A Signature of Circulating Fatty Acid Metabolites Associated with Incident Prediabetes in a Biracial Longitudinal Cohort

Presentation Number: OR42-6
Date of Presentation: April 3rd, 2017

Ibiye Owei*, Nkiru Umekwe, Frankie B Stentz and Samuel Dagogo-Jack
University of Tennessee, Memphis, TN

Abstract

Objective: Circulating metabolites, including amino acids, urea cycle intermediates, lipid moieties and acylcarnitines, have been associated with type 2 diabetes risk in predominantly Caucasians populations, but their link to prediabetes in diverse populations is unclear. Here we determined whether baseline plasma acylcarnitine levels were associated with progression to prediabetes during longitudinal follow-up of initially normoglycemic African Americans (AA) and European Americans (EA).

Methods: We analyzed baseline levels of 45 acylcarnitines (ACs) in 70 adults (35 AA, 35 EA) who had incident prediabetes (Progressors) during a mean 2.6-years follow up in the Pathobiology of Prediabetes in a Biracial Cohort study and 70 age, gender and ethnicity-matched participants who maintained normoglycemia during followup (Nonprogressors). Acylcarnitines were analyzed using stable isotope dilution techniques. The measurements were made by flow injection tandem mass spectrometry using sample preparation methods described previously (1,2). The data were acquired using a Waters triple quadrupole detector equipped with AcquityTM UPLC system and controlled by MassLynx 4.1 software platform (Waters, Milford, MA).Other assessments included insulin sensitivity (euglycemic clamp) and beta-cell function (FSIVGTT). Prediabetes status was confirmed with OGTT, using ADA criteria.

Results: Of the 45 ACs analyzed, Progressors and Nonprogressors were concordant for 36 and discordant for 9 ACs. Compared to Nonprogressors, the progressors had higher baseline levels of C8:1 (octenoyl carnitine ) (P=0.02), but lower levels of C4-OH ( beta-hydroxy butyryl carnitine), C4-DC/Ci4-DC (methylmalonyl carnitine/Succinyl carnitine), C5-DC (glutaryl carnitine), C5-OH/C3-DC (3-Hydroxy-isovaleryl carnitine/malonyl carnitine), C14 (myristoyl carnitine), C16 (palmitoyl carnitine), C18 (stearoyl carnitine) and C18:2 (linoleoyl carnitine) (P=0.01-<0.0001). Plasma levels of several of the ACs correlated with insulin sensitivity (r= 0.15-0.37; P=0.06-0.0003). In a multivariate regression model, including all 9 ACs, C4-OH (beta-hydroxy butyryl carnitine) (P=0.002) and C8:1(octenoyl carnitine ) (P=0.005) emerged as the strongest significant predictors of incident prediabetes.

Conclusion: In our biracial cohort of initially normoglycemic subjects, baseline plasma levels of several short and long chain acylcarnitines were associated with insulin action and predicted the risk of incident prediabetes, the association being strongest for C4-OH and C8:1. We conclude that circulating levels of fatty acid metabolites may be sensitive biomarkers of early dysglycemic risk.

 

Nothing to Disclose: IO, NU, FBS, SD