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Abstract Body

The “circadian clock” coordinates human physiology with the daily light/dark cycle. For persons living with type 1 diabetes (T1D) and type 2 diabetes (T2D), this clock is essential for proper metabolic control. Glucose metabolism is under strong circadian control, peaking in the circadian night in persons without diabetes. Glucose tolerance is lower in the evening than morning, possibly due to decreases in both insulin sensitivity and beta cell function. In persons with diabetes, insulin requirements vary by time of day. Many metabolic processes including the pancreatic islet transcriptome, insulin secretion and insulin action exhibit circadian patterns. Circadian rhythms also affect immune responses and circadian disruption has been linked to an increased likelihood of diabetes complication development.

“CLOCK” and “BMAL1”, the primary clock gene promotors of transcription, play important roles in diabetes. Disruption of either leads to hypoinsulinemia and diabetes. BMAL1 is also required for beta cell compensatory expansion, survival and metabolic adaption to diet-induced obesity in mice. Non-clock gene factors are also implicated, e.g., circadian misalignment in shift workers increases diabetes risk. Mice exposed to constant light have diminished glucose-stimulated insulin secretion. These mechanisms likely involve the dysregulation of hormones and energetics as the circadian clock machinery controls, and is itself controlled, by both hormones and metabolic status. Non-clock gene related circadian dysregulation in murine diabetes models has also been associated with the appearance and progression of complications and possibly reduced efficacy of targeted immunotherapies.

Peripheral circadian clocks regulate immune cell trafficking. We have shown human circadian rhythm alterations in immune populations thought to be key to T1D pathogenesis. Despite significant progress, Type 1 diabetes (“T1D”) remains an unpreventable and uncured disease. Current therapeutic approaches seek to optimize glycemia and/or to halt autoimmune pancreatic beta cell destruction. Ultimately, therapeutic approaches designed to ameliorate disrupted circadian patterns may also prove valuable.

Background and Aims

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is estimated to occur in 10% of children in general, and in 50% of children who exhibit sleep disordered breathing (SDB). The hyperactivity is related to adrenaline secretion during sleep to assist breathing through the airway obstruction. SBD is characterized by intermittent airway obstruction resulting in episodic hypoxia, sleep fragmentation, mouth breathing, and sleep deprivation. In our study, we compare the changes ADHD behavior before and after targeted upper airway surgery for SDB in children.

Methods

Methods:

A prospective pilot study to evaluate the effect of targeted nasal surgery on improving ADHD symptoms in children with SDB. 96 children with ADHD symptoms and SDB were included. The validated NOSE score and Barkley Deficits in Executive Functioning Scale were compared at baseline and 6 months after surgery. Parents completed the assessment tools.

Results

96 patients aged 6-17 years (M 89%; F 11%) completed the study. For ages 6-11 years, 44% of children showed normalization of their behavior, and another 20% improved between to 75-99% of normal. For children ages 12-17 years, these numbers were 17% and 67%, respectively. 10% of children had their ADHD worsen after surgery. Combined, 37.7% of children normalized their ADHD behavior, and another 26% improved to between 75-99% of normal. NOSE scores were also significantly improved after surgery (p< .05). There were no surgical complications in this study.

Conclusions

Conclusions:

Targeted minimally invasive upper airway surgery in children with SDB and ADHD symptoms can significantly improve their nasal breathing and executive functioning.

Background and Aims

There is evidence that early childhood multiple or persistent regulatory problems (RPs; crying, sleeping, or feeding problems) are associated with behavioural problems in adulthood. However, it is unclear whether early multiple or persistent RPs are associated with increased hypothalamic-pituitary-adrenal (HPA) axis activity in adulthood. Thus, we investigated if multiple or persistent RPs in early childhood are associated with young adulthood diurnal salivary cortisol, which is a marker of HPA-axis activity.

Methods

Participants were 308 individuals from the Arvo Ylppö Longitudinal Study (Finland) who were assessed at 5, 20, and 56 months for RPs, and in adulthood for salivary cortisol. The mean age of participants in adulthood was 25.37 years (SD= 0.60). Saliva samples for cortisol analyses were collected at awakening, 15 and 30 minutes after awakening, 10:30 am, 12:00 pm, 5:30 pm and at bedtime during one day. We conducted random coefficients mixed model regression controlling for sex, BMI in adulthood, and parental education level. Further, the analyses were repeated for those who had multiple and persistent RPs separately.

Results

There were 61 participants who had multiple or persistent RPs in early childhood, including 38 who had multiple and 27 who had persistent RPs. Our findings revealed no significant associations between early multiple or persistent RPs and diurnal salivary cortisol in young adulthood. Similarly, there were no significant associations when we repeated the analyses separately for those who had multiple and persistent RPs.

Conclusions

Early RPs might not have an influence on salivary cortisol during young adulthood.