Higher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosis

BMJ Open Diabetes Res Care. 2022 Nov;10(6):e002991. doi: 10.1136/bmjdrc-2022-002991.


Introduction: The progression to insulin deficiency in type 1 diabetes is heterogenous. This study aimed to identify early characteristics associated with rapid or slow decline of beta-cell function and how it affects the clinical course.

Research design and methods: Stimulated C-peptide was assessed by mixed meal tolerance test in 50 children (<18 years) during 2004-2017, at regular intervals for 6 years from type 1 diabetes diagnosis. 40% of the children had a rapid decline of stimulated C-peptide defined as no measurable C-peptide (<0.03 nmol/L) 30 months after diagnosis.

Results: At diagnosis, higher frequencies of detectable glutamic acid decarboxylase antibodies (GADA) and IA-2A (p=0.027) were associated with rapid loss of beta-cell function. C-peptide was predicted positively by age at 18 months (p=0.017) and 30 months duration (p=0.038). BMI SD scores (BMISDS) at diagnosis predicted higher C-peptide at diagnosis (p=0.006), 3 months (p=0.002), 9 months (p=0.005), 30 months (p=0.022), 3 years (p=0.009), 4 years (p=0.016) and 6 years (p=0.026), whereas high HbA1c and blood glucose at diagnosis predicted a lower C-peptide at diagnosis (p=<0.001) for both comparisons. Both GADA and IA-2A were negative predictors of C-peptide at 9 months (p=0.011), 18 months (p=0.008) and 30 months (p<0.001). Ten children had 22 events of severe hypoglycemia, and they had lower mean C-peptide at 18 months (p=0.025), 30 months (p=0.008) and 6 years (p=0.018) compared with others. Seven of them had a rapid decline of C-peptide (p=0.030), and the odds to experience a severe hypoglycemia were nearly fivefold increased (OR=4.846, p=0.04).

Conclusions: Low age and presence of multiple autoantibodies at diagnosis predicts a rapid loss of beta-cell function in children with type 1 diabetes. Low C-peptide is associated with an increased risk of severe hypoglycemia and higher Hemoglobin A1C. A high BMISDS at diagnosis is predictive of remaining beta-cell function during the 6 years of follow-up.

Keywords: C-Peptide; Diabetes Mellitus, Type 1; Hypoglycemia; Pediatrics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autoantibodies
  • C-Peptide
  • Child
  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / diagnosis
  • Humans
  • Hypoglycemia* / diagnosis
  • Infant
  • Insulin


  • C-Peptide
  • Autoantibodies
  • Insulin