Etiological approach to characterization of diabetes type: the SEARCH for Diabetes in Youth Study

To describe an etiologic approach to classification of diabetes types in youth based on the 1997 American Diabetes Association (ADA) framework, using data from the SEARCH for Diabetes in Youth Study.

SEARCH conducted a comprehensive assessment of 2,291 subjects aged <20 years with recently diagnosed diabetes. Using autoimmunity (at least one of two diabetes autoantibodies) and insulin sensitivity (equation validated against hyperinsulinemic-euglycemic clamps) as the main etiologic markers, we described four categories along a bidimensional spectrum: autoimmune plus insulin-sensitive (IS), autoimmune plus insulin-resistant (IR), nonautoimmune plus IS, and nonautoimmune plus IR. We then explored how characteristics, including genetic susceptibility to autoimmunity (HLA genotypes), insulin deficiency, and clinical factors varied across these four categories.

Most subjects fell into either the autoimmune plus IS (54.5%) or nonautoimmune plus IR categories (15.9%) and had characteristics that align with traditional descriptions of type 1 or type 2 diabetes. The group classified as autoimmune plus IR (19.5%) had similar prevalence and titers of diabetes autoantibodies and similar distribution of HLA risk genotypes to those in the autoimmune plus IS group, suggesting that it includes individuals with type 1 diabetes who are obese. The group classified as nonautoimmune plus IS (10.1%) likely includes individuals with undetected autoimmunity but may also include those with monogenic diabetes and thus requires further testing.

The SEARCH study offers researchers and clinicians a practical application for the etiologic classification of diabetes type and at the same time identifies a group of youths who would benefit from further testing.