エアロゾル質量分級装置(APM)の開発と性能評価

The objective of this doctoral thesis is to develop the aerosol particle mass analyzer (APM) as well as to evaluate its performance. Two types of APM, which use a new method for classifying the aerosol particles by using a balance of centrifugal force and electrostatic force, were developed and their classification performances were carefully evaluated. The application as aerosol measurement instrument for nanoparticle physical properties was also studied. The major points of this thesis are as follows: Chapter 1 describes the background of aerosol measurement, types of aerosol centrifuge and their principle, and includes technological advance for APM. Objective and outline of thesis are also described.……広島大学(Hiroshima University)博士(工学)Engineeringdoctora

Sleep Duration and Overweight among Elementary Schoolchildren:A Population-based Study in Japan

Although a number of studies have investigated the relationship of sleep duration to overweight and obesity, studies conducted among population-based elementary schoolchildren have been limited in Japan. The aim of the present study was to investigate the relationship between sleep duration and overweight among elementary schoolchildren in Japan. The study subjects were all fourth-grade schoolchildren (9 or 10 years of age) in Ina-town, Saitama Prefecture, Japan from 1999 to 2008. Information concerning each subjectʼs sex, age, and lifestyle was obtained using a self-administered questionnaire, while measurements of his or her height and weight were carried out. Childhood overweight was determined according to the definition established by the International Obesity Task Force. Data from 3,433 children were analyzed. In logistic regression analysis, a statistically significant dose-response relationship was observed between sleep duration and overweight among boys (p for trend＝0.014) but not among girls (p for trend＝0.149). Short sleep duration was associated with childhood overweight, and the sex difference in the association was observed. These findings suggested that it is important to consider sleep duration as part of any program to prevent overweight among elementary schoolchildren, especially among boys

Relationship between hemoglobin A1c and cardiovascular disease in mild-to-moderate hypercholesterolemic Japanese individuals: subanalysis of a large-scale randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Although the ADA/EASD/IDF International Expert Committee recommends using hemoglobin A1c (HbA1c) to define diabetes, the relation between HbA1c and cardiovascular disease (CVD) has not been thoroughly investigated. We analyzed this relation using clinical data on Japanese individuals with hypercholesterolemia.</p> <p>Methods</p> <p>In the large-scale MEGA Study 7832 patients aged 40 to 70 years old with mild-to-moderate hypercholesterolemia without CVD were randomized to diet alone or diet plus pravastatin and followed for >5 years. In the present subanalysis of that study a total of 4002 patients with baseline and follow-up HbA1c data were stratified according to having an average HbA1c during the first year of follow-up <6.0%, 6.0%-<6.5%, or ≥6.5% and their subsequent 5-year incidence rates of CVD compared according to sex, low-density lipoprotein cholesterol (LDL-C), and treatment arm.</p> <p>Results</p> <p>Overall, risk of CVD was significantly 2.4 times higher in individuals with HbA1c ≥6.5% versus <6.0%. A similar relation was noted in men and women (hazard ratio [HR], 2.1; p <0.01 and HR, 3.0; p <0.01, respectively) and was regardless of treatment arm (diet alone group: HR, 2.2; p <0.001; diet plus pravastatin group: HR, 1.8; p = 0.02). Spline curves showed a continuous risk increase according to HbA1c level in all subpopulations studied.</p> <p>Conclusions</p> <p>In hypercholesterolemic individuals the risk of CVD increases linearly with HbA1c level. This significant contribution by elevated HbA1c to increased CVD is independent of pravastatin therapy, and thus requires appropriate HbA1c management in addition to lipids reduction.</p

Changes in body mass index, leptin and adiponectin in Japanese children during a three-year follow-up period: a population-based cohort study

