Obstructive sleep apnoea increases lipolysis and deteriorates glucose homeostasis in patients with type 2 diabetes mellitus.

Obstructive sleep apnoea (OSA) is associated with type 2 diabetes mellitus (T2DM). However, mechanisms mediating association between these two conditions remain unclear. This study investigated, whether the OSA-associated changes in adipose tissue lipolysis might contribute to impaired glucose homeostasis in patient with T2DM. Thirty-five matched subjects were recruited into three groups: T2DM + severe OSA (T2DM + OSA, n = 11), T2DM with mild/no OSA (T2DM, n = 10) and healthy controls (n = 14). Subcutaneous abdominal adipose tissue microdialysis assessed spontaneous, epinephrine- and isoprenaline-stimulated lipolysis. Glucose metabolism was assessed by intravenous glucose tolerance test. Spontaneous lipolysis was higher in the T2DM + OSA compared with the T2DM (60.34 ± 23.40 vs. 42.53 ± 10.16 µmol/L, p = 0.013), as well as epinephrine-stimulated lipolysis (236.84 ± 103.90 vs. 167.39 ± 52.17 µmol/L, p < 0.001). Isoprenaline-stimulated lipolysis was unaffected by the presence of OSA (p = 0.750). The α2 anti-lipolytic effect was decreased in T2DM + OSA by 59% and 315% compared with T2DM and controls (p = 0.045 and p = 0.007, respectively). The severity of OSA (AHI) was positively associated with spontaneous (p = 0.037) and epinephrine-stimulated (p = 0.026) lipolysis. The α2-adrenergic anti-lipolytic effect (p = 0.043) decreased with increasing AHI. Spontaneous lipolysis was positively associated with Insulin resistance (r = 0.50, p = 0.002). Epinephrine-stimulated lipolysis was negatively associated with the Disposition index (r = - 0.34, p = 0.048). AHI was positively associated with Insulin resistance (p = 0.017) and negatively with the Disposition index (p = 0.038). Severe OSA in patients with T2DM increased adipose tissue lipolysis, probably due to inhibition of the α2-adrenergic anti-lipolytic effect. We suggest that dysregulated lipolysis might contribute to OSA-associated impairments in insulin secretion and sensitivity.

Metabolic disorders and sleep.

Epidemiologic studies show that both atypical sleep time and obstructive sleep apnea (OSA) are independently associated with higher risk of metabolic disease development, particularly obesity and type 2 diabetes mellitus (T2DM). OSA is an independent risk factor for cardiovascular mortality, which is amongst the most common causes of death in T2DM. It is advisable to screen patients for OSA due to the high prevalence of the disease in T2DM patients. For screening are recommended questionnaires and home sleep monitoring. OSA diagnosis is then verified by home sleep apnea testing (using polygraphy) or by polysomnography. Positive airway pressure (PAP) is a gold standard in the treatment of moderate and severe OSA. PAP prevents hypoxia and sleep fragmentation, eliminating excessive daytime sleepiness and decreasing the risk of cardiovascular diseases. Studies have not yet shown an effect of PAP treatment on T2DM compensation and glucose metabolism. Despite this a positive effect of PAP on insulin resistance and glucose tolerance has been proven in patients with prediabetes. PAP therapy is advised in obese patients of the central type with OSA, bariatric surgery has been proven to decrease the severity of OSA.

Effects of continuous positive airway pressure on neurocognitive and neuropsychiatric function in obstructive sleep apnea.

The aim of this study was to determine the neurocognitive and neuropsychiatric effects of continuous positive airway pressure treatment on patients with obstructive sleep apnea. This cross-sectional, prospective, observational study included 126 patients with sleep apnea. The following tests were performed: the Montreal Cognitive Assessment for the evaluation of cognitive impairment, the Beck Depression Inventory, and the State-Trait Anxiety Inventory, together with the Epworth Sleepiness Scale for the evaluation of neuropsychiatric symptoms and a person's general level of daytime sleepiness. The first measurement did not show neurocognitive impairment or a higher level of depressive and anxiety symptoms in 126 patients with obstructive sleep apnea in comparison to normative standards. After the 3-month treatment indicated for 43 patients with obstructive sleep apnea, we did not find any significant improvement in cognitive performance (p = .213). However, patients with sleep apnea with continuous positive airway pressure treatment did show significantly less daytime sleepiness, anxiety and depressive symptoms (all p < .001). In conclusion, short-term (3 months) treatment of patients with obstructive sleep apnea can substantially alleviate their daytime sleepiness, as well as depressive and anxiety symptoms.

