EARLY ENVIRONMENTAL EVENTS AS A CAUSE OF IDDM - EVIDENCE AND IMPLICATIONS

Insulin-dependent diabetes mellitus (IDDM) is caused by destruction of the insulin-secreting beta-cells of the islets of Langerhans. It is p roposed that the disease is caused by nongenetic, probably environment al, factors operating in a genetically susceptible host to initiate a destructive immune process. These environmental factors may operate ov er a limited period in early childhood to induce the immune process th at destroys the islet beta-cell. Thereafter, there is a long prodrome before the onset of clinical diabetes, during which clinical, immune, and metabolic changes can be detected. If these proposals are correct, epidemiological studies should focus on environmental events in early childhood that might induce, or accelerate, the disease process. More over, it should be possible to identify, from an early age, changes in the prediabetic period that persist to diagnosis and have predictive value. The variable age of presentation of IDDM may, therefore, reflec t different rates of disease progression rather than different ages of exposure to the critical environmental events. Those patients in whom the disease process is slow could present with IDDM as adults, develo p diabetes that does not require insulin treatment, or even fail to de velop diabetes altogether. These proposed features, if confirmed, woul d have important implications for the prediction of IDDM and raise the possibility that modulation of the destructive immune process could p revent progression to clinical diabetes.