles
Keywords
Laminin (LM) Procollagen III N‑terminal peptide (PIIINP) Urine albumin-creatinine ratio (UACR) Pre-diabetes Diabetes nephropathy

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Hasan AZ, I. Hamzh M, Khudhair MS. Impact of Procollagen III Amino Terminal Peptide and Laminin on Nephropathy in Pre-Diabetic and Type 2 Diabetic Patients. Acta Med Iran. 2026;64(4):195-201.