Assessment of DNA glycation in the prediabetic State: Early indicator of glycemic stress

Abstract

Introduction

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.

Design

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.

Results

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).

Conclusion

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.