Insulinopenic diabetes after rodenticide (Vacor) ingestion: a unique model of acquired diabetes in man.
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.
D000328:Adult; D001120:Arginine; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002648:Child; D003920:Diabetes Mellitus / Q000139:chemically induced*; D016883:Diabetic Ketoacidosis / Q000139:chemically induced; D003929:Diabetic Neuropathies / Q000139:chemically induced; D005934:Glucagon / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D007515:Islets of Langerhans / Q000187:drug effects; D008297:Male; D010671:Phenylurea Compounds / Q000494:pharmacology; D014044:Tolbutamide
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D010671:Phenylurea Compounds; D005934:Glucagon; D001120:Arginine; D014044:Tolbutamide; C012598:pyriminil