Latent autoimmune diabetes of adulthood (LADA) is a slowly progressive condition in which type 1 diabetes develops in adults, usually after age 30. LADA also displays some characteristics of, and is sometimes misdiagnosed as, type 2 diabetes.

One of the main differences between people with LADA and type 2 diabetes is that LADA patients tend to be younger and thinner. Also, individuals with LADA are usually insulin deficient rather than insulin resistant.

Someone who has been diagnosed with type 2 diabetes, is under age 50, has a lean build and no known relatives with type 2 diabetes may actually have LADA. Physicians can mistake LADA for type 2 diabetes because this form of the disease often responds initially to treatment for type 2 diabetes. Also, individuals with LADA at first lack signs of autoimmunity. LADA, like other forms of type 1 diabetes, is an autoimmune disease in which the body mistakenly attacks the insulin-making cells of the pancreas.

For those misdiagnosed, physicians may become aware of the presence of LADA only when the treatments for type 2 diabetes begin to fail, which can take years. This normally happens when patients can no longer control their glucose (blood sugar) through the standard type 2 treatments of diet, exercise and antidiabetic agents.

LADA is sometimes referred to as type 1.5 diabetes, a term that has also been used for double diabetes and for maturity-onset diabetes of the young (MODY).

The American Diabetes Association (ADA) defines latent autoimmune diabetes of adulthood (LADA) as the development of type 1 diabetes in adults. LADA also has some characteristics of, and is sometimes confused with, type 2 diabetes. It is known by a host of names as scientists attempt to classify this form of diabetes, which normally develops gradually in adults over the age of 30. Some of the other terms used to describe this condition include:

• Type 1.5 diabetes
• Autoimmune diabetes of adults
• Latent type 1 diabetes
• Late-onset autoimmune diabetes of adulthood
• Progressive insulin-dependent diabetes mellitus
• Slowly progressive type 1 diabetes
• Slow-onset type 1 diabetes
• Youth-onset diabetes of maturity
• Type one-and-a-half diabetes

While researchers continue to debate the proper name and classification for this type of diabetes, the two most common terms for this condition appear to be LADA and type 1.5. It should be noted that the term “type 1.5 diabetes” has also been used to describe at least two other conditions: double diabetes and maturity-onset diabetes of the young (MODY).

Compared to a child who develops symptoms of type 1 diabetes over a few weeks, the onset of LADA is more of a steady decrease in insulin production over months or years. The additional signs of ketoacidosis or ketosis (increased levels of acidic waste products called ketones in the blood and urine) and rapid unexplained weight loss, normally associated with type 1 diabetes, are also absent.

Most people diagnosed with LADA are not overweight or obese and have no family history of type 2 diabetes. They may or may not have a family history of type 1 diabetes.

Treatment for LADA patients incorrectly diagnosed with type 2 diabetes will ultimately fail, and patients will become insulin dependent. Although the physician may initially believe that the patient has failed to adhere to the recommended diet or medication regimen, a physiologic reaction is actually occurring inside the body.

At this point, the islets of Langerhans in the pancreas are under attack by the autoimmune process. The result is the failure of beta cells to release insulin, and thus the production of insulin stops. For patients with LADA, little or no insulin production takes place because body’s own immune system has destroyed the pancreatic beta cells. 

LADA is considered a less aggressive form of autoimmune diabetes than standard type 1. That may be the reason for the considerable amount of time that insulin is not required for these patients. LADA patients seldom possess some of the more common characteristics of a type 2 diabetic patient, including:

• Obesity or overweight
• A high occurrence of metabolic syndrome
• High blood pressure
• Unhealthy levels of triglycerides and cholesterol (hyperlipidemia)

As with other forms of diabetes, however, LADA can lead to complications such as heart problems. Some research suggests that people with LADA might be more prone to conditions involving microangiopathy (diseases of the small blood vessels), such as diabetic retinopathy. Patients can reduce their risk by controlling their glucose (blood sugar) and adhering to other aspects of their treatment plan.

Scientists have not established the incidence of LADA. With LADA patients sometimes misdiagnosed as having type 2 diabetes, some estimates attribute as many as 15 to 20 percent of diabetes cases to LADA. If correct, such figures would make LADA more common than (childhood-onset) type 1 diabetes, which accounts for 5 to 10 percent of diabetic cases, according to federal health agencies.

  Distinguishing LADA From Other Forms of Diabetes

Latent autoimmune diabetes of adulthood (LADA) can be vexing to physicians unfamiliar with this form of diabetes – and even to those who know it well. For example, LADA patients rarely display the classic symptoms of type 1 diabetes, such as rapid unexplained weight loss or a tendency to develop diabetic ketoacidosis (a dangerous condition involving  excess waste products called ketones in the blood).

With standard type 1 diabetes, the loss of insulin production is typically rapid. With LADA, the pancreas loses the ability to make insulin much more slowly than in standard type 1 but faster than is usual in type 2 diabetes. LADA patients, like those with type 1, have in their bloodstream abnormal antibodies (autoantibodies) to the insulin-making beta cells, which means that their immune system attacks these cells.

