Clinicopathologic characteristics, prevalence, and risk factors of spontaneous diabetes in sooty mangabeys (Cercocebus atys)

Abstract

In 2008, clinical observations in our colony of sooty mangabeys (Cercocebus atys) suggested a high frequency of type 2 diabetes. Postmortem studies of diabetic animals revealed dense amyloid deposits in pancreatic islets. To investigate these findings, we screened our colony (97 male mangabeys; 99 female mangabeys) for the disease from 2008 to 2012. The overall prevalence of diabetes was 11% and of prediabetes was 7%, which is nearly double that reported for other primate species (less than 6%). Fructosamine and triglyceride levels were the best indicators of diabetes; total cholesterol and glycated hemoglobin were not associated with disease. Increasing age was a significant risk factor: prevalence increased from 0% in infants, juveniles, and young adults to 11% in adults and 19% in geriatric mangabeys. Sex, medroxyprogesterone acetate exposure, and SIV status were unrelated to disease. Weight was marginally higher in prediabetics, but body condition did not indicate obesity. Of the 49 mangabeys that were necropsied after clinical euthanasia or death from natural causes, 22 were diabetic; all 22 animals demonstrated pancreatic amyloid, and most had more than 75% of islets replaced with amyloid. We conclude that type 2 diabetes is more common in mangabeys than in other primate species. Diabetes in mangabeys has some unusual pathologic characteristics, including the absence of altered cholesterol levels and glycated hemoglobin but a robust association of pancreatic insular amyloidosis with clinical diabetes. Future research will examine the genetic basis of mangabey diabetes and evaluate additional diagnostic tools using imaging and serum markers.

Figure 1.

Scheme for classification of pancreatic islet amyloid deposition.

Figure 2.

Mean (± SEM) of fasting serum blood glucose for nondiabetic (n = 137), prediabetic (n = 13), and diabetic (n = 22) female and male sooty mangabeys (P < 0.001).

Figure 3.

Pearson product-moment correlation was used to compare serum glucose measurements (in mg/dL) with those obtained with the glucometer (in mg/dL). The solid line represents the linear correlation. Pearson correlation, r = 0.541 (P < 0.001).

Figure 4.

Mean (± SEM) of fructosamine values for nondiabetic (n = 70), prediabetic (n = 9), and diabetic (n = 22) female and male sooty mangabeys (P < 0.001).

Figure 5.

Mean (± SEM) of HbA1c values for nondiabetic (n = 16), prediabetic (n = 2), and diabetic (n = 7) female and male sooty mangabeys (P > 0.10).

Figure 6.

Mean (± SEM) of triglyceride values for nondiabetic (n = 134), prediabetic (n = 13), and diabetic (n = 22) female and male sooty mangabeys (P < 0.001).

Figure 7.

Mean (± SEM) of total cholesterol values for Nondiabetic (n = 132), Prediabetic (n = 13), and Diabetic (n = 22) female and male sooty mangabeys (P = 0.05).

Figure 8.

(A) Pearson product-moment correlation was used to compare serum glucose measurements (in mg/dL) with age (in y). The solid line represents the linear correlation. Pearson correlation, r = 0.261 (P = 0.001). (B) Pearson product-moment correlation was used to compare fructosamine (in µmol/L) with age (in y). There was no significant linear correlation (Pearson correlation, r = 0.166 [P > 0.05]).

Figure 9.

Pancreas from a nondiabetic 17-y-old male sooty mangabey. Islets contain mild amyloid deposits (arrows) and numerous β cells. Hematoxylin and eosin stain; bar, 50 µm.

Figure 10.

Pancreas from a diabetic 19-y-old male sooty mangabey with a terminal blood glucose concentration of 311 mg/dL. The islet contains moderate amyloid deposits. The remaining β cells appear as small nuclei surrounded by amyloid. There are a few β cells remaining. Hematoxylin and eosin stain; bar, 50 µm.

Figure 11.

Pancreas from a diabetic 23-y-old female sooty mangabey with a terminal blood glucose of 230 mg/dL. (A) Islets have been totally replaced by marked amyloid deposits. Hematoxylin and eosin stain; bar, 100 µm. (B) Insular deposits stain positive for amyloid. Sulfated Alcian blue stain; bar, 100 µm. (C) Insular deposits stain positive for amyloid. Congo red stain; bar, 100 µm.