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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