LADA

Key considerations to improve identification of latent autoimmune diabetes in adults 

Latent autoimmune diabetes in adults (LADA) is characterized by a slower progression of autoimmune beta-cell destruction compared to classic Type 1 diabetes (T1D), often leading to its misclassification as Type 2 diabetes (T2D) at initial presentation. Research suggests up to 12% of the Type 2 diabetic population may have LADA, a diagnostic confusion that results in suboptimal treatment strategies, potentially accelerating beta-cell failure and complicating long-term disease management. With reports of LADA misdiagnosis continuing to circulate, ongoing challenges in its proper identification and management highlight a need for increased awareness and refined diagnostic approaches among healthcare providers. 

Identifying LADA

The slow destruction of beta-cell function in the pancreas, coupled with decreasing insulin sensitivity, triggers both symptoms and a treatment response characteristic of Types 1 and 2 diabetes, dubbing LADA Type 1.5 diabetes. Recognizing the difficulty in accurately detecting LADA, the American Diabetes Association (ADA) released a consensus statement in 2020 to provide guidance in its diagnosis. The panel advised screening for diabetes autoantibodies in newly diagnosed, non-insulin-requiring diabetes. 

Who is most at risk? 

Identification of LADA can be challenging, but recognizing its clinical and diagnostic characteristics can support correct treatment for patients. Those who should be tested for LADA indicators include:

• Patients presenting with poor glycemic control 
• Adults over 30 years of age, with fewer features of metabolic syndrome, such as:
  • Lower BMI 
  • Lower blood pressure* 

*It is important to note that high BMI does not preclude LADA, making diagnosis more challenging.

Autoantibody profile in LADA: Prevalence, testing and diagnostic considerations

Antibodies against GAD-65 are found to be the prevalent diabetes autoantibody in LADA patients while other autoantibodies such as islet cell autoantibodies (ICAs), tyrosine phosphatase-related islet antigen 2 (IA-2A), insulin autoantibodies (IAAs), and zinc transporter 8 antibodies (ZnT8As) are less frequent but have been described in case studies of LADA. The majority of assays measuring diabetes autoantibodies are either radioimmunoassay or enzyme-linked immunosorbent assay (ELISA), where the median specificity has been standardized to 98.9% for assays measuring antibodies against GAD-65. Moreover, LADA patients who test positive for N-terminally truncated GAD-65 but not the full-length GAD-65 assays typically have disease presentation more akin to classical T1D. When it comes to interpreting diabetes autoantibody positivity for the diagnosis of LADA, one caveat is that testing positive for only a single autoantibody may represent false positivity, especially in an adult patient lacking other suggestive clinical features of LADA. Therefore, clinical indications and additional testing may be helpful.

C-peptide is another biomarker that may help guide decisions on choosing the appropriate pharmacologic therapy. As a surrogate of insulin reserve, C-peptide will slowly decline in LADA, unlike in T1D where it will decline more rapidly or T2D where it remains normal or high for many years. While C-peptide levels alone cannot make the diagnosis of LADA, it can aid in its management. To that end, Labcorp’s C-peptide test offers additional insights that can bring clarity in the evaluation of LADA.

Overcoming challenges in LADA diagnosis

Adults with high blood sugar can easily be misdiagnosed with T2D, potentially leading to worsening disease outcomes or other complications associated with hyperglycemia, including diabetic ketoacidosis and hastened insulin insensitivity. While the diagnosis of LADA remains challenging, following the ADA guidance to screen newly diagnosed, non-insulin-requiring diabetic patients can help close gaps in care. This proactive approach can lead to a better prognosis for individuals with LADA, facilitating timely interventions that prevent mismanagement and its associated complications.

To support this crucial diagnostic process, Labcorp offers the Diabetes Autoimmune Profile to aid in the identification of T1D and LADA. The comprehensive profile includes four antibodies associated with autoimmune diabetes: GAD-65, ICA, IAA and ZnT8. Collectively, these four antibodies have a 98% detection rate, offering a reliable tool to better inform treatment decisions.