<p>Abstract</p> <p>Objective</p> <p>The study examined changes in and relationship between body mass index (BMI), leptin and adiponectin levels over a 3-year period in a pediatric population-based cohort.</p> <p>Study design</p> <p>A 3-year prospective cohort study of 268 boys and 251 girls aged 9–10 in Ina, Saitama, Japan.</p> <p>Results</p> <p>Median body mass index (BMI) significantly increased from baseline (age 9–10) to follow up (age 12–13) in boys from 17.1 to 18.3 kg/m²(<it>P </it>< 0.001) and in girls from 16.5 to 18.5 kg/m²(<it>P </it>< 0.001), respectively. Adiponectin values significantly decreased from baseline to follow up in boys (13.5 to 8.9 μg/ml, respectively) (<it>P </it>< 0.001) and in girls (12.4 to 9.5 μg/ml, respectively) (<it>P </it>< 0.001). Leptin values at follow up significantly decreased from baseline in boys (4.9 to 2.3 ng/dl, respectively) (<it>P </it>< 0.001) and also in girls (5.3 to 5.1 ng/dl, respectively) (<it>P </it>= 0.049).</p> <p>A relatively strong correlation was seen in BMI (Spearman's correlation coefficient, <it>r </it>= 0.864, <it>P </it>< 0.001 in boys; <it>r </it>= 0.873, <it>P </it>< 0.001 in girls), adiponectin (<it>r </it>= 0.705, <it>P </it>< 0.001 in boys; <it>r </it>= 0.695, <it>P </it>< 0.001 in girls), and leptin (<it>r </it>= 0.449, <it>P </it>< 0.001 in boys; <it>r </it>= 0.610, <it>P </it>< 0.001 in girls) before and after the three-year period.</p> <p>The ratio of follow up to baseline BMI was negatively correlated with that for adiponectin (<it>r </it>= -0.224, <it>P </it>< 0.001 in boys; <it>r </it>= -0.165, <it>P </it>= 0.001 in girls) and positively correlated with that for leptin (<it>r </it>= 0.518, <it>P </it>< 0.001 in boys; <it>r </it>= 0.609, <it>P </it>< 0.001 in girls).</p> <p>Conclusion</p> <p>This study demonstrated that baseline adiponectin, leptin and BMI values measured at ages 9–10 correlated with those measured three years later. However, adiponectin values decreased and leptin values increased in those subjects whose BMI increased during over this period.</p

Prevalence of albuminuria and renal dysfunction, and related clinical factors in Japanese patients with diabetes: The Japan Diabetes Complication and its Prevention prospective study 5

Aims/Introduction To clarify the prevalence of albuminuria and renal dysfunction, and related factors in Japanese patients with diabetes, we analyzed the baseline data of the Japan Diabetes Complication and its Prevention prospective study. Materials and Methods We used the data of 355 patients with type 1 diabetes and 5,194 patients with type 2 diabetes to evaluate the prevalence of albuminuria and renal dysfunction, and related factors. A binomial logistic regression analysis was used to investigate independent contributing factors for estimated glomerular filtration rate Results The prevalence of microalbuminuria and macroalbuminuria was 15.2% (54/355) and 3.1% (11/355) in type 1 diabetes patients, and 25.0% (1,298/5,194) and 5.1% (265/5,194) in type 2 diabetes patients, respectively. The proportion of renal dysfunction (estimated glomerular filtration rate Conclusions We showed the recent prevalence of albuminuria and renal dysfunction, and related factors in Japanese type 1 and type 2 diabetes patients using the baseline data of the Japan Diabetes Complication and its Prevention prospective study. The current results suggest that renal disease in patients with type 2 diabetes is heterogeneous, and different mechanisms might be involved in albuminuria and deterioration of renal function

Prospective randomized study for optimal insulin therapy in type 2 diabetic patients with secondary failure

<p>Abstract</p> <p>Background</p> <p>The large clinical trials proved that Basal-Bolus (BB) insulin therapy was effective in the prevention of diabetic complications and their progression. However, BB therapy needs multiple insulin injections per a day. In this regard, a biphasic insulin analogue needs only twice-daily injections, and is able to correct postprandial hyperglycemia. Therefore it may achieve the blood glucose control as same as that of BB therapy and prevent the diabetic complications including macroangiopathy.</p> <p>Methods</p> <p>In PROBE (Prospective, Randomized, Open, Blinded-Endpoint) design, forty-two type 2 diabetic patients (male: 73.8%, median(inter quartile range) age: 64.5(56.8~71.0)years) with secondary failure of sulfonylurea (SU) were randomly assigned to BB therapy with a thrice-daily insulin aspart and once-daily basal insulin (BB group) or to conventional therapy with a twice-daily biphasic insulin analogue (30 Mix group), and were followed up for 6 months to compare changes in HbA1c, daily glycemic profile, intima-media thickness (IMT) of carotid artery, adiponectin levels, amounts of insulin used, and QOL between the two groups.</p> <p>Results</p> <p>After 6 months, HbA1c was significantly reduced in both groups compared to baseline (30 Mix; 9.3(8.1~11.3) → 7.4(6.9~8.7)%, p < 0.01, vs BB;8.9(7.7~10.0) → 6.9(6.2~7.3)%, p < 0.01), with no significant difference between the groups in percentage change in HbA1c (30 Mix; -14.7(-32.5~-7.5)% vs BB -17.8(-30.1~-11.1)%, p = 0.32). There was a significant decrease in daily glycemic profile at all points except dinner time in both groups compared to baseline. There was a significant increase in the amount of insulin used in the 30 Mix group after treatment compared to baseline (30 Mix;0.30(0.17~0.44) → 0.39(0.31~0.42) IU/kg, p = 0.01). There was no significant difference in IMT, BMI, QOL or adiponectin levels in either group compared to baseline.</p> <p>Conclusion</p> <p>Both BB and 30 mix group produced comparable reductions in HbA1c in type 2 diabetic patients with secondary failure. There was no significant change in IMT as an indicator of early atherosclerotic changes between the two groups. The basal-bolus insulin therapy may not be necessarily needed if the type 2 diabetic patients have become secondary failure.</p> <p>Trial registration</p> <p>Current Controlled Trials number, NCT00348231</p

