TABLE 2:
Summary of 10 studies on CSF hypocretin-1 and metabolic function in children, women and men
| Author, Year Country | Research Question | Study Design | Study population | Exposure assessment | Outcome (s) assessment | HCRT1 Assessment | Main Findings |
|---|---|---|---|---|---|---|---|
| Arnulf, 2006, USA [54] | Association between HCRT 1 and leptin | Cross-sectional | 93 narcoleptic low HCRT1 72 narcoleptic normal HCRT1 89 w/other sleep disorders 111 controls |
HCRT1 deficiency | Serum, CSF leptin, CRP | Cerebrospinal fluid Radio-immunoassay |
Serum leptin similar in all groups; HCRT 1 was not associated with serum or CSF leptin; CRP levels similar across groups; Analyses adjusted for sex, age, BMI, CRP, sleep duration, meds use |
| Beitinger 2011, Germany [70] | Association between HCRT1 deficiency and glucose metabolism | Case-control | 17 adults with NC 17 controls |
HCRT1 deficiency | Glucose, insulin sensitivity following 4-hour oral glucose tolerance test | Cerebrospinal fluid Radio-immunoassay |
No differences in glucose metabolism between groups; Study matched for age, sex and BMI |
| Donadio 2014, Italy [74] | Association between HCRT 1, sympathetic and cardiovascular function | Cross-sectional | 19 adults with NC 19 controls |
HCRT1 deficiency | HR, BP | Cerebrospinal fluid Radio-immunoassay |
HCRT1 deficiency is associated with lower HR and BP; HCRT 1 correlated (positively) with HR, but not with BP; Study matched for age, sex |
| Fronczek 2008, Holland [72] | Association between HCRT1 and autonomic balance | Cross-sectional | 15 men with NC 15 controls |
HCRT1 deficiency | Resting MET rate, HR, BP | Cerebrospinal fluid Radio-immunoassay |
Similar resting MET rate, mean HR, systolic and diastolic BP among NC men and controls, but variability of HR and BP differed between groups; Study matched for sex, BMI, age |
| Heier 2011, Norway [67] | Association between HCRT 1 and metabolic risk factors | Cross-sectional | 26 adults with NC, deficient HCRT1 23 adults with NC, normal HCRT1 11 adults with IH 43 controls |
HCRT1 deficiency | BMI, HbA1C, serum and CSF leptin | Cerebrospinal fluid Radio-immunoassay |
Similar mean BMI in all groups; serum, CSF leptin not associated with HCRT 1 levels; similar HbA1C across all groups; Study matched for age, sex |
| Omokawa 2016, Japan [68] | Associations between HCRT1 and BMI | Cross-sectional | 14 patients with PWS 37 with NC 14 with IH |
HCRT1 | BMI | Cerebrospinal fluid Radio-immunoassay | Moderate HCRT1 in PWs significantly higher than NC patients, but lower than those with IH. HCRT 1 and BMI not correlated; Study controlled for race/ethnicity |
| Poli 2009, Italy [65] | Associations between HCRT 1, metabolic function and MET syndrome | Cross-sectional | 14 men with NC 14 men with IH |
HCRT1 deficiency | Adiposity measures, systolic, diastolic BP, HR, lipid profile, glucose, insulin | Cerebrospinal fluid Radio-immunoassay |
NC men had higher adiposity, BP, total cholesterol, triglycerides, insulin, leptin, but similar HR, lower HDL vs. IH men; MET syndrome only present in NC group (64%); Study controlled for age and sex; all patients were white and drug naive |
| Poli 2013, Italy [66] | Associations between HCRT 1deficiency, precocious puberty and BMI | Cross-sectional | 43 children with NC 52 obese controls |
HCRT1 deficiency | Adiposity measures, lipid profile, CRP, glucose, insulin, precocious puberty | Cerebrospinal fluid Radio-immunoassay |
HCRT1 lower in NC group with vs. without precocious puberty and with excessive vs. normal weight, statistically insignificant; Precocious puberty shown in 17% and 2% of NC patients and controls, respectively; Study matched for age |
| Santiago 2018, Germany [69] | Association between HCRT1 and body composition | Cross-sectional | 26 adults BMI≥25 15 adults normal weight |
HCRT1 | BMI, body weight, fat, fat-free mass, total water, WC | Cerebrospinal fluid Radio-immunoassay | Inverse associations between HCRT 1, body weight, WC, fat-free mass and total water; no association with BMI, fat mass, insulin, glucose and adiponectin; Study matched for race/ethnicity |
| Sieminski 2017, Finland [73] | Associations between HCRT1 deficiency and BP patterns | Cross-sectional | 11 adults with NC, HCRT1 depleted 10 adults with NC, HCRT1 deficient |
HCRT1 deficiency | BP patterns, daytime and nocturnal systolic, diastolic BP, Dip of systolic, diastolic BP | Cerebrospinal fluid Radio-immunoassay |
Nocturnal, daytime BP patterns similar in both groups; No information about control for confounding |
BMI=body mass index; BP=blood pressure; CSF=cerebrospinal fluid; HCRT1=hypocretin-1; HR=heart rate; IH=idiopathic hypersomnia; MS=metabolic syndrome; NC=narcolepsy and cataplexy; PWS=Prader-Willi Syndrome; WC=waist circumference;