Nine Amino Acids Are Associated With Decreased Insulin Secretion and Elevated Glucose Levels in a 7.4-Year Follow-up Study of 5,181 Finnish Men

Abstract

Several amino acids (AAs) have been shown to be associated with insulin resistance and increased risk of type 2 diabetes, but no previous studies have investigated the association of AAs with insulin secretion in a longitudinal setting. Our study included 5,181 participants of the cross-sectional METabolic Syndrome In Men (METSIM) study having metabolomics data on 20 AAs. A total of 4,851 had a 7.4-year follow-up visit. Nine AAs (phenylalanine, tryptophan, tyrosine, alanine, isoleucine, leucine, valine, aspartate, and glutamate) were significantly (P < 5.8 3 10 25) associated with decreases in insulin secretion (disposition index) and the elevation of fasting or 2-h glucose levels. Five of these AAs (tyrosine, alanine, isoleucine, aspartate, and glutamate) were also found to be significantly associated with an increased risk of incident type 2 diabetes after adjustment for confounding factors. Our study is the first population-based large cohort to report that AAs are associated not only with insulin resistance but also with decreased insulin secretion.

Altered Metabolome of Lipids and Amino Acids Species: A Source of Early Signature Biomarkers of T2DM

“…The four metabolites i.e., phenylalanine, alanine, palmitoylcarnitine and tyrosine were found consistently associated with the risk of T2DM. Another aliphatic AA called alanine is a hepatic substrate and stimulator for gluconeogenesis and glucagon secretion and its circulating amount was also found to be a predictive metabolite of T2DM risk in many cross-sectional and prospective studies [4,27]. Elevated levels of alanine have already been found to have a positive association with T2DM in Finland, UK, and South Asia populations, as stated above.…”

“…Moreover, the evident relationship of phenylalanine and tyrosine with the risk of T2DM was also significant due to an increase in insulin resistance through blocking the transport/phosphorylation of glucose. In the case of tyrosine, it is a far more powerful indicator of T2DM risk in South Asians [27]. The population-based KORA (Cooperative Health Research in the Region of Augsburg) and European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort study identified five baseline metabolites out of 131 (using pairwise comparison, multivariate (logistic) regression analyses followed by non-parametric random forest and the stepwise parametric regression) specifically associated with the pre-diabetic conditions to examine their ability to forecast the pre-diabetic conditions earlier [4].…”

Metabolomic Profiles Associated with BMI, Waist Circumference, and Diabetes and Inflammation Biomarkers in Women

“…The other metabolites associated with the biomarkers included some that had been previously reported. Phenylalanine, which was associated with c‐peptide, was previously associated with insulin secretion and resistance . γ‐Glutamylglycine, which is the lead metabolite for a cluster that includes glycine, was inversely associated with both BMI and WC as well as CRP.…”

L‐serine: a neglected amino acid with a potential therapeutic role in diabetes

“…A recent study looking at amino acid concentration in 5181 non‐diabetic men aged between 45 and 73 years from the Finnish town Kuopio in relation with the development of type 2 diabetes found that a high L‐serine concentration is correlated to improved insulin secretion and sensitivity . L‐Serine is also associated with an improved glucose tolerance after a 2‐h oral glucose tolerance test, although no correlation was found to the development of type 2 diabetes.…”