Editorial Article

Decreased Blood Catalase Activity in Diabetes

Nagy T1 and Góth L2,*
1Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Hungary
2Department of Medical Laboratory and Diagnostic Imaging, Faculty of Medicine, University of Debrecen, Hungary

*Corresponding author:

László Góth, Department of Medical Laboratory and Diagnostic Imaging, Faculty of Medicine, University of Debrecen, Debrecen POBox 55, Hungary H-4032, Email: goth@med.unideb.hu

The damaging effect of ROS (Reactive Oxygen Species) is well-known in conditions like diabetes mellitus, atherosclerosis, chronic hepatic conditions, kidney failure, tumors, rheumatoid arthritis and neurodegenerative diseases. Hydrogen peroxide is not a reactive oxygen species but derived from the toxic superoxide by superoxide dismutase enzyme. Its high concentration is also toxic while in low concentration is thought to be involved in several signaling pathways [1].

The second line of defense against damaging agents like hydrogen peroxide is provided by antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and catalase that seems to be of the greatest importance in the hydrogen peroxide removal.

Catalase (EC, hydrogen peroxide/ hydrogen peroxide oxidoreductase) forms a tetramer composed of four identical subunits with a molecular weight of 240 kDa. The speciality of the substrate decomposition is that the enzyme does not function if the concentration of H2O2 is physiological.

The blood cells contain the enzyme catalase in different concentrations with the highest in erythrocytes. More than 99 % of blood catalase derives from erythrocytes. It could be assumed that the catalase with its high concentration in blood also has a general protective role against the hydrogen peroxide.

The decreased activity of catalase could lead to early manifestation of several diseases like tumors, anemias, vitiligo and diabetes mellitus [2].

Catalase protein is coded by a single gene, which is located on the short arm of chromosome 11 at position 13. The gene spans 33,114 kb and has 13 exons and 12 introns. According to NCBI database by 2012 there were 245 nucleotide positions detected in the catalase gene were different from the consensus. The majority of polymorphisms result in a benign condition with no effect on enzymatic activity. They do not affect catalase protein expression and they either has no pathological effect or it has not yet been discovered.

The decrease in enzymatic activity could be related either to the known and unknown polymorphisms of catalase gene or to epigenetic factors.

Acatalasemia is a disorder marked by congenital absence of catalase, which is a genetically mutant homozygous condition with 1-8% of blood catalase activity. Hypocatalasemia is the heterozygous condition with about 50 % of the blood catalase. Acatalasemia was first found in Japan and then in further 12 countries. The examination of a large Hungarian population (n = 28,252) the acatalasemia has shown an incidence of 0.05/1000 and the detected mutations were named as the A, B, C, D, E types of the Hungarian acatalasemia [2].

Type 2 diabetes mellitus can be considered a complex condition. Its development is influenced by environmental and genetic factors alike. It was found that in inherited catalase deficiency the diabetes the frequency of diabetes was 12.7% ( 8/55) while no diabetic (0/66) in the normocatalasemic family member [3]. It may be supposed that the lack of catalase favors to the increase of the hydrogen peroxide concentration, which will exert a damaging effect on the pancreatic beta-cells highly sensitive to oxidation.

In the Hungarian diabetes and control group, the frequency of the C wild allele (68% and 72%) was higher than that of the T mutant allele (28% and 32%). The TT homozygous mutant genotype (12%) was higher in type 1 diabetes mellitus than in type 2 (9%, p < 0.02) and in the control group (9%, p < 0.02). Contrary, the catalase enzyme activity did not show any significant decrease for these cases. There is a significant association between the genotypes and the age (CC: 45 ± 13 years, CT: 39 ± 14 years, TT: 36 ± 10 years, p < 0.04). There was no significant differences in genotypes, lipid and carbohydrate parameters for type 1 diabetic patients (p > 0.08).

