New Research Points to Lactate-Related Genes in Type 1 Diabetes Development

Lactate is a molecule produced during cellular metabolism that plays roles in how our cells function and how our immune system responds. A chemical process called lactylation—where lactate attaches to proteins—influences both metabolic and immune processes in the body. Scientists have suspected that problems with lactate metabolism may be involved in Type 1 diabetes, but the genetic basis for this connection wasn't well understood until now.

An international team used a genetic research method called Mendelian randomization to examine whether inherited variations in 353 lactate-related genes were associated with Type 1 diabetes. This approach analyzes genetic data from large groups of people—in this case, 7,467 individuals with Type 1 diabetes and 10,218 without—to identify genetic signals that point toward disease risk.

The analysis focused on three types of genetic information: DNA methylation patterns (chemical tags on DNA that affect gene activity), gene expression levels (how active genes are), and protein levels. By examining these different layers of genetic information, the researchers could trace how inherited variations might influence diabetes risk.

The study identified three genes—PDAP1, PNKD, and HMGB1—as candidates linked to Type 1 diabetes through lactate-related processes. These genes showed associations at multiple levels: DNA methylation patterns, gene expression, and protein function.

For example, specific methylation patterns in PDAP1 were associated with higher diabetes risk, while certain methylation changes in PNKD and HMGB1 were associated with lower risk. At the gene expression level, higher activity of PDAP1 and HMGB1 was associated with reduced risk. These patterns suggest that how active or inactive these genes are may influence whether someone develops Type 1 diabetes.

The researchers validated their findings in two separate population databases (FinnGen cohorts), which strengthens confidence in the results. However, these findings represent an important first step. Genetic associations point toward potential biological mechanisms but don't prove that these genes directly cause Type 1 diabetes.

Much additional research will be needed to understand exactly how PDAP1, PNKD, and HMGB1 influence diabetes development, and whether targeting these genes could eventually lead to new prevention or treatment approaches. This work adds to the growing body of evidence that lactate metabolism and immune function are connected in Type 1 diabetes.

Source: Journal of diabetes research. Evidence type: PubMed indexed literature. Type1Cure is an information and intelligence hub, not a medical advice service. This article summarizes published research and does not provide diagnosis, treatment, or personal medical guidance. Always talk to your own care team before changing anything about your Type 1 diabetes management.