Tochigi, Japan
Tochigi, Japan

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Sone H.,University of Tsukuba | Tanaka S.,Kyoto University | Iimuro S.,University of Tokyo | Oida K.,Fukui Chuo Clinic | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Risk factors for cardiovascular complications in Japanese patients with diabetes have not been fully elucidated. Objective: Our objective was to determine incidence of and risk factors for coronary heart disease (CHD) and stroke in Japanese diabetic patients. Design and Settings: We conducted a prospective study at 59 hospitals throughout Japan. Patients: Patients included 940 men and 831 women with type 2 diabetes (mean age, 58.2 yr) without a history of cardiovascular complications who were followed for a median of 7.86 yr. Intervention: This was an observational study. Main Outcome Measures: Incidence of CHD and stroke was evaluated. Results: Incidences of CHD and stroke per 1000 person-years were 9.59 and 7.45, respectively, whereas those of myocardial and brain infarctions were 3.84 and 6.29, respectively. Multivariate Cox analysis revealed that the serum log-transformed triglyceride level was a potent and independent predictor of CHD [hazard ratio (HR) = 1.54;95% confidence interval (CI) = 1.22-1.94 per 1 SD increase), comparable to low-density lipoprotein (LDL) cholesterol (HR = 1.49; 95% CI = 1.25-1.78 per 1 SD increase). Triglycerides and LDL cholesterol linearly and continuously increased CHD risk, and subjects in the top third for both had markedly high risks of CHD, and their effects were possibly additive. However, serum triglycerides worked independently of blood pressure levels. Systolic blood pressure was the only significant predictor for stroke except for age (HR = 1.31; 95% CI = 1.04-1.65, per 1 SD increase). Conclusions: In Japanese patients with type 2 diabetes, the serum triglyceride level was a leading predictor of CHD, comparable to LDL cholesterol. Because the serum triglyceride level is not a leading predictor of CHD in diabetic subjects in Western countries, ethnic group-specific strategies for prevention of diabetic macroangiopathy may be indicated. Copyright © 2011 by The Endocrine Society.


Sone H.,University of Tsukuba | Tanaka S.,Tokyo University of Science | Iimuro S.,University of Tokyo | Tanaka S.,Kyoto University | And 11 more authors.
Diabetologia | Year: 2010

Aims/hypothesis: The aim of the study was to clarify whether a therapeutic intervention focused on lifestyle modification affected the incidence of vascular complications in patients with established diabetes. Methods: A total of 2,033 eligible Japanese men and women aged 40-70 years with type 2 diabetes from 59 institutes were randomised to a conventional treatment group (CON), which continued to receive the usual care, and a lifestyle intervention group (INT), which received education on lifestyle modification regarding dietary habits, physical activities and adherence to treatment by telephone counselling and at each outpatient clinic visit, in addition to the usual care. Randomisation and open-label allocation were done by a central computer system. Primary analysis regarding measurements of control status and occurrence of macro- and microvascular complications was based on 1,304 participants followed for an 8 year period. Results: Although status of control of most classic cardiovascular risk factors, including body weight, glycaemia, serum lipids and BP, did not differ between groups during the study period, the incidence of stroke in the INT group (5.48/1,000 patient-years) was significantly lower than in the CON group (9.52/1,000 patient-years) by Kaplan-Meier analysis (p = 0.02 by logrank test) and by multivariate Cox analysis (HR 0.62, 95% CI 0.39-0.98, p = 0.04). The incidence of CHD, retinopathy and nephropathy did not differ significantly between groups. Lipoprotein(a) was another significant independent risk factor for stroke. Conclusions/interpretation: These findings suggest that lifestyle modification had limited effects on most typical control variables, but did have a significant effect on stroke incidence in patients with established type 2 diabetes.


