C-peptide and Glucagon Profiles in Minority Children with Type 2 Diabetes Mellitus

Abstract

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 (Delta CP) 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 x min; 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). 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), > or =7.2% and <7.2%, respectively). There were no significant 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, > or =1 yr; short term, <1 yr). The CP 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 x 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 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.

Adult-onset idiopathic Type I or ketosis-prone Type II diabetes: evidence to revisit diabetes classification

“…Insulin secretion in response to glucose that is partially defective could be impaired in addition by glucose and/or lipotoxicity. Moreover, glucagon, the main ketogenic hormone in humans is increased in Type II diabetes and a relative hyperglucagonaemia was also evidenced in African-American children with acute-onset Type II diabetes [16]. We therefore hypothesise that this atypical diabetes is a subtype of Type II diabetes, which develops in patients with high sensitivity to glucotoxicity or lipotoxicity, or with dysregulation of glucagon secretion.…”

Youth Type 2 Diabetes

“…Another study in 9-to 20-year-old type 2 diabetic patients revealed relative hypoinsulinemia and hyperglucagonemia in response to a mixed liquid meal tolerance test (20). However, the insulin deficiency was not expressed relative to the degree of insulin resistance (not measured).…”

Type 2 Diabetes in Children: Clinical Aspects and Risk Factors

“…1) [25]. When youth with T2DM are compared with non-diabetic control subjects, stimulated C-peptide levels are lower while glucagon levels are not different [32, 33]. Similarly, insulin response to intravenous glucose stimulation is significantly deficient in adolescents with T2DM compared with non-diabetic adolescents [33].…”