Guanidinoacetic Acid and Creatine are Associated with Cardiometabolic Risk Factors in Healthy Men and Women: A Cross-Sectional Study

Abstract

Guanidinoacetic acid (GAA) conversion to creatine is thought to be involved in cardiometabolic disturbances through its role in biological methylation and insulin secretion. We evaluated the association of serum GAA and creatine with cardiometabolic risk factors in a cohort of 151 apparently healthy adults (82 women and 69 men) aged 18–63 years. Serum levels of GAA and creatine were measured with liquid chromatography-tandem mass spectrometry. A multiple linear regression model adjusted for age and sex was employed to examine the relationship of serum GAA and creatine with cardiometabolic risk factors. Higher GAA levels were associated with an unfavorable cardiometabolic risk profile (higher insulin, higher total homocysteine, and higher body fat percentage), while having elevated serum creatine levels (≥31.1 µmol/L) was associated with being overweight (body mass index ≥ 25.0 kg/m). The results from our study suggest a possible role of the GAA–creatine axis in the pathogenesis of cardiovascular and metabolic diseases.

Age-Related Changes in Serum Guanidinoacetic Acid in Women

“…Additional details about DiPAH, including Vol. 68 participants characteristics and study design, are available elsewhere (Ostojic et al 2018). The study was conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures were approved by the local IRB at the University of Novi Sad.…”

“…Abnormal serum GAA level is considered a clinical marker of altered bioenergetics in different inherited or acquired disorders, from inborn errors of creatine metabolism to cardiometabolic diseases to specific physiological conditions. Having high serum GAA could be a consequence of either augmented synthesis or GAA loading (Ostojic et al 2013), GAA accumulation caused by deficiency of enzyme catalyzing the methylation of GAA to creatine and transport blockage (Mercimek-Mahmutoglu and Salomons 2009), or limited excretion due to sex hormones-related impact on GAA recovery in the kidney (Joncquel-Chevalier Curt et al 2013). Specifically, a significant gender differences were observed in GAA biodynamics between healthy men and women, with values in GAA excretion significantly higher in female than in male subjects (90.0 vs. 77.6 mmol/mol creatinine), while serum GAA appears to be similar in both subsamples (1.5±0.6 µmol/l in men vs. 1.4±0.6 µmol/l in women) (Joncquel-Chevalier Curt et al 2013).…”

Obesity Connected Metabolic Changes in Type 2 Diabetic Patients Treated With Metformin

“…Limited studies have investigated the metabolic pattern of arginine and guanidoacetic acid regarding conditions such as metformin administration, T2DM, or obesity. In a cohort of healthy subjects, elevated serum level of guanidoacetic acid was associated with hyperinsulinemia, higher total homocysteine, and higher body fat percentage ( Ostojic et al, 2018 ), which all are features of obesity and T2DM. Therefore, future studies are required to investigate metformin's effect on the pathways that involve arginine and guanidoacetic acid in obesity.…”

Elevated uric acid levels in premenopausal female systemic lupus erythematosus patients: Association with potential or existing renal damage

“…On one hand, a high UA level is known to be caused by renal failure, which is marked by elevated serum CRE. However, serum CRE rises only after losing one-third of renal function, 10 and UA rises when renal damage is latent (before CRE increases). 11 The elevation in UA levels may be caused by tubular damage resulting from proteinuria.…”