Abstract:
Type 2 diabetes mellitus (T2DM) is an expanding global health concern, closely associated
with the epidemic of obesity. Individuals with diabetes are at high risk for microvascular and
macrovascular complications, which include retinopathy, neuropathy, and cardiovascular comorbidities.
Despite the availability of diagnostic tools for T2DM, approximately 30–60% of people with
T2DM in developed countries are never diagnosed or detected. Therefore, there is a strong need
for a simpler and more reliable technique for the early detection of T2DM. This study aimed to use
a non-targeted metabolomic approach to systematically identify novel biomarkers from the serum
samples of T2DM-induced Sprague Dawley (SD) rats using a comprehensive two-dimensional gas
chromatography coupled with a time-of-flight mass spectrometry (GCxGC-TOF/MS). Fifty-four
male Sprague Dawley rats weighing between 160–180 g were randomly assigned into two experimental
groups, namely the type 2 diabetes mellitus group (T2DM) (n = 36) and the non-diabetic
control group (n = 18). Results from this study showed that the metabolite signature of the diabetic
rats was different from that of the non-diabetic control group. The most significantly upregulated
metabolic pathway was aminoacyl-t-RNA biosynthesis. Metabolite changes observed between the
diabetic and non-diabetic control group was attributed to the increase in amino acids, such as glycine,
L-asparagine, and L-serine. Aromatic amino acids, including L-tyrosine, were associated with the
risk of future hyperglycemia and overt diabetes. The identified potential biomarkers depicted a
good predictive value of more than 0.8. It was concluded from the results that amino acids that
were associated with impaired insulin secretion were prospectively related to an increase in glucose
levels. Moreover, amino acids that were associated with impaired insulin secretion were prospectively
related to an increase in glucose levels.
