A 9-year-old cynomolgus monkey (Macaca fascicularis) infected orally with
bovine spongiform encephalopathy (BSE) was presented for necropsy following
euthanasia 4 years post
infection (p.i.). This macaque R984 was exposed to a BSE dose that causes a simian form of
variant Creutzfeldt-Jakob disease (vCJD) within 5 years p.i. in other macaques. All orally BSE-infected macaques developed a significant
weight gain within the first 2 years p.i. compared with non-BSE-infected age- and sex-matched control animals, suggesting increased risk of
type 2 diabetes (T2D). In contrast, macaque R984 developed rapid
weight loss,
hyperglycemia, and glucosuria and had to be euthanatized 4 years p.i. before clinical signs of vCJD. Pancreas histopathological evaluation revealed severe islet degeneration but, remarkably, no islet
amyloid deposits were present. Immunostaining of pancreas sections for
insulin and
glucagon confirmed the loss of endocrine cells. In addition,
prions were present in the adenohypophysis but not in other areas of the brain, indicating centripetal
prion spread from the gut during the preclinical phase of BSE
infection. Plasma
glucose and
insulin concentrations of macaque R984 became abnormal with age and resembled T2D. This unusual case of spontaneous T2D in the absence of islet
amyloid deposits could have been due to early
prion spread from the periphery to the endocrine system or could have occurred spontaneously.