Nonapnea Sleep Disorders Research Articles

Estimating the incidence rate ratio of common cold among patients with non-apnea sleep disorders: a retrospective cohort study

ABSTRACT The purpose was to explore the potential effects of nonapnea sleep disorders (NSDs) and hypnotic use on the incidence of common cold. This study adapted population-based retrospective cohort study designed. We used the data from the Taiwan National Health Insurance Research Database between 1998 and 2011. In total, 59,476 patients with NSDs were included in the study cohort, and the reference cohort comprised 59,476 propensity score-matched patients. We conducted a Poisson regression analysis to assess the incidence of common cold. The overall incidence of common cold was significantly higher than that in the reference cohort. Compared with the patients of the reference cohort without hypnotic use, those of the NSDs cohort with benzodiazepines and zolpidem use had higher incidence of common cold. In conclusion, study cohort had a higher incidence of developing common cold, and particularly pronounced in NSDs with hypnotic use.

This Nested Case-Control Study Revealed That Patients With Obesity Experienced More Severe OSA Than Did Those With NASD

Objectives: To compare whether nonapnea sleep disorders (NASDs) or obstructive sleep apnea (OSA)are associated with an increased risk of obesity. Methods: From January 1, 2000, to December 31, 2015, we identified 24 363 patients with obesity from the 2005 Longitudinal Health Insurance Database, which is part of Taiwan’s National Health Insurance Research Database; 97 452 patients without obesity were also identified from the same database. The age, sex, and index date were matched. Multiple logistic regression was used to analyze the previous exposure risk of patients with obesity and NASD or OSA. A P value of <.05 was considered significant. Results: Patients with obesity were more likely to be exposed to OSA than did those with NASD (OSA adjusted OR [AOR] = 2.927, 95% CI=1.878-4.194, P < .001; NASD adjusted OR [AOR]=1.693, 95% CI=1.575-1.821, P< .001). Furthermore, the closeness of the exposure period to the index time was positively associated with the severity of obesity, with a dose– response effect (OSA exposure <1 year, AOR=3.895; OSA exposure ≥ 1 year and <5 years, AOR=2.933; OSA exposure ≥5 years, AOR=2.486 ; NASD exposure <1 year, AOR=2.386; NASD exposure ≥1 year and <5 years, AOR=1.725; NASD exposure ≥5 years, AOR=1.422). The exposure duration of OSA in patients with obesity was 2.927 times than that of NASD was 1.693 times. Longer exposure durations were associated with more severe obesity with a dose–response effect (OSA exposure <1 year, AOR = 2.251; OSA exposure ≥1 year and <5 years, AOR=2.986; OSA exposure ≥5 years, AOR=3.452; NASD exposure <1 year, AOR=1.420; NASD exposure ≥1 year and <5 years, AOR=2.240; NASD exposure ≥5 years, AOR=2.863). Conclusions: The risk of obesity was determined to be significantly higher in patients with OSA than that of NASD in this nested case-control study. Longer exposure to OSA or NASD was associated with a higher likelihood of obesity, with a dose-response effect.

Increased Risk of Benign Paroxysmal Positional Vertigo in Patients With Non-Apnea Sleep Disorders: A Nationwide, Population-Based Cohort Study.

To investigate the association between non-apnea sleep disorders (NSD) and subsequent benign paroxysmal positional vertigo (BPPV) risk. This retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database from 2000 to 2013. We established an NSD group (n = 24,624) and an age-, sex- and index year-matched comparison group (n = 98,496). The primary outcome was the occurrence of BPPV. The incidence rates of BPPV in the two cohorts were compared with a 14-year follow-up. Cox proportional hazard regression analysis was used to evaluate the effects of NSD on BPPV risk. The incidence rate of BPPV was 43.33 per 100,000 person-years for the NSD cohort and 29.33 per 100,000 person-years for the comparison cohort. NSD significantly increased the risk of BPPV (adjusted hazard ratio [HR] = 2.487; 95% confidence interval = 1.996-3.099, P < .001). Subgroup analysis revealed that NSD increase the risk of development of BPPV by 2.357- to 3.658-fold in patients with hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and hyperlipidemia. Furthermore, when comparing different types of NSD, chronic insomnia carries the highest risk of BPPV (adjusted HR = 3.563), followed by organic sleep disorders (adjusted HR = 2.763), sleep disturbance (adjusted HR = 2.506), and acute insomnia (adjusted HR = 2.237). We demonstrate that NSD are associated with an increased risk of BPPV. Relative to other types of NSD, patients with chronic insomnia are at the highest risk for development of BPPV.

