title: The effect of glycemic variability on counterregulatory hormone responses to hypoglycemia in young children and adolescents with type 1 diabetes.
abstract: BACKGROUND
  Glycemic variability (GV) is associated with hypoglycemia and possibly diabetes-related outcomes. We hypothesized that GV and glucose excursion risk may predict counterregulatory (CR) hormone responses to hypoglycemia.
  
  
  METHODS
  This is a secondary analysis of a Diabetes Research in Children Network study containing continuous interstitial glucose monitoring records for 28 patients with type 1 diabetes between 3 to <8 or 12 to <18 years of age. GV and excursion measures, including continuous overall net glycemic action (CONGA), High Blood Glucose Index (HBGI), Low Blood Glucose Index (LBGI), and coefficient of variation (CV), were calculated 72 h prior to insulin-induced hypoglycemia. CR hormones were measured during the progressive fall in plasma glucose.
  
  
  RESULTS
  CV was inversely correlated with change in glucagon concentration (r=-0.41, P=0.046), but CONGA (log-transformed for better fit of the models) was not statistically significant in univariate analysis (r=-0.34, P=0.10). Other CR hormones were not significantly associated with measures of variability. In multivariate analysis, higher CONGA, but not CV, was associated with a smaller rise in glucagon following induced hypoglycemia (estimate=-9.73, P=0.048), independent of hemoglobin A1c, duration of diabetes, and insulin dose. HBGI, LBGI, and antecedent time spent in hypoglycemia were not significantly correlated with CR response to subsequent hypoglycemia.
  
  
  CONCLUSIONS
  CV and CONGA may be predictors of impaired glucagon responses to insulin-induced hypoglycemia in patients with type 1 diabetes. Further study is indicated to characterize the role of GV and glycemic excursions on the defensive response to hypoglycemia.
authors.affiliation: Department of Internal Medicine, Mount Carmel Health System, Columbus, Ohio, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Alghothani
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Dungan
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005934:Glucagon / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male
chemical_list: D001786:Blood Glucose; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human