Plasma Branched-Chain Amino Acids Are Associated With Greater Fasting and Postprandial Insulin Secretion in Non-diabetic Chinese Adults

Abstract

Background: Plasma branched-chain amino acids (BCAA) are consistently elevated in subjects with obesity and type 2 diabetes (T2DM) and correlate with insulin resistance. The association of BCAA with insulin secretion and clearance rates has not been adequately described. Objective: To evaluate the relationships between fasting and postprandial plasma BCAA, insulin secretion and insulin clearance. Design: Ninety-five non-diabetic Chinese subjects (43 females) underwent a mixed-meal tolerance test; blood biomarkers including BCAAs (leucine, isoleucine, valine) were measured for 6 h. Fasting and postprandial insulin secretion rates (ISR) and insulin clearance were determined by oral minimal modeling of glucose and C-peptide. Results: Fasting and postprandial plasma BCAA correlated strongly with each other (ρ = 0.796, P < 0.001), and both were positively associated with basal ISR (ρ = 0.45/0.36, P < 0.001), total postprandial ISR AUC (ρ = 0.37/0.45, P < 0.001), and negatively with insulin clearance (ρ = -0.29/-0.29, P < 0.01), after adjusting for sex and body mass index. These relationships largely persisted after adjusting further for insulin resistance and postprandial glucose. Compared with subjects in the middle and lowest tertiles for fasting or postprandial plasma BCAA, subjects in the highest tertile had significantly greater postprandial glucose (by 7-10%) and insulin (by 74-98%) concentrations, basal ISRs (by 34-53%), postprandial ISR AUCs (by 41-49%), and lower insulin clearance rates (by 17-22%) (all P < 0.05). Conclusions: Fasting and postprandial plasma BCAA levels are associated with greater fasting and postprandial insulin secretion and reduced insulin clearance in healthy Chinese subjects. These observations potentially highlight an additional layer of involvement of BCAA in the regulation of glucose homeostasis.

Keywords: BCAA; glucose homeostasis; insulin clearance; insulin metabolism; insulin resistance.

Figure 1

Time course of plasma leucine (A), isoleucine (B), valine (C) and total branched-chain amino acids (BCAA, D) after mixed meal ingestion. Data are mean ± SEM; n = 95.

Figure 2

Time courses and areas under the curve (AUC) of plasma glucose, insulin and C-peptide after ingestion of a mixed meal in subjects stratified in fasting branched-chain amino acid (BCAA) concentration tertiles. Glucose (A,B), insulin (C,D) and C-peptide (E,F) concentrations (linear mixed model) and AUCs (one-way ANOVA) after ingestion of a liquid mixed meal by fasting BCAA concentration tertiles. Data are mean ± SEM; n = 30–33 per group. All analyses have been adjusted for sex and BMI. Corresponding values are significantly different between groups (Šidák-corrected): **P < 0.01, ***P < 0.001.

Figure 3

Time courses and areas under the curve (AUC) of plasma glucose, insulin and C-peptide after ingestion of a mixed meal in subjects stratified in postprandial branched-chain amino acid (BCAA) AUC tertiles. Glucose (A,B), insulin (C,D) and C-peptide (E,F) concentrations (linear mixed model) and AUCs (one-way ANOVA) after ingestion of a liquid mixed meal by postprandial BCAA AUC tertiles. Data are mean ± SEM; n = 31–32 per group. All analyses have been adjusted for sex and BMI. Corresponding values are significantly different between groups (Šidák-corrected): *P < 0.01, **P < 0.05, ***P < 0.001.

Figure 4

Homeostasis Model Assessment of Insulin Resistance (HOMA-IR; A,B), basal insulin secretion rate (ISR; C,D), total postprandial ISR area under the curve (AUC; E,F) and insulin clearance (G,H) in relation to fasting BCAA concentration (left) and in subjects stratified to tertiles of fasting BCAA concentration (right). Data are mean ± SEM; n = 30–33 per group. Continuous analyses are depicted as partial correlation plots and differences among tertiles are determined by one-way ANOVA. All analyses have been adjusted for sex and BMI. Corresponding values are significantly different between groups (Šidák-corrected): *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 5

Homeostasis Model Assessment of Insulin Resistance (HOMA-IR; A,B), basal insulin secretion rate (ISR; C,D), total postprandial ISR area under the curve (AUC; E,F) and insulin clearance (G,H) in relation to postprandial BCAA AUC (left) and in subjects stratified to tertiles of postprandial BCAA AUC (right). Data are mean ± SEM; n = 31–32 per group. Continuous analyses are depicted as partial correlation plots and differences among tertiles are determined by one-way ANOVA. All analyses have been adjusted for sex and BMI. Corresponding values are significantly different between groups (Šidák-corrected): **P < 0.01, ***P < 0.001.