Sleep disorders associated with risk of rheumatoid arthritis.

Immune disorders impair sleep quality and sleep disorders (SDs) may derange immune function. The study evaluated the incidence and risk of rheumatoid arthritis (RA) in patients with SDs using a nationwide cohort. We recognized the patients with SDs from 1998 to 2002 by using the Taiwan National Health Insurance Research Database. One control patient for each SD patient was randomly selected and matched based on the proportion of age, sex, and index year. We calculated the person years of follow-up for each participant from the index date to RA diagnosis, censoring, or until December 31, 2011. The risk of RA was estimated by using Cox models incorporating demographics and comorbidities. We enrolled 65,754 patients with SDs and 65,753 controls and followed for 637,906 and 662,514 person-years, respectively. The patients with SDs exhibited a 1.49-fold greater risk of RA development compared with the comparison cohort when we adjusted for covariates. The patients with sleep apnea (SA) showed the greatest incidence density rate of RA, followed by those with non-apnea SDs and the non-SD cohort (4.11, 3.29, and 2.15 per 10,000 person-years, respectively). The SA cohort had a 2.56-fold adjusted hazard ratio (aHR) of RA (95% confidence interval [CI] = 1.11-5.91) and the non-apnea SD cohort had a 1.47-fold aHR of RA (95% CI = 1.18-1.84) compared with the non-SD cohort. Women with SDs presented a considerable risk of developing RA. This nationwide cohort study indicates that SDs are associated with the risk of RA development.

Impact of non-apnea sleep disorders on diabetic control and metabolic outcome - A population-based cohort study.

There has been a growing recognition that obstructive sleep apnea (OSA) could increase the propensity for type 2 diabetes the metabolic syndrome. However, studies concerning about the impact of non-apnea sleep disorders (NSD) on diabetes control and metabolic outcomes are relatively scarce. Our aim is to investigate the impact of non-apnea sleep disorders (NSD) on diabetic control and associated metabolic outcomes in patients with type 2 diabetes. The data were obtained from two nationwide population-based databases for a period 2007 to 2012. A total 66,992 patients with type 2 diabetes were enrolled and divided into two cohorts based on comorbidity with or without a NSD diagnosis, and were followed up four years. The primary outcomes were to compare rate of change in HbA1c and associated metabolic outcomes during follow-up visits between patients with or without NSD. The secondary outcome is to examine whether NSD were associated with poor glycemic control of the last clinical records while controlling for the baseline HbA1c value. Of the 66,992 patients with type 2 diabetes, 14.82% had comorbidity with a NSD. HbA1C decreases were significantly lower by 0.04% in the NSD group (P < 0.05), and triglyceride (TG) decreases remained significantly lower by 2.53% in the NSD group (P < 0.05). Furthermore, patients in the NSD group had an 8% higher risk of poor glycemic control (HbA1C >9) (OR = 1.08; 95%CI, 1.01-1.16). Our findings indicated patients with type 2 diabetes comorbid with NSD had a slower improvement in HbA1c compared with the comparison cohort. It may because there may exist potential floor effect given those with NSD having significantly lower HbA1c values at baseline. On the other hand, the poor diabetic control among those with NSD may be also affected by other confounders such as medical treatment or interventions. Nevertheless, given the rapidly increasing prevalence of metabolic diseases and subsequent complications, the results may highlight the importance of sleep in the clinical management of type 2 diabetes.