The Clinical Impact of Systematic Screening for Obstructive Sleep Apnea in a Type 2 Diabetes Population-Adherence to the Screening-Diagnostic Process and the Acceptance and Adherence to the CPAP Therapy Compared to Regular Sleep Clinic Patients.

Obstructive sleep apnea (OSA) is a common disorder in Type 2 diabetes (T2D) patients further increasing their already high cardiovascular risk. As T2D patients typically not report OSA symptoms, systematic screening for OSA in this population is warranted. We aimed to determine the readiness of T2D patients to undergo screening and to compare their adherence to continuous positive airway pressure (CPAP) therapy with "regular" sleep clinic patients who typically seek medical advice on their own initiative. We therefore recruited 494 consecutive T2D patients and offered them OSA screening using home sleep monitoring (type IV device). All participants in high risk of moderate-to-severe OSA were recommended home sleep apnea testing (HSAT) followed by CPAP therapy. Patients were followed-up for 12 months and outcomes compared to 228 consecutive sleep clinic patients undergoing HSAT. Among 307 screened T2D patients, 94 (31%) were identified at high risk of moderate-to-severe OSA. Subsequently, 54 patients underwent HSAT, 51 were recommended, and 38 patients initiated CPAP (acceptance 75%). Among 228 sleep clinic patients, 92 (40%) were recommended and 74 patients initiated CPAP (acceptance 80%). After 1 year, 15 (39%) T2D and 29 (39%) sleep clinic patients showed good CPAP adherence (use ≥ 4 h/night ≥ 70% nights). In conclusion, 20 T2D patients needed to be screened in order to obtain one successfully treated patient. OSA screening in T2D patients identified 31% with moderate-to-severe OSA. Once diagnosed, their CPAP acceptance and adherence did not differ from sleep clinic patients. However, the reasons for the high dropout during the screening-diagnostic process impacting the overall success of the screening program need to be identified and addressed.

Clinical Phenotypes and Comorbidity in European Sleep Apnoea Patients.

BACKGROUND: Clinical presentation phenotypes of obstructive sleep apnoea (OSA) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure (CPAP) treatment have not been established. METHODS: A prospective follow-up cohort of adult patients with OSA (apnoea-hypopnoea index (AHI) of ≥5/h) from 17 European countries and Israel (n = 6,555) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness ("EDS") and nocturnal sleep problems other than OSA (labelled as "insomnia"): 1) EDS (daytime+/nighttime-), 2) EDS/insomnia (daytime+/nighttime+), 3) non-EDS/non-insomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype. RESULTS: The EDS phenotype comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/insomnia type 23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only 5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%, p<0.001) despite more severe OSA in the EDS group (AHI 35.0±25.5/h vs. 27.9±22.5/h, p<0.001, respectively). Psychiatric comorbidity was associated with insomnia like OSA phenotypes independent of age, gender and body mass index (HR 1.5 (1.188-1.905), p<0.001). The EDS phenotype tended to associate with higher CPAP usage (22.7 min/d, p = 0.069) when controlled for age, gender, BMI and sleep apnoea severity. CONCLUSIONS: Phenotypes with insomnia symptoms comprised more than half of OSA patients and were more frequently linked with comorbidity than those with EDS, despite less severe OSA. CPAP usage was slightly higher in phenotypes with EDS.

