Arginine and Carnitine Metabolites Are Altered in Diabetic Retinopathy.

Purpose: To determine plasma metabolite and metabolic pathway differences between patients with type 2 diabetes with diabetic retinopathy (DR) and without retinopathy (diabetic controls), and between patients with proliferative DR (PDR) and nonproliferative DR (NPDR). Methods: Using high-resolution mass spectrometry with liquid chromatography, untargeted metabolomics was performed on plasma samples from 83 DR patients and 90 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis, and linear regression was used to adjust for age, sex, diabetes duration, and hemoglobin A1c. Pathway analysis was performed using Mummichog 2.0. Results: In the adjusted analysis, 126 metabolic features differed significantly between DR patients and diabetic controls. Pathway analysis revealed alterations in the metabolism of amino acids, leukotrienes, niacin, pyrimidine, and purine. Arginine, citrulline, glutamic γ-semialdehyde, and dehydroxycarnitine were key contributors to these pathway differences. A total of 151 features distinguished PDR patients from NPDR patients, and pathway analysis revealed alterations in the ß-oxidation of saturated fatty acids, fatty acid metabolism, and vitamin D3 metabolism. Carnitine was a major contributor to the pathway differences. Conclusions: This study demonstrates that arginine and citrulline-related pathways are dysregulated in DR, and fatty acid metabolism is altered in PDR patients compared with NPDR patients.

Surface ECG f Wave Analysis at Initial Onset of Paroxysmal and Persistent Atrial Fibrillation.

INTRODUCTION: Dominant frequency (DF) analysis of electrocardiograms (ECGs) from patients with paroxysmal (PAF) and persistent (PeAF) atrial fibrillation has identified higher DFs in PeAF. We therefore hypothesized that among patients initially presenting to the emergency department (ED) with new onset AF, surface ECG features could differentiate PeAF from PAF. METHODS AND RESULTS: Initial 12-lead ECGs from patients presenting to the ED with a first episode of symptomatic AF were analyzed. Following QRS-T subtraction, fast Fourier transform (FFT) analysis of the AF fibrillatory waves was performed to measure DF and organization index (OI). Median DF of all leads and the DF in the lead with maximum OI were determined. Maximum f wave amplitude and vector magnitudes were measured. One hundred sixty-one patients (age 59 ± 16 years, 68% men) were included in this analysis, of whom 96 (58%) spontaneously converted to sinus rhythm within 7 days (PAF group). The remaining 65 patients underwent cardioversion or remained in AF (PeAF group). ECG features (DF, OI, f wave amplitude, and vector magnitude) did not differ among PAF and PeAF patients. CONCLUSIONS: ECG features (DF, OI, amplitude, vector magnitude) do not differ among patients with PAF versus PeAF when the ECGs are obtained at the initial onset of symptoms. Thus, prior data showing higher DF in PeAF likely reflect electrophysiologic remodeling rather than a marker for any specific type of AF or extent of underlying substrate.