Ketosis-Prone Type 2 Diabetes: New Clues to an Immune Mix-Up

Ketosis-prone type 2 diabetes (KPD) is an uncommon presentation of diabetes that blurs the line between type 1 and type 2. It typically affects young people, predominantly men, who suddenly develop severe diabetes with dangerous ketoacidosis—a buildup of acids in the blood—without an obvious cause. Unlike classical type 2 diabetes, which develops gradually in older adults, KPD strikes suddenly and severely.

What makes KPD puzzling is its unpredictable course. Some people recover some insulin-producing capacity after insulin therapy, suggesting their pancreas isn't permanently damaged. Others progress to lifelong insulin dependence, more like type 1 diabetes. This variability suggests that KPD may not be a single disease but rather several different conditions that look similar on the surface.

A new study of 54 people with KPD found evidence that both endocrine (hormone-producing) and exocrine (enzyme-producing) parts of the pancreas may be under attack by the immune system. Researchers discovered that a specific genetic marker—HLA-DRB1*08:03—was more common in people with KPD than in healthy controls.

In people carrying this genetic marker, researchers found elevated levels of antibodies against carbonic anhydrase II (CA2), an enzyme made by the pancreas. These antibodies are typically seen in type 1 diabetes and suggest an autoimmune attack on pancreatic tissue. Importantly, CA2 antibody levels were especially high in people with the HLA-DRB1*08:03 marker who also showed signs of pancreatic inflammation.

About 30% of the study participants showed elevated levels of pancreatic enzymes in their blood, a sign that the exocrine pancreas—the part that produces digestive enzymes—may be inflamed. This finding is significant because exocrine pancreatic inflammation has been documented in type 1 diabetes but was not previously well-studied in KPD.

The presence of this inflammation in some KPD cases suggests that KPD may involve a broader immune attack on the pancreas than was previously understood, affecting both insulin-producing cells and enzyme-producing tissue.

These findings suggest that immune responses targeting the pancreas in KPD may be more complex than previously recognized. The connection between pancreatic inflammation and autoimmune markers hints that genetic factors (like the HLA-DRB1*08:03 marker) may determine who is at risk and how their immune system attacks the pancreas.

Understanding these mechanisms could eventually help doctors identify which people with KPD are likely to regain pancreatic function and which will need lifelong insulin therapy. However, this is early-stage research, and more studies are needed to confirm these findings and determine their clinical significance.

Source: Journal of the Endocrine Society. 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.