Background: Copeptin is a surrogate marker for arginine vasopressin (AVP) release in response to hyperosmolal stimuli such as diabetic ketoacidosis (DKA). We aimed to characterize the temporal course (kinetics) of serum osmolality and copeptin during rehydration and insulin therapy in children with type 1 diabetes (T1D) and DKA, and the relationship between both (dynamics).
Methods: An observational multi-center study was conducted including pediatric patients with T1D admitted for DKA and aged 1-18 years. Serial serum copeptin and osmolality measurements were taken at 14 time points from the start of rehydration therapy to 72 hours post rehydration start. Clinical parameters such as age, severity of DKA (mild = pH<7.3, moderate = pH<7.2, or severe pH<7.1) and Glasgow Coma Scale (GCS) were documented. Copeptin and osmolality kinetics and dynamics were further characterized using linear and non-linear mixed-effect regression modelling.
Results: Twenty-eight children with T1D (20 newly diagnosed) and DKA (mild: n=3, moderate: n=12, severe: n=13) were included in the study. Median [IQ range] age was 11.5 years [8, 14], GCS was 15 points [15, 15], no patient had GCS <12 or suffered from cerebral edema. 275 paired serum copeptin and osmolality measurements were obtained (median: 10 per patient). Kinetics were described by a mono-exponential decline (95%CI) [inter-individual variability, expressed as coefficient of variation]: Copeptin decreased from 98 pmol/L (58.4-137.6) [142%] to 10.3 pmol/L (8.8-11.8) [25%] with a 50% recovery time (t1/2) of 6.0 h (5.1-11.5) [98%]. Serum osmolality decreased from 321 mosmol/L (315-327) [4%] to 294 mosmol/L (292-296) [1%] with t1/2 of 4.3 h (3.0-5.6) [64 %]. Bi-exponential decrease was also tested, but did not show clear improvement compared to mono-exponential decline given available data (large standard errors in parameter estimates). Dynamics were described as exponential increase: copeptin levels doubled with each osmolality increase by 15 mosmol/L (10-27) [50%], baseline copeptin levels were 9.2 pmol/L (8.0-10.4) [2%] at 280 mosmol/L.
Conclusions: This is the first data set available on sequential copeptin levels in a hyperosmolal state in children. Copeptin and osmolality decreased in parallel during rehydration and insulin therapy in pediatric patients with DKA. Physiologic maximum copeptin response was not observed despite wide osmolality range, suggesting a large synthesis and release capacity of AVP in children. These data underline the usefulness of copeptin as a surrogate marker of hyperosmolar triggered AVP release and as a potential marker to guide rehydration therapy.
19 Sep 2019 - 21 Sep 2019