Latent autoimmune diabetes in adults (LADA) is a form of diabetes that shares features of both type 1 and type 2 diabetes. People with LADA have autoimmune destruction of insulin-producing cells like type 1 diabetes, but the progression is slower and initially doesn’t require insulin like type 2 diabetes (1).

What Is LADA?

LADA, sometimes called type 1.5 diabetes, typically appears in adults over 30 years old. Unlike classic type 1 diabetes which develops quickly in children and young adults, LADA progresses slowly. People with LADA can often manage their blood sugar without insulin for at least 6 months after diagnosis (2).

The condition affects about 2-12% of all people diagnosed with diabetes as adults. Among those initially diagnosed with type 2 diabetes, about 4-12% actually have LADA (3).

Note
LADA is often misdiagnosed as type 2 diabetes because it develops in adults and doesn’t immediately require insulin. Getting the right diagnosis is important because the treatment approach differs.

Symptoms of LADA

The symptoms of LADA are similar to other forms of diabetes. Common symptoms include:

  • Increased thirst and frequent urination
  • Unexplained weight loss
  • Blurred vision
  • Fatigue
  • Slow wound healing

Because LADA develops slowly, symptoms may be mild at first and easily overlooked. The gradual onset often leads to initial misdiagnosis as type 2 diabetes (4).

How LADA Differs from Type 1 and Type 2 Diabetes

Understanding how LADA differs from other diabetes types helps with proper diagnosis and treatment.

LADA vs Type 1 Diabetes

While both involve autoimmune destruction of insulin-producing cells, key differences exist:

  • Age at diagnosis: Type 1 usually appears in children and young adults, while LADA typically develops after age 30
  • Speed of progression: Type 1 develops rapidly over weeks or months, while LADA progresses slowly over years
  • Initial insulin need: People with type 1 need insulin immediately, while those with LADA can often go 6 months or more without it

Research shows that people with LADA have different genetic markers compared to those with classic type 1 diabetes. The frequency of certain high-risk genes is lower in LADA (5).

LADA vs Type 2 Diabetes

LADA is often mistaken for type 2 diabetes, but important differences exist:

  • Autoimmune component: LADA involves autoimmune attack on insulin-producing cells, while type 2 typically doesn’t
  • Body weight: People with LADA tend to be leaner than those with type 2 diabetes
  • Insulin production decline: Beta cell function declines much faster in LADA than in type 2 diabetes
  • Treatment response: LADA patients often don’t respond well to type 2 diabetes medications long-term

Studies show that people with LADA have a lower body mass index (BMI) and less metabolic syndrome compared to those with type 2 diabetes (6).

Causes and Risk Factors

LADA results from a combination of genetic susceptibility and environmental factors.

Genetic Factors

LADA has a strong genetic component. People with certain gene variants have a higher risk of developing the condition. The most important genetic risk factors are in the HLA region, similar to type 1 diabetes (7).

Interestingly, LADA also shares some genetic risk factors with type 2 diabetes. Certain gene variants associated with type 2 diabetes, particularly TCF7L2, also increase LADA risk (8).

Family History

Having family members with diabetes increases your risk of LADA. People with LADA are more likely to have relatives with either type 1 or type 2 diabetes. Having a family history of type 1 diabetes increases LADA risk almost 6-fold, while a family history of type 2 diabetes nearly doubles the risk (9).

Environmental and Lifestyle Factors

Several lifestyle factors associated with type 2 diabetes also increase LADA risk:

  • Overweight and obesity: Each 5-point increase in BMI raises LADA risk by 19%
  • Physical inactivity: Lack of exercise increases risk
  • Smoking: Current smoking increases LADA risk
  • Low birth weight: Being born with low birth weight increases risk

Research shows that lifestyle factors promoting insulin resistance, similar to type 2 diabetes, contribute to LADA development (10).

Low birth weight particularly stands out as a risk factor. People who weighed less than 3 kg at birth have more than double the risk of developing LADA compared to those who weighed 4 kg or more (11).

Tip
While you can’t change your genetic risk or birth weight, maintaining a healthy weight, exercising regularly, and not smoking may help reduce your risk of developing LADA.

