Sunday, January 28, 2024

Latent Autoimmune Diabetes in Adults (LADA): recognition and management

A recent KFF Health News article highlighted misdiagnoses of type 2 diabetes in several Black female patients who actually had latent autoimmune diabetes in adults (LADA), a slowly progressive form of type 1 diabetes. Although the article suggested that the patients’ race may have played a role in delaying their LADA diagnoses, this condition commonly goes unrecognized in primary care. According to Dr. Jeff Unger in a 2010 American Family Physician editorial, an estimated 10% of patients with a diagnosis of type 2 diabetes actually have LADA.

Unlike patients with classic type 1 diabetes, patients with LADA have initially preserved pancreatic beta cell function and thus may have a transient response to noninsulin therapy and lifestyle modifications. However, as the disease progresses, they will require insulin to maintain blood glucose control, generally within one year of diagnosis.

A feature that distinguishes LADA from type 2 diabetes is the presence of at least one autoantibody, most commonly islet call antibodies or antibodies to glutamic acid decarboxylase (GAD). While persons with type 2 diabetes have normal to high C-peptide levels, patients with LADA tend to have low levels. Dr. Unger provided other potential clues that should prompt clinicians to reconsider a type 2 diabetes diagnosis:

Suspicion of LADA should be heightened in patients with coexisting autoimmune disorders, such as hypothyroidism, who are not excessively overweight and who have deteriorating glycemic control despite intensification of oral therapies and the use of incretin mimetics. Physicians may consider GAD antibody testing to determine whether LADA is present.

A 2020 consensus statement from an international expert panel made treatment recommendations for patients with LADA. Although insulin is effective and safe, it is unclear if it should be given to patients in the early stages of LADA who may still respond to oral therapies such as metformin. The panel discouraged the use of sulfonylureas, which may accelerate loss of beta cell function. Dipeptidyl peptidase 4 inhibitors, glucagon-like peptide receptor 1 agonists, and sodium-glucose cotransporter 2 inhibitors have shown promise in small studies, but more research is required. The panel recommended that all patients with newly diagnosed type 2 diabetes be screened for LADA with a test for antibodies to GAD, followed by tests for other autoantibodies if clinical suspicion remains high.

In patients who have one or more autoantibodies and presumed LADA, the next step is C-peptide measurement. Those with C-peptide levels greater than 0.7 nmol/L can be managed similarly to patients with type 2 diabetes; those with levels lower than 0.3 nmol/L should start insulin. Patients in the “gray area” (with a C-peptide level between 0.3 and 0.7 nmol/L), should start metformin and other noninsulin agents based on blood glucose levels and cardiovascular and kidney disease risk; C-peptide levels should be rechecked every 6 months to monitor for the development of insulin deficiency.

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This post first appeared on the AFP Community Blog.