Latent Autoimmune Diabetes in Adults

Definition and Clinical Characteristics

LADA is defined by the presence of circulating islet autoantibodies, which distinguishes it from type 2 diabetes, and is characterized by autoimmune destruction of pancreatic beta-cells that progresses more slowly than classical type 1 diabetes, with insulin dependence typically developing over a few years rather than weeks to months, in adults typically diagnosed after age 30-35 years 1, 2
The presence of islet autoantibodies, particularly glutamic acid decarboxylase antibodies (GADA), protein tyrosine phosphatase antibodies, insulin autoantibodies, or zinc transporter protein antibodies, is a key diagnostic criterion for LADA, which distinguishes it from type 2 diabetes 1, 2

LADA accounts for approximately 5-10% of adults initially diagnosed with apparent type 2 diabetes, and patients often present with a phenotype that appears similar to type 2 diabetes, but with lower BMI, fewer metabolic risk factors, and better lipid profiles compared to true type 2 diabetes patients 3
Patients with LADA typically have clinical features suggestive of autoimmune diabetes, such as younger age at diagnosis, unintentional weight loss, lean body habitus, ketoacidosis, or rapid progression to insulin requirement, and personal or family history of autoimmune diseases 4, 5

Testing for islet autoantibodies, particularly GADA, should be considered in adults presenting with diabetes who have clinical features suggestive of autoimmune diabetes, such as younger age at diagnosis, unintentional weight loss, lean body habitus, ketoacidosis, or rapid progression to insulin requirement, and personal or family history of autoimmune diseases 3, 5
The American Diabetes Association recommends testing for islet autoantibodies in adults with apparent type 2 diabetes who have clinical features suggestive of autoimmune diabetes, to aid in the diagnosis of LADA 3

Antibody testing limitations, such as islet autoantibodies not being detectable in all patients and decreasing with age, approximately 5-10% of type 1 diabetes patients may be antibody-negative, highlight the importance of considering clinical features suggestive of autoimmune diabetes in the diagnosis of LADA 3, 6

The American Diabetes Association recommends standardized islet autoantibody tests for classification of diabetes in adults with phenotypic overlap between type 1 and type 2 diabetes 7
Order the following autoantibody panel: Glutamic acid decarboxylase antibodies (GADA), Islet antigen-2 antibodies (IA-2A), Zinc transporter 8 antibodies (ZnT8A), and Insulin autoantibodies (IAA) 7, 8
Standard diabetes workup should include fasting plasma glucose (≥126 mg/dL diagnostic for diabetes), HbA1c (≥6.5% diagnostic for diabetes), and C-peptide levels to assess beta-cell function 9, 10

Use the staging system for autoimmune diabetes: Stage 1 (multiple islet autoantibodies + normoglycemia + presymptomatic), Stage 2 (islet autoantibodies + dysglycemia + presymptomatic), and Stage 3 (islet autoantibodies + overt diabetes + symptomatic) 7, 8
Longitudinal follow-up of subjects with two or more islet autoantibodies is recommended to track disease progression through these stages 8

Single positive antibody (present in 1-2% of healthy individuals) has low predictive value for diabetes progression 7, 8
Antibody prevalence varies by race: 85-90% in white patients with type 1 diabetes versus only 19% in black or Hispanic patients 9