Naslov
Biogenesis of methylglyoxal-adducts is associated with LDL and triglyceride levels: implications for diabetic atherosclerosis

Autori
Turk, Zdenka ; Boras, Jozo

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
IDF2009 Abstract book / International Diabetes Federation - Montréal, 2009, 360-360

Skup
20th World Diabetes Congress

Mjesto i datum
Montréal, Kanada, 18.10.2009. - 22.10.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Diabetes; Atherosclerosis; Lipoprotein; Glycation adduct; Methylglyoxal

Sažetak
Aims Protein glycation leading to AGEs is enhanced in diabetes by increases in blood glucose per se, and collaterally, by endogenous production of reactive carbonyls. Low weight alpha-dicarbonyls are formed as glycolytic intermediates during metabolic conversion of glucose and/or during lipid peroxidation. Among AGE precursors, methylglyoxal (MG) is considered as one of the key intermediates. We hypothesized it to be a common product of both carbonyl and oxidative stress, and investigated the MG biogenesis in relation to glycemic and lipid status in diabetic patients. Methods Serum and urine MG-adduct content was measured by DELFIA method in 88 diabetic patients and 20 controls. Fasting (FG) and postprandial (PPG) glucose level, HbA1c, glucose profile M-index, LDL and HDL cholesterol, plasma triglyceride and homocysteine levels were determined. Results Significant positive relationship was observed between serum level of MG-adducts and LDL (r=0.31 p=0.003) whereas fasting glucose correlated inversely (r= -0.33 p=0.001) as well as postprandial glucose (r= -0.23 p=0.041) and HbA1c (r= -0.22 p=0.036). Similarly, significant correlations were also found between urinary levels of MG-adducts and postprandial glucose (r= -0.28 p=0.023), serum triglycerides (r=0.31 p=0.003), homocystein (r=0.57 p=0.0007), HDL (r= -0.28 p=0.007) and urine albumine/creatinine ratio (r=0.53 p=0.002). Multiple linear regression was performed using serum or urine MG-adducts as dependent variable and HbA1c, fasting and postprandial glucose, LDL, HDL, triglycerides, serum creatinine, homocystein and urine albumine/creatinine ratio as independent variables. Of these, only LDL-cholesterol and FG were independently associated with MG-adducts in serum (p<0.00046), whereas urine albumine/creatinine ratio, PPG, HDL and triglycerides were independently associated with urine MG-adducts (p<0.011). Patients with LDL-cholesterol >3.0 mmol/l, had a higher serum level of MG-adducts (616+/-400 ugEq/ml (range 183-2066) vs 424+/-237 ugEq/ml (53-1370) ; p=0.026). In addition, significant correlation between homocysteine and urinary excretion of MG-adducts (r=0.8 ; p=0.02) was recorded in patients with a history of macrovascular disease. Conclusion A highly significant relationship between LDL and MG-adduct production, as well as tight correlation between triglycerides and urinary MG-adduct excretion suggest that lipoxidation and glyceraldehyde-3-phosphate route, along with the glycolytic pathway, might be an important source in MG generation. The glycotoxin methylglyoxal seems to be a common factor linking the two dominant metabolic changes in diabetes, hyperglycemia and intensive lipolysis, with vascular pathobiochemistry of diabetes.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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