Circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration

Abstract A substantial number of subjects with Type 1 Diabetes (T1D) of long duration never develop albuminuria or renal function impairment, yet the underlying protective mechanisms remain unknown. Therefore, our study included 308 Joslin Kidney Study subjects who had T1D of long duration (median:...

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Autores principales:	Salina Moon, John J. Tsay, Heather Lampert, Zaipul I. Md Dom, Aleksandar D. Kostic, Adam Smiles, Monika A. Niewczas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7623be6c5615427c8d8ec936964eba27
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spelling	oai:doaj.org-article:7623be6c5615427c8d8ec936964eba272021-12-02T17:32:57ZCirculating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration10.1038/s41598-021-87585-12045-2322https://doaj.org/article/7623be6c5615427c8d8ec936964eba272021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87585-1https://doaj.org/toc/2045-2322Abstract A substantial number of subjects with Type 1 Diabetes (T1D) of long duration never develop albuminuria or renal function impairment, yet the underlying protective mechanisms remain unknown. Therefore, our study included 308 Joslin Kidney Study subjects who had T1D of long duration (median: 24 years), maintained normal renal function and had either normoalbuminuria or a broad range of albuminuria within the 2 years preceding the metabolomic determinations. Serum samples were subjected to global metabolomic profiling. 352 metabolites were detected in at least 80% of the study population. In the logistic analyses adjusted for multiple testing (Bonferroni corrected α = 0.000028), we identified 38 metabolites associated with persistent normoalbuminuria independently from clinical covariates. Protective metabolites were enriched in Medium Chain Fatty Acids (MCFAs) and in Short Chain Fatty Acids (SCFAs) and particularly involved odd-numbered and dicarboxylate Fatty Acids. One quartile change of nonanoate, the top protective MCFA, was associated with high odds of having persistent normoalbuminuria (OR (95% CI) 0.14 (0.09, 0.23); p < 10–12). Multivariable Random Forest analysis concordantly indicated to MCFAs as effective classifiers. Associations of the relevant Fatty Acids with albuminuria seemed to parallel associations with tubular biomarkers. Our findings suggest that MCFAs and SCFAs contribute to the metabolic processes underlying protection against albuminuria development in T1D that are independent from mechanisms associated with changes in renal function.Salina MoonJohn J. TsayHeather LampertZaipul I. Md DomAleksandar D. KosticAdam SmilesMonika A. NiewczasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Salina Moon John J. Tsay Heather Lampert Zaipul I. Md Dom Aleksandar D. Kostic Adam Smiles Monika A. Niewczas Circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration
description	Abstract A substantial number of subjects with Type 1 Diabetes (T1D) of long duration never develop albuminuria or renal function impairment, yet the underlying protective mechanisms remain unknown. Therefore, our study included 308 Joslin Kidney Study subjects who had T1D of long duration (median: 24 years), maintained normal renal function and had either normoalbuminuria or a broad range of albuminuria within the 2 years preceding the metabolomic determinations. Serum samples were subjected to global metabolomic profiling. 352 metabolites were detected in at least 80% of the study population. In the logistic analyses adjusted for multiple testing (Bonferroni corrected α = 0.000028), we identified 38 metabolites associated with persistent normoalbuminuria independently from clinical covariates. Protective metabolites were enriched in Medium Chain Fatty Acids (MCFAs) and in Short Chain Fatty Acids (SCFAs) and particularly involved odd-numbered and dicarboxylate Fatty Acids. One quartile change of nonanoate, the top protective MCFA, was associated with high odds of having persistent normoalbuminuria (OR (95% CI) 0.14 (0.09, 0.23); p < 10–12). Multivariable Random Forest analysis concordantly indicated to MCFAs as effective classifiers. Associations of the relevant Fatty Acids with albuminuria seemed to parallel associations with tubular biomarkers. Our findings suggest that MCFAs and SCFAs contribute to the metabolic processes underlying protection against albuminuria development in T1D that are independent from mechanisms associated with changes in renal function.
format	article
author	Salina Moon John J. Tsay Heather Lampert Zaipul I. Md Dom Aleksandar D. Kostic Adam Smiles Monika A. Niewczas
author_facet	Salina Moon John J. Tsay Heather Lampert Zaipul I. Md Dom Aleksandar D. Kostic Adam Smiles Monika A. Niewczas
author_sort	Salina Moon
title	Circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration
title_short	Circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration
title_full	Circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration
title_fullStr	Circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration
title_full_unstemmed	Circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration
title_sort	circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7623be6c5615427c8d8ec936964eba27
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Circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration

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