Abstract
The perturbation in plasma free amino acid metabolome has been observed previously in diabetes mellitus, and is associated with insulin resistance as well as the onset of cardiovascular disease in this population. In this study, we investigated, for the first time, changes in the amino acid profile in a group of people with and without type 2 diabetes (T2D) with normal BMI, from Jordan, who were only managed on metformin. Twenty one amino acids were evaluated in plasma samples from 124 people with T2D and 67 healthy controls, matched for age, gender and BMI, using amino acids analyser. Total amino acids, essential amino acids, non-essential amino acids and semi-essential amino acids were similar in T2D compared to healthy controls. Plasma concentrations of four essential amino acids were increased in the presence of T2D (Leucine, p < 0.01, Lysine, p < 0.001, Phenylalanine, p < 0.01, Tryptophan, p < 0.05). On the other hand, in relation to non-essential amino acids, Alanine and Serine were reduced in T2D (p < 0.01, p < 0.001, respectively), whereas Aspartate and Glutamate were increased in T2D compared to healthy controls (p < 0.001, p < 0.01, respectively). A semi-essential amino acid, Cystine, was also increased in T2D compared to healthy controls (p < 0.01). Citrulline, a metabolic indicator amino acid, demonstrated lower plasma concentration in T2D compared to healthy controls (p < 0.01). These amino acids were also correlated with fasting blood glucose and HbA1c (p < 0.05). Glutamate, glycine and arginine were correlated with the duration of metformin treatment (p < 0.05). No amino acid was correlated with lipid profiles. Disturbances in the metabolism of these amino acids are closely implicated in the pathogenesis of T2D and associated cardiovascular disease. Therefore, these perturbed amino acids could be explored as therapeutic targets to improve T2D management and prevent associated cardiovascular complications.
Highlights
According to the World Health Organisation, the number of people with diabetes increased from 108 million in 1980 to 422 million in 2014, and the prevalence of diabetes has been rising rapidly in the middle- and low-income countries (WHO, 2014)
To the best of our knowledge, this is the first study describing the association between type 2 diabetes (T2D) and plasma free amino acids (PFAA) concentrations in non-obese Jordanian participants treated with metformin only
A recent study conducted in China reported that there was a significant increase in plasma concentration of six essential amino acids (ILe, Leu, Lys, Phe, Trp and Val), three nonessential and semi-essential amino acids (Ala, Glu and Tyr) in T2D, and this increase was associated with higher risk of T2D prevalence and/or incidence (Lu et al, 2019)
Summary
According to the World Health Organisation, the number of people with diabetes increased from 108 million in 1980 to 422 million in 2014, and the prevalence of diabetes has been rising rapidly in the middle- and low-income countries (WHO, 2014). 2004, the prevalence of diabetes among Jordanian population aged between 25 and 70 was 17.1%, increasing to 23.7% in 2017, which is significantly higher than the world average. This increase in the prevalence of diabetes in Jordan is likely due to poor diet and a more sedentary lifestyle (Ajlouni et al, 2019). Diabetes mellitus is characterised by the following symptoms: thirst, polyuria, blurred vision, and weight loss These symptoms can be quiescent for a prolonged period of time resulting in retinopathy, nephropathy, neuropathy and cardiovascular complications due to persistent hyperglycaemia, occurring before the diagnosis of diabetes mellitus is established (WHO, 1999). Recent evidence has suggested that high sugar intake is associated with the risk of T2D (Malik et al, 2010)
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