Latent Autoimmune Diabetes In Adults (LADA): Facts You Should Know

Diabetes is one of the most common, yet complex, ailments of today. People generally categorize diabetic patients into either Type 1 or Type 2. However, the truth lies in the fact that these two kinds fail to capture the complete range of diagnosis with respect to diabetic patients. There is a particular kind known as 'Type 1.5 Diabetes', which is similar to type 1 in certain aspects but is still unique in some of the features that it demonstrates.

When the adult onset of diabetes is not insulin dependent, it is referred to as Type 1.5 diabetes, or in terms of medical science, referred to as 'Latent Autoimmune Diabetes in Adults (LADA)' ^[1] . Read on to know the specific features of this specific autoimmune disorder and what treatment plan works best for people with this ailment.

What Is Latent Autoimmune Diabetes In Adults (LADA)

Quite like type 1 diabetes, LADA occurs when your body starts making antibodies that cause the body's immune system to attack the insulin-producing cells of the pancreas. As the insulin-producing ability is lost, the body becomes unable to maintain the blood sugar levels. However, with LADA, the symptoms worsen very slowly over a long period of time and might go unnoticed during the initial stages ^[2] .

Researchers have attributed the type 1.5 diabetes with LADA because it is sometimes believed to be a subtype of type 1 diabetes. However, a few researchers also hold the opinion that LADA and its characteristics fall between that of type 1 and type 2 diabetes ^[3] .

The initial stages of LADA, when diagnosed, can be controlled with diet, exercise and oral medication. However, as the body keeps losing its ability to produce insulin, the patient might need to start receiving insulin shots ^[4] .

Latent Autoimmune Diabetes In Adults (LADA) - Neither Type 1 Nor Type 2

Type 1 diabetes is considered insulin dependent, whereas type 2 diabetes is considered insulin independent. However, a kind that is quite less recognized and belongs neither to type 1 nor type 2 is LADA. Researchers claim LADA to be a manifestation of Diabetes mellitus which affects adults with characteristics of type 2 diabetes. This ailment carries a great risk of insulin dependency progression ^[5] .

The following are the top noted usual features of patients with LADA ^[6] :

The onset of diabetes at about 25 years of age or more (in some cases only after the age of 30 years is reached)

• Clinically referred to as non-obese type 2 diabetic
• Rare chances of having a family history of diabetes
• Symptoms that can initially be controlled through diet and oral antidiabetic agents.

LADA possesses the following features of type 1 diabetes ^[7] :

• Low fasting C-peptide
• Lower Body Mass Index
• Autoimmunity against one or more of the following antibodies:
• Autoantibodies to glutamic acid decarboxylase (GAD)
• Islet cell autoantibodies (ICA)
• Tyrosine phosphatase - related islet antigen 2 (IA - 2)
• Insulin autoantibodies (IAA)

LADA possesses the following features of type 2 diabetes ^[8] :

• Older age at onset of diabetes
• Insulin resistance/deficiency

Characteristics that are LADA-specific and unique ^[9] :

• Intermediate level of β-cell dysfunction between those in type 1 and type 2 diabetes
• Quick decline of C-peptide when compared to that of type 2 diabetes
• Level of insulin resistance that is quite comparable to type 1 diabetes
• β-cell decline would be variable in LADA (when measured using C-peptide levels)

Studies say that about 20 per cent of the patients who have been diagnosed with type 2 diabetes actually may have LADA (which is about 5 to 10 per cent of the total diabetic population). However, in spite of the rising numbers, very few medical practitioners explore the possibilities of LADA in the patient ^[10] . Therefore, the need of the hour is to have a universal recommendation setting regarding testing for islet antibodies in adult-onset diabetes.

Symptoms Of Latent Autoimmune Diabetes In Adults (LADA) ^[11]

Symptoms of LADA is quite similar to what a patient with type 1 or type 2 diabetes would undergo - losing weight in spite of a good/increased appetite, blurry vision, urge to pee often, feeling thirsty, etc. Apart from these, the other common signs shown by LADA patients are

• weakness and tiredness,
• tingling sensation in the hands and the feet,
• feeling hungry soon after meals,
• dry and itchy skin, and
• frequent infections.

Diagnosis Of Latent Autoimmune Diabetes In Adults (LADA) ^[12]

The first sign of LADA in a patient is the fact that diabetes was detected after he or she turned 30 years of age. However, at times this factor could also be mistaken for type 2 diabetes. Nevertheless, if your condition does not seem to improve with the regular oral medication then suspecting LADA is quite obvious.

In spite of having a closer pathophysiological relationship to type 1 diabetes, few doctors often misinterpret and treat the patient for type 2 diabetes (when in reality the patient is suffering from LADA). Such form of treatment can result in insufficient glycemic control and cause a lot of harm to the patients.

