ABSTRACT

Molecular genetic aspects of non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent DM (IDDM) clearly point to an association of DM susceptibility with a certain pattern of arrangement of human leukocyte antigen (HLA) class II genes. Susceptibility to IDDM and NIDDM as an example of a variety of conditions in which the role of HLA is becoming progressively recognized. The key role of autoimmune responses resulting in the destruction of β cells has been defined and a working hypothesis of the etiology of IDDM proposed. Humoral autoimmune reactions complement the cell-mediated immunity in the development of IDDM. Cell-mediated immunity involving cytotoxic T cells leads to the destruction of the β cells at the later stages, rather than during an initial assault. Insulin resistance, present in virtually all NIDDM patients, interacts with deficient islet function and leads to compensatory hyperglycemia, the degree of which is proportional to the extent of β cell dysfunction.