Jenny Theorell-Haglöw

Sleep Apnea and Glucose Metabolism: A Long-term Follow-up in a Community-Based Sample

BACKGROUND It has been suggested that sleep-disordered breathing (SDB) is a risk factor for diabetes, but long-term follow-up studies are lacking. The aim of this community-based study was to analyze the influence of SDB on glucose metabolism after > 10 years. METHODS Men without diabetes (N = 141; mean age, 57.5 years) were investigated at baseline, including whole-night respiratory monitoring. After a mean period of 11 years and 4 months, they were followed up with an interview, anthropometric measurements, and blood sampling. Insulin resistance was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). ΔHOMA-IR was calculated as (HOMA-IR at follow-up − HOMA-IR at baseline). An oral glucose tolerance test was performed on 113 men to calculate the insulin sensitivity index. RESULTS The mean apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) at baseline were 4.7 and 3.3, respectively. At follow-up, 23 men had diabetes. An ODI > 5 was a predictor of developing diabetes (OR, 4.4; 95% CI, 1.1-18.1, after adjusting for age, BMI, and hypertension at baseline and ΔBMI and years with CPAP during follow-up). The ODI was inversely related to the insulin sensitivity index at follow-up (r = −0.27, P = .003). A deterioration in HOMA-IR was significantly related to all variables of SDB (AHI, AHI > 5; ODI, ODI > 5; minimum arterial oxygen saturation), even when adjusting for confounders. When excluding the variable years with CPAP from the multivariate model, all associations weakened. CONCLUSIONS SDB is independently related to the development of insulin resistance and, thereby, the risk of manifest diabetes mellitus.

Daytime Sleepiness Relates to Snoring Independent of the Apnea-Hypopnea Index in Women From the General Population

OBJECTIVES The aim was to investigate the significance of snoring and sleep apnea on daytime symptoms in a population-based sample of women. METHOD From the general population, 400 women aged 20 to 70 years were randomly selected, with oversampling of habitually snoring women. The women were investigated using full-night polysomnography and a questionnaire. The apnea-hypopnea index (AHI) was calculated, and women who acknowledged snoring loudly and disturbingly often or very often were considered habitual snorers. RESULTS Habitual snoring was independently related to excessive daytime sleepiness (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.31 to 3.99), to falling asleep involuntarily during the day (OR, 2.11; 95% CI, 1.06 to 4.21), to waking up unrefreshed (OR, 2.14; 95% CI, 1.30 to 3.52), to daytime fatigue (OR, 2.77; 95% CI, 1.54 to 4.99), and to a dry mouth on awakening (OR, 2.00; 95% CI, 1.22 to 3.27) after adjustment for AHI, age, body mass index (BMI), smoking, total sleep time, percentage of slow-wave sleep, and percentage of rapid eye movement (REM) sleep. An AHI > or = 15/h was only related to a dry mouth on awakening after adjustment for snoring, age, BMI, smoking, total sleep time, percentage of slow-wave sleep, and percentage of REM sleep (OR, 2.24; 95% CI, 1.14 to 4.40). An AHI of 5 to 15/h was not related to any daytime symptom. CONCLUSIONS Excessive daytime sleepiness and daytime fatigue are related to habitual snoring independent of the apnea-hypopnea frequency, age, obesity, smoking, and sleep parameters in a population-based sample of women, but not to the AHI. This indicates that snoring is an independent cause of excess daytime sleepiness and not merely a proxy for sleep apnea.

Obstructive sleep apnoea is associated with decreased insulin sensitivity in females

The aim of the present study was to assess associations between obstructive sleep apnoea and insulin sensitivity in a population-based sample of females. In total, 400 females aged 20–70 yrs underwent a full-night polysomnography, fasting blood sampling, measurement of anthropometric variables and oral glucose tolerance test with measurement of the insulin response (n = 358). The apnoea/hypopnoea index (AHI) was calculated from the results of the polysomnography. From the results of the oral glucose tolerance test, an insulin sensitivity index (ISI) was calculated. Females with an AHI <5 (n = 119) had a mean±sd ISI of 8.3±3.8, whereas females with an AHI ≥30 (n = 34) had an ISI of 6.2±4.0. Nocturnal minimal saturation was independently associated with decreased insulin sensitivity when controlling for age, waist/hip ratio, level of physical activity, smoking and alcohol consumption (95% confidence interval (CI) 0.004–0.14). When adjusting for confounders, the AHI was associated with increased fasting and 2-h insulin levels (95% CI 0.14–0.99 and 95% CI 0.28–6.47, respectively). Obstructive sleep apnoea was found to be independently associated with decreased insulin sensitivity in the present population-based sample of females.

Sleep duration and central obesity in women - differences between short sleepers and long sleepers.