Blood tests are the only way to confirm the diagnosis of LADA. The blood test conducted would check for the presence of antibodies against the insulin-making cells of the pancreas. A further test is most likely to be conducted to check for levels of a protein called C-peptide. This is the best way to attain information about how much insulin your body is producing ^[13] .

Apart from a full antibody panel, C-peptide is the ideal marker to differentiate between the various kinds of diabetes. C-peptide levels are most often undetectable in type 1 diabetes, whereas the levels are usually normal to high in type 2 diabetes. In case of LADA, the patient will tend to have low to normal initial C-peptide levels ^[14] . Evaluating C-peptide levels is the most cost-effective way of reaching a correct diagnosis when treating patients with LADA.

Response Of Latent Autoimmune Diabetes In Adults (LADA) Patients To Noninsulin Glucose-lowering Agents ^[15]

Unlike type 1 diabetes, LADA develops slowly - its β-cell functionality is lost quite gradually. Therefore, such patients may initially respond to noninsulin glucose-lowering agents. However, with time, as the functionality of the β-cell declines, the response to these medicinal agents starts diminishing.

Studies have shown that patients who have been misdiagnosed might initially respond to oral medicines, but it is quite certain that they would need insulin therapy within 5 years of diagnosis.

Treatment For Latent Autoimmune Diabetes In Adults (LADA) Patients

When misdiagnosed, doctors may keep evaluating and measuring the outcome based on oral medications considering reasons such as non-adherence. Doctors might suggest lifestyle modification when actually what the LADA patient requires is insulin therapy. Medicines that are designed to preserve β-cell functionality is found to be useful in treating patients with LADA ^[16] .

Incorrect diagnosis delays accurate treatment and can expose the patient to ^[17]

• adverse effects due to ineffective drugs,
• slow progress towards normoglycemia, and
• increased risk of long-term health complications.

According to the Immunology of Diabetes Society (IDS), the following are the proposed three criteria that standardize the definition of LADA ^[18] :

1. Age of the patient is usually 30 years or more
2. A positive titre for minimum one of the four autoantibodies
3. Not treated with insulin during the first six months post-diagnosis

GAD and ICA are the most dominant antibodies in LADA. Nevertheless, the presence of other antibodies indicates an underlying autoimmune process.

The primary reason behind patients being misdiagnosed is the consideration of age as the arbitrary screening criteria. Apart from testing positive for minimum one antibody, adding C-peptide measurement for screening purposes would be an added benefit to reach the right diagnostic conclusion ^[19] . Several research tests have revealed that C-peptide levels are much lower in people with LADA when compared to that of patients with type 2 diabetes.

Although there is no single optimal treatment for LADA, studies have revealed that early insulin therapy is safe and ensures the preservation of metabolic control. Apart from or in addition to insulin therapy, the other possible therapy/treatment options for preserving β-cell functionality are

• dipeptidyl peptidase-4 inhibitors ^[20] ,
• glucagon-like peptide 1 receptor agonists ^[21] , and
• thiazolidinediones ^[22] .

Therapy options such as sulfonylureas should be strictly avoided as they deplete the insulin levels drastically by increasing the rate of deterioration of C-peptide ^[23] .

Oral diabetes medicines like metformin only help in case of Type 2 diabetes and not if one has LADA ^[24] .

Research data shows that thiazolidinedione can help preserve beta cells in people having LADA. Incretin drugs such as liraglutide, exenatide, dulaglutide and albiglutide are also believed to increase beta-cell growth and improve glucose control ^[25] .

To Conclude...

Missing a LADA diagnosis is quite easy, especially considering the high prevalence of type 2 diabetes. To ensure an accurate treatment regimen that can effectively maintain glycemic control, it is essential that LADA gets diagnosed on time. Several studies have shown that people who were earlier misdiagnosed were found to have worse glycemic control along with high A1C levels and had to be rushed to insulin therapy ^[26] .

Ensuring early detection would potentially decrease the risk of long-term health complications due to poor glycemic control.

In general, when a patient has been diagnosed with LADA, it is quite natural to have him or her get screened for other autoimmune diseases as well. For instance, patients with LADA are more prone to thyroid disease ^[27] when compared to patients having type 2 diabetes.

It is therefore essential that health-care providers follow standardized guidelines, especially with respect to LADA, when diagnosing patients with diabetes.

Keeping the medical profession in mind, it is imperative to establish distinct practice guidelines for the diagnosis and treatment of LADA and for providers to recognize this clinical scenario as one that requires special testing to establish a proper diagnosis and thus improve patient safety and treatment efficacy.