Screening for obstructive sleep apnea syndrome in patients with type 2 diabetes mellitus: a prospective study on sensitivity of Berlin and STOP-Bang questionnaires.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in patients with Type 2 diabetes mellitus representing an additional risk factor for already increased cardiovascular mortality. As cardiovascular diseases are the main cause of death in this population, there is a need to identify patients with moderate to severe OSA indicated for treatment. We aimed to evaluate the performance of the Berlin, STOP, and STOP-Bang screening questionnaires in a population of patients with Type 2 diabetes mellitus. METHODS: 294 consecutive patients with Type 2 diabetes mellitus filled in the questionnaires and underwent overnight home sleep monitoring using a type IV sleep monitor. RESULTS: Severe, moderate, and mild OSA was found in 31 (10%), 61 (21%), and 121 (41%) patients, respectively. The questionnaires showed a similar sensitivity and specificity for AHI ≥ 15: 0.69 and 0.50 for Berlin, 0.65 and 0.49 for STOP, and 0.59 and 0.68 for STOP-Bang. However, the performance of the STOP-Bang questionnaire was different in men vs. women, sensitivity being 0.74 vs. 0.29 (p < 0.05) and specificity 0.56 vs. 0.82 (p < 0.05). CONCLUSIONS: Even the best-performing Berlin questionnaire failed to identify 31% of patients with moderate to severe OSA as being at high risk of OSA, thus preventing them from receiving a correct diagnosis and treatment. Considering that patients with Type 2 diabetes mellitus are at high risk of cardiovascular mortality and also have a high prevalence of moderate to severe OSA, we find screening based on the questionnaires suboptimal and suggest that OSA screening should be performed using home sleep monitoring devices.

Assessment of pregnancy outcomes in Czech and Slovak women with narcolepsy.

BACKGROUND: Narcolepsy is associated with altered metabolic functions. We sought to investigate the effect of narcolepsy on pregnancy and newborns. MATERIAL/METHODS: A retrospective cohort study of patients in whom the first symptoms of narcolepsy appeared before or after pregnancy. Our study included 54 women, mothers of a total of 110 children (37 with symptoms of narcolepsy before and during pregnancy, 17 developed the narcolepsy syndrome only after childbirth). With only 1 exception, none of the patients were treated with drugs during pregnancy. RESULTS: We did not find any significant differences between the 2 groups in the registered parameters of: age of mothers at delivery, history of spontaneous abortion, alcohol and nicotine consumption, medication, complications during pregnancy, symptoms of narcolepsy, weight gain during pregnancy, length of pregnancy and delivery, complications during delivery, and weight and length of the newborn. The women experiencing symptoms of narcolepsy before or during pregnancy were found to have a significantly higher total number of pregnancy complications (35.8%) than those with later onset of symptoms (9.1%), although the complications were not clinically significant. More patients in the symptomatic group tended to have impaired glucose tolerance or type 2 diabetes, compared to the asymptomatic group. CONCLUSIONS: The study revealed no clinically relevant adverse effects of narcolepsy on pregnancy, childbirth or the newborn.

Obesity accompanies narcolepsy with cataplexy but not narcolepsy without cataplexy.

BACKGROUND: Narcolepsy with cataplexy (NC) differs from narcolepsy without cataplexy (NwoC) in the cerebrospinal fluid levels of hypocretin. Since hypocretin is known to regulate not only wakefulness but also eating behaviour, we decided to compare the two entities for body mass index (BMI) and the presence of obesity. METHODS: Clinical data on patients with NC and NwoC was studied and examined, including nocturnal polysomnography and the Multiple Sleep Latency Test (MSLT). The results were rated against a group of age- and sex-matched healthy controls. RESULTS: The BMI in NC (29.1±SD=5.8) was significantly higher than in NwoC (25.4±4.4) or in the controls (25.8±3.9) (p<0.001, F=17.4, df= 323), while no difference in BMI was found between NwoC and the controls. The proportion of patients with BMI >30 was significantly greater in NC (39.0%) than in NwoC (13.8%) or than in the control group (13.0%). A negative correlation of BMI and sleep latency in MSLT (p=0.009) was found in the combined NC and NwoC groups. CONCLUSION: Unlike NC, NwoC has neither a higher BMI nor a higher incidence of obesity than the general population.

