The Role of Chemicals in the Etiology of Diabetes Mellitus

Abstract

Diabetes mellitus is a collection of diseases that culminate in defects in carbohydrate metabolism and result in inappropriate hyperglycemia. Most individuals with this disease can be categorized into 1 of 2 groups, depending upon their insulin requirements. Individuals who require insulin therapy to maintain life have been designated as having insulin-dependent diabetes mellitus (IDDM), while individuals who can live without insulin treatment have been classified as having noninsulin-dependent diabetes mellitus (NIDDM). The single most important pathological finding in IDDM is a substantial reduction in the number of insulin-secreting pancreatic beta cells. Compelling experimental and epidemiological evidence indicates that, at least in some forms of IDDM, environmental factors, such as chemical toxins, play an important role in the etiology of this disease. Chemical toxins can precipitate IDDM through a variety of mechanisms. They can poison beta cells directly and cause the destruction of a critical mass of beta cells; alternatively, they can trigger autoimmune processes directed against beta cells; or, finally, they can augment the diabetogenic properties of another agent, such as a virus, to hasten the onset of clinical manifestations. In NIDDM, impaired beta cell function appears to be the initial event observed at the onset of this syndrome. Functional defects similar to those seen in NIDDM can be produced in laboratory animals using a specific beta cell toxin. These animals develop permanent glucose intolerance and insulin resistance as a consequence of beta cell alteration. A variety of other chemicals also have been found to produce glucose intolerance; however, this condition is transient and is resolved when the chemical is removed. This review will focus on a discussion of chemicals that are known to cause IDDM, NIDDM or transient glucose intolerance and their putative mechanisms of action. Additionally, new methods for identifying and evaluating potential toxins will be considered.