Susumu Sakurai

Nocturnal intermittent hypoxia and the development of type 2 diabetes: the Circulatory Risk in Communities Study (CIRCS)

Aims/hypothesisAlthough the associations between obstructive sleep apnoea and type 2 diabetes mellitus have been reported in cross-sectional design studies, findings on the prospective association between the two conditions are limited. We examined prospectively the association between nocturnal intermittent hypoxia as a surrogate marker of obstructive sleep apnoea and risk of type 2 diabetes.MethodsA total of 4,398 community residents aged 40 to 69xa0years who had participated in sleep investigation studies between 2001 and 2005 were enrolled. Nocturnal intermittent hypoxia was assessed by pulse-oximetry and defined by the number of oxygen desaturation measurements ≤3% per h, with five to <15 per h corresponding to mild and 15 events or more per h corresponding to moderate-to-severe nocturnal intermittent hypoxia, respectively. The development of type 2 diabetes was defined by: (1) fasting serum glucose ≥7.00xa0mmol/l (126xa0mg/dl); (2) non-fasting serum glucose ≥11.1xa0mmol/l (200xa0mg/dl); and/or (3) initiation of glucose-lowering medication or insulin therapy. Multivariable model accounted for age, sex, BMI, smoking status, current alcohol intake, community, borderline type 2 diabetes, habitual snoring, excessive daytime sleepiness, sleep duration and (for women) menopausal status.ResultsBy the end of 2007, 92.2% of participants had been followed up (median follow-up duration [interquartile range] 3.0 [2.9–4.0] years) and 210 persons identified as having developed diabetes. The multivariable-adjusted hazard ratio (95% CI) for developing type 2 diabetes was 1.26 (0.91–1.76) among those with mild nocturnal intermittent hypoxia and 1.69 (1.04–2.76) among those with moderate-to-severe nocturnal intermittent hypoxia (pu2009=u20090.03 for trend).Conclusions/interpretationNocturnal intermittent hypoxia was associated with increased risk of developing type 2 diabetes among middle-aged Japanese.

Cross-cultural comparison of the sleep-disordered breathing prevalence among Americans and Japanese

The aim of the present study was to compare the prevalence of sleep-disordered breathing among Hispanic and white Americans and Japanese. A 1-night sleep study using a single-channel airflow monitor was performed on 211 Hispanics and 246 Whites from the Minnesota field centre (St Paul, MN, USA) of the Multi-Ethnic Study of Atherosclerosis (MESA), and 978 Japanese from three community-based cohorts of the Circulatory Risk in Communities Study (CIRCS) in Japan. The respiratory disturbance index and sleep-disordered breathing, defined as a respiratory disturbance index of ≥15 events·h−1, were estimated. The prevalence of sleep-disordered breathing was higher in males (34.2%) than females (14.7%), and among Hispanics (36.5%) and Whites (33.3%) than among Japanese (18.4%), corresponding to differences in body mass index. Within body mass index strata, the race difference in sleep-disordered breathing was attenuated. This was also true when body mass index was adjusted for instead of stratification. The strong association between body mass index and sleep-disordered breathing was similar in Japanese and Americans. The prevalence of sleep-disordered breathing was lower among Japanese than among Americans. However, the association of body mass index with sleep-disordered breathing was strong, and similar among the race/ethnic groups studied. The majority of the race/ethnic difference in sleep-disordered breathing prevalence was explained by a difference in body mass index distribution.

Decrease of suppressor-inducer (CD4+CD45RA) T lymphocytes and increase of serum immunoglobulin G due to perceived job stress in Japanese nuclear electric power plant workers

To clarify the effects of perceived job stress on the immune system, a cross-sectional study was conducted in 116 male Japanese workers of a nuclear electric power plant (age, 20 to 39; mean, 31 years). Perceived job stress, i.e., psychological job demand, job control, worksite social support, and job strain, was assessed by means of the Japanese version of the Job Content Questionnaire. The job strain score was calculated as the ratio of the job demand score to the job control score. Blood samples were taken from all workers, and numbers of T and natural killer cell subpopulations, B lymphocytes, total lymphocytes and white blood cells, and serum concentrations of immunoglobulins (IgG, IgM, IgA, IgE and IgD) in their blood were measured. The workers were divided into higher and lower strain groups according to their job strain scores. The number of CD4+ CD45RA+ T lymphocytes in the higher strain group having the job strain score of 0.5 or more (41 workers) was significantly smaller than that in the lower strain group having the score of less than 0.5 (75 workers). In contrast, the serum IgG concentration in the former group was significantly higher than that in the latter group (analysis of covariance with age and smoking as covariates). Also, the numbers of total CD4+ T and total T (CD3+) lymphocytes and of white blood cells in the former group were significantly smaller than those in the latter group. After controlling for age and smoking by the partial correlation coefficient in all 116 workers, the number of CD57+ CD16+ natural killer cells was inversely correlated with job demand and with job strain; the number of CD8+ T lymphocytes was positively correlated with worksite social support; and serum IgG and IgM concentrations were positively correlated with job strain. It is suggested that higher job strain decreases the number of CD4+ CD45RA+ T lymphocytes in male Japanese workers but increases serum IgG concentrations.

