title: Islet cell antibody-positive versus -negative phenotypic type 2 diabetes in youth: does the oral glucose tolerance test distinguish between the two?
abstract: 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.
authors.affiliation: Division of Weight Management and Wellness, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Hala
authors.initials: H
authors.lastname: Tfayli
authors.forename: Fida
authors.initials: F
authors.lastname: Bacha
authors.forename: Neslihan
authors.initials: N
authors.lastname: Gungor
authors.forename: Silva
authors.initials: S
authors.lastname: Arslanian
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000032:analysis / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis*; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000145:classification* / Q000175:diagnosis / Q000276:immunology; D005215:Fasting / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test / Q000706:statistics & numerical data; D038321:Glycemic Index; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D010641:Phenotype
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; C024211:islet cell antibody