Dietary cyanide and tropical malnutrition diabetes

Two categories of diabetes are recognized in the temperate zone--ketosis-prone diabetes requiring insulin and diabetes not requiring insulin. Another unique type of diabetes occurs in the tropics. It has two forms, both different from either form of temperate zone diabetes. Type J and pancreatic diabetes are both characterized by youth onset, antecedent malnutrition, substantial insulin requirement, and resistance to ketosis. In the tropical countries where they are found, both forms are associated with specific dietary practices, including a nutritionally marginal protein intake. The close association with low protein intake distinguishes this form of diabetes from that occurring in North America, Europe, and Oceania. The geographic distribution of malnutrition diabetes, in addition to being limited to the tropics, coincides regularly with the consumption of tapioca (cassava) or other foods that contain cyanide-yielding substances. Ingested cyanide is normally detoxified, principally, by conversion to thiocyanate. This detoxification requires sulfur, derived principally from amino acid sources. Studies in the rat indicate a remarkable ability to detoxify ingested cyanide, a reduction in urinary thiocyanate excretion when protein intake is lowered (especially during growth), production of marked hyperglycemia by either oral or parenteral cyanide, and the development of cyanosis and epidermal changes when there is prolonged exposure to cyanide. Both the association of malnutrition diabetes with food cyanogens and our laboratory observations support a role for cyanide in its pathogenesis.