LADA...More than Meets the Eye

What subtype of diabetes affects approximately 10% of individuals with it, yet often is misdiagnosed or under recognized and lacks consensus on crucial questions about it, such as how it develops and how it’s defined? Latent autoimmune diabetes in adults (LADA), also known as type 1.5 diabetes, is the answer. How do diabetologists describe and think about LADA?

Steven Edelman, MD, director and co-founder of Taking Control of Your Diabetes (TCOYD), remarked, "To me, LADA means type 1 diabetes developed later than the classic childhood ages. But also it is much tougher to diagnose and is missed a lot because there is slow beta cell destruction, so people do not crash and burn in the ICU due to DKA. Caregivers think they have type 2 because of their age, and they may also respond to oral agents but generally very poorly and eventually go on insulin and behave like a typical type 1."¹

Also weighing in was Anne Peters, MD, CDE, Professor of Medicine at the Keck School of Medicine of the University of Southern California (USC), and the Director of the USC Westside Center for Diabetes: "I don't think there is an official definition of LADA. It is simply autoimmune type 1 diabetes with onset in adulthood. Usually antiGAD antibodies are positive. Generally, it is a clinical diagnosis – a lean, new onset 30-year-old even with negative antibodies is still likely a type 1 (antibody negative LADA).¹

Serendipitously enough, in the 1970s, researchers were actually searching for something else – they were intending to investigate autoantibodies of those with T1DM. They successfully confirmed that T1DM is an autoimmune disease. When they examined these autoantibodies in individuals with T2DM and the general population, they were stunned to discover that these autoantibodies were positive in ~10% of those with T2DM; hence, the first description of LADA. Here are some other points that I find both interesting and practical, and hope you will, as well:

1. Patients with LADA are often mistakenly diagnosed with T2DM.

Patients have a clinical phenotype that resembles T2DM, but have islet autoantibodies and preserved beta-cell function, so the progression of beta-cell failure is slow. These patients thus do not typically require insulin, especially in the first six months after being diagnosed with diabetes. Approximately 80% of LADA patients will be on insulin five years after diagnosis. Currently, there are no consensus diagnostic criteria.

2. We don’t know how to treat these patients.

There are no large, randomized, prospective clinical trials on this question.² Experts debate about whether to start insulin early – as early as at the time of diagnosis of LADA – in an effort to attempt to preserve beta-cell function, or whether to hold off until the patient’s control worsens. No studies have yet examined using metformin in LADA patients.²

3. Do all patients with LADA have positive autoantibodies?

Since not all patients with LADA will be positive for glutamic acid decarboxylase (GAD) antibodies, a negative test does not necessarily rule out the diagnosis. Some may be positive only to other antibodies (Ab), such as islet cell Ab (ICA). Some may not have Ab early in their disease course, or GAD Ab may appear later in the course of LADA in other patients.

Much uncertainty surrounding LADA remains, and the above was just a brief summary of some of the unresolved questions. It’ll be intriguing to see whether future studies may help shed more light on diagnosis and management.

Disclosures:

1. Tenderich A. Some expert voices on LADA (Latent Autoimmune Diabetes in Adults). http://www.healthline.com/diabetesmine/some-expert-voices-on-lada-latent-autoimmune-diabetes-in-adults#2

2. Laugesen E, et al. Latent autoimmune diabetes of the adult: current knowledge and uncertainty. Diabet Med. 2015;32(7):843-842.