ABSTRACT
A very large amount of clinical and basic research supports our current understanding that there are two major types of diabetes, termed type 1 diabetes and type 2 diabetes. The underlying pathophysiologic disease processes for these are usually thought to be markedly different. The disease process in classical type 1 patients is believed to be autoimmune in nature, whereas the disease process in classical type 2 is not autoimmune (1-3). In 1974, two separate groups of investigators discovered that islet cell antibodies (ICAs) were common in the sera of patients with type 1 diabetes, and this provided strong evidence that the -cell lesion of type 1 diabetes was autoimmune in nature (4,5); autoimmune -cell destruction leads to insulin deficiency; and circulating autoantibodies, such as autoantibodies to islet cell cytoplasm and/or to glutamic acid decarboxylase 65 (GAD65; GADA) and/or to the intracytoplasmatic domain of the tyrosine phosphatase-like protein IA-2 (IA-2A), are markers of this process. However, in clinical practice, the diagnosis of type 1 and type 2 diabetes is made phenotypically using variables such as age at onset, apparent abruptness of onset of hyperglycemia, presence of ketosis, degree of obesity (especially central and intra-abdominal), prevalence of other autoimmune diseases, and apparent need for insulin replacement. This clinical distinction is recognized to be imperfect (6,7). Our ability to distinguish the type 1 versus the type 2 disease process also has limitations due to genetic (8), immunologic (9), and functional complexity (10). There are no reliable markers for type 2 diabetes and therefore the absence of markers or manifestations of type 1 diabetes is frequently taken as indicating type 2 diabetes.
