Endocrine Abstracts

Since 2011 trimethylamine N-oxide (TMAO) has been established as a cardiovascular risk biomarker in various patient populations. Previous studies have shown the association of TMAO levels with insulin resistance and diabetes. Additionally, a higher risk of cardiovascular events has been observed in patients with type 2 diabetes and higher levels of TMAO. However, the direct link between TMAO levels and kidney function in patients with diabetes is still unclear. Our objective was to investigate the association between the level of TMAO and the degree of renal damage in patients with diabetes mellitus. Patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) were involved in the study. Since the level of TMAO depends greatly on the composition of the diet, patients were instructed to refrain from eating fish and other seafood for two days before blood draw to avoid artificially high levels of TMAO. Blood sampling was performed in a fasted state to analyze biochemical markers: glucose, C-peptide, HbA1c, ALT, CRO, Urea, cystatin-C, creatinine, GFR, NGAL. Quantification of TMAO concentrations in plasma samples was performed by UPLC/MS/MS analysis. The data are presented as mean ± SEM. A total of 66 diabetes patients were subjected for testing: patients with T1D (n=16, 24%) and with T2D (n=50, 76%). The mean BMI of the patients was 30.8±0.94 kg/m². Of 66 patients, 29 (44%) were male and 37 (56%) were female. The mean age of the patients was 57.6 years, ranging from 19 to 84 years. The average concentration of TMAO in plasma of the patients was 8.05±1.36 μmol/l (min. 0.56 μmol/l; max. 66.34 μmol/l). Interestingly, HbA1c, fasting glucose, C-peptide levels, showed no correlation with TMAO level in plasma. Additionally, TMAO concentrations did not depend on the type of diabetes mellitus or the age of the patient. Meanwhile, markers of kidney glomerular function, creatinine, cystatin-C, GFR, showed a weaker correlation with TMAO levels (R²=0.292, R²=0.279, R²=0.223, respectively, P<0.0001) than Urea (R²=0.4155, P<0.0001), however a strong correlation was found with renal tubular damage marker NGAL (R²=0.6228, P<0.0001) and TMAO. Based on data collected in the clinical setting, we observed a noticeable relationship between kidney tubular damage and plasma TMAO in patients with diabetes. As kidney injury in diabetic patients typically occurs due to mixed pathophysiological mechanisms, additional testing in preclinical models should be employed to confirm the hypothesis that impaired kidney glomerular and tubular function are the initial driving factors of TMAO accumulation.