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Response of circulating metabolites to an oral glucose challenge and risk of cardiovascular disease and mortality in the community

Gonzalez Izundegui, Daniel ; Miller, Patricia E ; Shah, Ravi V ; Clish, Clary B ; Walker, Maura E ; Mitchell, Gary F ; Gerszten, Robert E ; Larson, Martin G ; Vasan, Ramachandran S ; Nayor, Matthew

Cardiovascular Diabetology, 2022-10, Vol.21 (1), p.213-213, Article 213 [Periódico revisado por pares]

England: BioMed Central Ltd

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Título:
Response of circulating metabolites to an oral glucose challenge and risk of cardiovascular disease and mortality in the community
Autor: Gonzalez Izundegui, Daniel ; Miller, Patricia E ; Shah, Ravi V ; Clish, Clary B ; Walker, Maura E ; Mitchell, Gary F ; Gerszten, Robert E ; Larson, Martin G ; Vasan, Ramachandran S ; Nayor, Matthew
Assuntos: Adipose tissue ; Age ; Arginine ; Biomarkers ; Blood pressure ; Body fat ; Body mass index ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - etiology ; Cholesterol ; Cholesterol, HDL ; Chromatography ; Coronary vessels ; Cross-Sectional Studies ; Deoxycholic Acid ; Dextrose ; Diabetes ; Diabetes mellitus ; Female ; Glucose ; Glucose tolerance ; Glucose tolerance tests ; Glucuronates ; Glutamate ; Glutamates ; Health aspects ; High density lipoprotein ; Humans ; Hypertension ; Inosine ; Insulin ; Insulin resistance ; Ketoglutaric acid ; Ketoglutaric Acids ; Lecithin ; Lysophosphatidylcholine ; Lysophosphatidylcholines ; Male ; Metabolism ; Metabolites ; Metabolomics ; Mortality ; Phenotypes ; Phosphatidylcholine ; Phosphatidylcholines ; Physiology ; Prevention ; Regression analysis ; Risk Factors ; Therapeutic targets ; Triglycerides ; Veins & arteries
É parte de: Cardiovascular Diabetology, 2022-10, Vol.21 (1), p.213-213, Article 213
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Descrição: New biomarkers to identify cardiovascular disease (CVD) risk earlier in its course are needed to enable targeted approaches for primordial prevention. We evaluated whether intraindividual changes in blood metabolites in response to an oral glucose tolerance test (OGTT) may provide incremental information regarding the risk of future CVD and mortality in the community. An OGTT (75 g glucose) was administered to a subsample of Framingham Heart Study participants free from diabetes (n = 361). Profiling of 211 plasma metabolites was performed from blood samples drawn before and 2 h after OGTT. The log2(post/pre) metabolite levels (Δmetabolites) were related to incident CVD and mortality in Cox regression models adjusted for age, sex, baseline metabolite level, systolic blood pressure, hypertension treatment, body mass index, smoking, and total/high-density lipoprotein cholesterol. Select metabolites were related to subclinical cardiometabolic phenotypes using Spearman correlations adjusted for age, sex, and fasting metabolite level. Our sample included 42% women, with a mean age of 56 ± 9 years and a body mass index of 30.2 ± 5.3 kg/m . The pre- to post-OGTT changes (Δmetabolite) were non-zero for 168 metabolites (at FDR ≤ 5%). A total of 132 CVD events and 144 deaths occurred during median follow-up of 24.9 years. In Cox models adjusted for clinical risk factors, four Δmetabolites were associated with incident CVD (higher glutamate and deoxycholate, lower inosine and lysophosphatidylcholine 18:2) and six Δmetabolites (higher hydroxyphenylacetate, triacylglycerol 56:5, alpha-ketogluturate, and lower phosphatidylcholine 32:0, glucuronate, N-monomethyl-arginine) were associated with death (P < 0.05). Notably, baseline metabolite levels were not associated with either outcome in models excluding Δmetabolites. The Δmetabolites exhibited varying cross-sectional correlation with subclinical risk factors such as visceral adiposity, insulin resistance, and vascular stiffness, but overall relations were modest. Significant Δmetabolites included those with established roles in cardiometabolic disease (e.g., glutamate, alpha-ketoglutarate) and metabolites with less defined roles (e.g., glucuronate, lipid species). Dynamic changes in metabolite levels with an OGTT are associated with incident CVD and mortality and have potential relevance for identifying CVD risk earlier in its development and for discovering new potential therapeutic targets.
Editor: England: BioMed Central Ltd
Idioma: Inglês

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Response of circulating metabolites to an oral glucose challenge and risk of cardiovascular disease and mortality in the community

Gonzalez Izundegui, Daniel ; Miller, Patricia E ; Shah, Ravi V ; Clish, Clary B ; Walker, Maura E ; Mitchell, Gary F ; Gerszten, Robert E ; Larson, Martin G ; Vasan, Ramachandran S ; Nayor, Matthew

England: BioMed Central Ltd

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