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Latent Autoimmune Diabetes in Adults (LADA) diagnosis and management

Consensus statement from an international expert panel on Latent Autoimmune Diabetes in Adults (LADA) diagnosis and management.

By Dale Cooke APD

Latent Autoimmune Diabetes in Adults (LADA) is part of the autoimmune diabetes spectrum, covered by the term type 1 diabetes, but with marked differences in endophenotypes (intermediate phenotypes which are more closely related to the root cause of LADA than the broad clinical phenotypes) across the spectrum.  It is also sometimes called type 1.5 diabetes or type 1a diabetes. While it is a well recognised form of diabetes there are no guidelines for its management. A panel of international experts gathered to develop a consensus statement for the management of LADA published in the journal, Diabetes.

Recommendations:

All those newly diagnosed with type 2 diabetes should be screened for GADA (glutamic acid decarboxylase) autoantibody positivity and potentially other autoantigens, to determine if LADA is present. Cost of testing may be a barrier but using the list below can help to select appropriate patients for further testing.

Key current diagnostic criteria for LADA are:

  • Adult-onset diabetes (greater than 30 years at diagnosis).
  • Family or personal history of autoimmunity.
  • Reduced frequency of metabolic syndrome compared with people living with type 2 diabetes:
    • lower HOMA (Homeostatic model assessment is a method for assessing beta-cell function and insulin resistance from fasting glucose and insulin or C-peptide concentrations),
    • lower body mass index,
    • lower blood pressure, and
    • normal HDL cholesterol.
  • No disease-specific difference in cardiovascular outcomes between these patients and those living with type 2 diabetes.
  • C-peptide levels decrease more slowly than in type 1 diabetes.
  • Positivity for glutamic acid decarboxylase (GADA) as the most sensitive marker; other autoantibodies less frequent (islet cell autoantibodies (ICA), tyrosine phosphatase (IA-2), autoantibodies (IA-2A), islet-specific zinc transporter isoform 8 (ZnT8A), and tetraspanin 7 autoantibodies).
  • Non–insulin requiring at onset of diabetes and for at least 6 months after diagnosis.

Note that none of these criteria are categorically definitive of LADA as it is clinically and metabolically a hybrid of type 1 and 2 diabetes.

The panel developed the following algorithms for diagnosis and treatment:

 

Figure 1: Algorithm for LADA diagnostic pathway based on autoantibody screening and C-peptide levels at diagnosis (to be used when financial restriction does not apply). **Consider also pancreatitis or monogenic diabetes.

C-peptide measurement should drive the decision-making process for the choice of LADA treatment. Three broad categories of C-peptide levels were suggested by the panel:

  • C-peptide levels <0.3 nmol/L: patients can be considered to have type 1 diabetes and approved national/international guidelines for insulin administration for type 1 diabetes can be followed.
  • C-peptide levels ≥0.3 and ≤0.7 nmol/L: defined by the panel as a “grey area” where a modified American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) algorithm for type 2 diabetes is recommended (see figures 2 and 3). The modification consists of avoiding the use of hypoglycaemic medications that may have an effect in deteriorating β-cell function. Insulin in combination with other therapies to manage or prevent complications should be considered. Follow-up of patients in this C-peptide category should take place at least every 6 months.
  • C-peptide levels >0.7 nmol/L: suggests using a modified ADA/EASD algorithm for type 2 diabetes. Patients should be followed with repeated C-peptide measurements if there is a deterioration of glucose control; note that some of these cases will have false positive autoantibodies and therefore be true type 2 diabetes.

Figure 2: Algorithm for glucose-lowering medications in LADA patients with C-peptide <0.3 mmol/L or with C-peptide ≥0.3 and ≤0.7 nmol/L. ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; CVD, cardiovascular disea

 

 

Figure 3: Algorithm for glucose-lowering medications in LADA patients with C-peptide levels ≥0.3 and ≤0.7 nmol/L without established ASCVD (atherosclerotic cardiovascular disease) or CKD (chronic kidney disease). *Deviation from ADA/EASD T2D algorithm. **Increased risk of diabetes ketoacidosis, especially in patients with BMI ≤27.

The overall objective of this personalised approach for the management of LADA is to achieve good metabolic management and to preserve β-cell function.

For this personalized approach to therapy, the first step is to establish the fundamental disease characteristics before deciding on a therapeutic path – basically which type of diabetes do they have?

The panel also recommended lifestyle modifications important in the management of LADA, including healthy eating, regular physical activity, achieving a healthy weight and smoking cessation.

They also noted more research is required to fill in key knowledge gaps for the diagnosis and treatment of LADA.

 

Reference:

Management of Latent Autoimmune Diabetes in Adults: A Consensus Statement From an International Expert Panel

Raffaella Buzzetti, Tiinamaija Tuomi, Didac Mauricio, Massimo Pietropaolo, Zhiguang Zhou, Paolo Pozzilli and Richard David Leslie

Diabetes 2020 Oct; 69(10): 2037-2047.

https://doi.org/10.2337/dbi20-0017

se; eGFR, estimated glomerular filtration rate; HF, heart failure.