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

Kai Luo, Guo Chong Chen, Yanbo Zhang, Jee Young Moon, Jiaqian Xing, Brandilyn A. Peters, Mykhaylo Usyk, Zheng Wang, Gang Hu, Jun Li, Elizabeth Selvin, Casey M. Rebholz, Tao Wang, Carmen R. Isasi, Bing Yu, Rob Knight, Eric Boerwinkle, Robert D. Burk, Robert C. Kaplan, Qibin Qi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)169-186
Number of pages18
JournalNature Metabolism
Volume6
Issue number1
DOIs
StatePublished - Jan 2024

ASJC Scopus subject areas

  • Physiology (medical)
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology

Fingerprint

Dive into the research topics of 'Variant of the lactase LCT gene explains association between milk intake and incident type 2 diabetes'. Together they form a unique fingerprint.

Cite this