Dr Gayova (Department of Internal Medicine, Faculty of Medicine, Pavol Jozef Šafárik University in Košice) and her colleagues published a work presenting the results of measurements of the concentration of carnosine in plasma, erythrocytes and urine of patients with diabetes mellitus type I. The aim of this research was to assess the relationship between the carnosine concentrations in patients with diabetes and compare the results to the concentrations of the control group.
The group consisted of 33 patients (15 men and 18 women) with diabetes mellitus type I. The average age of patients was 39,4 ± 13,8 years. Results were compared with a control group of healthy people. Carnosine in plasma, urine and erythrocytes was measured by automatic amino acid analyzer (MIKROTECHNA Company, Prague). Values of the level of carnosine were given in mmol/l and then converted to µmol/24h in urine. Concentrations of carnosine in the red blood cells were expressed in mmol/g Hb. Average duration of diabetes in the mentioned patients was 13,0 ± 9,7 years.
Renal function was assessed by endogenous creatinine clearance. The average amount of glomerular filtration in the group was 1,53 ± 0,52 ml/s.
Comparing the results of the concentration of carnosine in the plasma of patients with DM type I and the control group, no significant difference was observed. However, in patients with DM type I, carnosine concentrations in the erythrocytes were significantly lower (p <0,01), as well as the concentrations in urine (p <0.05), while the renal tubular reabsorption of carnosine was greater (p<0,01). A correlation between carnosine in the urine in 24 hours and glycosuria was analysed, and then described a linear relationship between the glycosuria and alanine levels in urine (p <0,01, r=0,448).
In examined patients with DM type I, lower carnosine concentrations in the erythrocytes were observed, and plasma carnosine concentrations stayed unchanged. Consequently, there might be a decrease in carnosine in other cells in the body. Lower excretion and higher tubular reabsorption of carnosine indicate the efforts of the organism to preserve this essential dipeptide. The kidneys are, in fact, the major site of catabolism of carnosine. Whether carnosine is excreted in unchanged form or divided into the basic components of histidine and β-alanine, remains to be investigated. A positive correlation between the glycosuria and alanine in urine, as described above, points more to the second option of the final metabolic process.
Carnosine concentration in muscles best demonstrates the level of carnosine supplies. In clinical practice, the best indicator for the evaluation of carnosine metabolism is the concentration in erythrocytes.
Examination on plasma is less accurate, because carnosine is degraded by carnosinase, and therefore fractional excretion and clearance of carnosine should be carefully considered. Indirectly, this also shows the results of reduction of carnosine in patients with diabetes mellitus type I compared to the control group, but only by its measurement in erythrocytes. When carnosine concentration in cells is low, carnosine is less available for metabolic processes, so its participation in the antioxidant defense reactions of the body is limited, as well as in nonenzymatic glycosylation of proteins. Carnosine is absorbed in the small intestine, specific active – transport system in the cell membrane of ciliated cells, it is then led in blood, and further transported to the kidneys, liver and muscles. The absorbed carnosine is used in the peripheral tissue, or it is hydrolyzed to β-alanine and histidine, and then metabolized in the kidneys, liver and brain. The ability of carnosine to reduce oxidation of LDL-cholesterol by chelated copper ions, indicates its ability to prevent the development of atherosclerosis, the formation of AGEs in the blood vessels of diabetic patients that damage the kidneys and other organs.
The study concludes that by carnosine supplementing and by reaching physiological carnosine concentrations, it is possible to achieve the positive effects in development of some chronic complications of diabetes or prevent tissue damage by free radicals.