DNA damage in leukocytes and serum nitrite concentration are negatively associated in type 1 diabetes

Abstract

Chronic hyperglycemia leads to DNA damage in diabetes and might be associated with nitrosative stress. In this study, we aimed at assessing the level of DNA strand breaks in leukocytes, serum nitrite, and nitrate in patients with type 1 diabetes and healthy controls and associations of these parameters with diabetes-related outcomes in a prospective study. The level of DNA damage was determined in 71 patients with type 1 diabetes and 57 healthy controls by comet assay, and scored with arbitrary units (AU). The chemiluminescence method was used to measure nitrite and nitrate. Clinical information and data on consumption of alcohol, physical activity and smoking were collected. Progression of complications in patients with diabetes was assessed after a follow-up time of 4-5 years. We observed a higher level of DNA damage in leukocytes of patients with type 1 diabetes compared to healthy subjects (type 1 diabetes AU 50 (36-74.5); control AU 30 (24.1-43), p<0.001). According to regression analysis type 1 diabetes leads to a two-fold increase in DNA damage. In the group of type 1 diabetes, DNA damage correlated positively with total cholesterol R=0.262, p=0.028; and negatively with serum glucose level R=-0.284; p=0.018 and serum nitrite R=-0.335; p=0.008. DNA damage was not significantly associated with HbA1c, diabetes duration, complications, and lifestyle factors. However, DNA damage above 57 AU was associated with statistically significantly lower serum nitrite and 1.52 higher risk of progression of complications of diabetes over the follow-up period. The latter result was not statistically significant due to insufficient study power (relative risk 1.52 (95% CI 0.68, 3.42, p=0.31). Our results confirm that type 1 diabetes is associated with a higher level of DNA strand breaks in leukocytes as compared to the reference group and demonstrate the negative association between DNA damage and serum nitrite concentration.

Prediction of type 1 diabetes with machine learning algorithms based on FTIR spectral data in peripheral blood mononuclear cells

“…66 ROS levels are elevated in PBMCs from T1D patients, 67 therefore, large molecules of cells are damaged, including phospholipids and the DNA molecule. 68 The fluctuations at a wavelength of 2956 cm −1 , detected in our study, may also indicate changes in lipid molecules including phospholipids, which in turn is also indicated by changes of the peak at 1070 cm −1 (ref. 69 and 70) (Table 3).…”

“…Spectrum changes of in the region 1040-1280 cm −1 could also indicate an extensive DNA rearrangement or even fragmentation. 71 We previously showed that patients with T1D have a higher level of DNA breaks in PBMC than individuals without impaired glucose tolerance, 68 probably related not only to glucose-induced processes but to autoimmune processes as well, as DNA damage is also registered in patients with another autoimmune diseases. [72][73][74][75] Therefore, a shi of absorption band at 1070 cm −1 , indicates changes between the symmetric -PO 2 vibrational absorption peak in nucleic acids or phospholipids, 69,70 but could also indicate bonds in carbohydrates.…”

The effect of glycemic variability on DNA damage in children with type 1 diabetes mellitus

“…25 Several studies have reported a significant increase in DNA damage in patients with diabetes. [9][10][11]16,[26][27][28] These studies have investigated the association between oxidative stress, hyperglycemia, and DNA damage in diabetes mellitus, but they were limited to adult populations, with most participants having type 2 diabetes. 9,11,16,[27][28][29][30] However, only a few clinical trials have studied DNA damage in children with T1DM.…”

“…[9][10][11]16,[26][27][28] These studies have investigated the association between oxidative stress, hyperglycemia, and DNA damage in diabetes mellitus, but they were limited to adult populations, with most participants having type 2 diabetes. 9,11,16,[27][28][29][30] However, only a few clinical trials have studied DNA damage in children with T1DM. 10,26 DNA damage was found to be increased in children with T1DM, and the enhanced oxidative stress resulting from hyperglycemia has been shown to cause DNA damage.…”

“…Hyperglycemia has been identified as a major cause of increased oxidative stress leading to DNA damage. [9][10][11] Another causative factor that induces oxidative stress was found to be GV. [11][12][13][14][15][16] Although there is a sufficient number of publications investigating both the relationship between oxidative stress and GV, and the link between hyperglycemia and DNA damage, no publication directly explores the relationship between GV and DNA damage.…”