Long-term duct-occluded segmental pancreatic autografts: absence of microvascular diabetic complications.
BACKGROUND
Current insulin therapies for control of glucose metabolism in patients with type I diabetes mellitus prevent major metabolic consequences of insulin deficiency, but none prevents or arrests long-term complications. In experimental models of canine diabetes, retinopathy, neuropathy, and nephropathy have been shown to develop within 5 years. The aim of this study was to determine in a canine model whether glucose control provided by segmental duct-occluded pancreas autografts could prevent the long-term complications of diabetes.


METHODS
Thirty-five outbred mongrel dogs underwent segmental pancreas autotransplantation with residual pancreatectomy. Follow-up over 5 years included endocrine, retinal fundus photography, fluorescein angiography, and nerve conduction studies. At endpoint, analysis of organ specific changes was undertaken.


RESULTS
Long-term survival was achieved in 14 dogs for 4 to 5 years and in 3 dogs for 3 to 5 years. Glycosylated hemoglobin levels remained within normal limits, although response to glucose challenge was suboptimal. Fundus photography and fluorescein angiography demonstrated the absence of retinal vascular aneurisms, capillary leakage, and obliteration. Retinal digest showed no vascular changes and normal endothelial/pericyte ratios. Nerve conduction was normal, and histology of nerves revealed normal density of myelinated fibers and absence of intrafascicular vessels and glycogen deposits, with no change in spectrum of fiber diameters and ovoids. Renal histology revealed no evidence of nephropathy with normal glomerular basement membranes.


CONCLUSIONS
We have demonstrated that duct-occluded segmental pancreatic autografts are capable of providing satisfactory metabolic control for up to 5 years, thereby preventing development of the long-term microvascular complications of diabetes.
Hawthorne
W J
WJ
Department of Immunology, Westmead Hospital, New South Wales, Australia.
Wilson
T G
TG
Williamson
P
P
Stewart
G J
GJ
Allen
R D
RD
Little
J M
JM
Deane
S A
SA
Ekberg
H
H
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000601:surgery*; D003925:Diabetic Angiopathies / Q000503:physiopathology / Q000517:prevention & control*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000503:physiopathology / Q000517:prevention & control*; D004285:Dogs; D005451:Fluorescein Angiography; D006442:Glycated Hemoglobin / Q000032:analysis; D006085:Graft Survival; D007668:Kidney / Q000473:pathology; D008833:Microcirculation / Q000473:pathology; D009431:Neural Conduction; D010179:Pancreas / Q000098:blood supply; D016035:Pancreas Transplantation / Q000401:mortality / Q000473:pathology / Q000502:physiology*; D010180:Pancreatectomy; D010183:Pancreatic Ducts / Q000502:physiology*; D015996:Survival Rate; D013997:Time Factors; D014182:Transplantation, Autologous
D006442:Glycated Hemoglobin