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Variant of the lactase LCT gene explains association between milk intake and incident type 2 diabetes.

TitleVariant of the lactase LCT gene explains association between milk intake and incident type 2 diabetes.
Publication TypePublication
Year2024
AuthorsLuo K, Chen G-C, Zhang Y, Moon J-Y, Xing J, Peters BA, Usyk M, Wang Z, Hu G, Li J, Selvin E, Rebholz CM, Wang T, Isasi CR, Yu B, Knight R, Boerwinkle E, Burk RD, Kaplan RC, Qi Q
JournalNat Metab
Volume6
Issue1
Pagination169-186
Date Published2024 Jan
ISSN2522-5812
KeywordsAnimals, Cattle, Diabetes Mellitus, Type 2, diet, Female, Genotype, Humans, Lactase, Male, Milk
Abstract

Cow's milk is frequently included in the human diet, but the relationship between milk intake and type 2 diabetes (T2D) remains controversial. Here, using data from the Hispanic Community Health Study/Study of Latinos, we show that in both sexes, higher milk intake is associated with lower risk of T2D in lactase non-persistent (LNP) individuals (determined by a variant of the lactase LCT gene, single nucleotide polymorphism rs4988235 ) but not in lactase persistent individuals. We validate this finding in the UK Biobank. Further analyses reveal that among LNP individuals, higher milk intake is associated with alterations in gut microbiota (for example, enriched Bifidobacterium and reduced Prevotella) and circulating metabolites (for example, increased indolepropionate and reduced branched-chain amino acid metabolites). Many of these metabolites are related to the identified milk-associated bacteria and partially mediate the association between milk intake and T2D in LNP individuals. Our study demonstrates a protective association between milk intake and T2D among LNP individuals and a potential involvement of gut microbiota and blood metabolites in this association.

DOI10.1038/s42255-023-00961-1
Alternate JournalNat Metab
PubMed ID38253929
PubMed Central IDPMC11097298
Grant ListR01 DK132011 / DK / NIDDK NIH HHS / United States
U54 GM104940 / GM / NIGMS NIH HHS / United States
MS#: 
1127
Manuscript Lead/Corresponding Author Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
ECI: 
Manuscript Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
Manuscript Status: 
Published