Type 1 diabetes mellitus is a chronic autoimmune disease in which autoantibodies against islet cells (ICA) and glutamate decarboxylase (GADA) destroy insulin-producing pancreatic beta cells (ß cells). In this process, autoantibodies are formed that are directed against substances and structures localized inside the beta cells. Note: Autoantibodies against ICA and GADA also occur in a subgroup of clinical type II diabetics (LADA) (see indications below). Beta-cell antibodies with high diagnostic value are:
- Anti-glutamic acid decarboxylase antibody/anti-glutamic acid decarboxylase autoantibody (anti-GAD65-Ak).
- Anti-tyrosine phosphatase antibody/autoantibody to protein tyrosine phosphatase IA 2 (IA-2-Ak), an islet cell antigen (anti-IA 2).
- Autoantibodies against insulin (insulin-Ak (IgG); insulin autoantibodies (IAA)).
Other markers useful for diagnosing type 1 diabetes include islet cell antibodies (islet cell-Ak; ICA-Ak) and autoantibodies against beta cell zinc transporter 8 (zinc transporter-8-Ak; ZnT8-Ak).
Method
Material Needed
- 1 ml serum
Interfering factors
- None
Beta cell antibody
| Name | Description | Prevalence (disease incidence) at first manifestation. | Incidence in relatives1. Degree |
| Anti-GAD65-Ak | Specific for type 1 diabetes and Stiff-Man syndrome; anti-GAD65-Ak remain detectable longer than islet cell-Ak during the disease course of diabetes mellitus (thus, they can be detected even after years of onset of autoimmune diabetes). | 65-80 % | 4 % |
| IA-2-Ak | IA-2-Ak are slightly less frequently positive than GAD65- or islet cell-Ak in type 1 diabetes. | (50)-60-80 % | 1,8 % |
| Insulin Ac | Antibodies against insulin can occur as part of an autoimmune process (insulin-Ak) or as a consequence of insulin therapy with exogenous insulin (hence no determination of insulin-Ak under insulin therapy).In most cases, insulin-Ak are the first autoantibodies that can often be detected several years before the clinical manifestation of type 1 diabetes. Occurrence of the antibodies strongly age-dependent. |
100 % (children < 5 years)
~90 % (children/adolescents < 17 years) <20 % (adults > 17 years) |
2,7 % |
| Zinc transporter-8-Ak | Zinc transporter-8-Ak is detected in 25-30% of cases without any of the other autoantibodies mentioned being positive. Thus, determination of this parameter is useful for increasing overall sensitivity (>90%) | 60-80 % | 1,6 % |
| Island Cell Ak | Although islet cell AK are often the first initial beta cell antibodies that can be detected many years before manifestation of diabetes mellitus, their value is increasingly considered to be lower than that of the other beta cell antibodies. | 60-90 % | 2-6% |
Indications
- Diagnosis of type 1 diabetes/differential diagnosis between type 1 and type 2 diabetes [anti-GAD65-Ak, anti-IA 2, insulin-AK].
- Prognosis for clinical course (insulin requirement) in the diagnosis of diabetes mellitus [anti-GAD65-Ak, anti-IA 2, insulin-AK].
- Differential diagnosis of type 2 diabetes vs. LADA (late onset autoimmune diabetes in the adult; late manifestation of type 2 diabetes mellitus) [anti-GAD65-Ak]
- Differential diagnosis in gestational diabetes [anti-GAD65-Ak]
- Prediabetic diagnosis in at-risk groups (family screening: screening of first-degree relatives): testing of children from the age of 2-3 years; second testing if negative at the age of about 10 years [IA-2-Ak].
Interpretation
- Positive detection of an antibody: low risk (<15%) of manifestation of type 1a diabetes within the next 10 years. Recommendation: annual controls are advised because detected antibodies may also be transient (temporary).
- Positive detection of ≥ 2 antibodies: high risk of developing type 1a diabetes. Approximately 70% of patients develop the disease within the following 10 years, 85% after 15 years and 100% after 20 years.After manifestation of diabetes, the titers of antibodies decrease continuously (exception: GAD65-Ak).
