LADA and GAD: Diagnosing Type 1.5 Diabetes


Researchers in Germany have further endorsed the effectiveness of a blood test that helps determine whether some adult diabetics diagnosed as type 2 diabetes are actually in the early stages of having type 1 diabetes.

Latent Autoimmune Diabetes of Adults (LADA) like type 1 diabetes, is an autoimmune response that that destroys insulin-producing beta cells in the pancreas. It is often misdiagnosed as type 2 diabetes because it looks and acts a lot like type 2– arising usually in adulthood and progressing slowly­– but, unlike type 2 diabetes, LADA results from the autoimmune destruction of insulin-producing beta cells.

A test for glutamic acid decarboxylase, or GAD, antibodies, has long been used as a method of differentiating between LADA (which is sometimes referred to at type 1.5 diabetes) and type 2 diabetes in people over age 30. With LADA as well as type 1 diabetes, the body’s immune system begins to attack its own beta cells. When the immune system attacks pathogens, one weapon in its arsenal is the creation of antibodies that bind to the foreign objects and mark them as invaders. In the case of autoimmune diabetes, the body begins to create antibodies against parts of proteins that are not foreign, but rather are associated with its own beta cells. GAD is one of the earliest proteins to be targeted by antibodies, and so by testing for the presence of GAD antibodies, doctors can determine whether there is an autoimmune reaction to beta cells taking place.

“At diagnosis, people with LADA usually do not require insulin right away because they are still producing some insulin,” according to Christy L. Parkin, MSN, RN, CDE, Associate Editor of Diabetes Forecast. “Because of their older age, they are often misdiagnosed as type 2 and started on oral medications. They may be normal weight or slightly overweight (not typical in type 2). LADA has characteristics of type 1 and may include insulin resistance, like type 2 diabetes. The main difference between LADA and type 2 is the autoimmune response, which is similar to type 1. The loss of beta cells is much more gradual in LADA than in type 1, though. It can take several years before blood glucose control starts to worsen.”

Given the differences between the necessary treatments for LADA and type 2 diabetes, a good diagnostic tool is clearly needed. However, up until now, the effectiveness of GAD antibody testing as a diagnostic has not been completely endorsed by the scientific community. Researchers at the Institute of Diabetes Research at the Helmholtz Zentrum München, partners in the Deutsches Zentrum für Diabetesforschung (DZD – German Center for Diabetes Research) however, have concluded a study that recommends use of the test in diagnosing LADA.

The study looked at reactions to injections of the GAD antibody in 46 LADA patients over 30 months. The subjects in the study were injected under the skin with different doses of GAD, or a placebo, producing an immune system reaction that impacted the insulin making beta cells. It was found that subjects with a strong reaction to the GAD antibody had correlating low insulin production.

“Our findings show that the GAD antibody affinity is a valuable … diagnostic marker in LADA patients,” according to lead investigator Dr. Peter Achenbach. “As with childhood type 1 diabetes, we can forecast the progression of the disease and adapt the therapeutic measures accordingly. The antibody affinity should now also be taken into consideration in clinical studies involving LADA patients.”

Other testing for type 1.5 diabetes that may be used in conjunction with the GAD test to determine if a person has LADA include determining c-peptide levels to measure insulin production levels, and tests for islet cell antibodies.

The supportive vote on GAD antibody testing is good news– it’s estimated that 10 percent of people diagnosed with type 2 diabetes have LADA (type 1.5), according to Dr. Jeff Unger, in the journal, American Family Physician.

In many cases, people who are diagnosed with type 2 but who have LADA will experience higher and higher blood sugars as insulin producing cells die off and oral medications do little or nothing to properly control their levels. High blood sugars might also be accompanied with weight loss, a classic symptom of untreated type 1 diabetes.

