THE ACTIVITY OF XANTHINE OXIDASE IN PLASMA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: THE RELATIONSHIP BETWEEN HYPERURICEMIA, INSULIN RESISTANCE, AND LIVER DYSFUNCTION

Authors

  • Chernyaeva A. O. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv; Kharkiv Medical Academy of postgraduate education of the Ministry of health of Ukraine, Kharkiv
  • Mykytyuk M. R. SI "V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine", Kharkiv https://orcid.org/0000-0002-6169-7628
  • Karachentsev Yu. I. SI «V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine», Kharkiv; Kharkiv National Medical University, Kharkiv, Ukraine https://orcid.org/0000-0003-1317-6999

DOI:

https://doi.org/10.21856/j-PEP.2022.3.08

Keywords:

xanthine oxidase activity, type 2 diabetes mellitus, insulin resistance, liver dysfunction

Abstract

We aimed to investigate the clinical implication of plasma xanthine oxidase (XO) activity in patients with type 2 diabetes mellitus (DM).

Materials and methods. 127 patients were examined for type 2 DM (72 female and 55 male). Serum biochemical variables include aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting (FPG) and postprandial (PPG) plasma glucose, glycohemoglobin A1c (HbA1c), total cholesterol, triglyceride, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, creatinine (Cre) and serum urine acid (SUA) was measured with a conventional automated analyzer. The level of fasting insulin (IRI) was determined by the immuno-chemiluminescent method. Homeostasis model assessment of insulin resistance (IR) (HOMA-IR) index was calculated by the formula: HOMA-IR=fasting insulin (μmol/L)×FPG(mmol/L)/22.5. The plasma XO activity was determined by a photometric method. The rate of glomerular filtration (eGFR) was calculated according to CKD-EPI formulas. All statistical analyses were performed using STATISTICA software version 10.0.

Results. The plasma lnXO activity was correlated with IRI (rs=0.52; P<0.001) and HOMA‐IR (rs=0.51; P<0.002). In addition, the plasma lnXO activity was correlated with BMI (rs=0.40; P<0.001). In contrast, plasma lnXO activity was not correlated with age (rs=-0.07; P=0.61), HbA1c (rs=-0.11; P=0.41), FPG (rs=-0,4; P=0.74) and PPG (rs=-0.09; P=0.57). lnXO activity and indices of liver dysfunction or parameters closely related to SUA level in patients with type 2 DM: lnALT (rs=0.73; P<0.001), lnAST (rs=0.69; P<0.001), ALT/AST (rs=0.85; P<0.001). The plasma lnXO activity was correlated with Cre (rs=-0.15; P=0.46) and eGFR (rs=0.13; P=0.34). In a series of multiple regression analyses, plasma lnXO activity was used as a dependent variable, and age, BMI, HbA1c, SUA, eGFR, lnAST, lnALT, IRI, and HOMA-IR as explanatory variables were carried out. When used as explanatory variables, the value of lnALT (Model 1) was an independent strong factor for determining plasma XO activity (R2=95.3%; P<0.00001). When used as explanatory variables, the value of lnALT (Model 2) was also an independent strong factor for determining the plasma XO activity (R2=97.2%; P<0.00001).

We aimed to investigate the clinical implication of plasma xanthine oxidase (XO) activity in patients with type 2 diabetes mellitus (DM).

Materials and methods. 127 patients were examined for type 2 DM (72 female and 55 male). Serum biochemical variables include aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting (FPG) and postprandial (PPG) plasma glucose, glycohemoglobin A1c (HbA1c), total cholesterol, triglyceride, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, creatinine (Cre) and serum urine acid (SUA) was measured with a conventional automated analyzer. The level of fasting insulin (IRI) was determined by the immuno-chemiluminescent method. Homeostasis model assessment of insulin resistance (IR) (HOMA-IR) index was calculated by the formula: HOMA-IR=fasting insulin (μmol/L)×FPG(mmol/L)/22.5. The plasma XO activity was determined by a photometric method. The rate of glomerular filtration (eGFR) was calculated according to CKD-EPI formulas. All statistical analyses were performed using STATISTICA software version 10.0.

