You may have heard of latent autoimmune diabetes in adults, but what is LADA? Latent autoimmune diabetes in adults (LADA) is a slow-progressing form of autoimmune diabetes. Since it emerges in adulthood, it can mimic (and be misdiagnosed as) type 2 diabetes (T2D); and, in fact, like T2D, lifestyle modifications such as exercise, diet and weight loss (together with medications, in many cases) can delay the need for insulin. Eventually, however, LADA progresses to a point, usually in years if not months, when insulin becomes required.

What Is LADA?

The question an increasing number of scientists and doctors alike are asking is not, “What is LADA?” but, rather, “Where does LADA occur on the continuum of diabetes?” Like many autoimmune disorders, diabetes appears to occur and progress along a continuum. In those terms, LADA falls between type 1 and type 2 diabetes, which is why some refer to it as type 1.5 diabetes. Other scientists, however, continue to believe that LADA is a subtype of type 1 diabetes, since your pancreas stops producing adequate insulin in both disorders — although with LADA, you typically don’t need insulin for several months to several years post-diagnosis.

Estimates of the number of people affected by LADA vary. As described in a comprehensive 2022 review paper, there may be anywhere from 17 to 50 million people with LADA, based on the approximation that 4-12% of the 422 million people who have diabetes globally (World Health Organization) have the LADA disorder.

The Immunology for Diabetes Society (IDS) has specified three criteria for the diagnosis of LADA:

1.  Age greater than 35 years
2.  Positive autoantibodies to islet beta cells
3.  Insulin independence for at least the initial 6 months after initial diagnosis

However, authors of the 2022 review note that “this set of criteria has been challenged, especially because the choice of insulin as a treatment is highly physician dependent.” They go on to explain that LADA is immunologically similar to T1D as antibodies to islet beta cells are present, albeit at lower titers; but with LADA, immune destruction progresses at a much slower rate when compared to classic T1D. The majority of LADA patients present with hyperglycemia (high blood glucose) that is not as dramatic as with T1D, and they are often misdiagnosed and managed as T2D. “Only later is it realized that they have poor control with many conventional agents, especially sulfonylureas, and eventually require insulin therapy.”

LADA itself is a heterogeneous disease, which meant that some patients have high antibody titers, a low body mass index (BMI) and progress to insulin therapy faster; others have low antibody titers, features of insulin resistance (like a higher BMI) and progress more slowly to requiring insulin.

How is LADA diagnosed?

The only way to confirm a diagnosis of LADA is through a blood test that checks for antibodies against the insulin-making cells of the pancreas. Your doctor may also check for levels of a protein called C-peptide to get information on how much insulin your body is making. 

Sometimes, a young adult with maturity-onset diabetes of the young (MODY) is mistakenly diagnosed as having LADA. MODY is a rare disorder, has a strong family history, and can be distinguished from LADA by different results on a C-peptide test.

According to Cleveland Clinic, “LADA should be considered in any non-obese patient who has onset of diabetes as a young adult, especially if frequent addition of oral glucose-lowering agents is needed to maintain glycemic control. This medication use pattern suggests insulinopenia, the main pathophysiologic defect in LADA. When LADA is suspected, glutamic acid decarboxylase and islet cell antibody testing should be performed. If these tests are positive for autoimmunity, then these patients should be switched to a regimen that includes insulin. If antibody testing is not done, but the patients have clinical features consistent with LADA — including progressive loss of glycemic control that is more rapid than commonly seen with type 2 diabetes — then insulin therapy should be initiated, even without testing for antibodies associated with type 1 diabetes.”

How is LADA treated?

As indicated above, physicians often begin insulin therapy for LADA patients who test positive for autoimmunity and have progressive loss of glycemic control. However, according to the Mayo Clinic, in the early months of LADA (in most cases), the disorder can be managed by controlling blood sugar with diet, losing weight if appropriate, upping your exercise and continuing certain oral medications. See: Non-pharmacological Treatments For Diabetes. 

After diagnosis and throughout the management of the disorder, routine tests similar to those conducted for other diabetes patients should be employed on LADA patients, at recommended intervals and as dictated by the clinical situation, such as:

• Fasting glucose
• Glycosylated hemoglobin (HbA1C)
• Self-monitoring of blood glucose (SMBG)
• Measures of glycemic variability - best done by continuous glucose monitoring (CGM)
• Lipid profile
• Estimated glomerular filtration rate (eGFR)
• Serum creatinine
• Urinalysis for albumin excretion (spot and 24-hour specimen with simultaneous creatinine)
• Tests for peripheral neuropathy (Semmes Weinstein monofilament test)
• Retinopathy screening by an ophthalmologist.

Source: Latent Autoimmune Diabetes, 2022.

If diabetes-related complications set in, other tests may be indicated.

As your body gradually loses its ability to produce insulin, you'll eventually need insulin shots.

More research is needed before the best way to treat LADA is established. Talk with your doctor about the best LADA treatment options for you. As with any type of diabetes, you'll need close follow-up to minimize progression of your diabetes and potential complications.

Prognosis

Patients with LADA have mortality as high as T2D despite having more favorable metabolic parameters. In the 2013 HUNT study, which is to date the largest population-based data on mortality in autoimmune diabetes (LADA), it was shown that hyperglycemia was the only significant influencing factor, and not the components of the metabolic syndrome, in determining mortality that was chiefly due to cardiovascular disease. Thus, strict glycemic control is the key to improving the prognosis in LADA. Importantly, recent studies also show that there is a defined “window of opportunity if detected early” as the treatment of hyperglycemia may reverse small-fiber neuropathy (SFN), which occurs early and with increased frequency in LADA when compared to T2D, and is related to higher HbA1C and poor glycemic control. 

Can you reduce the risk of getting LADA?

While it’s accepted that LADA is determined by genetic factors, it is also evident that many cases of LADA share several lifestyle risk factors with T2D: excess body weight, greater waist-hip ratio, low birth weight, intake of two or more sweetened beverages daily and heavy smoking. To date, however, there are a paucity of studies looking at such environmental factors, so their significance in terms of “causality” remains uncertain. However, a  2014 study concluded that increased physical activity, moderate alcohol use and the intake of fatty fish have a protective effect on the risk of LADA. Similarly, a 2019 meta-analysis concluded that “LADA may in part be preventable through the same lifestyle modifications as type 2 diabetes including weight loss, physical activity and smoking cessation.” However, authors added the cautionary comment that “current knowledge is hampered by the small number of studies and the fact that they exclusively are based on Scandinavian populations. There is a great need for additional studies exploring the role of lifestyle factors in the development of LADA.”

Key takeaways

LADA is a genetic disorder, but preliminary research indicates that, as with type 2 diabetes, you may be able to reduce the risk for and timing of the onset of LADA by ensuring that your blood glucose remains in a healthy range and you reduce your weight, eat a healthy diet, stop smoking and exercise regularly. Those same lifestyle modifications can also greatly benefit you if  indeed you have received a LADA diagnosis, as there are typically several months if not years when you can manage the disorder without the need for insulin if your metabolic profile is healthy, although you may need to take certain oral medications to keep your blood glucose in control. Ultimately, however, LADA patients, akin to those with type 1 diabetes, will require insulin.