Sleep disorders and an increased risk of Parkinson's disease in individuals with non-apnea sleep disorders: a population-based cohort study.

Sleep disorders are common non-motor symptoms in patients with Parkinson's disease. Our study aims to explore the relationship between non-apnea sleep disorders and future Parkinson's disease. This is a cohort study using a nationwide database. The participants were recruited from the Taiwan National Health Insurance Research Database between 2000 and 2003. A total of 91273 adult patients who had non-apnea sleep disorders without pre-existing Parkinson's disease were enrolled. An age-, gender-, income-, urbanization- and Charlson comorbidity index score-matched control cohort consisting of 91273 participants was selected for comparison. The two cohorts were followed for the occurrence of Parkinson's disease, death or until the end of 2010, whichever came first. The Kaplan-Meier analyses revealed patients with non-apnea sleep disorders tended to develop Parkinson's disease (log-rank test, P<0.001). After a multivariate adjustment in a Cox regression model, non-apnea sleep disorders was an independent risk factor for the development of Parkinson's disease [crude hazard ratio: 1.63, 95% confidence interval (CI): 1.54-1.73, P<0.001; adjusted hazard ratio: 1.18, 95% CI: 1.11-1.26, P<0.001]. In the subgroup analysis, patients with chronic insomnia (lasting more than 3months) had the greatest risk (crude hazard ratio: 2.91, 95% CI: 2.59-3.26, P<0.001; adjusted hazard ratio: 1.37, 95% CI: 1.21-1.55, P<0.001). In conclusion, this study revealed that non-apnea sleep disorders, especially chronic insomnia, are associated with a higher risk for future Parkinson's disease.

Men with nonapnea sleep disorders have a high risk of developing subsequent epilepsy: A nationwide population-based cohort study

ObjectiveThis nationwide population-based cohort study evaluated the effects of nonapnea sleep disorders (NSDs) on the development of epilepsy. MethodsWe identified 63,865 patients aged ≥20years, diagnosed with NSDs (ICD-9-CM: 307.4 or 780.5), and without coding for apnea-related sleep disorders (ICD-9-CM: 780.51, 780.53, or 780.57) during 2000–2003 as the NSD cohort. In addition, we enrolled a comparison cohort of 127,728 patients. We calculated the adjusted hazard ratio (aHR) for developing epilepsy (ICD-9-CM: 345) after adjustment for age, sex, comorbidities, and drug use. A Kaplan–Meier analysis was used to measure the cumulative incidence of epilepsy between the 2 groups until the end of 2011. ResultsThe cumulative incidence of epilepsy was significantly higher in the NSD cohort than in the comparison cohort. The aHR for developing epilepsy in the NSD cohort was 1.52 (95% CI=1.37–1.69). The risk of developing epilepsy was higher among males (aHR=1.41) than among females. The age-stratified effects of NSDs on developing epilepsy were the highest among patients aged ≥65years. When comorbidities and NSDs coexisted, the risk of epilepsy was specifically increased in patients having an NSD and stroke (aHR: 8.61, 95% CI: 7.43–9.98) in addition to brain tumors (aHR: 7.66, 95% CI: 5.06–11.6). ConclusionThis study indicated that patients with NSDs have a higher risk of developing epilepsy and that the risk is much higher among men and older patients. These findings suggest that NSDs constitute a predisposing, possibly independent factor for developing subsequent epilepsy in adulthood.

Nonapnea Sleep Disorders and the Risk of Acute Kidney Injury: A Nationwide Population-Based Study.