Age at Transition from Pediatric to Adult Care Has No Relationship with Mortality for Childhood-Onset Type 1 Diabetes in Japan: Diabetes Epidemiology Research International (DERI) Mortality Study

Objective\ud \ud To follow up Japanese patients with type 1 diabetes for a maximum of 40 years to examine when they transitioned from pediatric care to adult care and to explore whether the attending physician, i.e., pediatrician or internist, was associated with prognosis.\ud \ud Methods\ud \ud Participants consisted of 1,299 patients who had been diagnosed as having type 1 diabetes at less than 15 years old between 1965 and 1979 identified through two nationwide surveys. Patients were classified as having received either pediatric care or adult care at the age of 15 and 30, and were compared for differences in mortality associated with the attending physician.\ud \ud Results\ud \ud The attending physicians were confirmed for a total of 1,093 patients at the age of 15. Of these patients, 43.8% and 40.3% received pediatric care and adult care, respectively. Of the 569 patients receiving pediatric care, 74.2%, 56.6%, 53.4%, and 51.3% continued with pediatric care at 20, 30, 40, and 50 years old, respectively. The attending physicians (pediatrician or internist) at the age of 15 and 30 had no significant impact on their survival (P = 0. 892, 0.411, respectively).\ud \ud Conclusions\ud \ud More than half of the patients who had received pediatric care at the age of 15 continued to receive pediatric care even after the age of 30, suggesting that their transition was far from smooth, while the attending physician at the age of both 15 and 30 was not a prognostic factor for mortality. Thus, the timing for transition to adult care in these patients has no relationship with mortality in Japan

Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography

<p>Abstract</p> <p>Background</p> <p>Although oxidative stress by accumulation of reactive oxygen species (ROS) in diabetes has become evident, it remains unclear what genes, involved in redox balance, would determine susceptibility for development of atherosclerosis in diabetes. This study evaluated the effect of genetic polymorphism of enzymes producing or responsible for reducing ROS on coronary artery calcification in type 2 diabetes (T2D).</p> <p>Methods</p> <p>An index for coronary-arteriosclerosis, coronary artery calcium score (CACS) was evaluated in 91 T2D patients using a multi-slice computed tomography. Patients were genotyped for ROS-scavenging enzymes, <it>Glutathione peroxidase-1 (GPx-1)</it>, <it>Catalase, Mn-SOD</it>, <it>Cu/Zn-SOD</it>, as well as SNPs of <it>NADPH oxidase </it>as ROS-promoting elements, genes related to onset of T2D (<it>CAPN10, ADRB3, PPAR gamma, FATP4</it>). Age, blood pressure, BMI, HbA_1c, lipid and duration of diabetes were evaluated for a multivariate regression analysis.</p> <p>Results</p> <p>CACS with Pro/Leu genotype of the <it>GPx-1 </it>gene was significantly higher than in those with Pro/Pro (744 ± 1,291 vs. 245 ± 399, respectively, <it>p </it>= 0.006). In addition, genotype frequency of Pro/Leu in those with CACS ≥ 1000 was significantly higher than in those with CACS < 1000 (45.5% vs. 18.8%; <it>OR </it>= 3.61, <it>CI </it>= 0.97–13.42; <it>p </it>= 0.045) when tested for deviation from Hardy-Weinberg's equilibrium. Multivariate regression analyses revealed that CACS significantly correlated with <it>GPx-1 </it>genotypes and age.</p> <p>Conclusion</p> <p>The presence of Pro197Leu substitution of the <it>GPx-1 </it>gene may play a crucial role in determining genetic susceptibility to coronary-arteriosclerosis in T2D. The mechanism may be associated with a decreased ability to scavenge ROS with the variant <it>GPx-1</it>.</p