Abstract
Objectives:Plasma-free amino acid (PFAA) profiles have been associated with a future risk of developing diabetes or cardiovascular disease in nondiabetic subjects. These PFAA alterations might predominantly result from the metabolic shift caused by insulin resistance and visceral fat deposition. The variety of PFAA profiles within diabetic subjects is not well researched. In this study, we focused on type 2 diabetic subjects and examined the association between PFAA profiles and insulin- and glucose-related variables.Methods:Fifty-one Japanese subjects diagnosed with type 2 diabetes were recruited from an outpatient clinic. The plasma concentrations of 21 amino acids; glucose-related markers including glucose, hemoglobin A1c (HbA1c), glycoalbumin and 1,5-anhydroglucitol; insulin-related markers including insulin, C-peptide, and the homeostasis model assessment of insulin resistance; and adipocytokines including adiponectin and leptin were determined. The association of PFAA and other metabolic profiles were analyzed, and stratified analyses of the PFAAs and clinical characteristics were performed according to the fasting plasma insulin and HbA1c levels. In addition, the PFAA indices that correlate to visceral fat obesity were evaluated.Results:Although strong correlations between PFAAs and glucose-related markers were not observed, several amino acids (branched-chain amino acids, tryptophan, alanine, tyrosine, glutamate and proline) and PFAA indices that evaluate visceral obesity were highly correlated with insulin-related markers and adiponectin (P<0.001). In the group of diabetic patients with hyperinsulinemia, the amino acid levels were significantly increased, which generally demonstrated good concordance with insulin-related markers and adiponectin levels.Conclusions:The PFAA profiles in diabetic patients were strongly associated with hyperinsulinemia and hypoadiponectinemia, which might become risk evaluation factors for the development of cardiovascular diseases.
Highlights
Several recent reports showed that the plasma-free amino acid (PFAA) profiles are altered before the development of type 2 diabetes or cardiovascular events
We demonstrated a variety of PFAA profiles in type 2 diabetic patients and reported that the PFAA profiles and amino acid indices evaluating visceral obesity showed good correlations with insulin-related variables and adiponectin concentrations
In the network analysis with type 2 diabetic patients (Figure 1), the hierarchical cluster revealed that insulin-related variables such as plasma insulin, C-peptide and homeostasis model assessment of insulin resistance (HOMA-IR) were categorized into a group that was different from that of glucose-related variables such as fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), GA and 1,5-AG
Summary
Several recent reports showed that the plasma-free amino acid (PFAA) profiles are altered before the development of type 2 diabetes or cardiovascular events. Because hyperinsulinemia and the development of type 2 diabetes are strongly associated with visceral obesity, diabetic patients are expected to show different plasma amino acid patterns and a higher value of this index. The plasma concentrations of some amino acids have been reported to be altered in diabetic patients compared with those of healthy individuals,[4] the relationships between PFAA concentrations and the index value or other biochemical markers such as glucose- and insulin-related variables, within subjects with type 2 diabetes, remain unclear. This finding is supported by extensive epidemiological data[8,9] linking lower adiponectin levels to disease states including type 2 diabetes, metabolic syndrome, hypertension, cardiovascular disease and cancer
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