Nonapnea sleep disorders (NASDs) and associated problems, which are highly prevalent in patients with kidney diseases, are associated with unfavorable medical sequelae. Nonetheless, whether NASDs are associated with acute kidney injury (AKI) development has not been thoroughly analyzed. We examined the association between NASD and AKI. We conducted a population-based study by using 1,000,000 representative data from the Taiwan National Health Insurance Research Database for the period from January 1, 2000, to December 31, 2010. We studied the incidence and risk of AKI in 9178 newly diagnosed NASD patients compared with 27,534 people without NASD matched according to age, sex, index year, urbanization level, region of residence, and monthly income at a 1:3 ratio. The NASD cohort had an adjusted hazard ratio (hazard ratio [HR]; 95% confidence interval [CI] = 1.15-2.63) of subsequent AKI 1.74-fold higher than that of the control cohort. Older age and type 2 diabetes mellitus were significantly associated with an increased risk of AKI (P < 0.05). Among different types of NASDs, patients with insomnia had a 120% increased risk of developing AKI (95% CI = 1.38-3.51; P = 0.001), whereas patients with other sleep disorders had a 127% increased risk of subsequent AKI (95% CI = 1.07-4.80; P = 0.033). Men with NASDs were at a high risk of AKI (P < 0.05). This nationwide population-based cohort study provides evidence that patients with NASDs are at higher risk of developing AKI than people without NASDs.

Nonapnea Sleep Disorders in Patients Younger than 65 Years Are Significantly Associated with CKD: A Nationwide Population-Based Study

BackgroundNonapnea sleep disorders (NASD) and sleep-related problems are associated with poor health outcomes. However, the association between NASD and the development and prognosis of chronic kidney disease (CKD) has not been investigated thoroughly. We explored the association between CKD and NASD in Taiwan.MethodsWe conducted a population-based study using the Taiwan National Health Insurance database with1,000,000 representative data for the period from January 1, 2000 to December 31, 2009. We investigated the incidence and risk of CKD in 7,006 newly diagnosed NASD cases compared with 21,018 people without NASD matched according to age, sex, index year, urbanization, region, and monthly income at a 1:3 ratio.ResultsThe subsequent risk of CKD was 1.48-foldhigher in the NASD cohort than in the control cohort (95% confidence interval [CI] = 1.26–1.73, p< 0.001). Men, older age, type 2 diabetes mellitus, and gout were significant factors associated with the increased risk of CKD (p< 0.001). Among different types of NASDs, patients with insomnia had a 52% increased risk of developing CKD (95%CI = 1.23–1.84; P<0.01), whereas patients with sleep disturbance had a 49%increased risk of subsequent CKD (95% CI = 1.19–1.87; P<0.001). Younger women (aged < 65 years) were at a high risk of CKD with NASD (adjusted hazard ratio, [HR] = 1.81; 95% CI = 1.35–2.40, p< 0.001).ConclusionsIn this nationwide population-based cohort study, patients with NASD, particularly men of all ages and women aged younger than 65 years, were at high risk of CKD.

Nonapnea Sleep Disorders and the Risk of Acute Kidney Injury: A Population-based Retrospective Cohort Study

Nonapnea Sleep Disorders and the Risk of Acute Kidney Injury: A Population-based Retrospective Cohort Study

Risk of Type 2 Diabetes in Patients With Nonapnea Sleep Disorders in Using Different Types of Hypnotics: A Population-Based Retrospective Cohort Study.

There has been insufficient evidence on whether exposure to hypnotics affects the risk of type 2 diabetes (T2DM). The aim of this study was to examine patients with nonapnea sleep disorders using zolpidem, benzodiazepines (BZDs), or a combination of both, and their risk of T2DM.This was a population-based retrospective cohort study using data from 1997 to 2011. Data from the Taiwan National Health Insurance Research Database were employed for this study. A total of 45,602 patients with nonapnea sleep disorders and use of hypnotics were identified as the study cohort. The control cohort comprised 40,799 age- and sex-matched patients. We conducted a Cox proportional hazard regression analysis to estimate the effects of hypnotics on risk of T2DM.The overall incidence of T2DM was 20.1 per 1000 person-years for patients using zolpidem, which was significantly higher than that of the control group (11.9 per 1000 person-years). Overall, patients with nonapnea sleep disorders using zolpidem had a higher risk of T2DM compared with patients not using zolpidem and the control cohort (adjusted hazard ratio [HR] = 1.41, 95% confidence interval [CI] = 1.35–1.48). We also observed a significantly higher risk of T2DM in patients with both zolpidem and BZD use (adjusted HR = 1.77, 95% CI = 1.64–1.91) than that of those without zolpidem use and BZD use.Compared with patients not using hypnotics, patients using zolpidem had a higher risk of developing T2DM; the risk was particularly pronounced in those using both zolpidem and BZDs.

