To compare the long-term effectiveness of whole
pancreas transplantation and pancreatic islet
transplantation in controlling the metabolic disorders and preventing the kidney lesions of
alloxan diabetes, metabolic and morphologic studies were performed in four groups of rats: (1) NC-116 nondiabetic controls; (2) DC-273 untreated
alloxan-diabetic controls; (3) PDT-182 rats that received syngeneic pancreaticoduodenal transplants not long after induction of diabetes with
alloxan; and (4) IT-92 rats that received an intraportal injection of at least 1500 and usually 2000 syngeneic pancreatic islets soon after induction of diabetes with
alloxan. Each month for 24 months after diabetes was well established,
body weight and plasma concentrations of
glucose and
insulin were measured, and five lesions were scored by light microscopy in 50 glomeruli and related tubules in each kidney by a "blind" protocol: glomerular basement membrane thickening, mesangial enlargement, Bowman's capsule thickening, Armanni-Ebstein lesions of the tubules, and tubular
protein casts. There were progressive and highly significant increases in the incidence and severity of all five kidney lesions in the diabetic control rats compared with the nondiabetic control rats. No significant differences were found between the kidneys of Group
PDT and those of Group NC, demonstrating that whole
pancreas transplantation prevented all of the diabetic kidney lesions throughout the 2-year study period. In contrast, within 3-9 months after pancreatic islet
transplantation and thereafter, the incidence and severity of the five diabetic kidney lesions were similar in Group IT and Group DC. Whole
pancreas transplantation produced precise metabolic control of diabetes throughout the 24 months of study, whereas pancreatic islet
transplantation did not accomplish complete metabolic control, particularly beyond the first several months after
transplantation. The difference in the completeness of metabolic control achieved by the two types of transplants is the most likely explanation for their sharp difference in effectiveness in preventing
diabetic nephropathy.