Metabolomics Identifies Distinctive Metabolite Signatures for Measures of Glucose Homeostasis: The Insulin Resistance Atherosclerosis Family Study (IRAS-FS).

Metabolomics Identifies Distinctive Metabolite Signatures for Measures of Glucose Homeostasis: The Insulin Resistance Atherosclerosis Family Study (IRAS-FS).

J Clin Endocrinol Metab. 2018 Mar 13;:

Authors: Palmer ND, Okut H, Hsu FC, Ng MCY, Ida Chen YD, Goodarzi MO, Taylor KD, Norris JM, Lorenzo C, Rotter JI, Bergman RN, Langefeld CD, Wagenknecht LE, Bowden DW

Abstract
Context: Metabolomics provides a biochemical fingerprint which, when coupled with clinical phenotypes, can provide insight into physiological processes and disease.
Objective: Survey metabolites associated with dynamic and basal measures of glucose homeostasis.
Design: Analysis of 733 serum metabolites from the Insulin Resistance Atherosclerosis Family Study.
Setting: Community-based.
Participants: 1111 Mexican Americans.
Main Outcome: Dynamic measures were obtained from the intravenous glucose tolerance test (FSIGT) and included insulin sensitivity (SI) and acute insulin response (AIRg). Basal measures included homeostatic model assessment of insulin resistance (HOMAIR) and beta-cell function (HOMAB).
Results: SI was associated with 99 metabolites (P<6.82x10-5) explaining 28% of the variance (R2adj) beyond 28% by BMI. Beyond branched chain amino acids (BCAA; P=1.85x10-18-1.70x10-05, R2adj=8.1%) and phospholipids (P=3.51x10-17-3.00x10-05, R2adj=14%), novel signatures of long chain fatty acids (LCFAs; P=4.49x10-23-4.14x10-07, R2adj=11%) were observed. Conditional analysis suggested BCAA and LCFA signatures were independent. LCFAs were not associated with HOMAIR (P>0.024). AIRg was associated six metabolites; glucose had the strongest association (P=5.68x10-16). HOMAB had significant signatures from the urea cycle (P=9.64x10-14-7.27x10-06, R2adj=11%). Novel associations of poly unsaturated fatty acids (PUFA; P=2.58x10-13-6.70x10-05, R2adj=10%) and LCFA (P=9.06x10-15-3.93x10-07, R2adj=10%) were observed with glucose effectiveness (SG). Assessment of the hyperbolic relationship between insulin sensitivity and secretion through the disposition index (DI) revealed a distinctive signature of PUFA (P=1.55x10-12-5.81x10-06; R2adj=3.8%) beyond that of its component measures.
Conclusions: Metabolomics reveals distinct signatures which differentiate dynamic and basal measures of glucose homeostasis and further identifies new metabolite classes associated with dynamic measures providing expanded insight into the metabolic basis of insulin resistance. .

PMID: 29546329 [PubMed - as supplied by publisher]

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