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Abstract Diabetic Kidney disease (DKD) is an important cause of end-stage renal disease (ESRD) with expected global increase in its prevalence reaching 44% by 2030. DKD is a consequence of a complicated interaction among metabolic, inflammatory and hemodynamic changes with the involvement of energy pathwayrelated metabolites such as the fatty acids and Krebs cycle intermediates. Acylcarnitines (AcylCNs) consist of an acyl group esterified to carnitine, allowing crossing of long-chain fatty acids through the mitochondria membrane for βoxidation. They also participate during the branched-chain amino acids catabolism, with acylCoA intermediate status through carnitine acyltransferases. Additionally, if metabolites are pathognomic, they might also be new targets for treatment. However, although metabolomics have discovered pathways possibly related to DKD development and progression, targeted blood metabolomics studies are limited. The present study aimed to study the metabolic profiling of amino acids, AcylCNs that can provide superior definition of T2DM in Egyptian patients with normoalbuminuria, micro-albuminuria and macroalbuminuria compared to HbA1C using chromatography mass spectrometry as a sensitive and an accurate assay. This study was conducted on 100 diabetic patients and 25 healthy volunteers (normoglycemic subjects with normal glucose tolerance) as control group. Participants were divided into five groups: group I: 25 diabetic patient with normoalbuminuria (<30 mg/g). group II: 25 diabetic patient with microalbuminuria (30 to300 mg/g). group III: 25 diabetic patient with macroalbuminuria. (>300 mg/g). group IV: 25 healthy non diabetic subjects. All patients were submitted to clinical examination, laboratory testing for fasting blood glucose level, postprandial 2 hours oral glucose tolerance test (OGTT), HbA1c, Lipid profile, and renal function tests: serum creatinine and serum urea. Spot urine sample from each patient were taken to measure urinary albumin/creatinine ratio (ACR). Amino acid profile assay using High performance liquid chromatography was performed. Estimated glomerular filtration rate (eGFR) were be calculated. We found that Acylcarnitines are significantly correlated with T2D patients with various stages of albuminuria. The elevated Acylcarnitines in T2D patients with macroalbuminuria may enhance fatty acids oxidation. Acylcarnitines, especially C12, C5:1 and C5, may be more sensitive biomarkers for the diagnosis of early DKD in T2DM patients with normoalbuminria and microalbuminuria than HbA1c that might offer additional therapeutic goals for limiting DKD progression. |