OBJECTIVE To assess characteristics of short sleepers and long sleepers and to assess association between sleep duration and central obesity in a population-based sample of women. METHOD Non-pregnant women ≥20 years that were randomly selected from the population-registry of Uppsala, Sweden, answered a questionnaire (n=6461) including questions on sleeping habits and somatic disorders. RESULTS There was a U-shaped association between sleep duration and waist circumference. Short sleeping women (<5 h) had a waist circumference of 89.2±14.9 cm (mean±SD) decreasing to 82.9±11.9 cm for women sleeping 7-<8 h and increasing to 89.0±16.7 cm for women sleeping ≥10 h. Both short sleepers and long sleepers were more often physically inactive, smokers, ill or taking medication, and psychologically distressed than normal sleepers (6-<9 h). In women <50 years both short and long sleep duration were risk factors for central obesity. Short sleep duration remained a risk factor for central obesity, whereas the association with long sleep duration did not reach statistical significance after adjustments. CONCLUSIONS Short sleepers and long sleepers showed differences in characteristics compared to normal sleepers. Furthermore, we showed an independent association between short sleep duration and central obesity, which was strongest in younger women. It is important to identify short sleepers, especially in younger women.

The role of obstructive sleep apnea in metabolic syndrome: A population-based study in women

BACKGROUND The aim of this study was to assess associations between obstructive sleep apnea (OSA) and metabolic syndrome in a population-based sample of women. METHODS Four hundred women aged 20-70 years underwent a full-night polysomnography, fasting blood sampling and measurement of anthropometric variables. Metabolic syndrome was defined according to the National Cholesterol Education Program (NCEP) criteria. RESULTS The NCEP criteria of metabolic syndrome were fulfilled by 104 (26.0%) of the women. The frequency of metabolic syndrome increased from 10.5% in women with apnea-hypopnea-index (AHI) <5 to 57.1% in women with AHI ≥30 (p for trend <0.0001). In the multivariate analysis, the severity of OSA measured as AHI, ODI (oxygen desaturation index), minimal saturation or T(90) (percentage of time during night with saturation <90%) were associated with metabolic syndrome after adjustment for age, level of physical activity, smoking and alcohol consumption. AHI (adj. OR 1.45; 95% CI 1.11-1.91), ODI (1.37; 1.09-1.73) and minimal saturation level (0.93; 0.87-0.99) remained significantly associated with metabolic syndrome also when adjusting for the waist-to-hip-ratio. The three markers of OSA were independently associated with central obesity, hypertriglyceridemia and reduced HDL cholesterol concentration. CONCLUSION Measures of OSA were closely associated with metabolic syndrome and its components in this population-based sample of women also after adjustments. Therefore, when the health consequences of sleep-disordered breathing are investigated it is important to consider metabolic syndrome. Sleep-disordered breathing should also be considered when treating patients with metabolic syndrome.

Association between Obstructive Sleep Apnea and Elevated Levels of Type B Natriuretic Peptide in a Community-Based Sample of Women

STUDY OBJECTIVES Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. One contributory factor may be hemodynamic stress due to the negative intrathoracic pressure during each episode of apnea. Type B natriuretic peptide (BNP) is secreted by the cardiac ventricles in response to volume expansion and pressure load and the authors hypothesized that there would be an association between indices of OSA during the night and levels of BNP in the morning. SETTING Community-based in Uppsala, Sweden. PARTICIPANTS There were 349 women who participated. MEASUREMENTS AND RESULTS Participants underwent full-night polysomnography and anthropometric measurements, and answered questionnaires about medical conditions and current medication. The morning after the polysomnography, blood samples were drawn for analysis of plasma BNP, C-reactive protein, creatinine, and hemoglobin. There was an increase in mean BNP as the severity of sleep apnea increased, increasing from a mean value of 8.5 ng/L among women with an apnea-hypopnea index (AHI) < 5 to 18.0 ng/L in women with an AHI ≥ 30. Elevated BNP levels (≥ 20 ng/L) were found in 29.8% of the women, whereas 70.2% had normal levels. The odds ratio was 2.2 for elevated BNP levels for women with an AHI of 5-14.9 in relation to women with an AHI < 5, 3.1 for women with an AHI of 15-29.9, and 4.6 for women with an AHI ≥ 30 after adjustment for age, body mass index, systolic blood pressure, antihypertensive drugs, and creatinine. CONCLUSIONS There is a dose-response relationship in women between the severity of sleep apnea during the night and the levels of BNP in the morning.

Both habitual short sleepers and long sleepers are at greater risk of obesity: a population-based 10-year follow-up in women

