Non-insulin-dependent diabetes mellitus
by Julie Bagnasco
Non-insulin dependent diabetes mellitus (NIDDM), also known as Type II diabetes
or adult-onset diabetes mellitus, is a highly prevalent metabolic disorder
of glucose metabolism. The onset of this disease usually occurs middle-age
in humans, but signs of the conditions might be detectable earlier.
Normal human homeostatic glucose metabolism dipends on three factors: 1)
the ability of the pancreas secrete the hormone insulin in response to blood
glucose levels; 2)the ability of this important hormone to induce insulin
sensitivity (glucose uptake) in peripheral tissues; and 3) the ability of
insulin to suppress glucose production in the liver (Sacks et al, 150).
NIDDM is the result of metabolic defects in the first two of these three
factors. Type II diabetes is characterized by a problematic decrease in
insulin sensitivity --known as insulin resistance--compounded by the inability
of the pancreas cells to produce enough insulin to remedy this decreased
sensitivity. Chronic hyperglycemia is the trademark result of these dysfunctions.
The entire underlying cause of NIDDM is yet unknown, but previous, abundant
research has led scientists to characterize as a variably expressive, polygenic
disease, created by a combination of both genetic and environmental factors.
Studies of identical twins have shown that if one twin develops NIDDM, the
chance that his/her sibling will also is 90%. Further into the genetic side
of the story, researchers have tried to discover a candidate gene for NIDDM,
and though the search for this gene continues, useful information about
genes involved in the glucose pathway has been discovered and related to
its potential of, if not directly causing, then influencing NIDDM development.
Groop et al., have located two polymorphisms on the glycogen synthetase
gene, which is responsible for converting glucose into glycogen for storage
in tissues; this enzyme is characteristically deficient in Type II diabetics.
The researchers discovered these polymorphisms by using a cDNA probe--obtained
through the research of Browner et al.--the restiction enzyme, Xbal, and
Southern blot analysis.
These polymorphisms, occuring within an intron of the glycogen synthetase
gene, were caused by the substitution of a single base for another. Termed
the A1 and A2 alleles, these polymorphisms were studied in both Dutch NIDDM
individuals and unaffected Dutch individuals, in the hopes that some linkage
to NIDDM could be established. Statistical analysis led the researchers
to conclude the the A2 allele characterized a subgroup of patients who had
a strong history of NIDDM, and in whom high blood pressure and insulin resistance
were likewise found to exist. However, French scientists attempted to repeat
this study on French patients and got the opposite result--the frequency
of the A1 allele in their test subjects was higher in NIDDM individuals
than in non-NIDDM subjects. Furthermore, hypertension and insulin resistance
also characterized these A1 patients.
This has led Groop et al. to conclude that A2 alleles can only be used as
markers for NIDDM in certain ethnic populations.
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