Episodes of severe hypoglycemia is associated with a progressive increase in hemoglobin A1c in children and adolescents with type 1 diabetes

Pediatr Diabetes. 2020 Aug;21(5):808-813. doi: 10.1111/pedi.13020. Epub 2020 May 4.


Objective: To investigate the trajectory in glycemic control following episodes of severe hypoglycemia (SH) among children and adolescents with type 1 diabetes (T1D).

Methods: A Danish national population-based study comprising data from 2008-17. SH was defined according to the 2014 ISPAD guidelines. A mixed model was applied with HbA1c as outcome and SH episodes and time since first episode as explanatory variables. Data were adjusted for age, gender and diabetes duration.

Results: A total of 4244 children (51.6% boys) with 18 793 annual outpatient visits were included. Mean (SD) age at diabetes onset was 9.0 (4.1) years. Median diabetes duration at inclusion in the study was 1.2 (Q1 = 0.9, Q3 = 3.0) years, and median diabetes duration at last visit was 5.0 (Q1 = 2.7, Q3 = 8.1) years. A total of 506 children experienced at least one episode of SH during the nine-year follow-up; 294 children experienced one episode, 115 two episodes and 97 three or more episodes of SH. HbA1c increased with episodes of SH and in the years following the first episode. The glycemic trajectory peaked 2 to 3 years after an SH episode. The accumulated deterioration in glycemic control was in the range of 5% in patients with two or more episodes equivalent to an increase in HbA1c of 4 mmol/mol (HbA1c ~0.4%).

Conclusion: SH was followed by a progressive and lasting increase in HbA1c among Danish children and adolescents with T1D. Thus, in addition to the known risk of new episodes of hypoglycemia and cognitive impairment, SH contributes to long-term diabetes complications.

Keywords: HbA1c; adolescents; children; diabetes; severe hypoglycemia.

Publication types

  • Historical Article

MeSH terms

  • Adolescent
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Child
  • Child, Preschool
  • Cohort Studies
  • Denmark / epidemiology
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetic Ketoacidosis / blood
  • Diabetic Ketoacidosis / epidemiology
  • Diabetic Ketoacidosis / etiology
  • Female
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / drug effects
  • Glycated Hemoglobin / metabolism*
  • History, 21st Century
  • Humans
  • Hypoglycemia / blood*
  • Hypoglycemia / chemically induced
  • Hypoglycemia / epidemiology
  • Hypoglycemia / pathology
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Severity of Illness Index
  • Up-Regulation / drug effects


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents