LADA: The “Other” Type of Diabetes

By Jordan Perlman, MD

You’re in your mid-40s and healthy, relatively fit and close to your ideal weight. However, lately you’ve been getting up to go to the bathroom at night, sometimes twice, sometimes three times per night, and feeling a bit thirsty during the day. You haven’t been feeling well for the past week and have been suffering from nausea. While not debilitating, the nausea is getting worse although you haven’t felt like you need to throw up. Concerned that your condition isn’t improving, you go to the local emergency room to get checked out.

When the emergency room physician notes that you are thin, you share that you have always been thin and feel that your vegetarian diet has helped you keep your weight under control. When answering questions about your health and family medical history, you share that you were treated for hyperthyroidism (an overactive thyroid) 10 years ago and are now on thyroid hormone replacement medication. You add that your mother received treatment for an underactive thyroid, your maternal grandmother has insulin-dependent diabetes, and a maternal uncle also has been treated for an overactive thyroid gland.

After some medical tests are completed, the doctor delivers a confounding diagnosis: You’re told you have type 2 diabetes mellitus (T2DM) and are prescribed metformin to help lower your blood glucose (blood sugar) level. But the effect on your blood sugar is minimal. In fact, even after the addition of a second and then a third pill to control your diabetes, nothing seems to be working. You are then referred to an endocrinologist, and after new blood test results are back, you’re told you have latent autoimmune diabetes in adults, also known as LADA. What?

Latent autoimmune diabetes in adults – LADA – is a lesserknown, slowly progressive form of autoimmune diabetes mellitus that is often misdiagnosed as type 2 diabetes mellitus (T2DM) in its earlier stages. LADA should be suspected in any person who has autoimmune markers (tested by specific blood tests) that are antibodies to pancreatic tissues. The clue for considering this unusual type of diabetes is that classic physical characteristics often associated with T2DM aren’t present. You are more likely to be at a normal weight or thin, which is a big clue. And your family medical history, as well as your personal medical history, will usually reveal other hormone disorders that are linked with an autoimmune- or antibody-associated problems, such as thyroid disease, or other family members rapidly progressing to needing insulin for their diabetes blood sugar control.

It is important to identify the correct diagnosis of LADA because appropriate treatment may slow disease progression. Unfortunately, LADA causes destruction of pancreatic islet cells (insulin-producing cells), and once this happens, the need for multiple doses of insulin injections to control blood sugar levels is the only way to treat the disease.

To better understand LADA, it’s helpful to understand the immune system. As its name suggests, LADA is an autoimmune condition that causes a person’s own immune system to attack the pancreas. The soldiers in this attack are called T-cells. T-cells are meant to target and destroy foreign invaders like viruses and bacteria. In LADA, these same T-cells get confused and destroy the person’s own islet cells, the makers of insulin in your body. We don’t have a great way to detect these confused T-cells, so we use a different type of immune marker (called an antibody) as a diagnostic marker. The amount of antibody (or titer) seems to predict progression of diabetes. The most important LADA antibody is called GAD65 and targets an enzyme (glutamic acid decarboxylase) that is present in pancreatic islet cells.

The best way to distinguish between LADA and T2DM is to perform antibody testing through blood tests. While the high cost of the tests currently prohibits universal screening for LADA, this testing is being done more frequently when the type of diabetes present in an individual remains unclear. Physicians use a specific set of clinical criteria to determine who has the highest odds of testing positive for antibodies. The following characteristics are more common in LADA than T2DM: 1) age of patient at time of diabetes onset is less than 50 years; 2) the presence of certain symptoms before diagnosis (excessive thirst, excessive urination, unintentional weight loss); 3) a normal weight at time of diagnosis; 4) a personal history of autoimmune disease; and 5) a family history of autoimmune disease. It has been reported that if these criteria are used, the diagnosis of LADA could be made in at least 90 percent of cases in which the patient meets at least two of these criteria.

It’s important to recognize LADA as early as possible so you receive appropriate treatment. There is some evidence that suggests using sulfonylureas, a class of oral diabetes medication that increases the release of insulin from pancreatic islet cells, can increase the need for multiple insulin injections. There is also some data from animal testing that shows giving GLP-1 agonists (a class of injectable diabetes medication that slows glucose absorption into the bloodstream) could help regeneration of pancreatic islet cells that produce insulin. Unfortunately, this has not yet been tested in humans.

We do know that LADA patients get less effect from oral medications that lower blood sugars than what is seen in T2DM patients. However, recommendations for a carbohydrate-managed diet and frequent exercise also apply to those diagnosed with LADA, as these lifestyle modifications help decrease insulin resistance (when insulin is present but is not working as it should) and minimize the number of medications needed to control blood sugar.

Once those with LADA lose the ability to produce insulin, they need multiple daily injections to stay healthy, just like patients with type 1 diabetes mellitus (T1DM—previously called juvenile diabetes). Patients who have higher levels of GAD antibodies often need insulin shots much sooner after a diagnosis of LADA. But curiously, if insulin is started early following diagnosis, it can slow the need for large insulin doses and multiple injections of insulin. Many individuals with LADA can go years requiring just one, two, or three units of a long-acting insulin to control their blood sugars. But this must be started early.

Like other types of diabetes, LADA can lead to development of significant complications. An acute complication that can occur when your pancreas no longer makes insulin is diabetic ketoacidosis, a life-threatening condition that develops when cells in the body are unable to get the sugar (glucose) they need for energy because there is not enough insulin to transport the sugar into the cells. When the sugar can’t get into the cells, it stays in the blood. This situation requires immediate hospitalization for intravenous insulin treatment.

There’s no difference in the risk of cardiovascular complications between those who have LADA and those with typical T2DM. Very little data is available about the prevalence of kidney and eye disease in LADA, but researchers suspect this is also similar to T2DM. Plus, there have been several small studies suggesting nerve disease might be more common in those with the LADA type of diabetes. However, individuals who have higher levels of GAD antibodies are at increased risk for complications, regardless of blood sugar levels. The best way to avoid such complications is to control blood glucose levels.

It’s very important to ask your doctor what type of diabetes you have, especially if you don’t think you fit the usual profile for T2DM. If you’re young and of a normal weight, you might need a different kind of treatment to stay healthy. So request the antibody testing – your life could depend on it.