Obesity, Insulin Resistance, β-Cell Autoimmunity, and the Changing Clinical Epidemiology of Childhood Diabetes

Over the past half century, the nomenclature for the major forms of diabetes changed from juvenile- and adult-onset to insulin-dependent or ketosis-prone and non–insulin-dependent or ketosis-resistant and, most recently, in an attempt to shift from treatment to what is now known of pathogenesis as the basis, type 1 and type 2 diabetes.

Challenges to the concept of two main and distinct forms of diabetes go back to epidemiologic studies in the 1960s and 1970s. Yemenite immigrants to Israel had very few instances of diabetes but, after 25 years in the land of milk and honey, experienced a 40-fold increase in frequency of diabetes. The proportion of insulin dependency was similar to that in Israelis of European origin, suggesting common environmental influences (most likely nutritional) on the expression of both major forms of diabetes (1). In a comparison of diabetes expression in >1,500 siblings of middle-aged newly diagnosed patients (both insulin dependent and non–insulin dependent) and siblings of childhood-onset insulin-dependent patients who had reached the same age bracket, Gottlieb (2) described a tendency, but not a requirement, for similar disease expression in families. Of siblings of childhood-onset patients, 12% had developed diabetes, evenly divided between what we would now consider type 1 and type 2 diabetes; siblings of adult-onset insulin-dependent patients had similar frequency and proportions. Siblings of type 2 diabetic patients had an 11% diabetes frequency; one-fourth of them were insulin dependent. More recently, a study of 3,500 incident cases of type 1 diabetes in Sweden found a family history for type 2 diabetes to be three times more likely in patients with type 1 diabetes than in matched control subjects (two for each patient) and type 1 diabetes frequency to be increased in relatives of patients with type 2 diabetes (3).

Further assault on the view of type …