Peripheral leptin levels in narcoleptic patients.

Department of Psychiatry, University of Mainz, Mainz, Germany.
Diabetes Technology &amp Therapeutics (Impact Factor: 2.21). 09/2007; 9(4):348-53. DOI: 10.1089/dia.2006.0037
Source: PubMed

ABSTRACT Narcolepsy is a severe sleep disorder that in most patients is characterized by the deficiency of central orexin. Clinically, narcolepsy is associated with obesity. Currently, there is a literature controversy about the potential alteration of leptin levels in narcoleptic patients. Theoretically, diminished leptin levels could partially contribute to the observed overweight of patients. Two studies have reported decreased leptin levels, whereas a larger, recent study failed to detect differences between patients and controls.
To help settle the controversy, we have measured peripheral leptin levels in 42 narcoleptic patients and in 31 body mass index-matched controls.
No significant differences in leptin levels between the groups were observed. Mean leptin levels were 16.0 +/- 14.9 ng/mL in the narcoleptic men and 30.4 +/- 17.8 ng/mL in the narcoleptic women. The corresponding values for the controls were 21.2 +/- 17.0 ng/mL (P = 0.49, men) and 33.9 +/- 16.9 ng/mL (P = 0.31, women). In addition, no correlation was found between leptin levels and clinical symptomatology in the narcoleptic patients.
Taken together, the data argue against a major deterioration of leptin secretion in narcoleptic patients.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Narcolepsy is caused by a selective loss of hypocretin neurons and is associated with obesity. Ghrelin and leptin interact with hypocretin neurons to influence energy homeostasis. Here, we evaluated whether human hypocretin deficiency, or the narcolepsy therapeutic agent sodium oxybate, alter the levels of these hormones. Eight male, medication free, hypocretin deficient, narcolepsy with cataplexy patients, and 8 healthy controls matched for age, sex, body mass index (BMI), waisttohip ratio, and body fat percentage were assessed. Blood samples of total ghrelin and leptin were collected over 24 hours at 60 and 20-min intervals, respectively, during 2 study occasions: baseline, and during the last night of 5 consecutive nights of sodium oxybate administration (2 × 3.0 g/night). At baseline, mean 24-h total ghrelin (936 ± 142 vs. 949 ± 175 pg/mL, p = 0.873) and leptin (115 ± 5.0 vs. 79.0 ± 32 mg/L, p = 0.18) levels were not different between hypocretin deficient narcolepsy patients and controls. Furthermore, sodium oxybate did not significantly affect the plasma concentration of either one of these hormones. The increased BMI of narcolepsy patients is unlikely to be mediated by hypocretin deficiency-mediated alterations in total ghrelin or leptin levels. Thus, the effects of these hormones on hypocretin neurons may be mainly unidirectional. Although sodium oxybate may influence body weight, the underlying mechanism is unlikely to involve changes in total ghrelin or leptin secretion. Donjacour CEHM; Pardi D; Aziz NA; Frölich M; Roelfsema F; Overeem S; Pijl H; Lammers GJ. Plasma total ghrelin and leptin levels in human narcolepsy and matched healthy controls: basal concentrations and response to sodium oxybate. J Clin Sleep Med 2013;9(8):797-803.
    Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 01/2013; 9(8):797-803. · 2.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypocretin deficiency causes narcolepsy and may affect neuroendocrine systems and body composition. Additionally, growth hormone (GH) alterations my influence weight in narcolepsy. Symptoms can be treated effectively with sodium oxybate (SXB; γ-hydroxybutyrate) in many patients. This study compared growth hormone secretion in patients and matched controls and established the effect of SXB administration on GH and sleep in both groups. Eight male hypocretin-deficient patients with narcolepsy and cataplexy and eight controls matched for sex, age, BMI, waist-to-hip ratio, and fat percentage were enrolled. Blood was sampled before and on the 5th day of SXB administration. SXB was taken two times 3 g/night for 5 consecutive nights. Both groups underwent 24-h blood sampling at 10-min intervals for measurement of GH concentrations. The GH concentration time series were analyzed with AutoDecon and approximate entropy (ApEn). Basal and pulsatile GH secretion, pulse regularity, and frequency, as well as ApEn values, were similar in patients and controls. Administration of SXB caused a significant increase in total 24-h GH secretion rate in narcolepsy patients, but not in controls. After SXB, slow-wave sleep (SWS) and, importantly, the cross-correlation between GH levels and SWS more than doubled in both groups. In conclusion, SXB leads to a consistent increase in nocturnal GH secretion and strengthens the temporal relation between GH secretion and SWS. These data suggest that SXB may alter somatotropic tone in addition to its consolidating effect on nighttime sleep in narcolepsy. This could explain the suggested nonsleep effects of SXB, including body weight reduction.
    AJP Endocrinology and Metabolism 03/2011; 300(6):E1069-75. · 4.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The possible relationship between cerebrospinal fluid (CSF) hypocretin and leptin levels, overweight, and association to risk factors for diabetes 2 in narcolepsy with cataplexy were compared to patients with idiopathic hypersomnia and controls. 26 patients with narcolepsy, cataplexy, and hypocretin deficiency; 23 patients with narcolepsy, cataplexy, and normal hypocretin values; 11 patients with idiopathic hypersomnia; and 43 controls. Body mass index (BMI), serum leptin, and HbA1C were measured in patients and controls; and CSF hypocretin 1 and leptin measured in all patients. Female and male patients with narcolepsy and hypocretin deficiency had the highest mean BMI (27.8 and 26.2, respectively), not statistically different from patients with narcolepsy and normal hypocretin or controls, but statistically higher than the patients with idiopathic hypersomnia (p < 0.001 and 0.011, respectively). The number of obese patients (BMI > 30) was increased in both narcolepsy groups. Serum and CSF leptin levels correlated positively to BMI in patients and controls, but not to CSF hypocretin concentrations. HbA1C was within normal levels and similar in all groups. The study confirms a moderate tendency to obesity (BMI > 30) and overweight in patients with narcolepsy and cataplexy. Obesity was not correlated to hypocretin deficiency or reduced serum or CSF leptin concentrations. We suggest that overweight and possible metabolic changes previously reported in narcolepsy, may be caused by other mechanisms.
    Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 12/2011; 7(6):653-8. · 2.93 Impact Factor