January Grad Student Forum: Richard Jaramillo
April 22, 2015 | by Richard Jaramillo
Increased levels of advanced glycation endproducts (AGEs) have been reported in serum of patients with diabetes and are associated with increased probability of specific complications including cardiovascular disease and nephropathy. The numerous protein-AGEs that have been described and the lack of universally accepted metrological standards have hindered efforts to develop them as clinically useful markers for diagnosis and treatment monitoring. In contrast, DNA-AGEs consist of predominantly one adduct of 2’-deoxyguanosine, N2-(carboxyethyl)-2’-deoxyguanosine (CEdG), and validated quantitative methods for its measurement in urine and tissue have been described. Since all nucleated cells contain DNA, we propose that measurement of urinary CEdG might provide one index to evaluate systemic glycemic stress and/or dicarbonyl burden. We measured the DNA-AGE CEdG in urine of Leprdb/db, Lepr-/db and Lepr-/- mice and examined its correlation with fasting plasma glucose (FPG) and HbA1c. Diabetic mice, classified with an FPG of ≥ 200 mg/dl, displayed significantly elevated CEdG (p<0.0001) with a median value of 175.9 ± 24 pmol CEdG/24 hr [n=10]) compared to non-diabetic animals (7.5 ± 1.14 pmol CEdG/24 hr [n=14]. Using the median value determined for all animals (17 pmol/24h), linear regression analysis demonstrated that CEdG measurement alone was predictive of a diagnosis of diabetes (p=0.01). Over a 36-week period urinary CEdG positively correlated with 6 h fasting plasma glucose (r2 = 0.79, p < 0.001) and also displayed a similar, if somewhat weaker, association with HbA1c (r2 = 0.66, p < 0.01). These relationships were independent of the age and sex of the animals. These results suggest that CEdG measurement may provide an independent quantitative index that may be useful for the diagnosis and treatment monitoring of diabetes.