title: Beta-cell response to intravenous glucagon in African-American and Hispanic children with type 2 diabetes mellitus.
abstract: The incidence of type 2 diabetes mellitus (DM) in children and adolescents has substantially increased over the past decade. The present study was conducted to evaluate the beta-cell response to intravenous glucagon (a non-glucose secretagogue) in children with type 2 DM. Twenty pediatric patients with type 2 DM were compared to 15 control subjects matched for body mass index and sexual maturation. The patients' ages ranged between 10 and 19 years. The duration of DM ranged from 1 to 5 years. Nine patients were on insulin treatment and 11 were on diet alone (3 patients) or metformin (8 patients). The criteria for type 2 DM were absent islet cell (IA-2) and glutamic acid decarboxylase (GAD65) antibodies and a fasting serum C-peptide level of > or = 0.23 nmol/l. Plasma glucose and serum C-peptide levels were determined in the fasting state and six minutes after an intravenous injection of 1 mg of glucagon. The fasting and stimulated plasma glucose levels and the fasting serum C-peptide levels (1.02 +/- 0.43 vs 0.79 +/- 0.26 nmol/l, p < 0.05) were higher in the patients with DM compared to weight-matched control subjects. While the absolute C-peptide responses to glucagon were not different between the two groups, the stimulated C-peptide to glucose ratios were significantly lower in the patients with DM compared to controls (0.039 +/- 0.026 vs 0.062 +/- 0.033, p < 0.05). Patients with DM treated with diet or oral therapy had significantly greater basal and stimulated C-peptide concentrations, incremental C-peptide, and C-peptide to glucose ratios than patients on insulin treatment. Both the fasting and the stimulated C-peptide levels were inversely correlated with the duration of DM (r = -0.53, p < 0.05). HbA1c at one year follow-up was inversely correlated with glucagon-stimulated C-peptide levels at the time of the study (r = -0.658, p < 0.01) and positively correlated with the duration of diabetes (r = 0.671, p = 0.002). The apparently normal serum C-peptide levels measured after glucagon challenge in these children with type 2 DM reflect their higher glucose levels. The lower stimulated C-peptide to glucose ratios in these children with type 2 DM compared to normal controls demonstrate their diminished beta-cell response to intravenous glucagon, a non-glucose secretagogue. Among the patients with DM, a higher glucagon-stimulated serum C-peptide response was associated with diet/metformin treatment, a shorter duration of DM and predicted improved glycemic control up to one year later. Thus, the fasting and glucagon-stimulated serum C-peptide levels provide an estimate of the potential insulin secretory capacity of the beta-cell and may predict glycemic control in pediatric type 2 DM.
authors.affiliation: Department of Pediatrics, State University of New York Health Science Center at Brooklyn and Children's Medical Center of Brooklyn, USA.
authors.forename: Doris R
authors.initials: DR
authors.lastname: Taha
authors.forename: Salvador
authors.initials: S
authors.lastname: Castells
authors.forename: Vatcharapan
authors.initials: V
authors.lastname: Umpaichitra
authors.forename: William
authors.initials: W
authors.lastname: Bastian
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Banerji
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000008:administration & dosage; D006442:Glycated Hemoglobin / Q000378:metabolism; D006630:Hispanic or Latino; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007275:Injections, Intravenous; D007328:Insulin / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D010186:Pancreatic Function Tests
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin