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TheOtherDiabetes:LADA,orType1.5:ForecastDiabetesMagazine

The Healthy Living Magazine

www.diabetesforecast.org

The Other Diabetes: LADA, or Type 1.5

Latent autoimmune diabetes in adults is gradually being understood
By Erika Gebel, PhD
May 2010

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 identied 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 classied 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 dene 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 conrmed for the rst time that type 1 is an autoimmune disease in
which the body's immune system kills o 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).
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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 dierence 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 rst six months after diagnosis. This denition would distinguish LADA from
type 1because people diagnosed with type 1 typically need to start insulin immediatelyand
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 eect on beta cell health may be the key to dening the relationships
among type 1, type 2, and LADA. Scientists have discovered several dierent 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 dierent types and subtypes of diabetes satises scientic 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 dierent 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 ineective
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people with LADA, a misdiagnosis of type 2 may mean that they both take ineective 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 eective 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 DiabetesMODY

American Diabetes Association, 1701 N. Beauregard St., Alexandria, VA 22311

Copyright 2016 American Diabetes Association

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