Plasma Free Amino Acid Profiles Predict Four-Year Risk of Developing Diabetes, Metabolic Syndrome, Dyslipidemia, and Hypertension in Japanese Population

Abstract

Plasma free amino acid (PFAA) profile is highlighted in its association with visceral obesity and hyperinsulinemia, and future diabetes. Indeed PFAA profiling potentially can evaluate individuals' future risks of developing lifestyle-related diseases, in addition to diabetes. However, few studies have been performed especially in Asian populations, about the optimal combination of PFAAs for evaluating health risks. We quantified PFAA levels in 3,701 Japanese subjects, and determined visceral fat area (VFA) and two-hour post-challenge insulin (Ins120 min) values in 865 and 1,160 subjects, respectively. Then, models between PFAA levels and the VFA or Ins120 min values were constructed by multiple linear regression analysis with variable selection. Finally, a cohort study of 2,984 subjects to examine capabilities of the obtained models for predicting four-year risk of developing new-onset lifestyle-related diseases was conducted. The correlation coefficients of the obtained PFAA models against VFA or Ins120 min were higher than single PFAA level. Our models work well for future risk prediction. Even after adjusting for commonly accepted multiple risk factors, these models can predict future development of diabetes, metabolic syndrome, and dyslipidemia. PFAA profiles confer independent and differing contributions to increasing the lifestyle-related disease risks in addition to the currently known factors in a general Japanese population.

Figure 1. Correlation clustering using PFAA profiles and metabolic variables.

Pearson’s correlation coefficients were calculated, and hierarchical clustering was conducted. HbA1c: Hemoglobin A1c, FPG: Fasting plasma glucose, Glc120 min: Plasma glucose level 2-h after OGTT, Ins120 min: Serum insulin level 2-h after OGTT, HOMA-IR: Homeostasis model assessment of insulin resistance, VFA: Visceral fat area by computed tomography, BMI: Body mass index, TG: Triglyceride, GPT: Alanine aminotransferase, DBP: Diastolic blood pressure, SBP: Systolic blood pressure, GOT: Aspartate aminotransferase, γ-GTP: gamma-Glutamyl transpeptidase, Alb: Albumin, TP: Total protein, T-Bil: Total bilirubin, LDL-CHO: LDL cholesterol, CRP: C-reactive protein, ALP: Alkaline phosphatase, GA: Glycoalbumin, Amy: Amylase, LDH: Lactate dehydrogenase, T-CHO: Total cholesterol, 1,5-AG: 1,5-anhydro-D-glucitol, HDL-CHO: HDL cholesterol.

Figure 2. A schematic workflow of the study.

The PFAA indices were generated by the subjects with VFA data or with Ins120 min data. The number of subjects (male, female) used for the model construction and validation is shown. PFAA index: the index generated by plasma free amino acid (PFAA) profiles, VFA: Visceral fat area by computed tomography, Ins120 min: Serum insulin level 2-h after OGTT, LOOCV: leave-one-out cross-validation.