There are no formally established treatment procedures for LADA, according to the Mayo Clinic. Typically, however, patients diagnosed with LADA take insulin rather than oral diabetes medications, and otherwise treat their condition similarly to how they would be treated if they were diagnosed with type 1 diabetes. Once a diagnosis is made, the best option moving forward is to work with a physician to tailor a specific treatment plan.

For some people, such as Caraline McLeod, the diagnosis makes a world of difference in how they care for themselves.

Diagnosed with type 2, McLeod followed her doctor’s advice on exercising to lose weight, taking oral medication, and testing her blood sugars on a regular basis. Even though she reached her target weight and got in better shape, her blood sugars inexplicably continued to rise.

“I carried a deep sense that part of the puzzle was missing,” McLeod says in an interview with ABC Health and Wellbeing. “I became paranoid that some aspect of my lifestyle had contributed to this rapid progression, wondering if diet tonic water or my shampoo could be the hidden enemy. While I told myself that denial is one of the phases of grief and perhaps normal under the circumstances, I continued to obsess.”

When she learned about LADA, McLeod immediately went to her doctor for a GAD antibody test.

“Two weeks later the results came back strongly positive. Perhaps most people would have been unsettled with such a result, but I simply felt relief. In one fell swoop, my questions had been answered. I now knew why there had been no pre-diabetes and why exercise and diet had not spared me.

“I was referred to an endocrinologist who confirmed type 1 diabetes, and who encouraged me to be proactive in my own treatment. Indeed, he confirmed what I’d already read – that starting insulin early might spare my remaining beta cells.”

Like McLeod, for many diabetics diagnosed with a condition they don’t, in fact, suffer from, the correct diagnosis made though a GAD test provides the best chance for achieving improved long term health and happiness.

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6 years ago

I had the same experience! I lost 30 pounds (now size 4/6), ate healthy, exercised, and didn’t need to take meds for a few years. Last year my sugar numbers went up, so I lowered the carb intake even more. Towards the end I was only eating around 20g carbs a day, but had an A1C of 11.4. I finally asked the doctor to test for GAD65 antibodies and the test was highly positive! I don’t understand why this isn’t a routine test.

8 years ago

One thing I didn’t mention was that with the help of the Internet, I diagnosed my own LADA. When it became apparent to me that my (mis)diagnosis as a Type 2 wasn’t controlling my diabetes, i printed out some information about LADA, delivered it to my doctor–who, to his credit, is very open–and persuaded him to run the antibody tests. It was apparent what was going on when the results came back. I would encourage anyone who suspects something isn’t quite right about their diagnosis to have the full series of tests run, as you suggest, Melitta.  Jean: nice to… Read more »

8 years ago

Onoosh–interesting that you have arthritis too. Rheumatoid arthritis is another autoimmune disease. Autoimmune diseases often happen in clusters. I have a strong GAD response, hypothyroidism and a recurring oral flare up that all have been diagnoses as autoimmune. My large family has no diabetes, yet I did. My family members do tend to have autoimmune diseases though.
While still diagnosed as T2D, I failed to responds to Metformin, Januvia and Victoza inj. I’m now on insulin and well controlled.

9 years ago

It is important to remember that LADA is Type 1 diabetes, and should be treated as such.  It is also important to get the full suite of autoantibody tests (GAD, ICA, IA-2, IAA, ZnT8), not just GAD, because a small but significant percentage of people will be GAD negative but positive for one of the other autoantibodies.

Misdiagnosis (diagnosed as T2D when the person actually has T1D/LADA) is extremely serious and can lead to rapid onset of diabetic complications and even death.  Awareness and testing are needed!

9 years ago

Absolutely! If you suspect, ask your doctor to do the GAD antibody test. It explained everything happening in my case: continuing weight loss, but rising blood sugars. I do long-acting insulin, Metformin–which seems to add to the beneficial effect of the insulin–a low-carb diet, water aerobics, and as much other movement as possible, which helps my arthritis, too. The results are much lower glucose numbers and–for now, anyway–good control of my LADA.

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