Diabetes

Clinical information

Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the insulin-producing β-cells of the pancreatic islets of Langerhans are destroyed. The disease is considered to be caused by genetic predisposition or exogenous factors such as viral infections, nutrition and excess weight. The group of autoantibodies that occur with T1DM are referred to as islet cell antibodies (ICA) and are directed against several antigens of the pancreatic islet cells. The most important ones are the 65-kDa isoform of the enzyme glutamate decarboxylase (GAD65), insulinoma-associated antigen 2 (IA2), zinc transporter 8 (ZnT8) and insulin.

The autoimmune reaction usually sets on years before the hyperglycaemic T1DM symptoms. The destruction process, referred to as insulitis, is characterised by infiltration of immune cells into the pancreatic islets. T1DM manifests when the majority of β cells have died off and the blood sugar level can no longer be regulated. This occurs mostly in childhood or adolescence. T1DM is the most severe form of diabetes and leads to dependency on life-long insulin injections. 5 to 10% of all diabetes cases are of type 1. The worldwide incidence of T1DM increases by 3 to 5% each year.

Diagnostics

ICA are detected in 70 to 80% of newly diagnosed T1DM cases. Usually, the different antibodies of this group develop subsequently, and not in parallel. The development of ICA precedes the manifestation of T1DM by months, if not years. In 90% of patients, one or more ICA can be detected in serum even before clinical symptoms occur. The higher the number of different ICA in one person, the higher their risk of developing T1DM.

Autoantibodies against insulin (IAA) are usually the first ones to appear with T1DM. They can be found in almost all prediabetic persons. The prevalence of IAA at disease onset decreases with increasing patient age. In around 80% of patients under 10 years and in around 60% of patients between 10 and 20 years of age, IAA titers are detected. Children under the age of 5 years show the highest IAA titers.

Autoantibodies against GAD65 (GADA) are found in around 70 % of patients prior to the onset of T1DM and in 70 to 90% of T1DM patients at the onset of disease. GADA are the most sensitive marker for T1DM with onset in adult age and for latent autoimmune diabetes in adult age (LADA). LADA is present in 3 to 12% of patients with phenotypical diabetes mellitus type 2, characterised by insulin resistance and a disturbed insulin secretion of β cells. 90% of LADA patients have GADA and most of them are already GADA-positive even several years prior to the diagnosis.

Autoantibodies against IA2 (IA2A) are detected in 50 to 70% of children and adolescents and in 30 to 50% of adults with newly diagnosed T1DM. In around half of patients, IA2A are detected prior to the manifestation of the disease. IA2A are highly specific for T1DM.

Anti-ZnT8 antibodies are detectable in the serum of many children with prediabetes. They persist until manifestation of T1DM. Within the first years after disease onset, the anti-ZnT8 levels decline quickly. Anti-ZnT8 antibodies are also found in nearly 25% of LADA patients. Their presence, alongside that of other autoantibodies, may indicate the progression of the LADA patient into an insulin-depending stage.

The combined detection of antibodies against GAD65, IA2, ZnT8 and insulin helps to detect T1DM in 98% of cases already at disease onset.

Files

Test systems for the diagnosis of diabetes mellitus type I

Typ I diabetes mellitus