Endocrine Abstracts

Introduction: Autotaxin (ATX)[Ectonucleotide Pyrophosphatase /Phosphodiesterase family member 2 (ENPP2)] is a lysophospholipase D stimulating cell migration, metastasis and angiogenesis. ATX hydrolizes lysophosphatidylcholine (LPC) and produces bioactive lysophosphatidic acid(LPA). There are some clues about ATX–LPA pathway modulation may unlock the gate of metabolic derangement including diabetes formation or may impact formation of cardiovascular diseases via LPA’s role on platelet aggregation. We aimed to investigate ATX levels of individuals having type 2 diabetes mellitus (T2DM) or those having Cardiovascular Disease (CVD). Nondiabetic patients with normal fasting plasma glucose(FPG) level were randomly selected. The diabetic patients were diagnosed as diabetic in our clinic. Among those, patients who had CVD or not,were also discriminated in the study. Blood was collected from all the participants in serum separation tubes.Serum ATX was measured by ELISA.

Results: The study enrolled 82 individuals, 42 of them were T2DM patients, 40 was nondiabetic. Of those, 57 patients were categorized as CVD(−) while 25 patients were CVD(+). Mean HbA1c level was 8.2±2.1% for T2DM patients. ATX level of the patients having T2DM was greater than nondiabetic patients(4.6±0.5 mg/l vs 4.4±0.6 mg/l, P:0.046). CVD(+) patients had ATX levels indifferent from CVD(−) patients(4.4±0.5 mg/l vs 4.5±0.6 mg/l, P:0.46). In subgroup analysis, T2DM(+) CVD(−) had greater ATX levels than nondiabetic CVD(−) subjects. ATX was similar for T2DM(+) CVD(+) patients and T2DM(+) CVD(−) patients when T2DM(+) CVD(+) patients also had indifferent ATX compared to nondiabetic CVD(+) group. By regression analysis FPG(OR:0.22, P:0.05) and Hba1c (OR:0.39, P:0.01) were found correlated with ATX in the whole group. In CVD(-) patients ATX was related with FPG(OR:0.30, P:0.02) and Hba1c(OR:0.42, P:0.02) while in CVD(+) patients there was no correlation.

Discussion: In adult human body ATX’s upregulated levels have been described in chronic inflammatory diseases and cancer.The studies examining the probable relationship between serum ATX and glucose metabolism are so few, including no study on diabetic individuals. By our study, we found ATX was increased in T2DM patients compared to nondiabetics and an indifferent ATX level between CVD(+) and CVD(−) patients. In absence of CVD manifestation T2DM patients had higher ATX levels than nondiabetics, while CVD manifestation seems to destroy the difference between ATX level of T2DM and nondiabetic patients. It may emphasize that CVD manifestation impairs ATX production in diabetic patients. ATX inhibitors may be a challenge for treatment of T2DM or prevention of CVD manifestation in diabetics.