Risk factors for snoring among Japanese men and women: a community-based cross-sectional study

PurposeThis study seeks to examine risk factors for snoring, a major symptom of sleep-disordered breathing (SDB) because the evidence is limited in Asian populations.MethodsSubjects for the present cross-sectional study were 3,138 men and 5,345 women aged 35–79xa0years from three communities in Japan who participated in the Circulatory Risk in Communities Study. The data on snoring frequency and cardiovascular health were obtained during annual cardiovascular surveys between 2000 and 2005. The logistic regression model was used to estimate the odds ratios (ORs) for snoring associated with body mass index (BMI), alcohol consumption, and other cardiovascular risk factors.ResultsThe prevalence of almost everyday snoring was 24% among men and 10% among women. After adjustments for age, community, cigarette smoking, alcohol consumption, and for women, menopausal status, the multivariable-adjusted ORs for everyday snoring in the highest versus lowest quartiles of BMI categories were 3.4 (95% confidence interval (CI): 2.6–4.4) for men and 3.9 (2.8–5.4) for women. The respective ORs in ≥23xa0g ethanol per day versus never-drinkers categories were 1.4 (1.1–1.8) and 3.1 (1.8–5.3) and those in ≥20 cigarettes versus never-smokers categories were 1.4 (1.0–1.8) and 1.9 (0.9–3.7). The associations of alcohol consumption and cigarette smoking with everyday snoring were stronger for BMIu2009<u200925xa0kg/m2 than BMIu2009≥u200925xa0kg/m2 in both sexes.ConclusionBMI, alcohol consumption, and cigarette smoking were positively associated with habitual snoring for both men and women, especially in nonoverweight persons.

Nocturnal intermittent hypoxia as an associated risk factor for microalbuminuria in Japanese patients with type 2 diabetes mellitus

OBJECTIVEnWe estimated the prevalence of nocturnal intermittent hypoxia, a surrogate marker of obstructive sleep apnoea, among type 2 diabetes mellitus (T2DM) patients and examined the association between nocturnal intermittent hypoxia and microvascular diseases.nnnDESIGN AND METHODSnWe recruited 513 Japanese patients (292 men and 221 women) with T2DM. Nocturnal intermittent hypoxia was diagnosed using the 3% oxygen desaturation index, with less than five events per hour corresponding to normal and five events or more per hour corresponding to nocturnal intermittent hypoxia.nnnRESULTSnThe prevalence of nocturnal intermittent hypoxia was 45.4% among T2DM patients. The nocturnal intermittent hypoxia group was older and had a higher BMI, greater weight change since the age of 20 years, higher smoking rate and increased prevalence of hypertension, hyperlipidaemia, microalbuminuria and macroalbuminuria. Microalbuminuria (model 1: odds ratio (OR), 3.41; 95% CI, 1.85-6.40; model 2: OR, 3.69; 95% CI, 1.85-7.59 and model 3: OR, 3.12; 95% CI, 1.45-6.95) and nephropathy (model 1: OR, 4.51; 95% CI, 1.58-15.1; model 2: OR, 7.31; 95% CI, 2.11-31.6 and model 3: OR, 5.23; 95% CI, 1.45-23.8) were derived as factors from all the three statistical models and constantly associated with nocturnal intermittent hypoxia only in women.nnnCONCLUSIONSnNocturnal intermittent hypoxia was highly prevalent among T2DM patients and may be an independent associated risk factor for microalbuminuria in Japanese women with T2DM.

Relatively lower central aortic pressure in patients with impaired insulin sensitivity and resistance: the Toon Health Study.

