The ZDF strain initially presents as modestly hyperglycemic, but profoundly hyperinsulinemic, representing a state of considerable insulin resistance. Over time, the pancreas becomes exhausted, insulin secretion decreases (as it does in human diabetics) and plasma glucose increases in the face of insulin resistance.

The ZFR strain presents as an obese model with an elevated serum lipid profile, progressing hepatic steatosis, and a more moderate profile of impaired insulin sensitivity. Akin to the metabolic syndrome as a whole, this strain will become obese (hypertrophy and hyperplasia of adipocytes) driven largely by hyperphagia related to impaired leptin signaling.