Early loss and progressive deterioration of glucagon responses to hypoglycemia in children with type 1 diabetes
Authors' conclusion
Glucagon counterregulation is profoundly impaired early in pediatric T1D and deteriorates dynamically within the first 18 months after diagnosis. Glycemic instability and recurrent hypoglycemia are key determinants of α-cell dysfunction.
Study context
- Population
- Children and adolescents aged 2–17 years with newly diagnosed T1D and healthy first-degree relatives; insulin-induced hypoglycemia tests at diagnosis and at 6, 12 and 18 months (T1D)
- Participants
- 22 vs 8
- Exposure
- Children with newly diagnosed T1D vs healthy first-degree relatives
- T1Dn = 22
- Healthy relativesn = 8reference
- Outcome
- Evolution of glucagon secretion during insulin-induced hypoglycemia
- Follow-up
- Diagnosis, 6, 12 and 18 months
Methodological detailsmulticenter
- Multicenter
Main finding
As reported in the abstract
Glucagon response during insulin-induced hypoglycemia
- Healthy relatives: robust physiological increase in glucagon during hypoglycemia
- p<0.001
- T1D: glucagon responsiveness transiently improved at 6 months
- p=0.04
- T1D: glucagon responsiveness paradoxically suppressed at 18 months
- p=0.02
Observational data: associations, not effects.
Further findings
Continuous glucose monitoring (CGM) metrics and glucagon response
- CGM-based logistic model predicting impaired glucagon responses, AUC
- 0.79
- Glucagon responses correlated positively with CGM TIR (70-180 mg/dL) and negatively with glycemic variability and hypoglycemia frequency
Circulating biomarkers and glucagon secretion
- GIP, GLP-1, TNF-α and interferon-γ correlated positively with glucagon secretion; partial remission status did not
Original publication
Early loss and progressive deterioration of glucagon responses to hypoglycemia in children with type 1 diabetes. BMJ Open Diabetes Res Care. Published 26 August 2026. doi:10.
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