Histopathologic lesions of diabetes mellitus in a domestic ferret (2024)

Language: English | French

Abstract

A 2-year-old ferret was referred with a diagnosis of diabetes mellitus. The animal died despite insulin therapy and was submitted for necropsy. Light microscopic examination revealed a mild hepatic lipidosis and pancreatic lesions consisting of a diffuse vacuolation of the Langerhans’ islet cells with a periodic acid-Schiff positive material compatible with glycogen.

Résumé

A 2-year-old female ferret was referred by a veterinarian to the companion animal clinic of the University of Montreal following a diagnosis of diabetes mellitus with ketoacidosis. The ferret’s diet had been solely sweet cereals for over a year.

Case description

The animal was very lethargic, dehydrated, and showed muscle twitching and hind limb paresis. Severe emaciation and bilateral symmetrical alopecia were also noticed. The perineal area was soiled with diarrhea.

Initial diagnostic tests, performed at the Clinical Pathology Laboratory of the Faculty of Veterinary Medicine, included a complete blood (cell) count (CBC), plasma biochemical analysis, blood gas analysis, and urinalysis. Abnormal blood results included a moderate anemia (24%; reference range 47% to 51%), marked hyperglycemia (28.9 mmol/L; reference range 3.47 to 7.44 mmol/L), mild hypokalemia (3.77 mmol/L; reference range 4.3 to 5.3 mmol/L), and hypoalbuminemia (26.4 g/L; reference range 33 to 41 g/L) with a blood pH of 7.221. Urinalysis showed glycosuria (more than 55 mmol/L) and presence of ketones (1).

Administration of regular insulin (Novolin ge Toronto; Novo Nordisk Canada, Mississauga, Ontario), 0.1 IU, IM, q1h, and fluid therapy with NaCl 0.9% (Baxter, Toronto, Ontario) supplemented with 40 mEq/L of potassium chloride (AstaZeneca Canada, Mississauga, Ontario) was initiated. Despite all of the treatments, the ferret died 4 h after admission and was submitted for necropsy.

At necropsy, the ferret was alopecic and in very poor body condition. It weighed 460 g and no fat tissue deposits were present. The pancreas appeared grossly normal, as did the adrenal glands. The latter measured 1.5 × 3 × 6 mm, which is within normal limits (2,3). Tissue samples were collected, fixed in 10% buffered formalin, and embedded in paraffin. Sections (3 μm) were cut and stained with hematoxylin-phloxin-saffron (HPS) and periodic acid-Schiff (PAS), with and without amylase digestion. Immunoperoxidase staining for insulin was performed on a section of pancreas.

Microscopic examination of the adrenal glands did not show any abnormalities. In the liver, a mild, periportal, hepatic lipidosis was present. In the pancreas, the number of Langerhans’ islets was normal when compared with those in a normal ferret; however, the islet cells were diffusely and markedly vacuolated (Figure 1A), and contained PAS-positive material (Figure 1B). Cytoplasmic immunoreactivity for insulin was present in the vacuolated cells, confirming them as being beta cells. The epithelium of several renal tubules was mildly vacuolated and also PAS positive. The PAS-positive material present in those organs disappeared after digestion with amylase (Figure 1C), confirming it as being glycogen. In 1 eye, all layers of the retina were atrophied. The epidermis was multifocally atrophic with a mild, orthokeratotic hyperkeratosis. Follicles were sparse and in a state of telogen atrophy. A mild, subacute, suppurative bronchopneumonia was also found, and a Klebsiella sp. was isolated from the lungs.

Discussion

Although uncommon and not well characterized, spontaneous diabetes mellitus has been described in ferrets (4–7). One reported case of diabetes mellitus in a black-footed ferret (Mustela nigripes) was managed with 2 to 5 units of neutral protamine Hagedorn (NPH) insulin, given q24h (7); no lesions were observed in this ferret’s pancreas, and adequate numbers of beta cell granules were noted in the islets of Langerhans. Hillyer (5) reported treating 4 middle-aged ferrets for persistant hyperglycemia. All 4 animals died after temporary response to treatment with insulin, but the necropsy results were not published. This is the first report of a ferret diagnosed with diabetes mellitus and showing histopathologic lesions typical of this metabolic disorder: a material compatible with glycogen was observed within the diffusely vacuolated Langerhans’ islet cells and within several renal tubules (8,9).

Diabetes mellitus is due to either the lack of insulin secretion by beta-cells of the pancreatic islets or resistance to the action of secreted insulin (9). Extrapancreatic factors, such as diet, obesity, concurrent hormonal disease, heredity, and drugs, may also play a role in the development of the disease (9). Diabetes mellitus in ferrets has been associated with a diet high in refined sugar (10), so the inappropriate diet of this ferret may have been involved in the pathogenesis. The chronic hyperglycemia resulting from ingestion of sugar may impair insulin secretion by beta cells and induce peripheral insulin resistance by causing downregulation of the glucose transport systems (9). This phenomenon is referred to as “glucose toxicity” (9). Beta cells do not respond properly to stimulation by insulin secretagogues, thereby mimicking insulin-dependent diabetes mellitus.

Although vacuolation of the Langerhans’ islet cells is often described with severe, acute onset of diabetes mellitus (8), it has also been observed in chronic cases in cats (9). The poor body condition and severe muscular atrophy observed in this ferret, along with the history of long-term feeding with a sweet diet, are consistent with a chronic condition.

Atrophic dermatoses, as observed in this case, are described with several endocrinopathies (11,12) and are not specific for diabetes mellitus. Although an atrophy of all layers of the retina was observed in 1 eye, there were no concomitant vascular lesions, as described in primates and dogs (13). Therefore, the lesions were not compatible with diabetic retinopathy and could have been an incidental finding. It is not known whether the described mild bronchopneumonia was incidental or precipitated by the underlying disease in this animal. The exact cause of the paresis was not determined, therefore, it remains uncertain whether it was related to diabetes or to the extreme weakness of this ferret.

Regulation of blood glucose in ferrets with spontaneously occurring hyperglycemia is reported to be difficult (4–6). Transient hyperglycemia may occasionally be seen in this species following surgical excision of pancreatic islet cell tumors (14) and suppression of islet cells by residual, tumor-derived insulin may be involved (15). In these cases, treatment is rarely indicated, since blood glucose usually returns to normal within 1 to 2 wk (4). Transient diabetes, not related to surgical excision of an insulinoma, has been reported and the ferret no longer needed insulin after 1 y of therapy (5). CVJ

References