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DIABETES is a chronic metabolic disorder that
adversely affects the body's ability to manufacture
and use insulin, a hormone necessary for the
conversion of food into energy. The disease
greatly increases the risk of blindness, heart
disease, kidney failure, neurological disease and
other conditions for the approximately 16 million
Americans who are affected by it. Type I, or
juvenile onset diabetes, is the more severe form of
the illness.
Type I diabetes is what is known as a 'complex trait', which means that mutations in several genes likely contribute to the disease. For example, it is now known that the insulin-dependent diabetes mellitus (IDDM1) locus on chromosome 6 may harbor at least one susceptibility gene for Type I
diabetes. Exactly how a mutation at this locus
adds to patient risk is not clear, although a gene
maps to the region of chromosome 6 that also has
genes for antigens (the molecules that normally
tell the immune system not to attack itself). In Type
I diabetes, the body's immune system mounts an
immunological assault on its own insulin and the
pancreatic cells that manufacture it. However, the
mechanism of how this happens is not yet
understood.
About 10 loci in the human genome have now been found that seem to confer susceptibility to Type I diabetes. Among these are (1) a gene at the locus IDDM2 on chromosome 11 and (2) the gene for glucokinase (GCK), an enzyme that is key to glucose metabolism which helps modulate insulin secretion, on chromosome 7.
Conscientious patient care and daily insulin
dosages can keep patients comparatively healthy.
But in order to prevent the immunoresponses that
often cause diabetes, we will need to experiment
further with mouse models of the disease, and
advance our understanding of how genes on
other chromosomes might add to a patient's risk of
diabetes.