Amino acid signature predictive of incident prediabetes

A case-control study nested within the longitudinal pathobiology of prediabetes in a biracial cohort

Ibiye Owei, Nkiru Umekwe, Frankie Stentz, Jim Wan, Samuel Dagogo-Jack

Research output: Contribution to journalArticle

Abstract

Objective: Circulating branched-chain amino acids (BCAAs, isoleucine, leucine, valine) and aromatic amino acids (AAAs, tyrosine and phenylalanine) predicted type 2 diabetes mellitus (T2DM) risk in a Caucasian population. Here, we assessed amino acid levels in relation to incident prediabetes among initially normoglycemic African Americans (AA) and European Americans (EA). Research design and methods: Using a nested case-control design, we studied 70 adults (35 AA, 35 EA) who developed prediabetes (progressors) and 70 matched participants who maintained normoglycemia (nonprogressors) during 5.5 years of follow-up in the Pathobiology of Prediabetes in a Biracial Cohort study. Assessments included plasma amino acid levels, insulin sensitivity, and beta-cell function. Results: The total level of all 18 amino acid assayed was significantly associated with lean mass (r = 0.36, P < 0.0001), waist circumference (r = 0.27, P = 0.001), fasting plasma glucose (r = 0.24, P = 0.005), HOMA-IR (r = 0.22, P = 0.01) and HDL cholesterol (r = −0.18, P = 0.03). Individual amino acid levels were significantly associated with insulin sensitivity and insulin secretion. Compared with nonprogressors, progressors had higher baseline levels of asparagine and aspartic acid (P <0.0001), glutamine/glutamic acid (P = 0.005) and phenylalanine (P = 0.02), and lower histidine (P = 0.02) levels. In fully-adjusted logistic regression models, aspartic acid/asparagine (OR 2.72 [95% CI 1.91–3.87]) and histidine (OR 0.90 [95% CI 0.85–0.96]) were the only amino acids that significantly predicted incident prediabetes. Conclusions: Baseline plasma aspartic acid and asparagine levels predicted progression to prediabetes, whereas histidine levels were protective of prediabetes risk. Thus, the amino acid signature associated with prediabetes in a diverse population may be distinct from that previously linked to T2DM in Caucasians.

Original languageEnglish (US)
Pages (from-to)76-83
Number of pages8
JournalMetabolism: clinical and experimental
Volume98
DOIs
StatePublished - Sep 1 2019

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Prediabetic State
Glucose Intolerance
Asparagine
Histidine
Aspartic Acid
Insulin Resistance
Case-Control Studies
Amino Acids
Phenylalanine
African Americans
Type 2 Diabetes Mellitus
Logistic Models
Branched Chain Amino Acids
Aromatic Amino Acids
Isoleucine
Valine
Waist Circumference
Glutamine
Leucine
HDL Cholesterol

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

@article{1df55431deaf44e3a64ceea9033c1726,
title = "Amino acid signature predictive of incident prediabetes: A case-control study nested within the longitudinal pathobiology of prediabetes in a biracial cohort",
abstract = "Objective: Circulating branched-chain amino acids (BCAAs, isoleucine, leucine, valine) and aromatic amino acids (AAAs, tyrosine and phenylalanine) predicted type 2 diabetes mellitus (T2DM) risk in a Caucasian population. Here, we assessed amino acid levels in relation to incident prediabetes among initially normoglycemic African Americans (AA) and European Americans (EA). Research design and methods: Using a nested case-control design, we studied 70 adults (35 AA, 35 EA) who developed prediabetes (progressors) and 70 matched participants who maintained normoglycemia (nonprogressors) during 5.5 years of follow-up in the Pathobiology of Prediabetes in a Biracial Cohort study. Assessments included plasma amino acid levels, insulin sensitivity, and beta-cell function. Results: The total level of all 18 amino acid assayed was significantly associated with lean mass (r = 0.36, P < 0.0001), waist circumference (r = 0.27, P = 0.001), fasting plasma glucose (r = 0.24, P = 0.005), HOMA-IR (r = 0.22, P = 0.01) and HDL cholesterol (r = −0.18, P = 0.03). Individual amino acid levels were significantly associated with insulin sensitivity and insulin secretion. Compared with nonprogressors, progressors had higher baseline levels of asparagine and aspartic acid (P <0.0001), glutamine/glutamic acid (P = 0.005) and phenylalanine (P = 0.02), and lower histidine (P = 0.02) levels. In fully-adjusted logistic regression models, aspartic acid/asparagine (OR 2.72 [95{\%} CI 1.91–3.87]) and histidine (OR 0.90 [95{\%} CI 0.85–0.96]) were the only amino acids that significantly predicted incident prediabetes. Conclusions: Baseline plasma aspartic acid and asparagine levels predicted progression to prediabetes, whereas histidine levels were protective of prediabetes risk. Thus, the amino acid signature associated with prediabetes in a diverse population may be distinct from that previously linked to T2DM in Caucasians.",
author = "Ibiye Owei and Nkiru Umekwe and Frankie Stentz and Jim Wan and Samuel Dagogo-Jack",
year = "2019",
month = "9",
day = "1",
doi = "10.1016/j.metabol.2019.06.011",
language = "English (US)",
volume = "98",
pages = "76--83",
journal = "Metabolism: Clinical and Experimental",
issn = "0026-0495",
publisher = "W.B. Saunders Ltd",