A comparison of polysomnographic and actigraphic evaluation of periodic limb movements in sleep.

OBJECTIVE: As a standard method, periodic limb movements in sleep (PLMS) are detected by means of polysomnography (PSG). Actigraphic detection of PLMS is a recently developed method for performing of multiple-night recordings in an outpatient setting. The aim of our study was to assess sensitivity-related parameters of actigraphic detection of PLMS in comparison to the PSG, when mounted at ankles and at the base of the big toe. METHODS: We simultaneously performed PSG and actigraphic recordings at both ankles and at the bases of both big toes (Cambridge Actiwatch AW-64) for 40 nights. The PLM index (PLMI), number of periodic movements per hour of sleep, was the primary output of both methods. RESULTS: We have proven significant correlation of all resulting parameters when comparing actigraphy at either position to the PSG; however, the PLMI values obtained by the actigraphy at toes were significantly higher than by PSG (sign test, p<0.0001). At bases of the big toes, threshold of PLMI=7.6 was used as a cut off for positivity, while PLMI=5 at ankles was used for PSG. Comparing ankle versus toe actigraphic placement, sensitivity was 67% versus 94%, specificity was 95% versus 91% and negative predictive value was 78% versus 95%. The correlation of the results from actigraphy and PSG was not affected by presence of respiratory events. DISCUSSION: Our results suggest good validity of actigraphic PLM evaluation at the base of big toe using AW-64 devices and therefore, actigraphy seems suitable for screening purposes in both clinical and research usage.

Suggestive evidence of erythropoietin level abnormality in patients with sporadic and familial cases of the restless legs syndrome.

BACKGROUND: The restless legs syndrome (RLS) is divided into two forms: idiopathic and secondary. About half the cases of the former are found to have a positive family history. The lack of objective and quantitative parameters in familial RLS also represents a drawback for genetic studies. We tried to find a feature distinguishing the sporadic from the familial forms of the RLS. METHODS: RLS patients were examined for clinical picture and laboratory markers including erythropoietin levels. Patients with a priori known causes of secondary RLS, were excluded. All biochemical and hematological parameters were standardized for sex and age groups relative to the population mean and standard deviation. RESULTS: In our set of 311 patients (65.3% women, mean age 54.6 years, SD 14.7 years) 96 reported positive family history (64.6% women, mean age 53.1 years, SD 15.8 years). We found a significantly lower age at the onset of RLS symptoms in familial cases (mean 29.3 vs. 44.0, Z 5.9, p<0.0001), and, in sporadic cases, a significantly lower absolute count of red blood cells (Z -2.02, p=0.043 respectively). Erythropoietin levels in the familial cases were significantly lower than in the reference population (median -2.26 SDs from the mean). None of the other parameters were significantly different between the groups. CONCLUSIONS: Our results confirm previously published lower age at symptom onset in familial RLS and provide the first evidence of lower erythropoietin levels in RLS patients. These observations might help to identify the specific phenotype for genetic association studies.

Evening and morning plasma levels of protein S100B in patients with obstructive sleep apnea.

OBJECTIVE: Responsible for sleep brain perfusion changes, obstructive sleep apnea (OSA) constitutes a cardiovascular risk. To find out about any diffuse damage to the brain tissue, we studied the S100B protein, whose serum level is known to rise in stroke and craniocerebral trauma. METHODS: 60 men (mean age 51.7+/-11.8 years) referred to us for OSA without any major comorbidity were examined polygraphically. S100B was determined with electrochemiluminiscence immunoassay (ECLIA) from evening and morning blood samples. RESULTS: All sixty men were diagnosed with OSA. The difference between the evening level of S100B 0.068+/-0.030 microg/l and the morning level 0.059+/-0.029 microg/l was significant (p=0.0004). Patients with mild OSA were found to have the evening S100B 0.063+/-0.023 microg/l, the morning level 0.042+/-0.012 microg/l, the difference being significant (p=0.00051). In moderate OSA the difference between the evening -0.070+/-0.017 microg/l and morning levels -0.055+/-0.025 microg/l was less significant (p=0.043). In severe OSA no difference was found between the evening and morning concentrations of S100B (0.070+/-0.036 microg/l and 0.070+/-0.031 microg/l respectively). The difference between the evening and morning S100B levels correlated negatively with AHI and ODI and positively with basal saturation and average minimal oxygen saturation. CONCLUSIONS: Sleep with signs of severe OSA influences S100B protein release.

