PHILADELPHIA — Positive pancreatic antibodies and the presence of diabetic ketoacidosis appear to affect how insulin reserve changes over time in children with type 2 diabetes, based on the results of a natural history study of 66 children.
By studying the natural history of type 2 diabetes in children, the researchers hope to identify predictors of changes in insulin secretion that could lead to new treatments aimed at delaying β-cell failure.
Hemoglobin A1c and insulin dose differed between children who were nonacidotic and antibody negative at presentation, those who had diabetic ketoacidosis but were antibody negative at presentation, and those who were nonacidotic but antibody positive at presentation. HbA1c and insulin dose changed significantly over time in a complex curvilinear manner, said Marcia Hernandez, a third-year medical student at the Philadelphia College of Osteopathic Medicine, who presented the results at the annual meeting of the Eastern Society for Pediatric Research.
Ms. Hernandez, Dr. Lorraine E. Levitt Katz, and their colleagues at the Children's Hospital of Philadelphia recruited 66 children (55% girls, mean age 14 years) with type 2 diabetes between 1998 and 2002. The children were presumptively diagnosed with type 2 diabetes based on clinical features—obesity (body mass index greater than 85% for age and gender), acanthosis nigricans, and a family history of type 2 diabetes. Children were treated with metformin and/or insulin.
The researchers measured HbA1c, insulinlike growth factor-binding protein-1 (IGFBP-1), C-peptide, and the dose of exogenous insulin. Measurements were taken at diagnosis and at follow-up assessments every 3–6 months for 4 years.
In addition, pancreatic autoantibodies were measured at diagnosis. In accordance with the standard of care at the time, glutamic acid decarboxylase-65(Gad-65) antibodies were the only pancreatic antibodies measured at the time of diagnosis of diabetes, until 2001. After 2001, islet cell autoantigen 512 and insulin antibodies were measured in addition to Gad-65.
IGFBP-1 is secreted by the liver and circulates in the blood. Secretion is acutely inhibited by insulin. Higher fasting levels of IGFBP-1 have been found in individuals with type 1 diabetes, compared with those with type 2 diabetes. C-peptide reflects the amount of insulin produced by the body.
The children were divided into three groups: those who were nonacidotic and antibody negative at presentation (46), those who had diabetic ketoacidosis but were antibody negative at presentation (13), and those who were nonacidotic but antibody positive at presentation (7).
Those who presented with antibodies were younger at presentation. At baseline, HbA1c was strongly correlated to C-peptide and insulin dose. Insulin dose was strongly correlated to IGFBP-1 and C-peptide.
All of the groups had elevated HbA1c levels at baseline; those who had diabetic ketoacidosis but were antibody negative had the highest levels. HbA1c in all groups reached the lowest levels between 6 months and 1 year, and then began steadily rising.
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