Dysregulation of Plasma Nonessential Amino Acids in Early-Stage Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia due to insufficient insulin production or the body's poor response to insulin (insulin resistance). Amino acids are closely associated with glucose dysregulation, and disturbances of amino acid metabolism may break the balance of muscle breakdown, protein synthesis, and overactivation of gluconeogenesis, which precedes the onset of T2DM.

This study was designed to identify the levels of nonessential amino acids in recently developed T2DM patients, which may help in the early diagnosis of the disease.

The 180 individuals who participated in this study were categorized as healthy controls, prediabetes, and T2DM. Tests conducted for each participant included glucose using enzymatic methods, HbA1c and nonessential amino acids using ion-exchange high-performance liquid chromatography (HPLC); and insulin using a sandwich-based electrochemiluminescence immunoassay (ECLIA). Insulin resistance was calculated using the HOMA-IR formula.

Newly diagnosed T2DM patients had increased alanine, asparagine, aspartate, glutamate, and proline but decreased serine, arginine, cystine, glutamine, and glycine levels. Amino acid levels varied by obesity status, with alanine, aspartate, and serine rising with obesity, while asparagine, glutamate, arginine, and glycine decreased. Alanine, aspartate, and serine correlated positively with BMI, insulin, and HOMA-IR, whereas asparagine, glutamate, and arginine showed negative correlations. Cystine and glycine correlated negatively with age. Strong positive and negative interrelationships existed among these amino acids.

The study revealed that newly diagnosed T2DM and prediabetes are associated with increased levels of certain nonessential amino acids (alanine, asparagine, aspartate, glutamate, proline) and decreased serine, arginine, cystine, glutamine, and glycine compared to healthy controls. These amino acid levels were influenced by obesity and correlated with insulin resistance and BMI. Altered amino acid metabolism plays a role in early T2DM development and could serve as biomarkers for diagnosis and management.