Higher risk of developing a subsequent migraine in adults with nonapnea sleep disorders: A nationwide population-based cohort study

ObjectiveThis nationwide population-based cohort study evaluated the effect of nonapnea sleep disorders (NSDs) on the subsequent development of a migraine. MethodsWe identified 46,777 patients aged 20years and older who were diagnosed with an NSD (ICD-9-CM: 307.4 or 780.5) and without coding for apnea-sleep disorders (ICD-9-CM: 780.51, 780.53, or 780.57) between 2000 and 2002 as the sleep disorder (SD) cohort. A comparison cohort of 93,552 people was enrolled. We calculated the adjusted hazard ratio (aHR) for developing a migraine (ICD-9-CM: 346) after adjusting for age, sex, comorbidity, and drug use. A Kaplan–Meier analysis was used to measure the cumulative incidence of a migraine between 2 curves until the end of 2011. ResultsThe cumulative incidence of a migraine was significantly higher in the SD cohort. The aHR for developing a migraine in the SD cohort was 3.52 (95% CI=3.28–3.79). The risk of developing a migraine with an NSD was higher in men (aHR=4.31) than in women (aHR=3.35). The age-stratified effect of an NSD on developing a migraine was highest among patients aged 55years and younger. Higher risks of developing a migraine were observed among the participants without any comorbidity and without any drug treatment for their insomnia. ConclusionThe findings of this population-based cohort study indicate a higher risk of developing a subsequent migraine in patients with an NSD, which could be considered an independent, predisposing factor for developing subsequent a migraine in adulthood.

Nonapnea Sleep Disorders and Incident Chronic Kidney Disease

Nonapnea sleep disorders (NASDs) are associated with an increased risk of stroke, diabetes, and hypertension. No longitudinal study has yet examined the association between NASD and chronic kidney disease (CKD) by using epidemiologic study methods. To test this hypothesis, we examined the effect of NASD on the incidence of CKD in a large population-based retrospective cohort study.Based on a retrospective cohort study of a general population sample of 128 to 436 patients in the Taiwan National Health Insurance Research Database from January 1, 1998 to December 31, 2001, 42 to 812 NASD patients were followed up for 10.2 ± 3.12 years, and additional 85 to 624 individuals had no NASD at baseline. The International Classification of Diseases, Ninth Revision, Clinical Modification was used to identify the diagnosis of disease. Cox proportional hazard regression models were used to assess the association between NASD and subsequent CKD risk.The incidence rate of CKD was significantly higher in the NASD cohort than in the comparison cohort (2.68 vs 1.88 per 1000 person-years, respectively). After we adjusted for age, sex, and comorbidities, the risk of developing CKD was significant for patients with NASD (adjusted hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 1.05–1.22; P < 0.01). Among different types of NASDs, patients with sleep disturbance associated disorders had a 14% increased risk of developing CKD (95% CI = 1.03–1.26; P < 0.01), whereas patients with insomnia had a 13% increased risk of subsequent CKD (95% CI = 1.02–1.25; P < 0.05) compared with the non-NASD cohort. Kaplan–Meier survival analysis indicated that the CKD-free rate was 1% lower in the NASD cohort than in the comparison cohort (log-rank test, P < 0.0001).Our study provides evidence that patients with NASD have an increased risk of developing subsequent CKD compared with patients without NASD; men, elderly people, and patients with concomitant comorbidities are at the greatest risk.

