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

The present study was conducted to determine the extent of insulin deficien cy 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 gl ucagon action both regulate blood glucose concentration, we studied their r esponses 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 (pred ominantly African-Americans), matched for body mass index and sexual matura tion. All of those with diabetes were negative for antibodies to glutamic a cid decarboxylase. Plasma glucose, glucagon, and serum C-peptide concentrat ions were measured at 0, 30, 60, 90, and 120 min after a mixed liquid meal (Sustacal) ingestion (7 mL/kg body weight; maximum, 360 mt). The area under the curve (AUC) was calculated by trapezoidal estimation. The incremental C-peptide (Delta CP) in response to the mixed meal was calculated (peak - f asting C-peptide). The plasma glucose AUC was significantly greater in pati ents than in controls (mean +/- SEM, 1231 +/- 138 us. 591 +/- 13 mmol/L-. m in; P < 0.001). The Delta CP was significantly lower in those with diabetes than in controls (1168 +/- 162 vs. 1814 +/- 222 pmol/L; P < 0.02). Glucago n responses did not differ between the two groups. Hyperglycemia is known t o inhibit glucagon secretion. Therefore, our patients with substantial hype rglycemia would be expected to have decreased glucagon responses compared w ith controls and are thus relatively hyperglucagonemic. Patients were divid ed into poorly and well controlled subgroups (glycosylated hemoglobin A(1c) , greater than or equal to 7.2% and < 7.2%, respectively). There were no si gnificant differences in the Delta CP and glucagon responses between these two subgroups. We next analyzed the data in terms of duration of diabetes ( long term, greater than or equal to1 yr; short term, <1 yr). The Delta CP w as significantly lower in long- vs, short-term patients (768 +/- 232 us. 14 07 +/- 199 pmol/L; P < 0.05). The plasma glucagon AUC was significantly hig her in the long- us. short-term patients (9029 +/- 976 us. 6074 +/- 291 ng/ l(.)min; P < 0.001). Hemoglobin A(1c) did not differ between long- vs. shor t-term patients. Our results indicate that relative hypoinsulinemia and hyp erglucagonemia represent the pancreatic beta- and alpha -cell dysfunctions in children with type 2 diabetes. The severity of both beta and alpha -cell dysfunctions appears to be determined by the duration of diabetes.