In type 2 diabetes a significant decrease (p < 0.001) was detected for the catalase activity in CC and CT genotype samples when they were compared either to those of the controls and or to type 1 diabetics. In type 2 diabetes, a significant increase of glucose concentration was detected when the patients with the TT genotypes were compared to those with the CT genotypes (p < 0.02). Furthermore, hemoglobin A1c (p < 0.03) and ApoB (p < 0.05) concentrations were higher for CT genotypes than those of CC genotype [4].

For this polymorphism a significant decrease was detected for blood catalase activity in type 2 (91 ± 20 MU/L, p < 0.001) and in type 1 diabetes (95 ± 20 MU/L, p < 0.048) compared to the control group (105 ± 17 MU/L). In type 1 diabetes, genotype analysis showed changes in blood catalase activity for CC (96 ± 26 MU/L) and CT (94 ± 30 MU/L ) compared to controls (CC: 109 ± 25 MU/L, CT: 102 ± 16 MU/L, p < 0.05). In type 2 diabetes the blood catalase was found significantly decreased (p < 0,05) for all three genotypes (CC: 98 ± 30 MU/L, CT: 88 ± 34 MU/L, TT: 84 ± 23 MU/L) compared to the control group (105 ± 17 MU/L). The greatest difference was detected for the TT genotype group (p < 0.03) compared to the control group. There was a significant difference in genotypes of type 2 diabetes in carbohydrate biomarkers such as glucose (CC and TT, p < 0.02), HbA1c (CC and TT, p < 0.05) similarly to the lipid biomarkers of cholesterol (CC and TT, p < 0.01), HDL (CC and TT, p < 0.05), ApoB (CC and TT, p < 0.05).

No significant difference (p>0.1) was found between type 1, type 2 diabetics and the controls either for the genotypes or for alleles [4].

Of 617 patients 51 subjects yielded blood catalase activity below 50% of the reference mean. These patients had diabetes mellitus (18, 35%), microcytic anemia (14, 27%), presbyacusis (10, 19.7%) and beta-thalassemia (4, 7.8%). The mutation screening yielded 4 novel acatalasemia mutations G1,H1, H2, H3) in 7 patients. More than half of the new mutations (4, 57%) were found in diabetic patients. Of the 4 patients, three are type 2 and one with gestational diabetes.

In 44 patients (86.3%) with decreased blood catalase activity epigenetic or regulatory mechanisms may be causative [5]. Furthermore, the downregulation of catalase synthesis, rather than specific catalase gene mutations may be responsible for decreased blood catalase activity in type 2 diabetic subjects [6].

Inherited catalase deficiency may be a risk factor for type 2 diabetes due to its contribution to ROS. Decreased blood catalase in diabetes may be due to either catalase gene mutations or to other reasons causing downregulation of catalase expression.

1. Veal A, Day A (2011) Hydrogen peroxide as a signaling molecule. Antiox Redox Signal 15: 147-151.
2. Góth L, Nagy T (2013) Inherited catalase deficiency: Is it a benign or a factor in various age relate disorder? Mut Res/ Rev Mut Res 753: 147-154.
3. Góth L, Eaton JW (2000) Hereditary catalase deficiencies and increased risk of diabetes. Lancet 356: 1820-1821.
4. Góth L, Nagy T, Kósa , Fejes Z, Bhattoa HP, et al. (2012) Effects of rs769217 and rs1001179 polymorphisms of catalase gene on blood catalase, carbohydrate and lipid biomarkers in diabetes mellitus. Free Rad Res 46: 1249-1257.
5. Nagy T, Pászti E, Káplar M, Bhattoa HP, Góth L (2015) Further acatalasemia mutations in human patients from Hungary with diabetes and microcytic anemia. Mut Res/ Fund Mol Mech Mutagen 772: 10-14.
6. Góth L (2008) Catalase deficiency and type 2 diabetes. Diab Care 31: e93.

Citation: Nagy T, Goth L (2017) Decreased blood catalase activity in diabetes. J Diabetes Care Endocrin 1:e001

Published: 28 August 2017


© 2017 Nagy et al.. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.