Genioglossus advancement and hyoid myotomy in treating obstructive sleep apnoea syndrome - A follow-up study.

AIM: To assess the success of genioglossus advancement and hyoid myotomy in the obstructive sleep apnoea syndrome (OSAS) therapy by comparing pre- and postoperative respiratory values during sleep. One of the surgical methods of widening the upper airways is to advance the spina mandibulae together with the genioglossus insertion. Thus the whole tongue is advanced, including its base. Hyoid myotomy itself, leads to a very unaesthetic filling up of soft tissues in the submental space. Therefore, the original window method of genioglossus advancement was modified and the so-called tenon and mortise genioplasty according to Delaire was applied. PATIENTS AND METHODS: Thirty-one patients underwent genioglossus advancement by the modified genioplasty with hyoid myotomy (8 women and 23 men, mean age 53.2 years; range 35-69 years). Basic polysomnographic parameters were monitored (during sleep) before surgery and 7.3 months (range 3-6 months) postoperatively. RESULTS: The cumulative success rate was 74%. Subjective assessment of daily sleepiness using the Epworth scale dropped from preoperative 9.6 to 4.7. The average respiratory disturbance index decreased from 20.9 preoperatively to 10.3, the oxygen desaturation index dropped from 15.1 to 8.8, the average preoperative values of baseline oxygen saturation and average desaturation values had been 95.1% and 86.5%, respectively, and had increased postoperatively to 96.0% and 90.3%, respectively. On the average, preoperative desaturation lasted 36.7s whereas it lasted for 31.0 s postoperatively. CONCLUSION: Polysomonographic monitoring proved that changing the upper airways can favourably impact upon respiratory parameters during sleep in OSAS.

Cataplexy treated with escitalopram--clinical experience.

BACKGROUND: Narcolepsy with cataplexy is a debilitating sleep disease of which some symptoms can be treated with antidepressants. The antidepressant escitalopram is considered the most specific serotonin reuptake inhibitor. PATIENTS AND METHODS: Ten patients (5 men and 5 women, age range 18-77 years) suffering from narcolepsy with cataplexy occurring at least weekly were treated with escitalopram 5 or 10 mg a day for 28-98 days. These patients were barred from taking any drugs influencing cataplexy and also had no other diseases affecting sleep or vigilance. RESULTS: The mean number of cataplexies per week in 8 compliant patients declined significantly from 6.7 (+/-SD=7.2) to 0.3 (+/-0.6), P=0.02 (Sign test). Cataplexy completely disappeared in 6 patients. Subjective daytime sleepiness, power of concentration, quality of night sleep and mood remained unchanged. During the treatment, two patients had ejaculation disturbances. Two patients withdrew from the therapy (one because of ejaculation disturbance, the other for unknown reason). CONCLUSION: Escitalopram proved to have anticataplectic effects in this small-scale open-label study.

Management of restless legs syndrome by the partial D2-agonist terguride.

BACKGROUND: Terguride as a partial D2-receptors agonist seems suitable for treatment of restless legs syndrome (RLS). METHODS: Nine RLS patients without previous dopaminergic therapy received a daily dose of terguride (0.25 mg) 29.9+/-16.9 (SD) days. RESULTS: Two patients enrolled in the study failed to turn up for a successive check up. The seven subjects who were re-examined complied with the therapy. Their RLS symptoms improved (as measured on the International RLS intensity scale), decreasing from 24.3+/-5.3 to 14+/-4.7 (p=0.014). However, the terguride treatment did not significantly alter the daytime sleepiness or the subjective duration of nocturnal sleep. The daily dose was doubled in three patients who reported insufficient RLS improvement. One of the three patients later reported augmentation.