Identification and validation of serum amino acids as diagnostic biomarkers for diabetic peripheral neuropathy

Figure 1 Flow diagram of the cohorts used for the generation and validation of serum amino acid signatures. DPN: Diabetic peripheral neuropathy; T2DM: Type 2 diabetes mellitus.

Figure 2 Scatter plots of the serum relative concentrations of amino acids among diabetic peripheral neuropathy patients, type 2 diabetes mellitus patients and normal controls in the training cohort and validation cohort. ^aP < 0.05; ^bP < 0.01; ^cP < 0.001; ^dP < 0.0001; NS: Not significant; TC: Training cohort; VC: Validation cohort (one-way ANOVA).

Figure 3 Receiver operating characteristic area under the curve for the specificity and sensitivity of the predictive model in the training cohort and validation cohort. A: Performance of the prediction model for discriminating diabetic peripheral neuropathy (DPN) patients from type 2 diabetes mellitus (T2DM) patients; B: T2DM patients from normal controls; C: Discriminating DPN patients from T2DM patients; D: T2DM patients from normal controls. AUC: Area under the curve; T2DM: Type 2 diabetes mellitus; DPN: Diabetic peripheral neuropathy; TC: Training cohort; VC: Validation cohort.

Figure 4 Calibration curve for predicting the probability of diabetic peripheral neuropathy and type 2 diabetes mellitus. A: Training cohort (TC) of diabetic peripheral neuropathy (DPN) patients and type 2 diabetes mellitus (T2DM) patients; B: TC of T2DM patients and normal controls; C: Validation cohort (VC) of DPN patients and T2DM patients; D: VC of T2DM patients and normal controls. AUC: Area under the curve; T2DM: Type 2 diabetes mellitus; DPN: Diabetic peripheral neuropathy; TC: Training cohort; VC: Validation cohort.

Figure 5 Decision curve analysis. A and B: Decision curve analysis (DCA) for diabetic peripheral neuropathy prediction in the training cohort (A) and validation cohort (B); C and D: DCA for type 2 diabetes mellitus prediction in the training cohort (C) and validation cohort (D). T2DM: Type 2 diabetes mellitus; DPN: Diabetic peripheral neuropathy; TC: Training cohort; VC: Validation cohort.

Figure 6 Heatmap correlation between the measured serum amino acid levels and both electromyography parameters and clinical scores. A: Electromyography parameters; B: Clinical scores. ^aP < 0.05; ^bP < 0.01; ^cP < 0.001; PHQ: Patient health questionnaire; VAS: Visual analog scale; TCSS: Toronto Clinical Scoring System; GAD: Generalized anxiety disorder questionnaire.

Figure 7 Changes in the serum arginine, aspartic acid and tyrosine levels of 13 diabetic peripheral neuropathy patients after treatment for 3 months. ^aP < 0.05; ^dP < 0.0001.