In type 1, the cells are killed quickly, but LADA is a much slower process. Some physicians believe that this indicates that LADA is separate from type 1 and type 2 diabetes and that a different immune reaction is at work.

Also, people with type 2 diabetes are commonly overweight or obese, whereas people with LADA usually have a normal or lean build. LADA patients often lack the common related traits including metabolic syndrome, high triglyceride levels, low HDL (“good”) cholesterol or high blood pressure.

Considering the high number of LADA patients erroneously believed to have type 2 diabetes, LADA should be considered if the patient who is being diagnosed:

• Is between 30 and 50 years old. This is the typical age range, though younger or older adults have also been diagnosed with LADA.
  
  
• Has a lean build or normal to low body mass index .
  
  
• Has not had a significant unexplained weight loss.
  
  
• Does not present with ketoacidosis.
  
  
• Has no known relatives with type 2 diabetes.
  
  
• Has low c-peptide levels, an indicator of insulin levels in the blood.

The surest way to determine if a person has latent autoimmune diabetes of adulthood (LADA) is through a blood test for abnormal pancreatic antibodies. Though not yet part of standard clinical practice, this autoantibody testing may be performed if a physician suspects LADA.

Such testing reveals the presence of islet cell antibodies (ICA), insulin autoantibodies (IAA), tyrosine phosphatase antibodies and/or glutamic acid decarboxylase (a beta cell protein known as GAD). In people with LADA and other forms of type 1 diabetes, the body’s immune system mistakenly attacks the insulin-making beta cells of the pancreas. The most common of these autoantibodies is the GAD protein, but any of them can help confirm a LADA diagnosis.

Additionally, the level of c-peptide, a protein fragment generated during insulin production, may be checked in a c-peptide test. This blood test can help the physician differentiate LADA from type 2 diabetes and suggest the extent of damage to the beta cells.

For nearly half of patients with LADA, insulin administration is required within four years of diagnosis, a sharp contrast to the average of more than 10 years for patients with type 2 diabetes who become insulin dependent. In fact, it is possible for patients to go for months or even up to six years with type 2 treatments before it becomes obvious that they have LADA – and they might be diagnosed only when they become dependent on insulin.

Thus, if LADA has been determined, most physicians recommend that insulin treatment begin immediately upon diagnosis as it may retard the autoimmune destruction of beta cells. Studies are under way to investigate ways to preserve insulin function in patients with LADA.

Syringe injections are the most common way of delivering insulin. Other options may include inhaled insulin, insulin pens, jet injectors or an insulin pump. Some patients with LADA may qualify for a pancreas transplant or an islet cell transplant.

The physician will establish a target glucose range and schedule of glucose monitoring. The treatment plan typically includes diet and exercise to maintain health and prevent double diabetes. Regular medical care includes physical examinations and establishment of a sick-day plan. A pneumonia vaccination and annual flu shots are generally recommended. Patients, especially those at high risk for hypoglycemia, may be advised to carry a glucagon kit.

The physician will recommend a schedule of:

• Glycohemoglobin testing to assess long-term diabetic management
  
  
• Complete foot examinations to reduce the risk of foot problems
  
  
• Dilated pupil examinations to detect diabetic retinopathy, glaucoma, cataracts and other eye diseases
  
  
• Cholesterol tests and blood pressure monitoring to help prevent heart conditions and stroke
  
  
• Microalbuminuria tests to monitor kidney function and prevent diabetic nephropathy
  
  
• Neurological examinations to diagnose and control diabetic neuropathy

For LADA patients with unstable diabetes, an option to improve glycemic control may be a recently approved injectable antidiabetic agent called pramlintide.

Researchers are investigating whether thiazolidinediones and some other oral diabetes drugs may slow the autoimmune destruction of the pancreas and help preserve the insulin-producing beta cells. This area is being explored cautiously because some research has suggested that sulfonylureas may hasten pancreatic damage in people with LADA.

Although testing for LADA is not yet routine in the diagnosis of diabetes, it is expected that early identification of the condition may one day be standard. However, routine screening most likely will take place only after an effective immune intervention is developed – one that can stop the destruction of beta cells and meet the unique insulin requirements of these patients.

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about latent autoimmune diabetes of adulthood (LADA):

1. How is LADA different from the usual form of type 1 diabetes?
   
   
2. How is it different from type 2 diabetes?
   
   
3. What symptoms or signs of LADA should I watch for?
   
   
4. What diagnostic tests for LADA might I undergo?
   
   
5. What do my test results show?
   
   
6. What are my treatment options for LADA?
   
   
7. Will I definitely need to take insulin? Should I start now? What can happen if I delay insulin therapy?
   
   
8. What method of taking insulin do you recommend for me?
   
   
9. What is my glucose level, and what should it be?
   
   
10. How often should I perform glucose monitoring?
    
    
11. Do I also need to perform ketone tests or any other tests?
    
    
12. How often should I have physical examinations, complete eye exams, foot exams, microalbuminuria testing and other medical care?
    
    
13. How can I reduce my risk of double diabetes, diabetic neuropathy, diabetic retinopathy, diabetic nephropathy and other complications?
    
    
14. Is LADA likely to run in my family? Should relatives have an autoantibody test or other testing?