Diagnosis of LADA

Diagnosing LADA requires specific tests to detect autoimmune markers.

Warning
LADA is often misdiagnosed as type 2 diabetes. If you’re not responding well to type 2 diabetes medications or need insulin sooner than expected, ask your doctor about antibody testing. Proper diagnosis is crucial for getting the right treatment.

Autoantibody Testing

The key to diagnosing LADA is finding autoantibodies that attack insulin-producing cells. The most important test is for GAD antibodies (GADA). About 90% of people with LADA have positive GADA (12).

Other autoantibodies that may be tested include:

  • IA-2 antibodies (found in about 30% of LADA cases)
  • Zinc transporter 8 antibodies (ZnT8A)
  • Insulin autoantibodies

Who Should Be Tested?

Not everyone with adult-onset diabetes needs autoantibody testing. Consider testing if you:

  • Are diagnosed with diabetes before age 50
  • Have a BMI less than 25
  • Have a personal or family history of autoimmune disease
  • Don’t respond well to type 2 diabetes medications
  • Need insulin sooner than expected

The UKPDS study found that younger age at diagnosis, being Caucasian, and having a lower BMI were associated with higher likelihood of having autoantibodies (13).

C-Peptide Testing

C-peptide is a marker of how much insulin your body produces. People with LADA typically have C-peptide levels between those seen in type 1 and type 2 diabetes. This test helps assess remaining beta cell function and guide treatment decisions (14).

Fact
Studies show that 40% of people over 30 with type 1 diabetes may have initially been misdiagnosed with type 2 diabetes. Proper antibody testing can prevent this misdiagnosis.

Treatment Options

Treatment for LADA aims to preserve remaining insulin production and maintain blood sugar control.

Early Insulin Treatment

Starting insulin early may help preserve beta cell function in LADA. Studies show that people with high GAD antibody levels benefit from early insulin treatment rather than oral diabetes medications (15).

The international consensus recommends using insulin when C-peptide levels fall below certain thresholds. People with very low C-peptide (less than 0.3 nmol/L) should use multiple daily insulin injections, similar to type 1 diabetes treatment (1).

Oral Medications

Some oral medications may help in early LADA:

  • Metformin: Can be used initially, especially if overweight
  • DPP-4 inhibitors: May help preserve beta cell function
  • SGLT2 inhibitors: Can improve blood sugar but require careful monitoring

Sulfonylureas, commonly used for type 2 diabetes, should be avoided in LADA. They can exhaust remaining beta cells and lead to faster progression to insulin dependence (12).

Newer Treatments

Several newer treatments show promise for LADA:

  • DPP-4 inhibitors with vitamin D: Adding vitamin D to saxagliptin may help preserve beta cell function
  • GLP-1 receptor agonists: Dulaglutide has shown effectiveness in LADA patients
  • Combination therapy: Saxagliptin with dapagliflozin was non-inferior to insulin in preserving beta cell function

A recent study found that adding vitamin D (2000 IU daily) to saxagliptin helped maintain C-peptide levels in LADA patients over 12 months (16).

Warning
People with LADA using SGLT2 inhibitors have a higher risk of diabetic ketoacidosis (DKA), even with normal blood sugar levels. Close monitoring is essential if using these medications.

Disease Progression

LADA progression varies significantly between individuals.

Rate of Beta Cell Decline

The speed at which insulin production declines depends on several factors:

  • Antibody levels: Higher GADA levels predict faster progression
  • Number of antibodies: Having multiple autoantibodies means faster decline
  • Age at diagnosis: Younger people tend to progress faster
  • BMI: Lower BMI is associated with faster progression

Studies show that people with high GADA titers (above 180 U/mL) progress to insulin dependence much faster than those with low titers. About 71% of those with high titers need insulin within 7 years, compared to 42% with low titers (17).

Time to Insulin Requirement

Most people with LADA eventually need insulin, but the timeline varies:

  • 50% require insulin within 3-4 years of diagnosis
  • 80% need insulin within 6 years
  • Some may not need insulin for 10-12 years

Those with multiple autoantibodies typically need insulin within 5 years, while those with only GADA may take longer (2).