Results. The plasma lnXO activity was correlated with IRI (rs=0.52; P<0.001) and HOMA‐IR (rs=0.51; P<0.002). In addition, the plasma lnXO activity was correlated with BMI (rs=0.40; P<0.001). In contrast, plasma lnXO activity was not correlated with age (rs=-0.07; P=0.61), HbA1c (rs=-0.11; P=0.41), FPG (rs=-0,4; P=0.74) and PPG (rs=-0.09; P=0.57). lnXO activity and indices of liver dysfunction or parameters closely related to SUA level in patients with type 2 DM: lnALT (rs=0.73; P<0.001), lnAST (rs=0.69; P<0.001), ALT/AST (rs=0.85; P<0.001). The plasma lnXO activity was correlated with Cre (rs=-0.15; P=0.46) and eGFR (rs=0.13; P=0.34). In a series of multiple regression analyses, plasma lnXO activity was used as a dependent variable, and age, BMI, HbA1c, SUA, eGFR, lnAST, lnALT, IRI, and HOMA-IR as explanatory variables were carried out. When used as explanatory variables, the value of lnALT (Model 1) was an independent strong factor for determining plasma XO activity (R2=95.3%; P<0.00001). When used as explanatory variables, the value of lnALT (Model 2) was also an independent strong factor for determining the plasma XO activity (R2=97.2%; P<0.00001). When used as explanatory variables without parameters for liver functions, the value of HOMA‐IR was an independent factor for determining the plasma XO activity (Model 3) (R2=97.3%; P<0.00001). These data suggest that the values of ALT and HOMA-IR, a clinical marker for hepatic IR, might be independent factors for directly influencing the plasma XO activity in patients with type 2 DM.

Conclusions. The value of plasma xanthine oxidase activity was significantly correlated with indices of insulin resistance and liver dysfunction in patients with type 2 diabetes mellitus. The values of alanine aminotransferase and homeostatic model assessment for insulin resistance (HOMA-IR), a clinical marker for hepatic insulin resistance, might be independent factors for directly influencing the plasma xanthine oxidase activity in patients with type 2 diabetes mellitus.

References

Nakanishi K, Morita H. Int Heart J 2022;63(3): 423-425. http://doi.org/10.1536/ihj.22-127.

Dehlin M, Jacobsson L, Roddy E. Nat Rev Rheumatol 2020;6(7): 380-390. http://doi.org/10.1038/s41584-020-0441-1.

Ilundain-González AI, Gimeno-Orna JA, Sáenz-Abad D, et al. Endocrinol Diabetes Nutr 2018;65(6): 335-341. http://doi.org/10.1016/j.endinu.2018.01.004.

Kuwata H, Okamura S, Hayashino Y, et al. Diabetol Int 2016;7(4): 352-360. http://doi.org/10.1007/s13340-016-0254-2.

Jin M, Yang F, Yang I, et al. Front Biosci 2012;17: 656-669.

Spiekermann S, Landmesser U, Dikalov S, et al. Circulation 2003;107: 1383-1389.

Otaki Y, Watanabe T, Kinoshita D, et al. Int J Cardiol 2017;228: 151-157.

Berry CE, Hare JM. J Physiol 2004;555: 589-606.

Tsushima Y, Nishizawa H, Tochino Y, et al. J Biol Chem 2013;288: 27138-27149.

Rajeev Chawla, Madhu SV, Makkar BM, et al. J Endocrinol Metab 2020;24(1): 1-122. http://doi.org/10.4103/ijem.IJEM_225_20.

Feig DI, Kang DH, Johnson RJ. N Engl J Med 2008;359(17): 1811-1821.

https://www.kidney.org/professionals/kdoqi/gfr_calculator

Sunagawa S, Shirakura T, Hokama N, et al. Diabetes Investig 2019;10(1): 94-103. http://doi.org/10.1111/jdi.12870.

Li Y, Xu C, Yu C, Xu L, Miao M. J Hepatol 2009;50: 1029-1034. http://doi.org/10.1016/j.jhep.2008.11.021.

Xu C, Yu C, Xu L, Miao M, Li Y. PLoS One 2010;5: e11578. http://doi.org/10.1371/journal.pone.0011578.

Facchini F, Chen YD, Hollenbeck CB, et al. JAMA 1991;266: 3008-3011.

Zhu Y, et al. Biochem Biophys Res Commun 2014;447: 707-714. http://doi.org/10.1016/j.bbrc.2014.04.080.

Lanaspa MA, et al. J Biol Chem 2012;287: 40732-40744. http://doi.org/10.1074/jbc.M112.399899.

Yamamoto T, Moriwaki Y, Takahashi S. Clin Chim Acta 2005;356: 35-57. http://doi.org/10.1016/j.cccn.2005.01.024.

Downloads

Published

2022-09-15

How to Cite

Chernyaeva, A., Mykytyuk, M., & Karachentsev, . Y. (2022). THE ACTIVITY OF XANTHINE OXIDASE IN PLASMA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: THE RELATIONSHIP BETWEEN HYPERURICEMIA, INSULIN RESISTANCE, AND LIVER DYSFUNCTION. Problems of Endocrine Pathology, 79(3), 59-63. https://doi.org/10.21856/j-PEP.2022.3.08

Issue

Section

CLINICAL ENDOCRINOLOGY

Most read articles by the same author(s)