OBJECTIVE To assess how change in sleep duration is related to subsequent obesity. METHODS In this 10-year follow-up, 4903 non-pregnant participants answered a questionnaire on sleeping habits, obesity, and lifestyle factors (questions identical to baseline questionnaire). Habitual normal sleepers were defined as sleeping 6-9 h/night at both baseline and follow-up, whereas women sleeping <6 h/night or ≥9 h/night at both occasions were defined as habitual short sleepers and habitual long sleepers, respectively. Logistic regression was used to analyze associations between changes in sleep duration, general obesity (body mass index ≥30 kg/m(2)), weight gain (≥10 kg) and also, central obesity (waist circumference ≥88 cm), and increase in waist circumference (≥10 cm) at follow-up. RESULTS Among younger women (aged <40 years) both habitual short sleepers and habitual long sleepers had a higher prevalence of general (short: 31.3%, P < 0.0001; long: 38.1%, P = 0.01) and central obesity (short: 60.5%, P = 0.01; long: 82.4%, P = 0.01) compared with habitual normal sleepers (general obesity: 8.9%; central obesity: 35.9%) at follow-up. Younger women who were short sleepers at baseline but normal sleepers at the follow-up had a higher prevalence of both general (19.3%, P = 0.01) and central obesity (45.4%, P = 0.07) compared with habitual normal sleepers at follow-up. In adjusted analyses, both habitual short [adjusted odds ratio (aOR), 6.78; 95% confidence interval (CI), 2.71-17.0] and long (aOR, 4.64; 95% CI, 1.09-19.8) sleep durations were risk factors for general obesity in younger women. In younger women habitual long sleep duration was a risk factor also for central obesity (aOR, 6.05; 95% CI, 1.19-30.7) whereas habitual short sleep duration was not (aOR, 1.93; 95% CI, 0.87-4.81). Similar results were seen also for weight gain and increased waist circumference as dependent variables. In addition, decreased sleep duration from normal to short duration was a risk factor for both weight gain (aOR, 1.85; 95% CI, 1.14-3.02) and increased waist circumference (aOR, 1.84; 95% CI, 1.20-2.81). There were no associations between changes in sleep duration and any of the measures of obesity at the follow-up in women aged >40 years at baseline. CONCLUSION In younger women, both habitual short and long sleep duration was a risk factor for obesity, whereas no such relationship was seen in older women.

Age affects sleep microstructure more than sleep macrostructure

It is well known that the quantity and quality of physiological sleep changes across age. However, so far the effect of age on sleep microstructure has been mostly addressed in small samples. The current study examines the effect of age on several measures of sleep macro‐ and microstructure in 211 women (22–71 years old) of the ‘Sleep and Health in Women’ study for whom ambulatory polysomnography was registered. Older age was associated with significantly lower fast spindle (effect size f2 = 0.32) and K‐complex density (f2 = 0.19) during N2 sleep, as well as slow‐wave activity (log) in N3 sleep (f2 = 0.21). Moreover, total sleep time (f2 = 0.10), N3 sleep (min) (f2 = 0.10), rapid eye movement sleep (min) (f2 = 0.11) and sigma (log) (f2 = 0.05) and slow‐wave activity (log) during non‐rapid eye movement sleep (f2 = 0.09) were reduced, and N1 sleep (f2 = 0.03) was increased in older age. No significant effects of age were observed on slow spindle density, rapid eye movement density and beta power (log) during non‐rapid eye movement sleep. In conclusion, effect sizes indicate that traditional sleep stage scoring may underestimate age‐related changes in sleep.

The relation between polysomnography and subjective sleep and its dependence on age - poor sleep may become good sleep.

Women complain more about sleep than men, but polysomnography (PSG) seems to suggest worse sleep in men. This raises the question of how women (or men) perceive objective (PSG) sleep. The present study sought to investigate the relation between morning subjective sleep quality and PSG variables in older and younger women. A representative sample of 251 women was analysed in age groups above and below 51.5 years (median). PSG was recorded at home during one night. Perceived poor sleep was related to short total sleep time (TST), long wake within total sleep time (WTSP), low sleep efficiency and a high number of awakenings. The older women showed lower TST and sleep efficiency and higher WTSP for a rating of good sleep than did the younger women. For these PSG variables the values for good sleep in the older group were similar to the values for poor sleep in the young group. It was concluded that women perceive different levels of sleep duration, sleep efficiency and wake after sleep onset relatively well, but that older women adjust their objective criteria for good sleep downwards. It was also concluded that age is an important factor in the relation between subjective and objective sleep.

Increased risk of heart failure in women with symptoms of sleep-disordered breathing

BACKGROUND An association between obstructive sleep apnea and the incidence of heart failure has been reported in men but not in women. The aim of this study was to investigate whether a combination of snoring and excessive daytime sleepiness, the two main symptoms of obstructive sleep apnea syndrome, was able to predict incident heart failure in a population-based sample of women. METHODS The population-based cohort study Sleep and Health in Women (SHE; n = 5990 women born between 1901 and 1980) was used, with baseline questionnaire data from April 2000 relating to snoring, excessive daytime sleepiness, and covariates. Using data retrieved from the Swedish National Patient Register and Cause of Death Register, the follow-up of incident heart failure continued until 31 December 2011. RESULTS Among women with both snoring and excessive daytime sleepiness at baseline, 5.3% developed heart failure during follow-up compared with 0.9% in the reference group with neither snoring nor excessive daytime sleepiness. After adjustment for age, waist circumference, smoking, alcohol, hypertension, diabetes, previous myocardial infarction, physical inactivity, depressive symptoms, menopausal status, and hormone replacement therapy, women with the combination of snoring and excessive daytime sleepiness had a twofold increase in the risk of incident heart failure (hazard ratio [HR] 2.2 95% confidence interval [CI] 1.1-4.4). CONCLUSION Symptoms of obstructive sleep apnea, that is, the combination of snoring and excessive daytime sleepiness, are associated with an increased risk of developing heart failure in women.