COMMENTARY

What Is LADA and How Should We Treat It?

Anne L. Peters, MD

Disclosures

October 23, 2020

This transcript has been edited for clarity.

Today I'm going to discuss LADA, or latent autoimmune diabetes in the adult, which is an area that I've long felt perplexed about. I don't know how to define it. The ADA doesn't know how to define it. Nobody knows how to define it. And yet, a group of people from around the world just published in the journal Diabetes a consensus statement about LADA.

This consensus statement defines LADA and then talks about how it should be managed. I don't entirely agree with it, but I think it's a good starting point. Let's first discuss what they say and then I'll tell you what I think.

Defining LADA

The authors say that LADA is adult-onset diabetes with shared features of type 1 and type 2 diabetes. They say that patients with LADA resemble those with type 2 diabetes by not requiring initial insulin treatment, but they have immunogenic markers associated with type 1 diabetes, primarily anti-GAD antibodies. They say that LADA accounts for 2%-12% of all patients with adult-onset diabetes. Based on these, they think we should deviate from the standard treatment guidelines when treating these individuals and treat them based on changes in C-peptide levels.

There is a table titled "Broad Characteristics of LADA," and it defines the general characteristics of LADA as the following:

  • Age at onset > 30 years

  • A family or personal history of autoimmunity

  • A reduced frequency of metabolic syndrome compared with people with full-on type 2 diabetes: lower HOMA, lower body mass index, lower blood pressure, normal HDL compared with people with type 2 diabetes

  • No disease-specific difference in cardiovascular outcomes between these patients and those with type 2 diabetes

  • C-peptide levels fall more slowly than in traditional type 1 diabetes

  • Positivity for anti-GAD antibodies is the most sensitive marker, but other autoantibodies can be found as well, just less frequently

  • Non–insulin-requiring at onset

How Should We Treat It?

The authors define three categories of LADA based on random C-peptide levels. The first level includes people who look a lot like those with type 1 diabetes. The third level includes those who look like they have type 2 diabetes. And then there are those in the middle.

Category one is defined as a C-peptide level of < 0.3 nmol/L, and these people are treated with intensive insulin regimens.

Category two includes individuals with C-peptide values ≥ 0.3 and ≤ 0.7 nmol/L. These individuals fall into a gray area, meaning that maybe they need some insulin, maybe they don't, but you may need to follow them more closely because they have antibodies and low-ish C-peptide levels. The authors recommend using a modified ADA/EASD algorithm for the treatment of type 2 diabetes, with the caveat that one may need to start insulin therapy earlier to help modulate beta-cell failure and to limit diabetic complications.

In category three, which is C-peptide values > 0.7 nmol/L, they recommend a different modified ADA/EASD algorithm in which C-peptide levels are monitored to adjust treatment.

In terms of the treatment of patients with LADA, I'm not going to go through all of their algorithms, but here are the basics: You just have to remember that these are patients who have evidence of autoimmunity and they have varying C-peptide levels. If a patient isn't responding to type 2 medications, you're going to use insulin. And you're going to be more likely to use insulin sooner because, as a clinician, you know that these patients are relatively insulin deficient.

The algorithms recommend against using sulfonylurea reagents because they're concerned that these will burn out the patients' beta cells, although I'm not sure that this is based on much data. They also recommend caution when using SGLT2 inhibitors because they're afraid that if these patients are more like someone with type 1 diabetes, the risk for diabetic ketoacidosis could be increased.

Finally, for the patients who look most like those with type 2 diabetes, those with the highest C-peptide levels, they recommend monitoring C-peptide levels to determine which treatment to start next. This isn't based on any real data. No one has ever done this before.

My Take

I don't know if I entirely agree with it. We tend to follow patients clinically and look at their response to various therapies. But this is a good start, because it's beginning to create a framework for defining LADA. It's beginning to create a treatment paradigm based on whether these patients have residual beta-cell function.

I think it leads us to many questions for which there are no answers, but at least it's a beginning to try to help us out of the muddle of defining LADA.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California (USC) Keck School of Medicine and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

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