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Presentation and phases of diabetes
Type 1 diabetes in childhood and adolescence is characterized by the following phases
- Prediabetes
- Presentation of diabetes
- Partial remission (or ‘honeymoon’)
- Permanent insulin dependency
Prediabetes
Definition
A state preceding the clinical onset of diabetes by months or even years, characterized by the presence of antibodies to several islet cell antigens which are often, but not always, predictive of the development of type 1 diabetes. The antibodies have been used as markers to identify people at risk of developing type 1 diabetes
Immunological markers
- Islet cell autoantibodies (ICA) at a high titer (>20 JDF units) predict a 40–60% risk of type 1 diabetes over the next 5–7 years
- When multiple autoantibodies are present the risk prediction rate increases greatly, e.g. glutamic acid decarboxylase (65 kD GAD isoform) plus IA2 antibodies predict a risk of >70% over 5 years. Insulin autoantibodies (IAA) at high titer may also increase the risk prediction
Genetic markers
- Certain HLA markers, particularly when identical to those of a family member with diabetes, indicate increased risk
Examples of genetic markers conferring increased risk
HLA DR3–DQA1*0501-DQB1*0201
HLA DR4–DQA1*0301-DQB1*0302
Examples of genetic markers conferring decreased risk
HLA DR2–DQA1*0102-DQB1*0602
Insulin secretion
- During the phase of prediabetes, before clinical onset of diabetes, beta-cell destruction progresses and insulin secretion diminishes. In the research setting using a standard ICARUS protocol, insulin secretion has been tested by the IV glucose tolerance test. Severely impaired first-phase insulin release confers an almost 100% risk of type 1 diabetes over the next 5 years
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