HbA1c and Serum Levels of Advanced Glycation and Oxidation Protein Products in Poorly and Well Controlled Children and Adolescents with Type 1 Diabetes Mellitus

Abstract

Diabetes mellitus is associated with hyperglycemia and with accelerated non-enzymatic glycation, increased oxidative stress and free radical production. The aim of the present study was to evaluate the levels of proteins glycation and oxidation parameters, compare them between poorly and well controlled children with type 1 diabetes mellitus, and determine the impact of glycemic control on these parameters. Blood and serum were obtained from 81 patients with type 1 diabetes mellitus (DM1) (20 patients had long-term good glycemic control [GGC], 61 patients had long-term poor glycemic control [PGC]). Thirty-one healthy children were used as controls. Fructosamine (FAM) was determined by a spectrophotometric method, HbA1c was measured by LPLC, serum advanced glycation end-products (s-AGEs) were determined fluorimetrically, and advanced oxidation protein products (AOPP) were measured spectrophotometrically. We observed significantly higher FAM, HbA1c, s-AGEs and AOPP levels in the patients with DM1 compared with controls, and significantly higher FAM, HbA1c and sAGEs levels in the PGC group compared with the GGC group. AOPP was higher in the PGC group than in the GGC group, but not significantly. In the PGC group we observed significant correlations between HbA1c and HDL-C (r = -0.306, p = 0.01), HbA1c and s-AGEs (r = 0.486, p < 0.001), and HbA1c and AOPP (r = 0.447, p < 0.01). s-AGEs significantly correlated with triacylglycerols (TAG) (r = 0.537, p < 0.001) and AOPP with HDL-C (r = -0.336, p < 0.05), TAG (r = 0.739, p < 0.001) and s-AGEs (r = 0.577, p < 0.001). In conclusion, our results showed both glycative and oxidative stress are increased in the PGC diabetic group compared with controls, they are linked with glycemic control, and probably contribute to the development of diabetic complications. We suggest that the measurement of not only HbA1c but also s-AGEs and AOPP may be useful to predict the risk of development of diabetic complications.

Cardiovascular Disease Risk Factors in Youth With Diabetes Mellitus

“…Within the context of diabetes mellitus, chronic hyperglycemia and acute hyperglycemia produce free radicals and thereby increase levels of oxidative stress. 277 Most [278][279][280][281][282][283][284][285] but not all 286 studies report that oxidative stress levels are higher in youth with T1DM compared with healthy control subjects. Consistent with the hypothesis that uncontrolled hyperglycemia is one of the primary mechanisms responsible for oxidative stress in diabetes mellitus, multiple studies have suggested that levels of oxidative stress tend to be higher at diagnosis and subsequently decrease over time as glucose control is established.…”

“…Consistent with the hypothesis that uncontrolled hyperglycemia is one of the primary mechanisms responsible for oxidative stress in diabetes mellitus, multiple studies have suggested that levels of oxidative stress tend to be higher at diagnosis and subsequently decrease over time as glucose control is established. [282][283][284][285]287 Evidence suggests that oxidative stress in pediatric T1DM is associated with inflammation, endothelial activation, and other early signs of vascular dysfunction. 98,288,289,291 Although intervention studies are few, 1 study reported that vitamin E supplementation reduced levels of oxidative stress among children with T1DM.…”

Biomarkers of Oxidative Stress in Red Blood Cells

“…The HbA1c level is an indicator of the close relation between protein oxidation and glycation in type 2 diabetic patients 8,18 . Kostolanska et al showed that both glycative and oxidative stress were increased in a poor glycemic control diabetic group compared with controls and this contributed to the development of diabetic complications 19 .…”

Threshold serum concentrations of tumour necrosis factor alpha (TNFα) as a potential marker of the presence of microangiopathy in children and adolescents with type 1 diabetes mellitus (T1DM)

“…Meanwhile, soluble forms of RAGE receptors (sRAGE) have also been identified, which may act as decoy receptors, competing with the RAGE for AGE binding, thus limiting the development of vascular diabetic complications [25][26][27]. However, none of the currently published studies that have presented AGEs, sRAGE and other cytokines or growth factors specify threshold values which would point to the presence of microangiopathy in children with T1DM [20][21][22][28][29][30]. Therefore, the aim of this study was to estimate the threshold values for serum concentrations of AGEs, and sRAGE, as well as TNFa, VEGF 165 and IL-12 in predicting the occurrence of microangiopathy in children and adolescents with T1DM.…”