Sleep disorders increase the risk of osteoporosis: a nationwide population-based cohort study

BackgroundThis study evaluated the relationship between sleep disorders (SDs) and osteoporosis risk in Taiwan. MethodsFrom the Taiwan National Health Insurance data, we identified 44,690 newly diagnosed SD patients (846 with apnea and 43,844 without) from 1998 to 2001 and 89,380 comparisons without SD in the same period frequency matched by sex, age and diagnosis year. Incident osteoporosis was measured by the end of 2010. ResultPatients with apnea-SD and nonapnea SD exhibited a higher osteoporosis incidence rate than did the comparisons (9.97 and 13.3 vs. 6.77 per 1000 person-years, respectively). The Cox method estimated adjusted hazard ratio (HR) of osteoporosis was 2.98 (95% confidence interval [CI] = 2.36–3.74) in apnea-SD patients, compared with 2.76 (95% CI = 2.64–2.88) in nonapnea-SD patients after controlling for sex, age, comorbidities, and treatment. Greater HRs of osteoporosis were observed for female patients (4.00, 95% CI = 3.72–4.29) and those aged >64 years (42.0, 95% CI = 33.5–52.7) in the apnea SD sub-cohort. Apnea SD was associated with the highest risk of osteoporosis without fracture compared with both the nonapnea SD sub-cohort and comparisons. ConclusionPatients with sleep disorders have an elevated risk of osteoporosis, especially for women and the elderly.

Sleep Disorders and Increased Risk of Subsequent Acute Coronary Syndrome in Individuals without Sleep Apnea: A Nationwide Population-Based Cohort Study

Studies investigating the relationship between nonapnea sleep disorders and the risk of acute coronary syndrome (ACS) are scant. This study evaluated whether the risk of ACS is associated with sleep disorders other than sleep apnea in Taiwan. This longitudinal nationwide population-based cohort study investigated the incidence and risk of ACS in 49,099 cases of nonapnea sleep disorders newly diagnosed from January 1997 to December 2001. In total, 98,198 control participants without sleep disorders were randomly selected, frequency matched by age and sex from the general population. The follow-up period started from the date of entering the study cohort to the date of an ACS event, censoring, or December 31, 2010. We conducted Cox proportional hazard regression analysis to estimate the effects of nonapnea sleep disorders on ACS risk. The nonapnea sleep disorder cohort had an adjusted hazard ratio (HR; 95% confidence interval [CI] = 1.29-1.60) of subsequent ACS 1.43-fold higher than that of the cohort without sleep disorders. The highest crude effect of nonapnea sleep disorders on ACS incidence was detected among young adults. However, by adjusting for probable risk factors, the HR of ACS increased with age. Compared with women, men had an adjusted HR of 1.57 (95% CI = 1.42-1.75). Hypertension, diabetes mellitus (DM), and hyperlipidemia were also significant factors associated with the increased risk of ACS. This nationwide population-based cohort study provides evidence that patients with nonapnea sleep disorders are at higher risk of developing acute coronary syndrome, which increases with age.

Nonapnea sleep disorders are associated with subsequent ischemic stroke risk: a nationwide, population-based, retrospective cohort study

Background and objectivesObstructive sleep apnea (OSA) is related to an increased risk for stroke and cardiovascular disease. However, studies investigating the relationship between nonapnea sleep disorders (NSD) and the risk for subsequent ischemic stroke are scant. The objective of our study was to assess the association between NSD and the risk for acute ischemic stroke among patients in Taiwan. MethodsWe conducted our longitudinal nationwide, population-based, retrospective study using Taiwan’s National Health Insurance Research Database (NHIRD) from January 1997 to December 2001. All study participants were followed until the incidence of ischemic stroke, or until censoring due to death; until withdrawal from the insurance program; or until they were lost to follow-up by the end of 2010. Cox proportional hazard regression analysis was used to assess the association between NSD and subsequent ischemic stroke risk. ResultsWe analyzed the data collected from 94,160 participants as a comparison cohort and 47,080 participants as a NSD cohort with the diagnosis date as the index date. The age range of cohorts was 20.0–101.7years and 64% were women. The average follow-up duration was 9.61years for the NSD cohort and 9.42years for the reference cohort. Overall, the ischemic stroke incidence was 1.48-fold higher in the NSD cohort than in the reference cohort (8.87 vs 6.00/1000 individual-years), with an adjusted hazard ratio (HR) of 1.19 after controlling for age, sex, and comorbidities. Our study also showed a 1.35-fold significantly higher risk for developing ischemic stroke in men compared to women. The adjusted HR was 31.2 for elderly patients compared with participants aged ⩽35years. ConclusionsOur nationwide, population-based, retrospective cohort study provides evidence that patients with NSD were at increased risk for developing ischemic stroke compared to patients without diagnosed sleep disorder, with men and the elderly being at greatest risk.

