Characterizing Associations Of Qtc Interval With Nocturnal Glycemic Control In Children With Type 1 Diabetes.

An association between QTc prolongation of 7 ms (QTcB: Bazett) and nocturnal hypoglycemia, compared to euglycemia, has been observed in children with type 1 diabetes (T1D). The objective of this pharmacometric analysis was to quantitatively understand this association and other sources of QTc variability. Data originate from a prospective observational study (25 cardiac healthy children with T1D, 8.1-17.6 years) with continuous subcutaneous glucose and electrocardiogram measurements for 5 consecutive nights. Mixed-effect modelling was used to compare Bazett with individual heart-rate correction (QTcB/QTcI). Covariate models accounting for circadian variation, age and sex were evaluated, followed by investigation of glucose-QTc relationships (univariable and combined adjusted analysis). Factors potentially modifying sensitivity to QTc-lengthening were explored. Random inter-individual variability was reduced in the QTcI versus QTcB model (±12.6 versus 14.1 ms), and further reduced in the adjusted covariate model (±9.7 ms) accounting for significantly (P<0.01) shortened QTc in adolescent boys (-14.6 ms), circadian variation (amplitude = 19.2 ms, shift = 2.9h), and linear glucose-QTc relationship (delay rate: 0.56 , slope: 0.76 ms (95%CI: 0.67-0.85 ms) per 1 mmol/L decrease in glucose). Different sensitivity was suggested depending on HbA1c, T1D duration, and time in nocturnal hypoglycemia. In conclusion, a clinically mild association of QTc prolongation with nocturnal hypoglycemia was confirmed and quantified in this pharmacometric analysis, and longest QTc interval around 03:00 AM. The characterized delayed association with glucose highlights relevance of both extent and duration of hypoglycemia. Further clinical studies are warranted to investigate whether these factors contribute to increased risk of hypoglycemia-associated cardiac arrhythmia in children with T1D. This article is protected by copyright. All rights reserved.