Autoimmune Type 2 may need early treatment

Autoimmunity to pancreatic islet cells has always been believed to be a characteristic of Type 1 diabetes, but there is growing evidence of a subset of Type 2 diabetes in which patients develop autoimmunity similar to what is seen in Type 1.

Universal antibody screening of patients with Type 2 diabetes should be considered to determine if early insulin treatment might stave off the development of this subset as the patient ages, says the lead author of a study published in the January 2000 issue of Diabetes.

"This appears almost to be a different disease in some patients," says Massimo Pietropaolo, MD, associate professor at the University of Pittsburgh School of Medicine and a staff member at Pittsburgh Children’s Hospital.

"Screening for GAD65 and IA-2 antibodies might help, since we have determined that 10% to 15% of Type 2 patients display these antibodies," he says. "This subgroup likely will develop a requirement for insulin over time. Early treatment with insulin may reduce the risk of coronary artery disease connected to the immune system pathogenesis."

Pietropaolo’s most recent study showed a 12% incidence of GAD65 and IA-2 antibodies among 290 patients older than 65, but the autoimmune response has been detected in younger patients as well. "We’ve seen it in people with Type 2 diabetes who are in their 30s and 40s."

Pietropaolo and his colleagues will soon begin a larger study with 11,000 patients to determine if the prevalence holds true with larger numbers of subjects.

The medical community is far from convinced that universal screening would change the treatment options for patients who display autoimmune-type diabetes. "Clinically, the concept of universal screening is premature at the moment," says Jerry Palmer, MD, professor of Medicine at the University of Washington at Seattle and director of endocrinology, metabolism, and nutrition at the Department of Veterans Affairs Puget Sound Health Care System. He says it is clear there is a subset of patients with Type 2 diabetes who display antibodies usually associated with Type 1 diabetes, but it is not clear if they should be treated differently than patients who are antibody-negative. Palmer says it is possible that patients with the antibodies that indicate beta cell failure tend to have a more severe disease process. "But we don’t really know."

There is also no defining evidence to show that starting insulin early would have a protective effect, although he says researchers are currently conducting clinical studies in hopes of finding an answer to that question. "To make clinical recommendations for millions of people with diabetes is jumping the gun a little right now, although we may find out that this screening would be beneficial." The take-home message is that all Type 2 diabetes is not the same and there are subsets of the disease which may ultimately require different treatment, "but the evidence just isn’t out there right now," Palmer says. "[In practice], people who are antibody-positive are more likely to need insulin, and you would increase their meds anyway if they are not responding."

The concept of latent autoimmune diabetes in adults (LADA) is not a new one, says Steven Elbein, MD, an endocrinologist and professor of medicine at the University of Arkansas in Little Rock, who says he suspects this subset is really a late onset Type 1 diabetes.

Elbein considers Pietropaolo’s data to be "pretty strong," and agrees that about 10% of patients with Type 2 diabetes will show signs of an autoimmune reaction. He still doesn’t recommend universal GAD65 and IA-2 screening. "There’s a question whether GAD is the best indicator, and there is no commercially available IA-2 screen now. GAD screenings aren’t very useful anyway unless they are done by a lab you can trust."

In practical terms, Elbein echoes Palmer’s recommendations. "You can tell when someone is not responding to oral agents and take the steps you need to help them get into glycemic control."

[Contact Massimo Pietropaolo at (412) 692-65570, Jerry Palmer at (206) 764-2495, and Steven Elbein at (501) 257-5814.]