Complications and Associated Conditions

People with LADA face similar complications to other forms of diabetes, plus some unique challenges.

Diabetes Complications

LADA can lead to the same complications as other diabetes types:

  • Diabetic ketoacidosis (DKA): A life-threatening condition where the body produces high levels of acids called ketones
  • Diabetic retinopathy: Eye damage that can lead to vision loss
  • Diabetic neuropathy: Nerve damage causing pain or numbness
  • Diabetic nephropathy: Kidney damage
  • Cardiovascular disease: Heart disease and stroke

Diabetic ketoacidosis is a particular concern for people with LADA. As beta cell function declines and insulin production decreases, the risk of DKA increases. This can happen even before you start insulin therapy. DKA symptoms include excessive thirst, frequent urination, nausea, vomiting, stomach pain, and fruity-smelling breath. It requires immediate medical attention.

Interestingly, people with LADA may have more severe neuropathy compared to those with type 2 diabetes, despite similar disease duration. This includes both large and small nerve fiber damage (18).

Other Autoimmune Conditions

People with LADA have a higher risk of developing other autoimmune diseases:

  • Thyroid disease: Both overactive and underactive thyroid
  • Celiac disease: Gluten intolerance
  • Addison’s disease: Adrenal gland insufficiency
  • Vitamin B12 deficiency: Due to pernicious anemia

Regular screening for thyroid disease is particularly important, as it’s the most common associated autoimmune condition (19).

Metabolic Syndrome

While less common than in type 2 diabetes, many people with LADA develop metabolic syndrome. About 37% have metabolic syndrome, compared to 67% with type 2 diabetes. This includes:

  • High blood pressure
  • Abnormal cholesterol levels
  • Excess belly fat

Having metabolic syndrome along with LADA increases cardiovascular risk (20).

Life Expectancy and Long-Term Outlook

Understanding the long-term outlook for LADA helps with planning treatment and lifestyle choices.

Mortality Risk

Research shows mixed findings about mortality risk in LADA:

  • Some studies show LADA has a higher mortality risk compared to people without diabetes. One Swedish study found a 44% increased risk of death (hazard ratio 1.44) in people with LADA compared to non-diabetic controls (21).
  • Other studies suggest LADA may have lower mortality compared to type 2 diabetes. A Danish study of over 4,000 patients found LADA was associated with lower mortality and fewer cardiovascular events compared to both type 2 diabetes and insulin-deficient diabetes (22).

Importance of Blood Sugar Control

The most important factor affecting life expectancy appears to be blood sugar control. A large Norwegian study found that mortality in autoimmune diabetes was as high as in type 2 diabetes, despite having a better metabolic profile. The excess risk was mainly associated with poor glycemic control (23).

This highlights that maintaining good blood sugar control is crucial for improving long-term outcomes in LADA.

Cardiovascular Disease Risk

People with LADA have different cardiovascular risk patterns compared to type 2 diabetes:

  • Initially, LADA patients may have a lower risk of heart disease due to being leaner and having less metabolic syndrome
  • However, over time, poor blood sugar control can increase cardiovascular risk
  • UK data showed that the long-term risk of major cardiovascular events was lower in LADA compared to type 2 diabetes, but this difference disappeared when accounting for traditional risk factors like blood pressure and cholesterol (24)

Complication Risk Over Time

The risk of diabetes complications in LADA changes over time:

  • In the first 9 years after diagnosis, people with LADA have a lower risk of microvascular complications compared to type 2 diabetes
  • After 9 years, the risk becomes higher than in type 2 diabetes
  • This increased later risk is entirely explained by poorer blood sugar control in LADA patients over time (25)
Fact
Studies show that people with LADA who maintain good blood sugar control have similar life expectancy to those with type 2 diabetes. The key is early diagnosis, appropriate treatment, and consistent management.

