Paraoxonase-1 Activity and AOPP Levels in Patients with Type 2 Diabetes Mellitus
Abstract
Aim: Paraoxonase 1 (PON1) is a calcium-dependent esterase and exerts antioxidant and anti-atherogenic properties. Advanced oxidation protein products (AOPP) are a group of carbonylated protein products showing oxidant-mediated protein damage. This study aimed to determine serum PON1 activities and AOPP concentrations in diabetic patients and to evaluate these parameters in terms of their relationships with diabetes mellitus (DM) and related factors.
Methods: A total of 93 patients diagnosed with type 2 DM and 30 healthy controls were enrolled in the study. Serum AOPP levels and PON1 activities were measured spectrophotometrically. Other measurements and clinical/demographic data were ordered for all patients, measured in the routine blood chemistry laboratory, and retrieved from patient files.
Results: Serum PON1 activity was significantly lower in patients with DM (31.6 [21.49-48.45] U/mL) compared to controls (41.08 [29.07-54.35] U/mL) (p=0.028). Serum AOPP concentration was significantly higher in diabetic patients (584.6 [453.8-778.6] µmol/L) than in controls (173.9 [98.77-224.1] µmol/L) (p<0.001). PON1 activity negatively correlated with AOPP concentration, and positively with serum HDL-1 levels. AOPP concentration positively correlated with age, weight, HbA1c, glucose, total cholesterol, and LDL-C. A PON1 activity cut-off of ≤25 U/mL predicted DM with a sensitivity of 36.56% and specificity of 90% (AUC: 0.634, p=0.028). An AOPP concentration cut-off of >340 µmol/L predicted DM with a sensitivity of 89.25% and specificity of 93.33% (AUC: 0.965). Both PON1 (OR: 10.821, 95% CI: 1.959 - 59.778, p=0.006) and AOPP (OR: 190.068, 95% CI: 20.102 - 1797.148, p<0.001) were independently associated with DM after adjusting for age, sex, and weight.
Conclusions: AOPP and PON1 may play a significant role in the development and progression of DM. Particularly serum AOPP concentrations appear to be distinctive among patients with new-onset DM.
References
2. Samadi A, Sabuncuoglu S, Samadi M, Isikhan SY, Chirumbolo S, Peana M, et al. A Comprehensive Review on Oxysterols and Related Diseases. Current Medicinal Chemistry. 2021;28(1):110-36.
3. Guo L, Xiao X. Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition). Aging Medicine. 2024.
4. Harding JL, Weber MB, Shaw JE. The Global Burden of Diabetes. Textbook of Diabetes. 2024:28-40.
5. Lima YdMM, Martins FA, Ramalho AA. Epidemiology of Diabetes Mellitus in Adults and Seniors in Rio Branco, Acre, Western Brazilian Amazon. Diabetology. 2024;5(2):151-61.
6. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes research and clinical practice. 2019;157:107843.
7. Preedy VR. Diabetes: Oxidative stress and dietary antioxidants: Academic Press; 2020.
8. Kunachowicz D, Ściskalska M, Kepinska M. Modulatory effect of lifestyle-related, environmental and genetic factors on paraoxonase-1 activity: a review. International Journal of Environmental Research and Public Health. 2023;20(4):2813.
9. Yalcinkaya A, Unal S, Oztas Y. Altered HDL particle in sickle cell disease: decreased cholesterol content is associated with hemolysis, whereas decreased Apolipoprotein A1 is linked to inflammation. Lipids in Health and Disease. 2019;18(1):225.
10. Mahrooz A, Khosravi-Asrami OF, Alizadeh A, Mohmmadi N, Bagheri A, Kashi Z, et al. Can HDL cholesterol be replaced by paraoxonase 1 activity in the prediction of severe coronary artery disease in patients with type 2 diabetes? Nutrition, Metabolism and Cardiovascular Diseases. 2023;33(8):1599-607.
11. Shokri Y, Variji A, Nosrati M, Khonakdar-Tarsi A, Kianmehr A, Kashi Z, et al. Importance of paraoxonase 1 (PON1) as an antioxidant and antiatherogenic enzyme in the cardiovascular complications of type 2 diabetes: Genotypic and phenotypic evaluation. Diabetes research and clinical practice. 2020;161:108067.
12. Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, et al. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney international. 1996;49(5):1304-13.
13. de Brum GF, Bochi GV. Are Advanced Oxidation Protein Products (AOPPs) Levels Altered in Neuropsychiatric Disorders? An Integrative Review. Molecular Neurobiology. 2024:1-17.
