What Is LADA, and Why Are Scientists Studying Lactate and Gene Switches?

Latent autoimmune diabetes in adults (LADA) is sometimes called "type 1.5 diabetes" because it shares features of both type 1 and type 2 diabetes. Like type 1, LADA involves the immune system gradually attacking the body's insulin-producing beta cells. Like type 2, it develops slowly in adults rather than appearing suddenly in children.

People with LADA experience progressive loss of beta-cell function, which means their ability to produce insulin declines over time. How much insulin they eventually need varies from person to person, making LADA a heterogeneous disease that can look different in each patient.

For many years, scientists viewed lactate—a product of metabolism—as simply a waste product. Recent research has revealed a more complex role: lactate acts as a signaling molecule that can influence how genes are expressed in cells.

This gene regulation happens through a process called histone lactylation, where lactate molecules attach to proteins called histones. Histones are like the spools around which DNA winds; when molecules attach to them, they can turn genes on or off. Two specific histone marks have captured researchers' attention: H3K9la and H3K18la.

Scientists have proposed that elevated lactate and certain histone lactylation marks might influence whether beta cells remain functional or lose their specialized identity. Additionally, H3K18la—a histone mark found at active gene enhancers—may play a role in regulating immune genes that could contribute to the autoimmune attack on beta cells.

However, it is important to note that most of this evidence comes indirectly from studies of type 1 diabetes, general beta-cell biology, other autoimmune diseases, and cancer research. Direct evidence specific to LADA is still sparse.

While the lactate-histone lactylation pathway is biologically plausible—meaning it makes scientific sense as a mechanism—it remains unproven in LADA. The research community has identified gaps: there are few longitudinal studies following LADA patients over time, and cell-type-specific validation of these mechanisms in people with LADA is lacking.

Scientists emphasize that before any biomarkers could be developed or new treatments explored, LADA-specific evidence would be required. This means researchers need to test these theories directly in people with LADA and in laboratory models of the disease, rather than relying on findings from related conditions.

Source: Frontiers in endocrinology. 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.