C-peptide and glucagon profiles in minority children with type 2 diabetes mellitus

The present study was conducted to determine the extent of insulin deficiency and glucagon excess in the hyperglycemia of type 2 diabetes in children. The incidence of type 2 diabetes mellitus in children and adolescents has increased substantially over the past several years. Because insulin and glucagon action both regulate blood glucose concentration, we studied their responses to mixed meals in children with type 2 diabetes. Subjects were 24 patients with type 2 diabetes compared with 24 controls, aged 9-20 yr (predominantly African-Americans), matched for body mass index and sexual maturation. All of those with diabetes were negative for antibodies to glutamic acid decarboxylase. Plasma glucose, glucagon, and serum C-peptide concentrations were measured at 0, 30, 60, 90, and 120 min after a mixed liquid meal (Sustacal) ingestion (7 mL/kg body weight; maximum, 360 mL). The area under the curve (AUC) was calculated by trapezoidal estimation. The incremental C-peptide (ACP) in response to the mixed meal was calculated (peak - fasting C-peptide), The plasma glucose AUC was significantly greater in patients than in controls (mean ± SEM, 1231 ± 138 vs. 591 ± 13 mmol/L·min; P < 0.001). The ACP was significantly lower in those with diabetes than in controls (1168 ± 162 vs. 1814 ± 222 pmol/L; P < 0.02). Glucagon responses did not differ between the two groups. Hyperglycemia is known to inhibit glucagon secretion. Therefore, our patients with substantial hyperglycemia would be expected to have decreased glucagon responses compared with controls and are thus relatively hyperglucagonemic. Patients were divided into poorly and well controlled subgroups (glycosylated hemoglobin A_1C, ≥7.2% and <7.2%, respectively). There were no significant differences in the ΔCP and glucagon responses between these two subgroups. We next analyzed the data in terms of duration of diabetes (long term, ≥1 yr; short term, <1 yr), The ΔCP was significantly lower in long- vs. short-term patients (768 ± 232 vs. 1407 ± 199 pmol/L; P < 0.05). The plasma glucagon AUC was significantly higher in the long- vs. short-term patients (9029 ± 976 vs. 6074 ± 291 ng/L·min; P < 0.001). Hemoglobin A_1c did not differ between long- vs. short-term patients. Our results indicate that relative hypoinsulinemia and hyperglucagonemia represent the pancreatic β- and α-cell dysfunctions in children with type 2 diabetes. The severity of both β- and α-cell dysfunctions appears to be determined by the duration of diabetes.