Glycemic control and its impact on oxidative stress biomarkers in type 2 diabetic patients treated with metformin: a cross-sectional analysis
DOI:
https://doi.org/10.15448/1980-6108.2019.2.33630Keywords:
antioxidant capacity, chronic hyperglycemia, glycated hemoglobin, glycemic control, lipid peroxidation, metformin, oxidative stress, type 2 diabetes mellitus.Abstract
AIMS: Evidence shows that diabetic patients may be predisposed to oxidative stress owing to increased glyco-oxidation and lipid peroxidation processes in consequence of chronic hyperglycemia. However, there is dearth of information whether glycemic control positively affects the antioxidant defense system in type 2 diabetes mellitus (T2DM). We investigated the potential association between glycemic control and oxidative stress biomarkers in controlled and uncontrolled diabetic states.
METHODS: After obtaining ethical clearance, we included patients receiving metformin with glycated hemoglobin A1c ˂7.0% (glycemic control); newly diagnosed T2DM patients without glycemic control with hemoglobin A1c ˃7.0%; and apparently healthy normoglycemic individuals. The following biomarkers were determined: fasting glycemia level, malondialdehyde, glutathione peroxidase activity, catalase activity, total antioxidant capacity and total cholesterol level. The comparisons between the groups were made by ANOVA.
RESULTS: The participants were 260 in number: 80 with controlled diabetes, 80 uncontrolled and 100 controls. All participants were between 40 and 71 years old. Fasting glycemia level and hemoglobin A1c showed significant reductions (p<0.05) in controlled T2DM against the uncontrolled T2DM group, all the same both were significantly higher (p<0.05) against the controls. Likewise, malondialdehyde levels showed significant elevations (p<0.05) correspondingly in both uncontrolled and controlled T2DM against the controls, accompanied with significant reductions (p<0.05) in the antioxidative enzyme activities (glutathione peroxidase activity and catalase activity) and total antioxidant capacity levels against the controls. In addition, total cholesterol was significantly reduced (p<0.05) in controlled T2DM against both uncontrolled T2DM and controls, respectively. There were significant correlations between hemoglobin A1c and oxidative stress biomarkers (p<0.05).
CONCLUSION: There was no remarkable difference in oxidative stress states between glycemic controlled and uncontrolled T2DM, despite differences in their fasting glycemia and glycated hemoglobin levels. Our data, therefore, suggest that chronic hyperglycemia and possibly anti-diabetic medication may both equally associate with oxidative stress.
Downloads
References
Fakhruddin S, Alanazi W, Jackson KE. Diabetes-induced reactive oxygen species: mechanism of their generation and role in renal injury. J Diabetes Res. 2017;2017:8379327. https://doi.org/10.1155/2017/8379327
Sifuentes-Franco S, Padilla-Tejeda DE, Carrillo-Ibarra S, Miranda-Díaz AG. Oxidative stress, apoptosis, and mitochondrial function in diabetic nephropathy. Int J Endocrinol. 2018;2018:1875870. https://doi.org/10.1155/2018/1875870
Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, Nogueira-Machado JA. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis. 2018;9(2):119. https://doi.org/10.1038/s41419-017-0135-z
Kitada M, Zhang Z, Mima A, King GL. Molecular mechanisms of diabetic vascular complications. J Diabetes Investig. 2010;1(3):77-89. https://doi.org/10.1111/j.2040-1124.2010.00018.x
Beckman JA, Creager MA. Vascular complications of diabetes. Circ Res. 2016;118(11):1771-85. https://doi.org/10.1161/circresaha.115.306884
Trinder P. Glucose assay: a colorimetric enzyme-kinetic method assay. Ann Clin Biochem. 1969;6:24.
Uloko AE, Musa BM, Ramalan MA, Gezawa ID, Puepet FH, Uloko AT, Borodo MM, Sada KB. Prevalence and risk factors for diabetes mellitus in Nigeria: a systematic review and meta-analysis. Diabetes Ther. 2018;9(3):1307-16. https://doi.org/10.1007/s13300-018-0441-1
American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(1):S13-S27. https://doi.org/10.2337/dc18-s002
Nathan DM, Singer DE, Hurxthal K, Goodson JD. The clinical information value of the glycosylated hemoglobin assay. N Engl J Med. 1984;310(6):341-6. https://doi.org/10.1056/nejm198402093100602
Varshney R, Kale RK. Effect of calmodulin antagonist on radiationinduced lipid peroxidation in microsomes. Int J Rad Biol. 1990;58(5):733-43.
Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):158-69.
Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-6.
Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem. 1996;239(1):70-6. https://doi.org/10.1006/abio.1996.0292
Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem. 1974;20(4):470-5.
