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Abstract
As the major cause of disability and death in insulin-dependent diabetes, microangiopathy
is obviously of major concern to diabetologists. Unlike macroangiopathy, which can
readily be prevented by means that are currently on hand, the origin and treatment
of microangiopathy remain far more problematical. The complexity of this lesion is
indicated by the findings in this laboratory that hyperglycemia induced by the rodenticide,
vacor, can cause microangiopathy independent of genetic diabetes, yet significant
microangiopathic lesions can be detected in genetic diabetic patients before the appearance
of hyperglycemia. Further, there is now intriguing evidence based both on basement
membrane measurements from our laboratory and on clinical studies showing that significantly
microangiopathy only rarely occurs prior to the onset of puberty. The evidence that
control or even normalization of blood glucose levels does not influence the course
of established microangiopathy is becoming increasingly convincing. Five prospective,
randomized studies over the past five years have shown that strict regulation of glucose
has no consistent benefit on, and in some studies may, at least transiently, accelerate,
the retinopathy of diabetes. Moreover, the first controlled study of successful pancreatic
transplantation to achieve normalization of blood glucose levels has again demonstrated
that established retinopathy is neither prevented nor even delayed by normal glucose
levels. This review, therefore, emphasizes that, though hyperglycemia is required
for clinically significant microangiopathy to occur, clearly other factors, genetic,
environmental, or both, must play major roles in determining the course of microangiopathy.
It is toward these nonglycemic factors in the development of diabetic microangiopathy
that future research should increasingly be directed.
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© 1998 Published by Elsevier Inc.
