Η επίδραση της καρνιτίνης στην αναερόβια διάσπαση της γλυκόζης στους ασθενείς με υποκατάσταση νεφρικής λειτουργίας

Abstract

The purpose of the study was to find out an eventual relation beΩween the carnitine levels and the dysfunction of the aerobic glycolytic sequence of reactions (citric acid cycle) among the patients undergoing renal replacement therapy with well known established deficiency of carnitine according the literature. This dysfunction was controlled indirectly through the measurement of the lactic acid levels before and after an oral 60 gr. glucose load (OGL). Parallel to that, levels of b-hydroxybutyric acid were measured as an indicator of fatty acids metabolism. The first study group was consisted of 47 patients (32 under hemodialysis HD, 15 under peritoneal dialysis CAPD). Initially morning blood samples were taken from the HD patients on a day without hemodialysis session and from CAPD patients during the first isotonic morning change, after 12 hours fast and 30 minutes rest. Serum lipids (cholesterol, triglycerides, HDL), parathormone (PTH), body mass index (BMI), and levels of total (TC), free (FC) and acylcarnitine (AC) and the ratio AC/FC were also measured. The second blood sample was taken one hour after an oral 60 gr glucose load. The blood takings were done without ligation. 34 patients participated at the second phase of the study. The repetition of the experiment was done after a six month carnitine supplementation therapy. Results: All the patients were under severe deficiency of carnitine at the first part of the study. Carnitine levels were not related to the age, sex, replacement therapy, duration of replacement therapy, lipid profile, PTH and BMI. According the increase of lactic acid after the oral glucose load (OGL) compared to the initial one, the patients were divided in two groups. Group A (an increase equal or greater of 40%) was consisted of 53% of the patients and the group B. There were not statistically significant differences between group A and B except FC, (smaller levels in group A) AC and AC/FC (greater levels in group A). Regression analysis revealed that the levels of lactic acid after OGL were related only to the levels of lactic acid before OGL, levels of FC (negative correlation) and the levels of AC and AC/FC ratio (positive correlation). The mathematic formula is: Lactic acid after the load = 0.958+(lactic acid before ? 0.822)- (FC ? 0.03462) + (AC ? 0.04668). The levels of b-hydroxybutyric acid were diminished after the glucose charge as it was expected. Supplementation of carnitine during 6 months interval was capable to correct the deficit of carnitine of ESRF patients. The repetition of experimental part revealed: The percentage of group A pts was diminished from 53% to 41%. There was not any statistical difference between group A and B concerning the levels of FC, AC and AC/FC. The regression analysis revealed that the lactic acid after OGL was related only to the levels of lactic acid before OGL. None of subgroups (diabetic pts, old age , men, women etc) were favored from carnitine supplementation. The exogenous carnitine failed to improve statistically significant the difference between the values of lactic acid before and after the OGL during the second part of the study. The above mentioned results indicate that there is a balance disorder between aerobic and anaerobic ATP supply and that carnitine is one contributing factor. The failure of exogenous supplementation of carnitine to improve this mismatch suggest that there are probably inadequate tissue levels of carnitine and other endogenous intracellular factors may play role such as mitochondrial dysfunction, lack of energy substrates, disorders of critical enzymes of metabolism of carnitine and metabolic pathways like CPT I, CAT, TSC and CPT I.