Faculty of Medicine, University of Latvia, Jelgavas Street 3, LV1004 Riga, Latvia.
Residency Development Program, University of Latvia, Aspazijas Bvd. 5, LV1050 Riga, Latvia.
Mutagenesis. 2021 Jul 7;36(3):213-222. doi: 10.1093/mutage/geab015.
Chronic hyperglycaemia 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 with healthy subjects [type 1 diabetes AU 50 (36-74.5); control AU 30 (24.1-43), P < 0.001]. According to regression, type 1 diabetes leads to a 2-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 > 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% confidence interval = 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 when compared with the reference group and demonstrate the negative association between DNA damage and serum nitrite concentration.
慢性高血糖可导致糖尿病患者的 DNA 损伤，并且可能与硝化应激有关。在这项研究中，我们旨在评估白细胞中的 DNA 链断裂水平、1 型糖尿病患者和健康对照组的血清亚硝酸盐和硝酸盐，并在一项前瞻性研究中评估这些参数与糖尿病相关结局的相关性。通过彗星试验测定 71 例 1 型糖尿病患者和 57 例健康对照者的 DNA 损伤水平，并以任意单位（AU）评分。采用化学发光法测定亚硝酸盐和硝酸盐。收集临床资料以及酒精、体力活动和吸烟的相关数据。在随访 4-5 年后，评估糖尿病患者并发症的进展情况。与健康受试者相比，我们观察到 1 型糖尿病患者白细胞中的 DNA 损伤水平更高[1 型糖尿病 AU50（36-74.5）；对照 AU30（24.1-43），P<0.001]。根据回归分析，1 型糖尿病使 DNA 损伤增加了 2 倍。在 1 型糖尿病组中，DNA 损伤与总胆固醇呈正相关（R=0.262，P=0.028），与血清葡萄糖水平呈负相关（R=-0.284；P=0.018），与血清亚硝酸盐呈负相关（R=-0.335；P=0.008）。DNA 损伤与 HbA1c、糖尿病病程、并发症和生活方式因素无显著相关性。然而，DNA 损伤>57 AU 与血清亚硝酸盐显著降低和糖尿病并发症进展风险增加 1.52 倍相关。由于研究能力不足，后者的结果无统计学意义[相对风险 1.52（95%置信区间 0.68-3.42，P=0.31)]。我们的研究结果证实，与参考组相比，1 型糖尿病患者白细胞中的 DNA 链断裂水平更高，并表明 DNA 损伤与血清亚硝酸盐浓度之间存在负相关。