The risk of cancer among patients with sleep disturbance: a nationwide retrospective study in Taiwan

PurposeTo investigate the risk of cancer among patients with nonapnea sleep disorders (SDs). MethodsWe included newly diagnosed SD patients aged 20 years and older without antecedent cancer between 2000 and 2010 from the National Health Insurance Research Database. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of patients with SD with that of the general population. ResultsDuring the 10-year study period, 2062 cancers developed among 63,381 SD patients, who were observed for 382,826 person-years (median follow-up of 6.23 years). The SIR for all cancers was 1.19 (95% confidence interval [CI], 1.14–1.24). For specific cancer types, SD patients exhibited an increased SIR for liver and lung cancers (1.44; 95% CI, 1.28–1.61 and 1.34; 95% CI, 1.18–1.51, respectively). ConclusionsWe observed that overall cancer risk is increased among Asian SD patients. In terms of individual cancers, the risks of liver and lung cancers were elevated. Clinicians should be aware of the possibility of increased liver and lung cancers among SD patients in Taiwan. A prospective study is necessary to confirm these findings.

Population-based cohort study on the increase in the risk for type 2 diabetes mellitus development from nonapnea sleep disorders

ObjectivesThe evidence concerning the relationship between nonapnea sleep disorders and the risk for type 2 diabetes mellitus (DM) is scant and elusive. Our study aimed to examine if nonapnea sleep disorders increase the risk for DM using a population-based retrospective cohort study from 1997 to 2010. MethodsIn the Taiwan’s National Health Insurance Research Database (NHIRD), 45,602 patients with nonapnea sleep disorders were identified as the study cohort. The comparison cohort was formed by 91,204 age- and gender-matched controls. Cox proportional hazards regression model was used to estimate the risk for developing DM. ResultsIn 45,602 patients with nonapnea sleep disorders, 7241 new cases of DM were reported during the follow-up period. The mean follow-up time was 9.04 (standard deviation [SD], 3.33) and 8.96 (SD, 3.47) for the nonapnea sleep disorders cohort and the comparison cohort, respectively. The incidence rate of DM was higher in the nonapnea sleep disorder cohort than in the comparison cohort (17.6 vs 13.3 per 1000 individuals-years). Overall, patients with nonapnea sleep disorders had a higher risk for DM compared to patients without nonapnea sleep disorders (adjusted hazard ratio [HR], 1.05 [95% confidence interval {CI}, 1.02–1.08]). Men with nonapnea sleep disorders had a higher risk for DM than the men in the comparison group (adjusted HR, 1.08 [95% CI, 1.03–1.14]). Among subjects aged less than 40years, patients with nonapnea sleep disorders had a higher risk for DM than the comparison group (adjusted HR, 1.42 [95% CI, 1.27–1.59]). Compared with the comparison cohort, patients with sleep disturbance had an 11% higher risk for DM (adjusted HR, 1.11 [95% CI, 1.07–1.16]). ConclusionCompared to patients without nonapnea sleep disorders, patients with nonapnea sleep disorders had a higher risk for developing DM, especially among those who were less than 40years of age and who had sleep disturbances.

