Insulin Resistance Associated With Metabolic Disturbances in Pediatric Narcolepsy

Patricia Franco, MD, PhD

Recent results from a retrospective study published in Sleep showed insulin resistance as a core metabolic disturbance in children with narcolepsy, regardless of whether patients were obese or not. These results suggest that early evaluation and management may be beneficial for children with this sleep disorder to prevent complications in the future.¹

Among the 58 children with narcolepsy, metabolic syndrome was reported in 17.2% of the patients. Additionally, 79.3% had high homeostasis model assessment for insulin resistance (HOMA-IR), 25.9% with high body mass index (BMI), 24.1% with low high-density lipoprotein cholesterol (HDL-C), and 12.1% with high triglycerides. Notably, patients with narcolepsy who had at least 2 components of metabolic syndrome showed more severe daytime sleepiness and a higher prevalence of night eating behaviors.

Senior author Patricia Franco, MD, PhD, professor in the Faculty of Medicine at Claude Bernard University in Lyon, France, and colleagues wrote, “Despite a higher prevalence of obesity in children with narcolepsy, the higher prevalence of metabolic syndrome in adults could possibly be explained by the increase in metabolic syndrome prevalence according to age. Another explanation could implicate the hypocretin loss in these patients.”¹

The study included de novo children with narcolepsy with a median age of 12.7 years old and not on any previous narcolepsy treatments. Of note, 48.3% of the enrolled cohort were young boys. The data came from the pediatric sleep unit of the Hôpital Femme Mère Enfant in Lyon, France, between 2008 and 2020, using metabolic syndrome criteria. The participants were evaluated at home with a sleep log for 15 days to record their sleep-wake habits.

Following the evaluation period, patients underwent a systematic interview and clinical examination during hospitalization with a sleep specialist. After a nocturnal polysomnography evaluation, participants completed 4 (n = 48) or 5 (n = 10) standard multiple sleep latency tests (MSLT). The clinical and sleep characteristics were analyzed according to the different components in metabolic syndrome.

In patients with narcolepsy who had only one MS component, 92.3% reported high HOMA-IR levels and 7.7% showed low HDL-C levels. Researchers observed that all the patients with 2 and at least 3 MS components demonstrated high HOMA-IR levels. Investigators observed significantly higher levels of triglycerides (at least 3 compared to 0, 1, or 2 components involved), insulin (at least 3 components compared to 0 or 1 component, 1 or 2 components compared to 0 component), and HOMA-IR (at least 3 compared to 0 or 1 component, and 1 and 2 components compared to 0 component).

“Given their higher insulin and leptin levels, it is possible that these altered hormonal levels could result in night-eating behavior in children with narcolepsy. Obesity per se could be related to night eating behavior,” Franco et al noted.¹

The patients who had at least 2 metabolic syndrome components recorded more night eating behaviors (P = .033), showed a lower percentage of slow wave sleep, and reported more fragmented sleep. According to the data from the MSLT, investigators observed that these patients had shorter mean sleep latencies to rapid eye movement (REM)(P = .005), nonrapid eye movement sleep (P = .035), and had more sleep onset REM periods (P = .187) compared with those who had less than 2 metabolic syndrome components.

Franco and colleagues noted, “Fragmented sleep because of hypocretin loss could also be another factor [of night eating behavior], as some patients reported eating during the night to fall asleep more easily. The hypocretin system also has connections with cells of the arcuated nucleus producing the precursor of melanocortin. Hence, hypocretin deficiency may directly influence melanocortin signaling.”¹

In terms of limitations of the study, the blood pressure data consisted of a single measurement compared with a continuous measurement, which would have identified children who are at risk of dipping or nondipping during their sleep. There was no consensus regarding the criteria for metabolic syndrome in children under 10 years old, as 13 children in the study were in that age category and used criteria from a previous study.² Also, some of the results showed a tendency rather than a statistical significance when adjusting for multiple comparisons for the different metabolic syndrome components. The design of the study did not allow for causal associations to be confirmed and authors noted that a prospective study in the future could enable provide further data analysis.

“Additional parameters must be taken into account, in particular, the age of patients and their needs regarding sleep quality and quantity, as more frequent night-eating behavior has been reported in children compared to adult patients with narcolepsy,” Franco et al wrote.¹

REFERENCES
1. Zhang M, Thieux M, Arvis L, et al. Metabolic disturbances in children with narcolepsy: a retrospective study. Sleep. 2023;zsad076. doi:10.1093/sleep/zsad076
2. Roche J, Corgosinho FC, Dâmaso AR, et al. Sleep-disordered breathing in adolescents with obesity: When does it start to affect cardiometabolic health?. Nutr Metab Cardiovasc Dis. 2020;30(4):683-693. doi:10.1016/j.numecd.2019.12.003