Generation of long-chain fatty acids through hydrolysis of fat is a critical step for fat-induced stimulation of GLP-1 in humans; the signal is mediated via CCK release and CCK-1 receptors.

Background Several studies have investigated copeptin as a prognostic marker of different acute diseases and as a diagnostic marker in disorders of water and salt homeostasis. However, no data of the normal circadian rhythm of copeptin in healthy subjects are available. Aim To investigate the circadian rhythm of copeptin in healthy subjects under standardized conditions. Methods 19 healthy volunteers aged 18 to 53 years, male and female, were studied in a prospective observational study. In all 19 participants, blood samples for copeptin were taken in regular intervals of 30 minutes for 24 hours after a fasting period of minimum 8 hours. Results The mean values of copeptin showed a circadian rhythm, similar to that described for AVP release, with a trend towards higher levels (5.9 ± 1 pmol/L) at night and early morning between 4 am and 6 am and lowest levels (2.3 ± 0.2 pmol/L) in the late afternoon between 5 pm and 7 pm. This finding was only observed in individuals with initial higher copeptin levels, whereas in individuals with lower basal copeptin levels no circadian rhythm was observed. Conclusion There is evidence for a circadian rhythm in copeptin release during 24 hours, however, of minor extent. These findings suggest that copeptin levels can be determined irrespectively of the time of the day.

Context Copeptin is a surrogate marker for arginine vasopressin (AVP) release in response to hyperosmolal stimuli such as diabetic ketoacidosis (DKA). Objective Characterize kinetics of copeptin and osmolality, and their dynamic relationship during rehydration and insulin therapy in children with type 1 diabetes (T1D) and DKA. Design and Setting Prospective observational multi-centre study. Patients and Intervention Children with T1D admitted for DKA underwent serial serum copeptin and osmolality measurements from start of rehydration at 14 time points during 72 hours. Main Outcome Measures Temporal course of copeptin and osmolality (kinetics), relationship between both (dynamics), associated between-subject variability [CV%]. Results Twenty-eight children (20 newly diagnosed T1D) aged 1 to 16 years were included. Copeptin decreased from 95pmol/L (95%CI: 55-136) [CV%: 158%] to 9.7pmol/L (8.1-11.4) [31%] with a 50% recovery time (t1/2) of 7.1 (5.1-11.5) [114%] h. Serum osmolality decreased from 321mOsm/kg (315-327) [4%] to 294mOsm/kg (292-296) [1%] with t1/2 of 4.3 (3.0-5.6) [64%] h. Copeptin levels doubled with each osmolality increase by 15mOsm/kg (10-21) [59%], from 9.8pmol/L (7.3-12.3) [48%] at 280mOsm/kg. Copeptin kinetics differed between newly diagnosed and known T1D patients (P=0.0001), and less between mild versus moderate-severe DKA (P=0.044). Conclusions First, this study characterized for the first time copeptin kinetics and dynamics in the high hyperosmolar range in children with DKA. Second, it revealed significant differences in copeptin kinetics between newly diagnosed and known T1D patients that may be explained by changes at the osmoreceptor and renal AVP receptor level due to longstanding osmotic diuresis and DKA.