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TY - JOUR

T1 - Amino acid signature predictive of incident prediabetes

T2 - A case-control study nested within the longitudinal pathobiology of prediabetes in a biracial cohort

AU - Owei, Ibiye

AU - Umekwe, Nkiru

AU - Stentz, Frankie

AU - Wan, Jim

AU - Dagogo-Jack, Samuel

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Objective: Circulating branched-chain amino acids (BCAAs, isoleucine, leucine, valine) and aromatic amino acids (AAAs, tyrosine and phenylalanine) predicted type 2 diabetes mellitus (T2DM) risk in a Caucasian population. Here, we assessed amino acid levels in relation to incident prediabetes among initially normoglycemic African Americans (AA) and European Americans (EA). Research design and methods: Using a nested case-control design, we studied 70 adults (35 AA, 35 EA) who developed prediabetes (progressors) and 70 matched participants who maintained normoglycemia (nonprogressors) during 5.5 years of follow-up in the Pathobiology of Prediabetes in a Biracial Cohort study. Assessments included plasma amino acid levels, insulin sensitivity, and beta-cell function. Results: The total level of all 18 amino acid assayed was significantly associated with lean mass (r = 0.36, P < 0.0001), waist circumference (r = 0.27, P = 0.001), fasting plasma glucose (r = 0.24, P = 0.005), HOMA-IR (r = 0.22, P = 0.01) and HDL cholesterol (r = −0.18, P = 0.03). Individual amino acid levels were significantly associated with insulin sensitivity and insulin secretion. Compared with nonprogressors, progressors had higher baseline levels of asparagine and aspartic acid (P <0.0001), glutamine/glutamic acid (P = 0.005) and phenylalanine (P = 0.02), and lower histidine (P = 0.02) levels. In fully-adjusted logistic regression models, aspartic acid/asparagine (OR 2.72 [95% CI 1.91–3.87]) and histidine (OR 0.90 [95% CI 0.85–0.96]) were the only amino acids that significantly predicted incident prediabetes. Conclusions: Baseline plasma aspartic acid and asparagine levels predicted progression to prediabetes, whereas histidine levels were protective of prediabetes risk. Thus, the amino acid signature associated with prediabetes in a diverse population may be distinct from that previously linked to T2DM in Caucasians.

AB - Objective: Circulating branched-chain amino acids (BCAAs, isoleucine, leucine, valine) and aromatic amino acids (AAAs, tyrosine and phenylalanine) predicted type 2 diabetes mellitus (T2DM) risk in a Caucasian population. Here, we assessed amino acid levels in relation to incident prediabetes among initially normoglycemic African Americans (AA) and European Americans (EA). Research design and methods: Using a nested case-control design, we studied 70 adults (35 AA, 35 EA) who developed prediabetes (progressors) and 70 matched participants who maintained normoglycemia (nonprogressors) during 5.5 years of follow-up in the Pathobiology of Prediabetes in a Biracial Cohort study. Assessments included plasma amino acid levels, insulin sensitivity, and beta-cell function. Results: The total level of all 18 amino acid assayed was significantly associated with lean mass (r = 0.36, P < 0.0001), waist circumference (r = 0.27, P = 0.001), fasting plasma glucose (r = 0.24, P = 0.005), HOMA-IR (r = 0.22, P = 0.01) and HDL cholesterol (r = −0.18, P = 0.03). Individual amino acid levels were significantly associated with insulin sensitivity and insulin secretion. Compared with nonprogressors, progressors had higher baseline levels of asparagine and aspartic acid (P <0.0001), glutamine/glutamic acid (P = 0.005) and phenylalanine (P = 0.02), and lower histidine (P = 0.02) levels. In fully-adjusted logistic regression models, aspartic acid/asparagine (OR 2.72 [95% CI 1.91–3.87]) and histidine (OR 0.90 [95% CI 0.85–0.96]) were the only amino acids that significantly predicted incident prediabetes. Conclusions: Baseline plasma aspartic acid and asparagine levels predicted progression to prediabetes, whereas histidine levels were protective of prediabetes risk. Thus, the amino acid signature associated with prediabetes in a diverse population may be distinct from that previously linked to T2DM in Caucasians.

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