LADA
- Not just a slow motor vehicle but also an important subtype of slow onset diabetes type 1 in the adults

    Antibodies to glutamic acid decarboxylase (anti-GAD) are an important marker of autoimmune pancreatic beta-cell destruction, and are reported to be present in about 80% of European patients with, or who subsequently develop type 1 diabetes (1). Anti-GAD positively is also an important feature of Latent Autoimmune Diabetes in Adults (LADA), a condition we described and designed with this acronym in 1993 (2). This form of diabetes is now well established as a clinical entity and is recognized in the latest 1999 WHO classification of diabetes and related syndrome (3).

Type 1 is a diabetes of all ages
   The concept that type 1 diabetes is only a disorder of children and youth is incorrect. Type 1 diabetes occurs at all ages, and some 44% of all new cases in Denmark for example is diagnosed after 30 years (1). The clinical presentation can vary with age, and it generally has a classical dramatic clinical and biochemical presentation, especially in children. Failure to treat immediately with insulin can be life-threatenining.

Adult Type 1
    There is a failure to recognize the high frequency of type 1 diabetes in adults, ie, LADA, given that its presentation is not always as dramatic as in children. In addition, the age of onset of type 2 diabetes is now several decades earlier than previously described, which has confused the picture. LADA usually masquerades as insulin-requiring type 2 diabetes, and it is usually only recognized when there has been a progressive failure of standard therapies and insulin deficiency. A recent editorial in Clinical Diabetes described the implications of the identificationof the LADA grouo as "tremendous"! (5).

LADA is a masquerader
    In adults, type 1 diabetes may masquerade as type 2 diabetes at presentation with a slow detoriation in metabolic control and later progress to insulin deficiency. We designed this as LADA (2), which, in the new classification, falls within type 1 autoimmune diabetes but is a slowly progressive form. Diagnosis becomes even more of a challenge given that the age of onset of type 2 diabetes appears to have moved several decades; it is not uncommon in the 25- to 35-year age group, particularly in high-prevalence populations.

Testing?
    We suggested that testing for anti-GAD in adult onset, particularly nonobese, diabetic patients would eventually become routine for predicting future insulin dependency at a much earlier stage for initiating more appropriate therapy, and that the test assist in the correct classification of diabetes (1,2). There was considerable resistance to this idea from researchers who considered islet cell antibodies as the "gold standard". However, evidence has mounted from a host of studies that anti-GAD has a clear role in diagnosing slow-onset type 1 diabetes in adults and, indeed, in predicting future insulin dependency.

    Other workers have recommended, as we have, that all women with gestational diabetes should have an anti-GAD test. Only the widespread lack of inexpensive commerical anti-GAD assays has hindered the more widespread use in clinical practice for classification of diabetes in adults, but this will change as the assay becomes more widely available and used. Professor Paul Zimmet, Melbourne, Australia

References
1. Zimmet PZ. Diabetologia 1999;42;499-518
2. Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR. Diabetes 1993;42:359-362
3. WHO. Report of a WHO consultation. WHO, 1999
4. WHO. Technical Report Seies No 727. Geneva WHO 1985
5. Hirsch IB, Clinical Diabetes 1999;17:146-147

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