Metabolomic Profiling of Nonproteinogenic Amino Acids in Patients with Type 2 Diabetes and Hypertension

Introduction: Identifying the amino acid signature of increased blood pressure might help us understand hypertension pathophysiology. We aimed to investigate the relationship of non-proteinogenic amino acids with ambulatory blood pressure mean and variability in type 2 diabetes patients.

Methods: Serum non-proteinogenic amino acids’ profiling was performed by high performance liquid chromatography coupled with mass spectroscopy analysis. Blood pressure variability was calculated as standard deviation of mean systolic and diastolic blood pressure evaluated over 24-hour ambulatory monitoring.

Results: The study population consisted of type 2 diabetes hypertensive patients (n=80), 58% women, aged 59.8±7.7 years old with diabetes duration 9.0±8.7 years. Serum non-proteinogenic amino acids levels (nmol/mL) were: gamma-aminobutyric acid 0.2±0.1, aminoisobutyric acid 22.6±7.9, beta-aminoisobutyric acid 1.2±0.7, 4-hydroxyproline 12.2±9.9, 3-methylhistidine 4.7±2.8, alpha-aminoadipic acid 1.0±0.5, sarcosine 11.3±5.6. In linear regression analysis, aminoisobutyric acid was significantly associated with 24-hour systolic blood pressure variability (r=0.23; p=0.044), sarcosine was significantly associated with nighttime systolic blood pressure variability (r=0.27; p=0.017), while beta-aminoisobutyric acid was significantly associated with mean daytime (r=-0.25; p=0.024) and 24-hour (r=-0.24; p=0.032) diastolic blood pressure.

Conclusion: Serum metabolomes aminoisobutyric acid and sarcosine directly associated with ambulatory systolic blood pressure variability, while beta-aminoisobutyric acid inversely associated with mean diastolic blood pressure. Our results indicate changes in serum non-proteinogenic amino acids as consequences of increased blood pressure that should be further evaluated in connection to cardiovascular disease, particularly in the presence of type 2 diabetes.