Cardiovascular Validation
  1. Acceptable Animal Models of VASCULAR Disease in Diabetes

    1. Hyperglycemic (type 1 or type 2 diabetes) or insulin resistant animals that develop accelerated atherosclerotic lesions compared to normoglycemic, insulin sensitive controls. Acceleration of atherosclerosis is defined as a 25 percent faster lesion progression.
    2. Lesions acceleration must not be solely due to elevated circulating cholesterol levels (could be due to an exacerbation of an insulin resistant or diabetic pattern).
    3. Model shows increased size of early lesions, or progression to fibrous plaques, or plaque rupture or occlusion compared to nondiabetic controls. As a secondary criteria, models should show signs of increased inflammation and/or thrombotic tendencies of lesions compared to normal controls.

  2. Acceptable Animal Models of CARDIOMYOPATHY in Diabetes

    1. Insulin resistant or diabetic animal that develops cardiac hypertrophy, diastolic and/or systolic dysfunction and histological changes of increased interstitial or replacement fibrosis and myocyte hypertrophy compared to insulin sensitive or non-diabetic control. Given the possibility that STZ in high doses may have direct cardiotoxicity, for changes in type 1 models to be deemed specific, they should be present in independent models of islet cell failure such as the NOD or the Akita mouse. Moreover, these changes (if acute) should be reversed or ameliorated by treatment of the diabetes by insulin. It is recognized that chronic changes might not necessarily be reversible.
    2. Correction of hyperglycemia, in general, attenuates cardiac changes in type 1 diabetes models.