Factors Affecting Prognosis

Several factors influence long-term outcomes in LADA:

  • Early diagnosis and treatment: Starting appropriate therapy early helps preserve beta cell function
  • Blood sugar control: Maintaining HbA1c at target levels reduces complication risk
  • Cardiovascular risk management: Controlling blood pressure, cholesterol, and other risk factors is important
  • Regular monitoring: Screening for complications allows early intervention

The overall message is encouraging: with proper management, people with LADA can have good long-term outcomes. The key is getting the right diagnosis, starting appropriate treatment, and maintaining good control of blood sugar and other risk factors.

Can LADA Be Prevented?

Unlike type 2 diabetes, which can often be prevented or delayed through lifestyle changes, LADA cannot be prevented. This is because LADA is an autoimmune condition where your immune system mistakenly attacks insulin-producing cells.

While you can’t prevent the autoimmune process, research suggests that maintaining a healthy lifestyle might delay when symptoms appear or slow disease progression. Lifestyle factors like maintaining healthy weight, exercising regularly, and not smoking may influence when LADA develops in people who are genetically susceptible (10).

Getting an early diagnosis and starting appropriate treatment is the best way to manage LADA and prevent complications.

Living with LADA

Managing LADA successfully involves more than just controlling blood sugar.

Blood Sugar Monitoring

Regular monitoring helps track disease progression and treatment effectiveness:

  • Check blood sugar levels as recommended by your healthcare provider
  • Monitor HbA1c every 3-6 months
  • Consider continuous glucose monitoring if on insulin

Lifestyle Management

Healthy lifestyle choices are important for managing LADA:

  • Diet: Focus on balanced meals with controlled carbohydrates
  • Exercise: Regular physical activity improves insulin sensitivity
  • Weight management: Maintaining healthy weight can slow progression
  • Stress management: Chronic stress can affect blood sugar control

Regular Medical Care

People with LADA need regular medical follow-up:

  • Diabetes specialist visits every 3-6 months
  • Annual screening for complications
  • Regular C-peptide testing to monitor beta cell function
  • Screening for other autoimmune conditions
Tip
Keep a record of your blood sugar levels, medications, and how you feel. This information helps your healthcare team adjust your treatment plan as LADA progresses.

Future Outlook

Research continues to improve our understanding and treatment of LADA.

Emerging Treatments

Several promising treatments are being studied:

  • Immunomodulation therapy: GAD-alum injections to slow autoimmune attack
  • Combination therapies: Using multiple medications to preserve beta cells
  • Personalized medicine: Tailoring treatment based on antibody levels and genetics

Recent trials show that intra-lymphatic GAD-alum injections may help preserve beta cell function in LADA patients (26).

Importance of Early Detection

Identifying LADA early allows for:

  • Appropriate treatment to preserve beta cell function
  • Better long-term blood sugar control
  • Reduced risk of complications
  • Screening for associated autoimmune conditions

When to See a Healthcare Provider

Knowing when to seek medical attention is important for managing LADA effectively.

Seek Immediate Medical Care If You Experience:

  • Symptoms of diabetic ketoacidosis: excessive thirst, frequent urination, nausea, vomiting, stomach pain, fruity breath odor, or confusion
  • Severe low blood sugar that doesn’t improve with treatment
  • Signs of infection that won’t heal
  • Sudden vision changes
  • Chest pain or difficulty breathing

Schedule an Appointment If You Notice:

  • Your blood sugar levels are consistently higher than target despite following your treatment plan
  • You’re having frequent low blood sugar episodes
  • New or worsening numbness or tingling in your hands or feet
  • Wounds or sores that are slow to heal
  • Unexplained weight loss
  • Increased fatigue despite good blood sugar control

Consider LADA Testing If:

  • You were diagnosed with type 2 diabetes but aren’t responding well to oral medications
  • You’re leaner than typical for type 2 diabetes (BMI less than 25)
  • You have a personal or family history of autoimmune conditions
  • You needed insulin sooner than expected after diagnosis

Conclusion

LADA is a unique form of diabetes that requires specific management

If you’ve been diagnosed with type 2 diabetes but aren’t responding well to standard treatments, or if you’re leaner than typical for type 2 diabetes, consider asking your doctor about LADA testing. Early recognition and proper treatment can make a significant difference in managing this condition effectively.

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