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Circulating metabolites associate with and improve the prediction of all-cause mortality in type 2 diabetesScarale, Maria Giovanna ...Death rate is increased in type 2 diabetes. Unraveling biomarkers of novel pathogenic pathways capable to identify high-risk patients is instrumental to tackle this burden. We investigated the ... association between serum metabolites and all-cause mortality in type 2 diabetes and then whether the associated metabolites mediate the effect of inflammation on mortality risk and improve ENFORCE (EstimatioN oF mORtality risk in type2 diabetic patiEnts) and RECODe (Risk Equation for Complications Of type 2 Diabetes), two well-established all-cause mortality prediction models in diabetes. Two cohorts comprising 856 individuals (279 all-cause deaths) were analyzed. Serum metabolites (n = 188) and pro- and anti-inflammatory cytokines (n = 7) were measured. In the pooled analysis, hexanoylcarnitine, kynurenine, and tryptophan were significantly and independently associated with mortality (hazard ratio [HR] 1.60 [95% CI 1.43-1.80]; 1.53 [1.37-1.71]; and 0.71 [0.62-0.80] per 1 SD). The kynurenine-to-tryptophan ratio (KTR), a proxy of indoleamine-2,3-dioxygenase, which degrades tryptophan to kynurenine and contributes to a proinflammatory status, mediated 42% of the significant association between the antiatherogenic interleukin (IL) 13 and mortality. Adding the three metabolites improved discrimination and reclassification (all P < 0.01) of both mortality prediction models. In type 2 diabetes, hexanoylcarnitine, tryptophan, and kynurenine are associated to and improve the prediction of all-cause mortality. Further studies are needed to investigate whether interventions aimed at reducing KTR also reduce the risk of death, especially in patients with low IL-13.Source: Diabetes. - ISSN 0012-1797 (Vol. 71, iss. 6, 2022, str. 1363-1370)Type of material - article, component part ; adult, seriousPublish date - 2022Language - englishCOBISS.SI-ID - 138163459
Author
Scarale, Maria Giovanna |
Mastroianno, Mario |
Prehn, Cornelia |
Copetti, Massimiliano |
Salvemini, Lucia |
Adamski, Jerzy, molekularna biologija |
De Cosmo, Salvatore |
Trischitta, Vincenzo |
Menzaghi, Claudia
Topics
type 2 diabetes |
death rate |
metabolites |
sladkorna boleznen tip 2 |
stopnja umrljivosti |
metaboliti
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Scarale, Maria Giovanna | ![]() |
Mastroianno, Mario | ![]() |
Prehn, Cornelia | ![]() |
Copetti, Massimiliano | ![]() |
Salvemini, Lucia | ![]() |
Adamski, Jerzy, molekularna biologija | 55378 |
De Cosmo, Salvatore | ![]() |
Trischitta, Vincenzo | ![]() |
Menzaghi, Claudia | ![]() |
Source: Personal bibliographies
and: SICRIS
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