Objective Central aortic blood pressure (BP) has been postulated to correlate more closely with cardiovascular disease risk than brachial cuff BP. However, the effect of insulin sensitivity and resistance on central BP is not fully understood. Here, we evaluated the associations between insulin sensitivity/resistance and central BP using the oral glucose tolerance test. Methods A total of 1034 Japanese participants were enrolled in this study. The absolute pressure of the late systolic peak (SBP2) of the brachial BP obtained by the radial waveform was considered to be the central systolic BP. Oral glucose tolerance test was performed by administering 75u200ag of glucose, and blood samples were obtained at 0, 60, 120u200amin after glucose loading. Results Mean SBP2 was found to be lower than mean brachial systolic BP (SBP) (119u200a±u200a20, 126u200a±u200a19u200ammHg, Pu200a<u200a0.001), and differences between SBP and SBP2 were significantly larger in patients with reduced insulin sensitivity (−8.2u200a±u200a5.2, −7.2u200a±u200a5.3, −7.1u200a±u200a5.1, and −6.5u200a±u200a4.9u200ammHg, in the first, second, third and fourth quartiles, respectively; Pu200a=u200a0.002) and increased insulin resistance (−6.6u200a±u200a5.1, −6.6u200a±u200a4.8, −7.3u200a±u200a4.8, −8.5u200a±u200a5.6u200ammHg, Pu200a<u200a0.001). Multiple linear regression analysis identified reduced insulin sensitivity (&bgr;u200a=u200a0.067, Pu200a=u200a0.033) and increased insulin resistance (&bgr;u200a=u200a−0.081, Pu200a=u200a0.009) as independent determinants of the difference between SBP and SBP2. Conclusion Given that both insulin sensitivity and insulin resistance were found to be significant determinants of the difference between SBP and SBP2 in a healthy general population, we suggest measuring the SBP2 in individuals with impaired insulin action in order to accurately assess their risk of developing cardiovascular disease.

Nocturnal intermittent hypoxia and C reactive protein among middle-aged community residents: a cross-sectional survey

Background There are conflicting results for the association between obstructive sleep apnoea and raised C reactive protein (CRP) levels. A study was undertaken to investigate whether nocturnal intermittent hypoxia, a surrogate marker for obstructive sleep apnoea, was associated with CRP levels among a community-dwelling Japanese population. Methods Among participants in the Circulatory Risk in Communities Study (CIRCS), 1422 male and 2466 female community residents aged 40–69u2005years were tested during sleep. No nocturnal intermittent hypoxia, mild nocturnal intermittent hypoxia and moderate to severe nocturnal intermittent hypoxia were defined using 3% oxygen desaturation index cut-off points at 5 and 15 events/h, respectively. High-sensitivity CRP levels were measured using a latex particle-enhanced immunonephelometric assay. Multivariate analysis was adjusted for age, sex, body mass index, smoking status, current alcohol intake, hypertension, hypercholesterolaemia, diabetes mellitus and menopausal status for women. Results Multivariable-adjusted mean CRP levels among men were 0.70u2005mg/l (95% CI 0.65 to 0.75) for no nocturnal intermittent hypoxia, 0.82u2005mg/l (95% CI 0.74 to 0.89) for mild nocturnal intermittent hypoxia and 0.84u2005mg/l (95% CI 0.70 to 1.00) for moderate to severe nocturnal intermittent hypoxia (p for trend=0.03). The values for women were 0.59u2005mg/l (95% CI 0.57 to 0.62), 0.66u2005mg/l (95% CI 0.59 to 0.73) and 0.82u2005mg/l (95% CI 0.62 to 1.03), respectively (p for trend=0.008). Compared with no nocturnal intermittent hypoxia, the prevalence of a high CRP level (≥1.0u2005mg/l) was 1.4–1.7-fold higher for mild to severe nocturnal intermittent hypoxia in both sexes. Conclusions Nocturnal intermittent hypoxia is associated with raised serum CRP levels among middle-aged Japanese subjects.

Self-reported snoring frequency and incidence of cardiovascular disease: the Circulatory Risk in Communities Study (CIRCS).

Background Although associations between snoring and cardiovascular disease have been reported in several prospective studies, there is limited evidence from Asian populations. The objective of this study was to determine if there is an association between self-reported snoring frequency and the incidence of cardiovascular disease in Japanese. Methods The subjects were 2350 men and 4163 women aged 40 to 69 years who lived in 3 communities in Japan. All subjects were participants in the Circulatory Risk in Communities Study (CIRCS) and were followed for 6 years. Incidence of cardiovascular disease during the follow-up period comprised events of myocardial infarction, angina pectoris, sudden cardiac death and stroke. Results During the 6-year follow-up period, 97 participants (56 men and 41 women) had cardiovascular events. After adjustment for potential confounding factors, self-reported snoring frequency was associated with an increased risk of cardiovascular events among women but not men. The hazard ratios (95% CI) for cardiovascular events were 0.9 (0.4–2.0) for sometimes snoring and 2.5 (1.0–6.1) for everyday snoring in women and 0.7 (0.3–1.3) and 1.0 (0.5–2.1), respectively, in men. Further adjustment for body mass index attenuated the association in women; the respective hazard ratios for cardiovascular events were 0.9 (0.4–1.9) and 2.1 (0.9–5.4). Conclusions Self-reported habitual snoring was associated with increased risk of cardiovascular events among Japanese women. Overweight may partly mediate this association.

