Altered Plasma Amino Acids and Lipids Associated with Abnormal Glucose Metabolism and Insulin Resistance in Older Adults

Richard David Semba, Marta Gonzalez-Freire, Ruin Moaddel, Kai Sun, Elisa Fabbri, Pingbo Zhang, Olga D. Carlson, Mohammed Khadeer, Chee W. Chia, Norman Salem, Luigi Ferrucci

Research output: Contribution to journalArticle

Abstract

Context and Objectives: Glucose metabolism becomes progressively impaired with older age. Fasting glucose and insulin resistance are risk factors for premature death and other adverse outcomes. We aimed to identifying plasma metabolites associated with altered glucose metabolism and insulin resistance in older community-dwelling adults. Participants and Methods: A targeted metabolomics approach was used to identify plasma metabolites associated with impaired fasting plasma glucose, 2-hour plasma glucose on oral glucose tolerance testing, and homeostatic model assessment insulin resistance (HOMA-IR) in 472 participants who participated in the Baltimore Longitudinal Study of Aging, with a mean (SD) age of 70.7 (9.9) years. Results: We measured 143 plasma metabolites. In ordinal logistic regression analyses, using a false discovery rate of 5% and adjusting for potential confounders, we found that alanine, glutamic acid, and proline were significantly associated with increased odds of abnormal fasting plasma glucose. Phosphatidylcholine (diacyl C34:4, alkyl-acyl C32:1, C32:2, C34:2, C34:3, and C36:3) was associated with decreased odds of abnormal fasting plasma glucose. Glutamic and acid phosphatidylcholine alkyl-acyl C34:2 were associated with increased and decreased odds of 2-hour plasma glucose, respectively. Glutamic acid was associated with increased odds of higher tertiles of HOMA-IR. Glycine; phosphatidylcholine (diacyl C32:0, alkyl-acyl C32:1, C32:2, C34:1, C34:2, C34:3, C36:2, C36:3, C40:5, C40:6, C42:3, C42:4, and C42:5); sphingomyelin C16:0, C24:1, and C26:1; and lysophosphatidylcholine C18:1 were associated with decreased odds of abnormal HOMA-IR. Conclusions: Targeted metabolomics identified four plasma amino acids and 16 plasma lipid species, primarily containing polyunsaturated fatty acids, that were associated with abnormal glucose metabolism and insulin resistance in older adults.

Original languageEnglish (US)
Pages (from-to)3331-3339
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number9
DOIs
StatePublished - Sep 1 2018

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Semba, R. D., Gonzalez-Freire, M., Moaddel, R., Sun, K., Fabbri, E., Zhang, P., Carlson, O. D., Khadeer, M., Chia, C. W., Salem, N., & Ferrucci, L. (2018). Altered Plasma Amino Acids and Lipids Associated with Abnormal Glucose Metabolism and Insulin Resistance in Older Adults. Journal of Clinical Endocrinology and Metabolism, 103(9), 3331-3339. https://doi.org/10.1210/jc.2018-00480