Examination of advanced glycation end-products in children with type 1 diabetes

Han, Yingchun (2007) Examination of advanced glycation end-products in children with type 1 diabetes. Masters thesis, Memorial University of Newfoundland.

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Abstract

Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of the insulin producing β cells in the pancreas. In T1DM, insulin deficiency induces abnormal metabolism of glucose, lipids and protein that may result in elevation of reactive aldehydes methylglyoxal and glyoxal. Hyperglycemia and high levels of methylglyoxal and glyoxal can modify cell protein, promoting the formation of advanced glycation end-products (AGEs), which may contribute to the development of diabetic complications. In this research, novel high-performance liquid chromatograph coupled with tandem mass spectrometric detection (LC-MS/MS) methods to measure plasma methylglyoxal, glyoxal and some of AGEs were developed. Plasma methylglyoxal, glyoxal and one AGE (MGH1) were measured in young humans with complication-free T1DM. The activity of the ubiquitous membrane enzyme, Na⁺1K⁺-ATPase, was also assessed. Fifty-six patients with T1DM (DM group), 6 to 22 years, and 18 non-diabetics (ND group), 6 to 21 years, were enrolled in the study. Mean hemoglobin A1C (%) was higher in the DM group (8 .5 ± 1.3; mean ± standard deviation) as compared to the control group (5.0 ± 0.3). The mean plasma methylglyoxal (nmo1/L) and glyoxal level (nmo1L), respectively, were found higher in the DM group (842 ± 238, 1052 ± 515) versus the control group (439 ± 90, 328 ± 208). Plasma free AGE, MG-H1 (mg/L), was also found to be higher in the DM group (2.7 ± 1.1) versus the ND group (1.7 ± 0.9), and weakly correlated with methylglyoxal levels but not glycemia as determined by A1C. Erythrocyte membrane Na⁺1K⁺-ATPase activity (nmo1 NADH oxidized/ min/mg protein) was elevated in the DM group (4.47 ± 0.98) compared to the ND group (2.16 ± 0.59). A1C correlated with plasma methylglyoxal and glyoxal, and both aldehydes correlated with each other. A high correlation of A1C with Na⁺K⁺-ATPase activity, and a regression analysis which showed that A1C was a good predictor of this enzyme activity, suggests that glucose may play a role in promoting membrane alterations. Increased plasma methylglyoxal, glyoxal, plasma free MG-H1 and erythrocyte Na⁺1K⁺-ATPase activity may predict the occurrence of future diabetic complications which may be prevented by early aggressive insulin treatment.

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