LADA (Latent Autoimmune Diabetes of Adulthood)

LADA ( Latent Autoimmune Diabetes of Adulthood), or Type 1.5 (type one-and-a-half) diabetes

Dr. Mitalee Barman, Consultant Diabetologist
M.V Hospital for Diabetes

Till recently, people had either Type 1 diabetes (where the body stops making insulin) or Type 2 diabetes (where insulin is produced but the body cannot use it). There was also gestational diabetes – high blood glucose levels during pregnancy, which with good prenatal care, returned to normal after delivery.

LADA or Latent Autoimmune Diabetes of Adulthood is a relatively new kind of diabetes that affects adults and shares some features of both Type 1 and Type 2 diabetes.

Doctors came across LADA in the 1970s while they were conducting tests to identify proteins called auto­-antibodies in the blood of people with type 1 diabetes.

As part of their study, the researchers also looked for the same auto antibodies in the general population and in people with type 2 diabetes (which is not an autoimmune disease).The proteins were almost absent in the general population, but they were seen in about 10 percent of people diagnosed with Type 2.

How is LADA different from Type 1 and Type 2 Diabetes?

LADA is a genetically-linked, hereditary autoimmune disorder where the body confuses the pancreas with foreign bodies and reacts by attacking and slowly destroying the insulin-producing beta islet cells. But the attack is a slow progressive one with LADA, compared to the fast and aggressive attack on the beta cells in Type 1 diabetes. These same proteins are absent in those with Type 2 diabetes.

LADA has genetic features of both Type 1 and Type 2. Genetic testing recently revealed that people with LADA not only have immunity-related genetic errors very similar to people with juvenile onset Type 1 diabetes but also have defects in a gene, TCF7L2, (responsible for insulin resistance), that are frequently found in people with Type 2.


So LADA appears to be between Types 1 and 2 though perhaps it is more like Type 1. The difference between LADA and classic Type 1 is the speed with which beta cells are destroyed. People with LADA may take up to a decade to lose all their insulin-secreting capacity whereas in some people with Type 1 it can happen within a week!

People with type 1 become dependent on insulin at diagnosis while those with LADA usually need it within 6 years and Type 2 takes a lot more time, if at all necessary.

Age of onset of LADA is typically over the ages of 25-30 years and the first manifestation imitates Type 2 symptoms. Type 1 diabetes is more commonly diagnosed in childhood or under the age of 25, however, LADA shows a striking resemblance to the juvenile form of Type 1.

Progression to insulin dependence in Type 1 is rapid (days or weeks).In cases of LADA it may be delayed (months to years) and in Type 2 it is very slow.


Many LADA patients are slender and active instead of being overweight and sedentary as most Type 2 diabetes patients are. But not all people with LADA are slim. People with defective autoimmune genes are also likely to get thyroid disease and rheumatoid arthritis both of which can promote obesity. Thyroid disease which is not treated correctly makes a person obese, and people with rheumatoid arthritis cannot exercise too much and in addition, this is often treated with steroids that promote weight gain.

Unlike Type 2 diabetes patients, people with LADA have little or no insulin resistance. But like Type 2 diabetes patients, those with LADA have some remaining healthy beta cells -- at least in the beginning. So, at first they can keep their blood glucose under control with diet and oral medications. The typical person with LADA requires insulin injections usually within 6 years which is much quicker than the average person with Type 2 diabetes.


How is LADA diagnosed?

Due to its similarities to Type 1 and Type 2, LADA can often be misdiagnosed as Type 2 diabetes as it initially mimics non-obese type 2 diabetes.

The main difference between LADA and Type 2 diabetes is that there is an autoimmune response present with LADA that is similar to that of Type 1 diabetes.

The only way to confirm whether a person has Type 2 diabetes or LADA is to test adults, especially those who are thin or normal weight, for the presence of auto antibodies. The antibodies tested for are: GAD antibodies, Islet cell antibodies, and more rarely, tyrosine phosphatase antibodies.

Tests that detect LADA

1. A fasting C-peptide test. If the value is low, it suggests LADA.

2. GAD ( glutamic acid decarboxylase test)and Islets antibody tests. High levels of these antibodies show the presence of LADA and can also predict the rate of progression towards insulin dependency. Higher levels of antibodies suggest a faster progression to insulin.

Low levels of antibodies relate to type 2 diabetes and people are more likely to be over- weight , have some insulin resistance and respond to tablets that act on insulin resistance.

Very high antibody levels are similar to type 1 diabetes and people are likely to have acute symptoms (thirst, unexplained weight loss, frequent urination, dry mouth) , are less likely to be overweight and may need insulin treatment soon after diagnosis.

Symptoms:

LADA has the classic symptoms of diabetes. These are increased thirst, increased need to urinate, fatigue, dry mouth, blurry vision, and slow healing of cuts or sores.

Other indicators of LADA:



* The symptoms appear over a period of several weeks or longer,
* There is someone with Type 1 diabetes in the close family,
* The person has another autoimmune condition such as Rheumatoid Arthritis or Coeliac disease.
* Blood sugar remains high despite treatment with oral drugs and carbohydrate restriction.





It is important to know whether you have LADA or T2DM

Knowing whether you have LADA or Type 2 diabetes is important, because management of the two conditions differs. Type 1 diabetes that begins at any age requires a finely tuned insulin regimen, while people with Type 2 diabetes sometimes do not need insulin at all or, when they do, may need injections just once a day.

People with LADA are often thin, so if you are thin and have been diagnosed with Type 2 diabetes, test for LADA.

Managing LADA


* As with other types of diabetes, eat a healthy, balanced diet and be active.

*Reducing carbohydrate intake and using less starchy vegetables should help to control blood sugar levels.


*The sooner insulin is started the easier it will be to control blood sugar .Insulin injections may be able to stop the attack on beta cells completely.

*Counseling, therapy and participation in support groups can play an important and positive role in the lives of persons with LADA.

*It is important to learn about diet, exercise, stress management, and how to handle diabetes on sick- days .Patients need to understand how to recognize, treat, and prevent hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar).

*Blood glucose levels should be checked. The doctor will provide target ranges for blood glucose levels and how often it needs to be tested.

Treatment for LADA



Initially, a person with LADA may respond to oral diabetes medications and lifestyle changes, however, beta cells continue to be destroyed and LADA patients should be closely monitored. Once blood glucose can no longer be managed through lifestyle and medications, daily insulin injections will be required.

Long-term complications of LADA

The risk of long-term effects are directly related to how well the disease is managed from time of onset as well as over a period of time.

Uncontrolled diabetes results in high blood glucose levels (hyperglycemia) which, over time may cause, diabetic neuropathy, diabetic retinopathy, kidney failure, heart disease, high blood pressure, stroke, peripheral arterial disease (PAD), chronic infections and wounds that may not heal, erectile and other urologic dysfunction, gastroparesis (delayed emptying of stomach contents), blindness, amputation, lactic acidosis, and diabetic ketoacidosis (DKA).

LADA patients will become dependent on insulin to keep blood glucose control , but it is possible to lead a normal life. Patient education, motivation, and state of mental health all play an important role in how well a person with LADA will be able to manage their disease.

Food for thought

A few decades ago this was a rare syndrome. Could this rapid increase be the result of environmental pollution? Chemicals, radiation, and viruses can all cause cancer in people in which case they could also be a reason for autoimmune diabetes in people with defects in their autoimmune genes.