Diabetes Forecast

The Other Diabetes: LADA, or Type 1.5

Latent autoimmune diabetes in adults is gradually being understood

By Erika Gebel, PhD ,

Diabetes Types

Key characteristics of type 1, LADA (latent autoimmune diabetes in adults), and type 2.

  Type 1 LADA Type 2
Typical age of onset Youth or adult Adult Adult
Progression to insulin dependence Rapid (days/weeks) Latent (months/years) Slow (years)
Presence of autoantibodies* Yes Yes No
Insulin dependence At diagnosis Within 6 years Over time, if at all
Insulin resistance No Some Yes
*Proteins that indicate the body has launched an autoimmune attack on the insulin-producing beta cells in the pancreas.

Once, there were two types of diabetes; children mainly got one type and adults mostly got the other. Today, we know that younger people can get type 2 and that type 1 often appears in adulthood. During pregnancy, women can get gestational diabetes, which resembles type 2 and usually disappears after childbirth. And scientists have identified several other diabetes subtypes beyond types 1 and 2. The most common of these is called latent autoimmune diabetes in adults (LADA), and it accounts for roughly 10 percent of people with diabetes, making it probably more widespread than type 1.

So why haven't more people heard of it? LADA can be classified as a more slowly progressing variation of type 1 diabetes, yet it is often misdiagnosed as type 2. As of now, there is still a lot of uncertainty over how exactly to define LADA, how it develops, and how important it is for patients to know if they have it.

Surprise Finding

Doctors stumbled upon the LADA phenomenon quite by accident back in the 1970s. They were testing a way of identifying proteins called auto­antibodies in the blood of people with type 1. The presence of these proteins is evidence of an attack by one's own immune system. The new test was successful and confirmed for the first time that type 1 is an autoimmune disease in which the body's immune system kills off the beta cells in the pancreas, the makers of insulin.

As part of their study, the researchers also looked for the same autoantibodies in the general population and in people with type 2 diabetes (which is not an autoimmune disease). The proteins were virtually absent in the general population, but they showed up, to the scientists' surprise, in about 10 percent of people diagnosed with type 2. This suggested that there was a subcategory of people who could now be diagnosed as having LADA instead, even though there was no obvious difference in their symptoms from those of people with type 2.

While not everyone has settled on calling the condition LADA (some prefer "type 1.5"), or even whether it's distinct from type 1, researchers are working on a set of criteria for its diagnosis: 1) the presence of auto­antibodies in the blood, 2) adult age at onset, and 3) no need for insulin treatment in the first six months after diagnosis. This definition would distinguish LADA from type 1—because people diagnosed with type 1 typically need to start insulin immediately—and from type 2, because of the presence of autoantibodies in the blood. There is still some controversy about whether these are the best criteria for diagnosing LADA. But "the general concept is very well accepted," says Jerry Palmer, MD, a professor at the University of Washington in Seattle.

The debate over LADA has led some doctors to move away from the idea that the various types of diabetes are truly separate entities. "We think there is a continuum in diabetes overall," says Suat Simsek, MD, a professor at VU University Medical Center in the Netherlands. Autoantibodies and their effect on beta cell health may be the key to defining the relationships among type 1, type 2, and LADA. Scientists have discovered several different types of auto­antibodies related to diabetes. People with type 1 have higher levels and more types of these proteins than do those with LADA, which may be the reason beta cells are destroyed faster in type 1 than in LADA. In type 2 diabetes, autoantibodies are generally absent and, as a consequence, beta cell decline is the slowest.

There was some hope that genetics would help to draw the diabetes boundaries. But a 2008 study in Diabetes found that, genetically, LADA has features of both type 1 and type 2. So, in autoantibodies and genetics, LADA appears to fall somewhere between types 1 and 2 on the diabetes spectrum, though perhaps closer to type 1.

Does It Matter?

Sorting out the different types and subtypes of diabetes satisfies scientific curiosity, but is there good reason to look for LADA? Would it help health care providers to give better treatment or people with diabetes to achieve better blood glucose control and fewer complications?

Blood tests for LADA measure autoantibodies and insulin production, but they may not be necessary for most people diagnosed with type 2, according to Simsek. In a severely obese person (with a body mass index of 35 or more), "it doesn't make sense to test," he says, in part because treatment for LADA wouldn't really be different from that of someone with type 2: diet, exercise, and, if necessary, medication. But testing could be a good idea for leaner, physically active adults who are more likely to have LADA and should not be overly insulin resistant, a characteristic of type 2.

One potentially critical reason to test for LADA is that, someday, the results may help tailor treatment. For people with LADA, there is already some evidence that early insulin treatment may keep beta cells in the business of producing insulin, at least for a while. A 2008 Japanese study in the Journal of Clinical Endocrinology & Metabolism compared insulin and sulfonylurea treatment in 4,000 adults with LADA. Treating people early with insulin helped them avoid total dependence on insulin longer than those who took sulfonylureas.

"Insulin treatment can preserve beta cell function," says principal investigator Tetsuro Kobayashi, MD, PhD, a professor at the University of Yamanashi in Japan. "If you use other oral agents, you lose function faster and go to an insulin-dependent state very, very quickly." So, for people with LADA, a misdiagnosis of type 2 may mean that they both take ineffective oral medications and lose their insulin-producing beta cells faster.

Another reason to test is that medicines being developed to prevent or cure type 1 diabetes may also turn out to be effective against LADA. "What we need is another therapy besides insulin, one that alters the underlying disease process," says Palmer. "Then it will be of prime importance whether or not you have LADA. But right now we don't have that therapy." If such a therapy does emerge, the hope is that by then LADA will be better understood and more accurately diagnosed, so that people with this form of diabetes can get the treatment they need.

Also: Another Kind of Diabetes—MODY



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