Phenotypic Type 2 Diabetes in Obese Youth: Insulin Sensitivity and Secretion in Islet-cell Antibody Negative vs. Antibody Positive Patients

Abstract

Objective: Some obese youth with a clinical diagnosis of type 2 diabetes (CDx-T2DM) have evidence of islet-cell autoimmunity with positive autoantibodies. In this study we investigated the differences in insulin sensitivity (IS) and secretion between autoantibody negative (Ab⁻) and positive (Ab⁺) youth with a CDx-T2DM in comparison with controls.

Research Design and Methods: Sixteen Ab⁻, 26 Ab⁺ CDx-T2DM and 39 obese control youth underwent evaluation of IS (3-hr hyperinsulinemic—euglycemic clamp), substrate oxidation (indirect calorimetry), 1^st and 2^nd phase insulin secretion (1^stPI, 2^ndPI) (2-hr hyperglycemic clamp), body composition and abdominal adiposity (DEXA and CT scan respectively), and glucose disposition index (GDI) (1^stPI x IS).

Results: Insulin-stimulated total, oxidative and non oxidative glucose disposal, and suppression of fat oxidation during hyperinsulinemia were significantly lower in Ab⁻ compared with Ab⁺ CDx-T2DM and control subjects with no difference between the latter two. First and 2^nd PI and C-peptide were lower in Ab⁺ compared with Ab⁻ T2DM. GDI was not different between the Ab⁻ and Ab⁺ CDx-T2DM but both were significantly lower than controls. Systolic blood pressure and ALT were higher in Ab⁻ vs Ab⁺ CDx-T2DM while the frequency of ketonuria at diagnosis was higher in Ab⁺ vs Ab⁻ patients.

Conclusion: Islet cell Ab⁻ CDx-T2DM youth are characterized with severe insulin resistance and relative insulin deficiency, while Ab⁺ youth have severe insulin deficiency and β-cell failure. The former group has additional features of insulin resistance. These important metabolic differences could influence the natural history of hyperglycemia, insulin dependence and clinical outcomes in these youth.