Dataset Information

Characterization of Post-Hypoglycemic Hyperglycemia in Children and Adolescents With Type 1 Diabetes: The EPHICA Study

ABSTRACT:

Background

In patients with diabetes, the dynamics in which hypoglycemia recovers impacts cardiovascular disease risk. Our study investigated the extents of “post-hypoglycemic hyperglycemia (PHH)” (i.e. hypoglycemia that recover to hyperglycemia in any circumstance) and factors likely to influence PHH characteristics in a pediatric cohort of patients with type 1 diabetes (T1D).

Methods

We collected retrospective continuous glucose monitoring (CGM) data from 142 pediatric patients with T1D to characterize episodes of PHH during a two-month follow-up period. Factors influencing PHH were determined using univariate and multivariate analyses.

Results

In our EPHICA cohort, PHH rate was 0.6 ± 0.3 episode/day and correlated (r=0.33; p<0.0001) with hyperglycemia rate (2.6 ± 0.5 episodes/day). The global proportion of hyperglycemia corresponding to PHH was 0.22 ± 0.1, yet 14.8% of patients had more than 1/3 of hyperglycemia related to PHH. Episodes of PHH lasted 239.6 ± 124.8 minutes with a hyperglycemic peak of 258.8 ± 47.1 mg/dL. Only 12.2% of PHH occurred at night. While a younger age (<12 years) and lower body mass index (BMI) (SDS: -2 to 1.6) were associated with higher daily PHH rates, teenagers (≥12 years) and obese patients experienced longer PHH and higher hyperglycemic peaks. Parameters of glycemic variability (i.e. HbA1C, IDAA1C and GTAA1C) moderately correlated with PHH duration and related hyperglycemic peak. Multivariate analysis confirmed these results, as factors likely to influence PHH rate were phenotype (age and BMI) and glycemic variability parameters (time in range, mean glycemia, HbA1C and GTAA1C).

Conclusion

Our EPHICA study highlights the importance of PHH as a prominent component of hyperglycemia in some children and adolescents with T1D. Factors associated with PHH features are age, BMI and parameters of glycemic control. Young and lean children are more prone to experience hypoglycemia that recover with hyperglycemia, but adolescents and obese children tend to experience hyperglycemia of longer duration.

SUBMITTER: Colinet V

PROVIDER: S-EPMC9272988 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsTo evaluate whether parameters of post-hypoglycemic hyperglycemia (PHH) correlated with glucose homeostasis during the first year after type 1 diabetes onset and helped to distinguish pediatric patients undergoing partial remission or not.MethodsIn the GLUREDIA (GLUcagon Response to hypoglycemia in children and adolescents with new-onset type 1 DIAbetes) study, longitudinal values of clinical parameters, continuous glucose monitoring metrics and residual β-cell secretion from children with new-onset type 1 diabetes were analyzed during the first year after disease onset. PHH parameters were calculated using an in-house algorithm. Correlations between PHH parameters (i.e., PHH frequency, PHH duration, PHH area under the curve [PHHAUC]) and glycemic homeostasis markers were studied using adjusted mixed-effects models.ResultsPHH parameters were strong markers to differentiate remitters from non-remitters with PHH/Hyperglycemia duration ratio being the most sensitive (ratio<0.02; sensitivity = 86% and specificity = 68%). PHHAUC moderately correlated with parameters of glucose homeostasis including TIR (R2 = 0.35, p-value < 0.05), coefficient of variation (R2 = 0.22, p-value < 0.05) and Insulin-Dose Adjusted A1c (IDAA1C) (R2 = 0.32, p-value < 0.05) and with residual β-cell secretion (R2 = 0.17, p-value < 0.05). Classification of patients into four previously described glucotypes independently validated PHH parameters as reliable markers of glucose homeostasis and improved the segregation of patients with intermediate values of IDAA1C and estimated C-peptide (CPEPEST). Finally, a combination of PHH parameters identified groups of patients with specific patterns of hypoglycemia.ConclusionPHH parameters are new minimal-invasive markers to discriminate remitters from non-remitters and evaluate glycemic homeostasis during the first year of type 1 diabetes. PHH parameters may also allow patient-targeted therapeutic management of hypoglycemic episodes.

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