Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome

Abstract

Context To our knowledge, circadian rhythms have not been examined in girls with polycystic ovarian syndrome (PCOS), despite the typical delayed circadian timing of adolescence, which is an emerging link between circadian health and insulin sensitivity (SI), and decreased SI in PCOS. Objective To examine differences in the circadian melatonin rhythm between obese adolescent girls with PCOS and control subjects, and evaluate relationships between circadian variables and SI. Design Cross-sectional study. Participants Obese adolescent girls with PCOS (n = 59) or without PCOS (n = 33). Outcome Measures Estimated sleep duration and timing from home actigraphy monitoring, in-laboratory hourly sampled dim-light, salivary-melatonin and fasting hormone analysis. Results All participants obtained insufficient sleep. Girls with PCOS had later clock-hour of melatonin offset, later melatonin offset relative to sleep timing, and longer duration of melatonin secretion than control subjects. A later melatonin offset after wake time (i.e., morning wakefulness occurring during the biological night) was associated with higher serum free testosterone levels and worse SI regardless of group. Analyses remained significant after controlling for daytime sleepiness and sleep-disordered breathing. Conclusion Circadian misalignment in girls with PCOS is characterized by later melatonin offset relative to clock time and sleep timing. Morning circadian misalignment was associated with metabolic dysregulation in girls with PCOS and obesity. Clinical care of girls with PCOS and obesity would benefit from assessment of sleep and circadian health. Additional research is needed to understand mechanisms underlying the relationship between morning circadian misalignment and SI in this population.

Continuous Light-Induced PCOS-Like Changes in Reproduction, Metabolism, and Gut Microbiota in Sprague-Dawley Rats

“…Among the environmental factors that may contribute to PCOS, circadian rhythm disruption has recently received significant interest (Simon et al, 2019). In cases where the timing of the light-dark cycle altered as a result of transmeridian flight or shift work, the circadian system frequently is misaligned with the external physical environment, leading to poor health outcomes (Farhud and Aryan, 2018).…”

A Model of Adolescent Sleep Health and Risk for Type 2 Diabetes

“…Compared with adults and younger children, however, adolescents demonstrate a pubertally-related delay in melatonin secretion and the forced early rise times common for high school students results in adolescents being awake at inappropriate circadian times [82]. Indeed, morning circadian misalignment, or wakefulness while melatonin levels remained elevated, was associated with IR (HOMA-IR) in adolescent girls with obesity [83]. Further research examining the impact of circadian misalignment on IR is needed in other adolescent populations particularly given the increased risk for delayed circadian rhythm in this age group.…”

In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond

“…One such environmental factor is the disruption of the circadian cycle [ 68 ], which has for some time been suspected to be a contributing factor for PCOS pathogenesis, but has only recently been investigated experimentally [ 69 ]—prolonged exposure to continuous light was found to induce several PCOS-like changes in rats; i.e., the ovarian morphology showed abundant atretic cyst-like follicles and reduced the number of corpora lutea, demonstrating oligo/anovulation. AMH levels were significantly elevated in comparison with the control groups; the glucose metabolism, evidenced by a lower basal insulin level and decreased homeostatic model assessment, was also impaired.…”