Baweja Tanish, Dikshit Abhishek, Bano Shazia, Bansal Sanjiv Kumar, Alam Sana
Hamdard Institute of Medical Sciences and Research, New Delhi, 110062, India.
Department of Biochemistry, Hamdard Institute of Medical Sciences and Research, New Delhi, 110062, India.
Metabol Open. 2025 Jun 1;26:100372. doi: 10.1016/j.metop.2025.100372. eCollection 2025 Jun.
Glycation of nucleic acids secondary to hyperglycemia can lead to structural alterations and the formation of neoantigens. These molecular changes may elicit an early immune response. This study investigates the interaction between serum autoantibodies from prediabetic individuals and fructose-glycated human placental DNA, aiming to assess DNA glycation as a potential early indicator of glycemic stress.
and Methods: To investigate structural modifications in DNA produced by glycation, purified placental DNA was incubated with fructose (25 mM) at 37 °C for 5, 10, and 15 days, followed by spectrophotometric analysis. Peripheral blood samples were collected from 50 normoglycemic (mean age: 39.70 ± 6.63 years; 26 males, 24 females) and 50 prediabetic (mean age: 40.84 ± 5.44 years; 23 males, 27 females) adult patients, matched for age, sex, body mass index, and socio-economic conditions. The presence of circulating antibodies against glycated DNA was evaluated using direct and competitive ELISA.
Fructose-mediated glycation of DNA resulted in hyperchromicity and a new absorbance peak at 360 nm, indicating structural modification. Direct ELISA revealed significantly higher levels of anti-DNA autoantibodies in prediabetic sera (0.367 ± 0.225) compared to controls (0.239 ± 0.118; p = 0.003). Competitive ELISA showed that these antibodies had greater specificity for glycated DNA, with maximum inhibition by fructose-modified DNA at 37.86 ± 2.57 %, versus 23.01 ± 2.33 % for native DNA (p < 0.01).
The study concludes that DNA glycation occurs in prediabetic patients with intermediate hyperglycemia as a result of high blood glucose. This suggests that glycated DNA may serve as an early molecular indicator of glycemic stress, with potential applications in risk assessment and early detection strategies for individuals at risk of progressing to type 2 diabetes.
高血糖继发的核酸糖基化可导致结构改变并形成新抗原。这些分子变化可能引发早期免疫反应。本研究调查糖尿病前期个体血清自身抗体与果糖糖化人胎盘DNA之间的相互作用，旨在评估DNA糖基化作为血糖应激潜在早期指标的可能性。
为研究糖基化导致的DNA结构修饰，将纯化的胎盘DNA与果糖（25 mM）在37℃孵育5、10和15天，随后进行分光光度分析。从50名血糖正常（平均年龄：39.70±6.63岁；男性26名，女性24名）和50名糖尿病前期（平均年龄：40.84±5.44岁；男性23名，女性27名）成年患者中采集外周血样本，这些患者在年龄、性别、体重指数和社会经济状况方面相匹配。使用直接ELISA和竞争ELISA评估针对糖化DNA的循环抗体的存在情况。
果糖介导的DNA糖基化导致增色效应，并在360 nm处出现新的吸收峰，表明结构发生了修饰。直接ELISA显示，糖尿病前期血清中抗DNA自身抗体水平（0.367±0.225）显著高于对照组（0.239±0.118；p = 0.003）。竞争ELISA表明，这些抗体对糖化DNA具有更高的特异性，果糖修饰的DNA对其最大抑制率为37.86±2.57%，而天然DNA为23.01±2.33%（p < 0.01）。
该研究得出结论，糖尿病前期中度高血糖患者由于血糖升高会发生DNA糖基化。这表明糖化DNA可能作为血糖应激的早期分子指标，在2型糖尿病高危个体的风险评估和早期检测策略中具有潜在应用价值。
