Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from the cell-mediated destruction of islet beta cells. Approximately 12,000 to 15,000 children and adults annually develop T1DM. Over a period of 50 years, this amounts to 600,000 to 750,000 affected individuals. As well, these figures do not include cases of slowly-progressive T1DM that can be classified as latent autoimmune diabetes of adulthood (LADA) (1).

Two recent papers in the Lancet (2) highlight research efforts to intervene at the onset of T1DM to preserve beta-cell mass, preserve C-peptide secretion and reduce insulin requirements. In one study, two or three 20 mcg injections of glutamic acid decarboxylase (GAD)-alum were administered beginning within 100 days of the diagnosis of T1DM. Conceptually, GAD was administered to induce immunologic tolerance to a major beta cell autoantigen. Such tolerance might foster beta-cell preservation or endogenous beta-cell replacement. Unfortunately this therapy was ineffective. However in the second paper, over 2 years, the administration of abatacept was beneficial in slowing the decline in beta-cell function that otherwise occurs following the diagnosis of T1DM. Abatacept is a CTLA4–immunoglobulin fusion protein. During normal T-cell activation, B7 (on antigen-presenting cells) and CD28 (on T cells) interact providing the second signal to naïve T cells that is necessary for their activation. Soluble CTLA (abatacept) binds to B7 and blocks the B7-CD28 interaction therefore impairing the initial activation of such naïve T cells.

So what does this have to do with clinical chemistry?

My thought is…that the day is coming closer when islet autoantibody screening will become necessary. Once T1DM can either be prevented or reversed at onset, islet autoantibody testing will be required to predict T1DM or confirm that a case of new-onset diabetes is indeed autoimmune in etiology.

Such screening will very likely take place in clinical chemistry laboratories. At the present time there are 4 major autoantibody indicators of autoimmunity to the islets: islet cell cytoplasmic autoantibodies (ICA), insulin autoantibodies (IAA), glutamic acid decarboxylase autoantibodies (GADA), and insulinoma-2 associated autoantibodies (IA-2A). If 4,000,000 children were tested yearly, up to 16,000,000 islet autoantibody tests might be required yearly. In addition, since re-screening may be required to identify children that convert from islet cell autoantibody negative to positive, up to 32,000,000 islet autoantibody tests might then be required yearly.

If this topic interests you, my two brown-bag sessions at the AACC Annual meeting are on July 27 (7:30 AM and 12:30 PM; registration is required) and are entitled: "Serological Markers of Type 1 Diabetes."

So…what are your thoughts?


  1. Nambam B, Aggarwal S, Jain A. Latent autoimmune diabetes in adults: A distinct but heterogeneous clinical entity. World J Diabetes. 2010 Sep 15;1(4):111-5
  2. Wherrett DK, Bundy B, Becker DJ, et al:  Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial.  Lancet [Epub June 27, 2011]
  3. Orban T, Bundy B, Becker DJ, et al:  Co-Stimulation Modulation with Abatacept in Patients with Recent-Onset Type 1 Diabetes: A Randomized Double-Masked Controlled Trial.  Lancet [Epub June 28, 2011]