A weakness of many animal models of
diabetes mellitus is the failure to use
insulin therapy, which typically results in severe body wasting. Data collected from such studies must be interpreted cautiously to separate the effects of
hyperglycemia from those of
starvation. We provide several algorithms that were used by us in two long-term (20-week) experiments in which
hyperglycemia (300 to 400 mg/dl),
dyslipidemia (
cholesterol [280 to 405 mg/dl] and
triglycerides [55 to 106 mg/dl] concentrations), and positive energy balance were maintained in swine. Yucatan miniature swine groups included control,
alloxan-induced
diabetes mellitus,
diabetes mellitus plus diet-induced
dyslipidemia, and exercise-trained diabetic dyslipidemic pigs. The algorithms were developed for the porcine model because of several similarities to humans, including: cardiac anatomy and physiology, propensity for sedentary behavior, and metabolism of
dietary carbohydrates and
lipids. Acute toxic effects of
alloxan (
hypoglycemia,
hyperglycemia, nephrotoxicosis) were minimized by preventive fluid loading and by use of algorithms in which
insulin, food, and
fluid therapy were administered. Long-term
insulin and food maintenance algorithms elicited normal body weight gain in all three diabetic groups (lean experiment) and threefold greater
body weight gain in pigs of an
obesity experiment. Exercise-trained pigs of both experiments manifested significantly increased work performance and did not experience medical complications. We conclude that these algorithms can be used in swine, or similar algorithms can be developed for other animal species to maintain
hyperglycemia and/or
dyslipidemia, while avoiding diabetes-induced wasting. Importantly, animal models of
diabetes mellitus that maintain positive energy balance and poor
glycemic control provide a marked improvement over other models by more closely mimicking the human presentation of
diabetes mellitus.