Islet cell antibody-positive versus -negative phenotypic type 2 diabetes in youth: does the oral glucose tolerance test distinguish between the two?

Diabetes Care. 2010 Mar;33(3):632-8. doi: 10.2337/dc09-0305. Epub 2009 Dec 22.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Autoantibodies / analysis
  • Autoantibodies / blood*
  • Blood Glucose / analysis*
  • C-Peptide / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / classification*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / immunology
  • Fasting / blood
  • Female
  • Glucose Tolerance Test / statistics & numerical data
  • Glycemic Index
  • Humans
  • Immunoassay / methods
  • Insulin / blood
  • Insulin Resistance
  • Male
  • Phenotype


  • Autoantibodies
  • Blood Glucose
  • C-Peptide
  • Insulin
  • islet cell antibody