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Children with Type 1 Diabetes Show Early Abnormalities in Glucagon Response

A new study revealed young type 1 diabetes patients exhibited abnormal plasma glucagon responses to mixed meal tolerance tests within two years of diagnosis, according to researchers from the Diabetes Research in Children Network…. 

Lead researcher Dr. Jennifer Sherr, Yale University School of Medicine in New Haven, Connecticut, said, "The findings demonstrate that dysregulation in glucagon secretion is seen early in the course of disease, being demonstrated in some of our subjects within the first year after diagnosis."

She added that, "These data provide compelling evidence for the use of adjunctive therapies that suppress glucagon secretion in youth regardless of disease duration." In many patients with type 1 diabetes, exaggerated alpha-cell responses to amino acid stimulation, manifested by higher glucagon levels, may contribute to postprandial hyperglycemia.

Dr. Sherr and colleagues compared the magnitudes of glucagon responses to a standard mixed-meal tolerance test in 25 youth with type 1 diabetes and 20 non-diabetic, age- and sex-matched children.

During the first year after diagnosis, children with diabetes had significantly lower fasting and peak stimulated plasma C-peptide levels than did non-diabetic children, but only one type 1 diabetic had a peak stimulated C-peptide value below 0.2 mmol/L. Plus, by the end of the second year, though, seven of the 25 diabetic children had peak stimulated C-peptide values below 0.2 mmol/L

Fasting plasma glucagon levels did not differ between diabetic and non-diabetic children during years 1 and 2. In contrast, peak increases in glucagon levels after the mixed meal were significantly higher in diabetic children than in their non-diabetic peers.

All but two diabetic children had clinically relevant increases in plasma glucagon by year 2, compared with 40% of control subjects. The rise in total glucagon secretion paralleled the increasing duration of type 1 diabetes.

Unger et al. suggested, "More than 40 years ago, that diabetes was a bihormonal disease characterized by too little insulin and too much glucagon," the authors explain. "Interest in this question faded during the early intensive treatment era when attention turned to impaired glucagon responses to hypoglycemia."

"These observations provide a compelling rationale for further studies on the benefits of agents like pramlintide and GLP-1 agonists that can suppress abnormal glucagon responses to feeding in the treatment of youth with type 1 diabetes," they conclude.

"Importantly, the degree of dysregulated glucagon secretion in these youth with type 1 diabetes approximates the glucagon secretion seen in healthy, young adults in response to insulin-induced hypoglycemia," Dr. Sherr said.

While treatment of type 1 diabetes has largely been limited to insulin therapy, further exploration of and application of adjunctive therapies may prove to be as important in the management of type 1 diabetes in both the adult and pediatric populations.