Background Diabetic Kidney Disease (DKD) is one of the microvascular complications of Type 2 Diabetes Mellitus (T2DM) which tended not to be detected early, necessitating more effective biomarkers for its detection. HbA1c showed a negative correlation with the estimated glomerular filtration rate (eGFR) and was significantly associated with an increased urine albumin-creatinine ratio (UACR), thereby influencing the progression of DKD. Objective This study was an untargeted metabolomics study and aimed to compare the urinary metabolites of low DKD risk T2DM patients with controlled and uncontrolled HbA1c in patients taking metformin-glimepiride. Materials and Methods This study conducted as a cross-sectional study using non-probability sampling at Pasar Minggu District Health Center, 32 samples were divided into controlled (n=16) and uncontrolled HbA1c groups (n=16). Blood samples were collected for HbA1c and eGFR measurements, while urine samples were analyzed for UACR and metabolites. Analysis was performed using LC/MS-QTOF and the data was processed using MetaboAnalyst 6.0 and various databases. The discrimination results of the two groups were visualized through Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA). The significance of metabolites between groups was selected with the parameters VIP>1, log2(FC)>1.2, and p-value0.65): oxaloacetate and 5′-phosphoribosyl-N-formylglycinamidine, which decreased in the uncontrolled HbA1c group, and (S)-dihydroorotate, which increased in the uncontrolled HbA1c group. The involved metabolic pathways included (1) alanine, aspartate, and glutamate, (2) citric acid (Krebs cycle), (3) gluconeogenesis, (4) pyruvate, (5) pyrimidine, and (6) purine. Conclusion Based on these results, there’s a significant difference in urine metabolites of the two groups that potentially be the biomarkers for DKD progression with controlled and uncontrolled HbA1c.
Wijaya et al. (Sat,) studied this question.