Associations between weight change since 20 years of age and sleep-disordered breathing among male truck drivers

Background:Limited evidence for association of weight gain with sleep-disordered breathing (SDB) has been produced for Asian populations whose body mass index (BMI) levels are lower than in western countries.Objective:The aim of this study was to examine weight change since 20 years of age and risk of SDB among Japanese.Design:Retrospective cohort study.Subjects:This study includes a large sample of 5320 male Japanese truck drivers aged 30–69 years.Measurements:The respiratory disturbance index (RDI) was selected as an indicator of SDB, and it was estimated with a one-night sleep test using an airflow monitor, and the Epworth Sleepiness Scale (ESS) was used to estimate excessive daytime sleepiness.Results:Respiratory disturbance and sleepiness were more prevalent among men with BMI of 25.0–29.9 and ⩾30.0u2009kg/m2 than among those with BMI of 18.5–24.9; multivariable odds ratios (ORs) were 1.8(1.5–2.0), P<0.001 and 4.4(3.5–5.5), P<0.001 for RDI ⩾10, and 1.2(0.9–1.4), P=0.18 and 1.5(1.1–2.1), P=0.02 for ESS ⩾11, respectively. Compared with men showing BMI changes within ±1.0, the respective multivariable ORs for those with BMI changes of 3.0–4.9 and ⩾5.0 were 1.4(1.2–1.6), P<0.001 and 2.4(2.0–2.9), P<0.001 for RDI ⩾10, and 1.2(0.9–1.6), P=0.22 and 2.0(1.5–2.6), P<0.001 for ESS ⩾11. The corresponding ORs for weight gain of ⩾10.0u2009kg compared with weight change less than ±5.0u2009kg were 2.0(1.7–2.4), P<0.001 for RDI ⩾10 and 1.5(1.2–2.0), P=0.002 for ESS ⩾11. Similar trends were observed for RDI ⩾20.Conclusion:Our results suggest that an increase in BMI of ⩾5u2009kg/m2 or weight gain of ⩾10u2009kg is a risk factor for SDB and excessive daytime sleepiness among Japanese truck drivers.

Association of hematological parameters with insulin resistance, insulin sensitivity, and asymptomatic cerebrovascular damage: The J-SHIP and Toon Health Study

BACKGROUNDnElevated hematocrit levels have been suggested to be an independent determinant of insulin resistance and type 2 diabetes. To clarify the diagnostic significance of hematocrit level, we investigated the association with hemodynamic profiles, insulin resistance and insulin sensitivity, arterial properties, and asymptomatic cerebrovascular damage in a general Japanese population.nnnMETHODSnThis study included 1,978 participants from two independent cohorts. Insulin sensitivity was assessed by the oral 75 g glucose tolerance test. Carotid ultrasonography was performed to evaluate atherosclerosis and wall shear stress. Periventricular hyperintensity and lacunar infarction were assessed by brain magnetic resonance imaging.nnnRESULTSnHematocrit quartile showed a stepwise association with insulin sensitivity (Q1: 2.2±0.7, Q2: 2.0±0.7, Q3: 1.9±0.7, Q4: 1.8±0.6, p<0.001) and insulin resistance (1.0±0.6, 1.2±0.7, 1.3±0.8, 1.5±1.0, p<0.001). Multiple linear regression analysis adjusted for possible covariates identified hematocrit as an independent determinant of insulin sensitivity (β=-0.074, p=0.019) and insulin resistance (β=0.115, p<0.001). However, this association was lost after further adjustment for visceral fat area and plasma alanine aminotransferase level. Further, no significant association was observed between hematocrit and carotid intima-media thickness (p=0.306) where as wall shear stress was inversely associated with the carotid atherosclerosis (r=-0.250, p<0.001). In contrast, a low hematocrit level was independently associated with periventricular hyperintensity (odds ratio 0.87 (95% CI 0.80-0.95), p=0.001).nnnCONCLUSIONnHematocrit was positively associated with insulin resistance and insulin sensitivity. This association was epiphenomenon of visceral and hepatic adiposity. Conversely, low hematocrit was a significant risk factor for periventricular hyperintensity independent of insulin resistance.