KOK, SIMON W., SEBASTIAAN OVEREEM, TOMMY L.S. VISSCHER, GERT JAN LAMMERS, JAAP C. SEIDELL, HANNO PIJL, AND AREND E. MEINDERS. Hypocretin deficiency in narcoleptic humans is associated with abdominal obesity. Obes Res. 2003;11:1147-1154. Objective: To determine the prevalence of obesity among patients with narcolepsy, to estimate associated long-term health risks on the basis of waist circumference, and to distinguish the impact of hypocretin deficiency from that of increased daytime sleepiness (i.e., reduced physical activity) on these anthropometric measures. Research Methods and Procedures:A cross-sectional, case-control study was conducted. Patients with narcolepsy (n ϭ 138) or idiopathic hypersomnia (IH) (n ϭ 33) were included. Age-matched, healthy members of the Dutch population (Monitoring Project on Risk Factors for Chronic Diseases and Doetinchem Project; n ϭ 10,526) were used as controls. BMI and waist circumference were determined. Results: Obesity (BMI Ն 30 kg/m 2 ) and overweight (BMI 25 to 30 kg/m 2 ) occurred more often among narcolepsy patients [prevalence: 33% (narcoleptics) vs. 12.5% (controls) and 43% (narcoleptics) vs. 36% (controls), respectively; both p Ͻ 0.05]. Narcoleptics had a larger waist circumference (mean difference 5 Ϯ 1.4 cm, p Ͻ 0.001). The BMI of patients with IH was significantly lower than that of narcolepsy patients (25.6 Ϯ 3.6 vs. 28.5 Ϯ 5.4 kg/m 2 ; p ϭ 0.004). Discussion: Overweight and obesity occur frequently in patients with narcolepsy. Moreover, these patients have an increased waist circumference, indicating excess fat storage in abdominal depots. The fact that patients with IH had a lower BMI than narcoleptics supports the notion that excessive daytime sleepiness (i.e., inactivity) cannot account for excess body fat in narcoleptic patients.

Summary.  Background: Accurate diagnosis of acute recurrent deep vein thrombosis (DVT) is relevant to avoid improper diagnosis and unnecessary life‐long anticoagulant treatment. Compression ultrasound has high accuracy for a first episode of DVT, but is often unreliable in suspected recurrent disease. Magnetic resonance direct thrombus imaging (MR DTI) has been shown to accurately detect acute DVT. The purpose of this prospective study was to determine the MR signal change during 6 months follow‐up in patients with acute DVT. Patients/methods: This study was a prospective study of 43 consecutive patients with a first episode of acute DVT demonstrated by compression ultrasound. All patients underwent MR DTI. Follow‐up was performed with MR‐DTI and compression ultrasound at 3 and 6 months respectively. All data were coded, stored and assessed by two blinded observers. Results: MR direct thrombus imaging identified acute DVT in 41 of 43 patients (sensitivity 95%). There was no abnormal MR‐signal in controls, or in the contralateral extremity of patients with DVT (specificity 100%). In none of the 39 patients available at 6 months follow‐up was the abnormal MR‐signal at the initial acute DVT observed, whereas in 12 of these patients (30.8%) compression ultrasound was still abnormal. Conclusion: Magnetic resonance direct thrombus imaging normalizes over a period of 6 months in all patients with diagnosed DVT, while compression ultrasound remains abnormal in a third of these patients. MR‐DTI may potentially allow for accurate detection in patients with acute suspected recurrent DVT, and this should be studied prospectively.

The microvascular complications shown by patients with CFRD are similar to those seen in patients with DM1 but with a lower prevalence of retinopathy and a higher prevalence of microalbuminuria. The latter may reflect the influence of other cystic fibrosis-related factors on renal function.

We hypothesized that a high circulating free fatty acid (FFA) concentration is involved in the pathogenesis of hyposomatotropism associated with obesity. To evaluate this hypothesis, 10 healthy premenopausal women (body mass index 33.8 +/- 1.0 kg/m(2)) were studied in the follicular phase of their menstrual cycle at two occasions with a time interval of at least 8 wk, where body weight remained stable. Subjects were randomly assigned to treatment with either acipimox (an inhibitor of lipolysis, 250 mg orally 4 times daily) or placebo in a double-blind crossover design, starting 1 day before admission until the end of the blood sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of growth hormone (GH) concentrations, and GH secretion was estimated by deconvolution analysis. Identical methodology was used to study GH secretion in a historical control group of age-matched normal weight women. GH secretion was clearly blunted in obese women (total daily release 66 +/- 10 vs. lean controls: 201 +/- 23 mU x l(Vd)(-1) x 24 h(-1), P = 0.005, where l(Vd) is lite of distribution volume). Acipimox considerably enhanced total (113 +/- 50 vs. 66 +/- 10 mU x l(Vd)(-1) x 24 h(-1), P = 0.02) and pulsatile GH secretion (109 +/- 49 vs. 62 +/- 30 mU x l(Vd)(-1) x 24 h(-1), P = 0.02), but GH output remained lower compared with lean controls. Further analysis did not show any relationship between the effects of acipimox on GH secretion and regional body fat distribution. In conclusion, acipimox unleashes spontaneous GH secretion in obese women. It specifically enhances GH secretory burst mass. This might mean that lowering of systemic FFA concentrations by acipimox modulates neuroendocrine mechanisms that orchestrate the activity of the somatotropic ensemble.

Hypocretin (orexin) peptides are involved in the regulation of energy balance and pituitary hormone release. Narcolepsy is a sleep disorder characterized by disruption of hypocretin neurotransmission. Pituitary LH secretion is diminished in hypocretin-deficient animal models, and intracerebroventricular administration of hypocretin-1 activates the hypothalamo-pituitary-gonadal axis in rats. We evaluated whether hypocretin deficiency affects gonadotropin release in humans. To this end, we deconvolved 24-h serum concentrations of LH and FSH in seven hypocretin-deficient narcoleptic males (N) and seven controls (C) matched for age, body mass index, and sex. Basal plasma concentrations of testosterone, estradiol, and sex hormone-binding globulin were similar in both groups. Mean 24-h LH concentration was significantly lower in narcolepsy patients [3.0 +/- 0.4 (N) vs. 4.2 +/- 0.3 (C) U/l, P = 0.01], which was primarily due to a reduction of pulsatile LH secretion [23.5 +/- 1.6 (N) vs. 34.3 +/- 4.9 (C) U.l(-1).24 h(-1), P = 0.02]. The orderliness of LH and FSH secretion, quantitated by the approximate entropy statistic, was greater in patients than in controls. In contrast, all other features of FSH release were similar in narcoleptic and control groups. Also, LH and FSH secretions in response to intravenous administration of 100 microg of GnRH were similar in patients and controls. These data indicate that endogenous hypocretins are involved in the regulation of the hypothalamo-pituitary-gonadal axis activity in humans. In particular, reduced LH release in the face of normal pituitary responsivity to GnRH stimulation in narcoleptic men suggests that hypocretins promote endogenous GnRH secretion.