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). 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. 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. 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.