The Vicious Cycle of Leptin-Insulin Resistance Predicts Impaired Glucose Metabolism in Obese Adults with Obstructive Sleep Apnea

le tt e r t o t H e e d it o r S is an overlooked area of metabolic processes and an important modulator of endocrine function. Despite a large body of evidence suggesting that obstructive sleep apnea (OSA) is an independent risk factor for type 2 diabetes, the underlying pathogenesis of impaired glucose metabolism (IGM) in OSA remains less well understood. The recent fi ndings of Papaioannou and colleagues showed no clinically signifi cant abnormalities of appetite regulating hormones in OSA that would suggest a cause for IGM.1 While the study provides an important insight into the phenotypic spectrum of OSA, it also raises questions related to possible yet unexplored more complex pathomechanisms linking appetite hormones with IGM in OSA. From a pathophysiological point of view, insulin resistance (IR) and beta-cell dysfunction both play a role in the development of IGM. While research has documented that OSA can contribute to IR independent of obesity, there is a paucity of information on leptin resistance-related IR in OSA that may potentially impair glucose homeostasis. Leptin is a wellknown adipose tissue-derived hormone that binds to receptors in the brain and inhibits expression of neuropeptide Y (NPY). Most obese humans produce large quantities of leptin but are insensitive to its effects. The suggested mechanisms underlying leptin resistance include defective leptin receptors and/or post-receptor signal transduction, reduced numbers of leptin receptors, interactions between leptin and plasma circulating factors, and other factors that override the leptin satiety signal. It is plausible that OSA-stress-related release of NPY from sympathetic nerves and activation of its Y2 receptors in the adipose tissue might stimulate fat angiogenesis and the proliferation and differentiation of new adipocytes, resulting in abdominal obesity, while closing a vicious cycle of increasing leptin-insulin resistance. Considering different receptor-mediated effects of NPY, the plasma level of NPY might not necessarily be the best parameter to assess NPY effects in peripheral tissues. In our study,2 we demonstrated that OSA is associated with specifi c cytokines that refl ect link between OSA and glucose metabolism. Specifi cally, nocturnal oxyhemoglobin desaturations in OSA were closely associated with interleukin-6 (IL-6) production in obese women with IGM, but not in controls with normal glucose metabolism matched individually for sex, age, adiposity, and apnea-hypopnea index. Moreover, cross-sectional data from our study showed additional close associations of IL-6 with leptin-to-leptin receptor ratio and markers of adiposity only in IGM. These fi ndings support the role that IL-6 plays in obesity and extend it to possible pathophysiological processes linking obesity to IGM via leptin resistance and hypoxic stress in OSA. Further prospective studies are needed to explore the dynamic interactions among appetite regulating hormones, their receptors, and glucose homeostasis in OSA to develop novel interventions to prevent metabolic sequelae of OSA.

Non-apnea sleep disorders will increase subsequent liver cancer risk – A nationwide population-based cohort study

It is well known that patients with sleep disorders (SD) have an increased risk of cardiovascular disease, diabetes mellitus, obesity, and total mortality. However, little information exists regarding the relationship between non-apnea SD and the risk of cancer. The goal of this study was to determine if any association between SD and malignancy exists in Taiwan. We used data from the National Health Insurance system of Taiwan to assess this issue. The SD cohort contained 42,351 patients, and each patient was randomly frequency-matched by age and sex with two people from the general population without SD. The Cox's proportional hazard regression analysis was conducted to estimate the effects of SD on cancer risk. In patients with SD, the overall risk of developing cancer was significantly higher than in normal healthy subjects (adjusted Hazard ratio [HR]=1.12, 95% confidence interval=1.06-1.18). This held true even when we analyzed males and females separately. In regards to individual types of cancer, the risk for developing liver cancer among patients with SD was significantly higher than in subjects without SD. For breast cancer the risk showed a marginally significant increase. The nationwide population-based cohort study found Taiwanese patients with SD have a higher risk of developing cancer, particularly liver cancer and, possibly, breast cancer.