Determination of Endogenous Levels of Retinoic Acid Isomers in Type II Diabetes Mellitus Patients. Possible Correlation with HbA1c Values.

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Abstract
A sensitive HPLC method for simultaneous determination of endogenous levels of all-trans-(ATRA), 13-cis-(13cRA), and 9-cis-retinoic acids (9cRA) was applied to serum samples from healthy volunteers and type II diabetes mellitus patients. Levels of 9cRA (around 0.2 ng/ml in both groups) were below the limit of quantification. The concentrations of ATRA and 13cRA were reliably quantified, and the within-day and between-days variances indicated that they were well maintained with little variation. Concentrations of serum ATRA and 13cRA of diabetic patients (ATRA: 1.76 +/- 0.54 ng/ml; 13cRA: 1.77 +/- 0.39ng/ml, n=13) were rather lower than those of healthy subjects (ATRA: 2.08 +/- 0.53 ng/ml; 13cRA: 2.05 +/- 0.26 ng/ml, n = 18), but the differences were not significant, except for the sum of ATRA and 13cRA (p = 0.033). Interestingly, the serum levels of retinoic acids in diabetic patients correlated positively with the hemoglobin A1c (HbA1c) values (ATRA: r = 0.57, p < 0.05; 13cRA: r = 0.62, p < 0.05). The results warrant further studies on the possible involvement of uncontrolled serum retinoic acids levels in the pathogenesis and/or treatment of diabetes mellitus.