Islet Cell Antibody–Positive Versus –Negative Phenotypic Type 2 Diabetes in Youth

OBJECTIVE Using the clamp technique, youths with a clinical diagnosis of type 2 diabetes (CDx-type 2 diabetes) and positive pancreatic autoantibodies (Ab(+)) were shown to have severe impairment in insulin secretion and less insulin resistance than their peers with negative antibodies (Ab(-)). In this study, we investigated whether oral glucose tolerance test (OGTT)-derived indexes of insulin secretion and sensitivity could distinguish between these two groups. RESEARCH DESIGN AND METHODS A total of 25 Ab(-), 11 Ab(+) CDx-type 2 diabetic, and 21 obese control youths had an OGTT. Fasting and OGTT-derived indexes of insulin sensitivity (including the Matsuda index, homeostasis model assessment [HOMA] of insulin resistance, quantitative insulin sensitivity check index, and glucose-to-insulin ratio) and insulin secretion (HOMA of insulin secretion and 30-min insulogenic and C-peptide indexes) were used. Glucagon and glucagon-like peptide (GLP)-1 responses were assessed. RESULTS Fasting C-peptide and C-peptide-to-glucose ratio, and C-peptide area under the curve (AUC) were significantly lower in the Ab(+) CDx-type 2 diabetic patients. Other OGTT-derived surrogate indexes of insulin sensitivity and secretion were not different between the Ab(+) versus Ab(-) patients. GLP-1 during the OGTT was highest in the Ab(+) youths compared with the other two groups, but this difference disappeared after adjusting for BMI. Ab(+) and Ab(-) CDx-type 2 diabetes had relative hyperglucagonemia compared with control subjects. CONCLUSIONS The clinical measures of fasting and OGTT-derived surrogate indexes of insulin sensitivity and secretion, except for fasting C-peptide and C-peptide AUC, are less sensitive tools to distinguish metabolic/pathopysiological differences, detected by the clamp, between Ab(+) and Ab(-) CDx-type 2 diabetic youths. This underscores the importance of using more sensitive methods and the importance of determining antibody status in obese youths with CDx-type 2 diabetes.