Acute pancreatitis with coexistent diabetes mellitus: An experimental study in the dog

Abstract

A syndrome of acute pancreatitis with coexistent diabetes mellitus was produced in 16 dogs to test the hypothesis that acute pancreatitis is a key factor in producing permanent diabetes mellitus. To increase susceptibility to diabetes mellitus, 50% partial pancreatectomy was performed in all dogs, followed 9 days later by a regimen of bovine growth hormone (BGH; 5 mg/kg of body weight intramuscularly (I.M.), b.i.d.) and dexamethasone (0.02 mg/kg of body weight I.M., b.i.d.). There were mild signs of pancreatitis after partial pancreatectomy was done, with transient increases in serum amylase and serum lipase activities and with transient reduction in glucose tolerance. By the 3rd day of hormonal treatment, all dogs had hyperglycemia, glycosuria, and decreased glucose tolerance. The dogs were then paired and the 2nd surgical procedure was done. Of each pair, the dog having the greater decreased glucose tolerance was subjected to sham operation of the pancreas and was continued on the hormonal regimen for 2 more days. The other dog of the pair, having the more normal lucose tolerance, was given staphylococcic alpha toxin by pancreatic intraductal injection at operation. Hormonal treatment of this dog of the pair was discontinued. The resultant acute pancreatitis produced the following effects in 8 dogs: Three dogs became only mildly ill and had little further increase in blood glucose concentration above that produced by hormonal treatment. Serum amylase and serum lipase activities were increased. All 3 dogs survived. Three dogs became severely ill and manifested ketoacidosis with Kussmaul's respiration, hyperglycemia, and increased serum amylase and serum lipase activities. One dog died 3 days after treatment with toxin, and the 2 surviving dogs had clinical diabetes mellitus and persistently decreased glucose tolerance. Two dogs became comatose from the coexistent acute pancreatitis and ketoacidotic diabetes mellitus. Serum amylase, serum lipase, and blood glucose values were greatly increased, and glucose tolerance was markedly decreased. Both dogs died within 24 hr after toxin was given. The 8 dogs that were continued on the hormonal regimen after sham operation survived. Blood glucose concentration and glucose tolerance rapidly returned to normal after hormone injections were discontinued. This induced form of acute pancreatitis with coexistent diabetes mellitus had many similarities to the naturally occurring disease complex in dogs and to the counterpart disease in man. The preparation is readily reproducible and will be useful for studies of pathogenesis and treatment.