Development of spontaneous diabetes has been monitored in individual Macaca nigra. In this study, pancreatic biopsies were taken, islets were assessed morphologically, and results were related to the metabolic/clinical status. A biopsy or autopsy sample was obtained 4 to 10 years later, and the islet morphological state was again related to the metabolic/clinical status. Metabolic deterioration was correlated to the islet lesion, in which there was gradual loss of islet secretory cells and concurrent amyloid deposition. As nondiabetic monkeys with 0 to 3% islet amyloid progressed up to 20 to 40% amyloid, the insulin secretion and glucose clearance were both decreased (p less than or equal to 0.01), and the glucose and glucagon levels increased (p = 0.05). Impaired monkeys progressed to overt diabetes when islet amyloid exceeded 50 to 60%. Diabetic monkeys developed hyperglycaemia, along with impaired insulin secretion and glucose clearance (p less than 0.01). Loss of islet cells results in metabolic deterioration. The lesion precedes development of overt diabetes in Macaca nigra.

Report prepared by ~. Lernmark 1, J. L. Molenaar 2, W. A. M. van Beers 2' Y. Yamaguchi3; S. Nagataki 3' J. Ludvigsson 4 and N. K. Maclaren s on behalf of the Immunology and Diabetes Workshops and participating laboratories*

A 6‐y retrospective case note review was performed to determine the causes of ketoacidosis. 135 patients and 463 diabetic years were involved. Fifty‐two ketoacidosis episodes occurred: 19 episodes in new patients and 33 episodes in 19 patients with established diabetes. 27% of newly diagnosed patients presented in ketoacidosis. They were similar in terms of age, sex and proportion living in single parent families to those presenting without ketoacidosis. The 33 ketoacidosis episodes occurring in established patients included 12 episodes in 3 children who were transferred to our care because of uncontrolled diabetes. Insulin omission was the cause of ketoacidosis in 9/19 (47%) patients, and was suspected in a further 5/19 (26%). Family and school problems were common and 14/19 patients came from single parent families. Established patients aged ≥11 y were predominantly female (10F, 2M), whereas patients aged ≥10y were predominantly male (6M, 1F). 7 patients with multiple ketoacidosis episodes were all ≥11 y and 6 were female. Families with ≥2 diabetic children appeared vulnerable, 4 cases coming from 3/7 such families.

Nonhuman primates have been used for a variety of studies on diabetes meiiitus. Spontaneous, natural forms of diabetes have been well documented in several species; there are limited data on numerous other species that indicate diabetes or a diabetes-like syndrome. The causes and manifestations of spontaneous diabetes, their prevalence, and their severity vary among species. Diabetes has also been induced in nonhuman primates with streptozotocin, alloxan, hypothalamic lesions, or pancreatectomy. The extent and severity of metabolic and hormonal abnormalities vary according to the method of induction, the individual monkey, and the species. Metabolic, hormonal, and pathologic abnormalities present in human diabetics also occur in monkeys with either spontaneous or induced diabetes. Hyperglcemia, and impaired glucose clearance are common, lipid concentrations are elevated, and hemoglobin A1c concentrations are increased in Hyperglycemic monkeys. Monkeys may have fasting hypo- or hyperinsulinemia; insulin responses are often impaired in glucose tolerance tests. Glucagon concentrations may be increased. Aortic atherosclerosis, muscle capillary microangiopathies, cataracts, and glomeruio-sclerosis have been documented. Primate size and longevity allow longitudinal studies with procedures that may not be feasible in smaller animals or in human beings. Nonhuman primates may be the models of choice for studies on selected aspects of diabetes and its secondary complications.

In a closed breeding colony of Macaca nigra (black Celebes apes) there was a marked proclivity for a spontaneous diabetic-like state closely analogous to human diabetes. Numerous diabetic signs were present, including abnormal intravenous and oral glucose tolerance tests, hyperglycemia, impaired insulin response, hypertriglyceridemia, increased prebetalipoprotein, retinal vascular aberrations, abnormalities in the islets of Langerhans, and pronounced weight loss in a few severely diabetic monkeys. A classification of diabetic status established primarily on deviation of the intravenous glucose tolerance test from results in normal Celebes apes places over 50 per cent of these interrelated monkeys in nonnormal categories. DIABETES 21: 1077 -90, November, 1972