14. Bagyura Z, Takács A, Kiss L, Dósa E, Vadas R, Nguyen TD, et al. Level of advanced oxidation protein products is associated with subclinical atherosclerosis. BMC Cardiovascular Disorders. 2022;22:1-9.
15. Heidari F, Rabizadeh S, Rajab A, Heidari F, Mouodi M, Mirmiranpour H, et al. Advanced glycation end-products and advanced oxidation protein products levels are correlates of duration of type 2 diabetes. Life sciences. 2020;260:118422.
16. Organization WH. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation. Part 1, Diagnosis and classification of diabetes mellitus. World health organization; 1999.
17. Eckerson HW, Wyte CM, La Du B. The human serum paraoxonase/arylesterase polymorphism. American journal of human genetics. 1983;35(6):1126.
18. Bhatti JS, Sehrawat A, Mishra J, Sidhu IS, Navik U, Khullar N, et al. Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radical Biology and Medicine. 2022;184:114-34.
19. Ighodaro OM. Molecular pathways associated with oxidative stress in diabetes mellitus. Biomedicine & pharmacotherapy. 2018;108:656-62.
20. Oztas Y, Yalcinkaya A. Oxidative alterations in sickle cell disease: Possible involvement in disease pathogenesis. World Journal of Hematology. 2017;6(3):55-61.
21. Yalcinkaya A, Samadi A, Lay I, Unal S, Sabuncuoglu S, Oztas Y. Oxysterol concentrations are associated with cholesterol concentrations and anemia in pediatric patients with sickle cell disease. Scandinavian Journal of Clinical and Laboratory Investigation. 2019;79(6):381-7.
22. Chawla D, Tripathi AK. Role of advanced glycation end products (AGEs) and its receptor (RAGE)-mediated diabetic vascular complications. Integr Food Nutr Metab. 2019;6(5):1-6.
23. Shen C-Y, Lu C-H, Wu C-H, Li K-J, Kuo Y-M, Hsieh S-C, Yu C-L. The development of maillard reaction, and advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling inhibitors as novel therapeutic strategies for patients with AGE-related diseases. Molecules. 2020;25(23):5591.
24. Cristani M, Speciale A, Saija A, Gangemi S, Lucia Minciullo P, Cimino F. Circulating advanced oxidation protein products as oxidative stress biomarkers and progression mediators in pathological conditions related to inflammation and immune dysregulation. Current medicinal chemistry. 2016;23(34):3862-82.
25. Eroğlu DÜ, KIYICI S, Üstündağ Y, SIĞIRLI D, Pekel NB, Nizameddin K, et al. The investigation of thiol-disulfide homeostasis in patients with diabetic peripheral neuropathy. The European Research Journal. 2022:1-9.
26. Liang M, Wang J, Xie C, Yang Y, Tian JW, Xue YM, Hou FF. Increased plasma advanced oxidation protein products is an early marker of endothelial dysfunction in type 2 diabetes patients without albuminuria 血浆晚期蛋白氧化产物浓度升高是无白蛋白尿的 2 型糖尿病患者内皮细胞功能异常的早期标志物. Journal of Diabetes. 2014;6(5):417-26.
27. Yousefian M, Abedimanesh S, Yadegar A, Nakhjavani M, Bathaie SZ. Co-administration of “L-Lysine, Vitamin C, and Zinc” increased the antioxidant activity, decreased insulin resistance, and improved lipid profile in streptozotocin-induced diabetic rats. Biomedicine & Pharmacotherapy. 2024;174:116525.
28. Durrington PN, Bashir B, Soran H. Paraoxonase 1 and atherosclerosis. Frontiers in Cardiovascular Medicine. 2023;10:1065967.
29. Importance of Oxidative Stress and Antioxidant System in Health and Disease. Rijeka: IntechOpen; 2023.
30. Meneses MJ, Silvestre R, Sousa-Lima I, Macedo MP. Paraoxonase-1 as a regulator of glucose and lipid homeostasis: impact on the onset and progression of metabolic disorders. International journal of molecular sciences. 2019;20(16):4049.
31. Srivastava RAK. Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease. Molecular and cellular biochemistry. 2018;440(1):167-87.
32. Luc K, Schramm-Luc A, Guzik T, Mikolajczyk T. Oxidative stress and inflammatory markers in prediabetes and diabetes. Journal of Physiology & Pharmacology. 2019;70(6).
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