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PATHOGENESIS
OF TYPE 2 DIABETES MELLITUS:
While much has been
learned in recent years, the pathogenesis of type 2 diabetes remains enigmatic.
Environmental factors, such as a sedentary life style and dietary habits,
clearly play a role, as will become evident when obesity is considered.
Nevertheless, genetic factors are even more important than in type 1diabetes.
Among identical twins, the concordance rate is 50% to 90%, while among
first degree relatives with type 2
diabetes (and in fraternal twins), the risk of developing the disease is 20% to
40%, compared to 5% to 7% in the population at large. Unlike type 1diabetes,
however, the disease is not linked to genes involved in immune tolerance and
regulation, and there is no evidence to suggest an autoimmune basis for type 2
diabetes.
The two metabolic
defects that characterize type 2 diabetes are
(1) a decreased ability
of peripheral tissues to respond to insulin (insulin resistance) and
(2) b - cell
dysfunction that is manifested as inadequate insulin secretion in the face of
insulin resistance and hyperglycemia.
In most cases, insulin
resistance is the primary event, and is followed by increasing degrees of b - cell
dysfunction.
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