Insulinopenic Diabetes After Rodenticide (Vacor) Ingestion: A Unique Model of Acquired Diabetes in Man

Abstract

A clinical syndrome, characterized by acute diabetic ketoacidosis associated with a toxic neuropathy, developed in five men who intentionally ingested a recently introduced rodenticide (Vacor) containing N-3-pyridylmethyl-N'-p-nitrophenyl urea (RH-787). A 7-yr-old boy, who accidentally ingested this poison, died within 14 h. Marked insulinopenia, without a reduction in glucagon levels, suggested a specific beta-cytotoxic effect, which was supported after autopsy in three cases by histopathologic evidence of extensive beta cell destruction. Lethal effects in rats prevented investigation of RH-787's diabetogenicity in vivo; however, studies in isolated rat islets confirmed a direct inhibitory effect, which was prevented by concomitant incubation with nicotinamide, suggesting a mechanism of action similar to that of streptozotocin. We detected islet cell-surface antibodies in two of four patients studied. These findings indicate that this nongenetic, acquired form of insulinopenic diabetes, which has persisted in the surviving patients for up to 3 yr, presents a unique opportunity to test in man the concept that hyperglycemia and the accompanying metabolic consequences of insulinopenia can induced diabetic microangiopathy in the absence of genetic predisposition.

Environmental contaminants as etiologic factors for diabetes.

“…The environmental factors usually considered etiologically relevant are infectious agents or dietary factors that stimulate an immune response (10). Poisonings with the rodenticide Vacor (Rohm and Haas Co., Philadelphia, PA), however, have caused type 1 diabetes (11). Furthermore, certain drugs, such as pentamidine, can be toxic to β cells (12).…”

Possible dietary factors in the induction of diabetes and its inheritance in man, with studies in mice

“…This is true for STZ and also for the rodenticide Vacor (Lee et at. 1977;Karam et al 1980). Smaller doses of STZ can produce diabetes in rodents with lymphocytic infiltration of the islets of Langerhans (Like & Rossini, 1976) and systemic MHC expression (Cockfield et al 1989), as occurs in juvenile human diabetes, whereas larger doses destroy the insulin-producing cells without any autoimmune component in the process.…”

“…Apart from the nitrosamide, STZ, N-nitrosomethylurea (Wilander & Tjalve, 1975) and N-nitrosoethylurea (Anderson et al 1975) have been proved to be directly diabetogenic and more recently the rodenticide Vacor, which is chemically related to the Nnitrosureas, has been shown to be diabetogenic in man (Karam et al 1980). This list has been extended to nitrosothiazolidine and its carboxylic acid (Helgason et al 1984).…”

Genes Mediating Environment Interactions in Type 1 Diabetes

“…This issue was brought to the fore when a series of cases of attempted suicide with the rodenticide Vacor (containing N-3-pyridylmethyl-N'-p-nitrophenyl urea; RH-787) resulted in direct β-cell toxicity and onset of insulin-dependent diabetes [153]. Streptozotocin, derived from Steptomyces spp, also induces T1D through a direct toxic action on β-cells in certain inbred mouse strains [154].…”