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Type I diabetes mellitus in monozygotic twins: chronic progressive beta cell dysfunction
Annals of Internal Medicine
|September 1, 1983
Summary
Type I diabetes in identical twins shows a long prediabetic phase. Islet cell antibodies appear years before diagnosis, linked to declining beta cell function and insulin response.
Area of Science:
- Immunology
- Endocrinology
- Genetics
Background:
- Type I diabetes mellitus (TIDM) is an autoimmune disease.
- Monozygotic twins offer a unique model to study genetic and environmental factors in TIDM.
Purpose of the Study:
- To investigate the natural history of beta cell function and immunologic markers in monozygotic twins discordant for TIDM.
- To characterize the prediabetic phase of TIDM.
Main Methods:
- Prospective longitudinal study over 21 years.
- Serial assessment of islet cell antibodies (ICAs) and beta cell function (insulin response to glucose).
- Genetic typing for HLA-DR antigens.
Main Results:
- Four of 24 monozygotic twins developed TIDM.
- In 3 of 4 twins, ICAs preceded TIDM diagnosis by 5-8 years.
- ICA positivity was associated with progressive decline in first-phase insulin response during the prediabetic phase.
- Hyperglycemia and impaired glucose tolerance tests appeared late in the disease course.
Conclusions:
- TIDM in monozygotic twins exhibits a prolonged prediabetic phase.
- Progressive beta cell dysfunction and immunologic abnormalities (ICAs) characterize this prediabetic phase.
- ICAs are early indicators of autoimmune beta cell destruction preceding clinical diagnosis.