Kassaian SE, Goodarzynejad H, Boroumand MA, Salarifar M, Masoudkabir F, Mohajeri-Tehrani MR, Pourhoseini H, Sadeghian S, Ramezanpour N, Alidoosti M, Hakki E, Saadat S, Nematipour E. Glycosylated hemoglobin (HbA1c) levels and clinical outcomes in diabetic patients following coronary artery stenting. Cardiovasc Diabetol. 2012;11:82. https://doi.org/10.1186/1475-2840-11-82
Pieme CA, Tatangmo JA, Simo G, Nya PCB, Moor VJA, Moukette BM, Nzufo FT, Nono BLN, Sobngwi E. Relationship between hyperglycemia, antioxidant capacity and some enzymatic and non-enzymatic antioxidants in African patients with type 2 diabetes. BMC Res Notes. 2017;10:141. https://doi.org/10.1186/s13104-017-2463-6
Yan LJ. Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress. J Diabetes Res. 2014;2014:137919.
Wells-Knecht KJ, Zyzak DV, Litchfield JE, Thorpe SR, Baynes JW. Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose. Biochemistry. 1995;34(11):3702-9. https://doi.org/10.1021/bi00011a027
Mishra S, Mishra BB. Study of lipid peroxidation, nitric oxide end product, and trace element status in type 2 diabetes mellitus with and without complications. Int J Appl Basic Med Res. 2017;7(2):88-93. https://doi.org/10.4103/2229-516x.205813
ALrefai AA, Alsalamony AM, Fatani SH, Kamel HFM. Effect of variable antidiabetic treatments strategy on oxidative stress markers in obese patients with T2DM. Diabetol Metab Syndr. 2017;9:27. https://doi.org/10.1186/s13098-017-0220-6
Aouacheri O, Saka S, Krim M, Messaadia A, Maidi I. The investigation of the oxidative stress-related parameters in type 2 diabetes mellitus. Can J Diabetes. 2015;39(1):4449. https://doi.org/10.1016/j.jcjd.2014.03.002
Góth L. Catalase deficiencyandtype 2 diabetes. Diabetes.Care 2008;31(12):e93.
Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem. 2014;30(1):11-26. https://doi.org/10.1007/s12291-014-0446-0
Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 2002;23(5):599-622. https://doi.org/10.1210/er.2001-0039
Pendyala G, Thomas B, Joshi SR. Evaluation of total antioxidant capacity of saliva in type 2 diabetic patients with and without periodontal disease: a case-control study. N Am J Med Sci. 2013;5(1):51-7. https://doi.org/10.4103/1947-2714.106208
Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J. 2015;24(5): 547-53. https://doi.org/10.1016/j.jsps.2015.03.013
Papatheodorou K, Banach M, Edmonds M, Papanas N, Papazoglou D. Complications of diabetes. J Diabetes Res. 2015;2015:189525. https://doi.org/10.1155/2015/189525
Srivastava KK, Kumar R. Stress, oxidative injury and disease. Indian J Clin Biochem. 2015;30(1):3-10.
Srivastava RAK. Life-style-induced metabolic derangement and epigenetic changes promote diabetes and oxidative stress leading to NASH and atherosclerosis severity. J Diabetes MetabDisord. 2018;17(2):381-91. https://doi.org/10.1007/s40200-018-0378-y
Madsen A, Bozickovic O, Bjune JI, Mellgren G, Sagen JV. Metformin inhibits hepatocellular glucose, lipid and cholesterol biosynthetic pathways by transcriptionally suppressing steroid receptor coactivator 2 (SRC-2). Sci Rep. 2015;5:16430. https://doi.org/10.1038/srep16430
Sliwinska A, Drzewoski J. Molecular action of metformin in hepatocytes: an updated insight. Curr Diabetes Rev. 2015; 11(3):175-81. https://doi.org/10.2174/1573399811666150325233108
van Stee MF, de Graaf AA, Groen AK. Actions of metformin and statins on lipid and glucose metabolism and possible benefit of combination therapy. Cardiovasc Diabetol. 2018;17(1):94. https://doi.org/10.1186/s12933-018-0738-4
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2019 Scientia Medica
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright
The submission of originals to Scientia Medica implies the transfer by the authors of the right for publication. Authors retain copyright and grant the journal right of first publication. If the authors wish to include the same data into another publication, they must cite Scientia Medica as the site of original publication.
Creative Commons License
Except where otherwise specified, material published in this journal is licensed under a Creative Commons Attribution 4.0 International license, which allows unrestricted use, distribution and reproduction in any medium, provided the original publication is correctly cited.