Clinical_Rounds_in_Endocrinology_Volume_II_-_Pediatric_Endocrinology

405

During the initial stage, T-cell-mediated (CD-4 positive) β-cell injury

results in insulitis. This stage is characterized by the appearance of multiple

islet cell autoantibodies (ICAs). With progressive β-cell damage, there is a

loss of first-phase insulin response followed by the development of glucose

intolerance. This phase is referred as prediabetes phase of T1DM and is

usually observed 1–2 years prior to the development of overt diabetes.

Eventually, with further progression of β-cell destruction (>95 %), there is

development of severe hyperglycemia and ketoacidosis. However, the pre-

diabetes phase is usually not appreciated in patients with T1DM because of

rapid destruction of β-cells.

11. What is the islet antibody profile in patients with type 1 DM?

The islet autoantibodies in patients with T1DM include anti-GAD-65 anti-

body, islet cell autoantibody (ICA), insulinoma-associated antigen 2 (IA-

2) antibody, anti-insulin antibody (IAA), and anti-zinc transporter antibody

(ZnT8). One or more of these autoantibodies are present in >95 % of newly

diagnosed patients with T1DM, and the presence of ≥2 autoantibodies

have a high predictive value for the diagnosis of T1DM. The characteris-

tics of islet antibodies in patients with T1DM are summarized in the table

given below.

Autoantibody

Age at diagnosis Duration of disease

<15 years (%) >15 years (%) At diagnosis (%) At 10 years (%)

ICA 80–85 60–80 85 10

Anti-GAD-65 65 70–80 80 50

IA-2 70–80 40–60 80 50

IAA 30–65 20–35 – –

ZnT8 – – 60–80 –

In those with onset of T1DM in childhood, ICA and IA-2 are the most prevalent

autoantibodies, while anti-GAD-65 autoantibodies are the most common anti-

bodies in adolescents and adults. Nevertheless, prevalence of autoantibody

positivity progressively declines with advancing duration of disease. However,

anti-GAD-65 antibody is positive in 50 % of patients even 10 years after the

onset of disease.

12. What is GAD-65?

Glutamic acid decarboxylase (GAD) is an enzyme which catalyzes the decar-

boxylation of glutamate to gamma-aminobutyric acid (GABA). There are two

isoforms of GAD: GAD65 expressed in the pancreas and GAD67 in the central

nervous system. In pancreas, GAD-65 is selectively expressed in β-cells and

mediates the synthesis of GABA which inhibits insulin and glucagon secretion

in a paracrine manner.

12 Diabetes in the Young