From the Guidelines
The workup for Latent Autoimmune Diabetes (LAD) should include clinical assessment and laboratory testing, with a focus on autoantibody screening, particularly glutamic acid decarboxylase antibodies (GAD65), and measurement of C-peptide levels to assess endogenous insulin production. The diagnosis of LAD is crucial as it affects the management and treatment of the disease, with LAD patients often requiring early insulin therapy to preserve beta cell function 1.
Clinical Assessment
The clinical presentation of LAD often includes adults over 30 years with features atypical for type 2 diabetes, such as a lean body habitus, absence of metabolic syndrome, and poor response to oral medications. A comprehensive medical history and physical examination should be performed to identify any signs or symptoms of autoimmune disorders, such as Hashimoto thyroiditis, Graves disease, or celiac disease.
Laboratory Testing
The key diagnostic tests for LAD include:
- Autoantibody screening, particularly GAD65, which is positive in 70-80% of LAD patients
- Additional antibody tests like islet cell antibodies (ICA), insulin autoantibodies (IAA), and zinc transporter 8 antibodies (ZnT8) to increase diagnostic sensitivity
- Measurement of C-peptide levels to assess endogenous insulin production; LAD patients typically have detectable but lower levels than type 2 diabetes patients
- Genetic testing for HLA-DR3 and HLA-DR4 haplotypes, which are associated with autoimmune diabetes
Management and Treatment
Early identification of LAD is crucial as these patients progress to insulin dependence more rapidly than type 2 diabetes patients, usually within 5 years of diagnosis. Early insulin therapy is generally recommended to preserve beta cell function, starting with basal insulin at 0.1-0.2 units/kg/day, with adjustments based on glucose monitoring 1. The goal of treatment is to achieve optimal glucose control, prevent complications, and improve quality of life.
Key Considerations
- The rate of beta cell destruction is variable, and some patients may retain sufficient beta cell function to prevent diabetic ketoacidosis (DKA) for many years
- Adults with LAD may have remission or decreased insulin needs for months or years, but eventually become dependent on insulin for survival and are at risk for DKA
- Genetic testing is important for genetic counseling and identifying potential associated conditions.
From the Research
Diagnostic Criteria for Latent Autoimmune Diabetes (LAD)
The workup for Latent Autoimmune Diabetes (LAD) involves several diagnostic criteria, including:
- Age of onset: typically <50 years old 2
- Initial response to oral hypoglycemic agents: may be treated initially without insulin 3
- Presence of specific antibodies for diabetes: such as autoantibodies against pancreatic beta cells, including glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2), and insulin 4
- C-peptide levels: normal or close to normal values 2
- BMI: <25 kg/m2 2
- Magnitude of postprandial and basal hyperglycemia: low 2
Laboratory Tests
Laboratory tests used to diagnose LAD include:
- Autoantibody testing: to detect autoantibodies against β-cells, such as GAD, IA-2, and insulin 4, 5
- C-peptide levels: to assess β-cell function 2, 5
- Glycated hemoglobin (HbA1c): to assess glucose control 2
- Homeostasis model assessment of β-cell function and insulin resistance: to assess β-cell function and insulin sensitivity 2
Challenges in Diagnosis
Diagnosing LAD can be challenging due to its similarity to type 2 diabetes, and the lack of clear diagnostic criteria 6, 3, 5. Autoantibody testing may not be feasible in all cases, and the disease may be misdiagnosed as type 2 diabetes 5. Therefore, a high index of suspicion and careful evaluation of clinical and laboratory features are necessary to make an accurate diagnosis.