Sone H.,Niigata University | Sone H.,University of Tsukuba | Tanaka S.,Kyoto University | Suzuki S.,Ohta General Hospital | And 9 more authors.
Diabetologia | Year: 2013

Aims/hypothesis: Our aim was to clarify the association between leisure-time physical activity (LTPA) and cardiovascular events and total mortality in a nationwide cohort of Japanese diabetic patients. Methods: Eligible patients (1,702) with type 2 diabetes (mean age, 58.5 years; 47% women) from 59 institutes were followed for a median of 8.05 years. A comprehensive lifestyle survey including LTPA and occupation was performed using standardised questionnaires. Outcome was occurrence of coronary heart disease (CHD), stroke and total mortality. The adjusted HR and 95% CI were calculated by Cox regression analysis. Results: A significant reduction in HR in patients in the top (≥15.4 metabolic equivalents [MET] h/week) vs the bottom tertile (≤3.7 MET h/week) of LTPA, adjusted by age, sex and diabetes duration, was observed in stroke (HR 0.55, 95% CI 0.32, 0.94) and total mortality (HR 0.49, 95% CI 0.26, 0.91) but not in CHD (HR 0.77, 95% CI 0.48, 1.25). The HR for stroke became borderline significant or nonsignificant after adjustment for lifestyle or clinical variables including diet or serum lipids. The significantly reduced total mortality by LTPA was independent of these variables and seemed not to be, at least mainly, attributed to reduced cardiovascular disease. Conclusions/interpretation: In Japanese persons with type 2 diabetes, LTPA of 15.4 MET h/week or more was associated with a significantly lower risk of stroke partly through ameliorating combinations of cardiovascular risk factors. It was also associated with significantly reduced total mortality but independently of cardiovascular risk factors or events. These findings, implying differences from Western diabetic populations, should be considered in the clinical management of East Asians with diabetes. © 2013 Springer-Verlag Berlin Heidelberg.


Kuroda T.,Keio University | Nishijima E.,Takatsuki Hospital | Maeda K.,Jichi Medical College | Fuchimoto Y.,National Center for Child Health and Development | And 4 more authors.
Pediatric Surgery International | Year: 2016

Purpose: The current study aimed to assess the perinatal risk and clinical features of congenital cystic lung diseases (CCLD). Materials and methods: Of the 874 CCLD patients identified in a nationwide survey, 428 patients born between 1992 and 2012 and treated at 10 high-volume centers, were retrospectively reviewed. Results: Fetal hydrops was visualized using MRI in 9.2 % of the patients. Prenatal interventions were described for 221 of the 428 patients, including the maternal administration of steroid and pleuro-amniotic shunting. Postnatally, a right-to-left shunt flow through a persistent ductus arteriosus was observed in 7.8 % of the patients. The fetal lung lesion volume ratio (LVR) was significantly higher among these symptomatic patients (2.04 ± 1.71 vs. 0.98 ± 0.50, P < 0.00071), and decreased to a greater degree in non-CCAM patients compared with CCAM patients during the late gestational period (from 1.37 ± 1.28 to 1.14 ± 0.84 in CCAM and from 1.08 ± 0.47 to 0.46 ± 0.64 in non-CCAM). Conclusions: An estimated 8–9 % of prenatally diagnosed patients carry the highest risk of perinatal respiratory distress. Fetal LVR remaining at a high level during the late gestational period seems to predict a high risk. © 2016, Springer-Verlag Berlin Heidelberg.


PubMed | Takatsuki Hospital, Osaka University, Keio University, Osaka Medical Center and Research Institute for Maternal and Child Health and 3 more.
Type: Journal Article | Journal: Pediatric surgery international | Year: 2016

The current study aimed to assess the perinatal risk and clinical features of congenital cystic lung diseases (CCLD).Of the 874 CCLD patients identified in a nationwide survey, 428 patients born between 1992 and 2012 and treated at 10 high-volume centers, were retrospectively reviewed.Fetal hydrops was visualized using MRI in 9.2% of the patients. Prenatal interventions were described for 221 of the 428 patients, including the maternal administration of steroid and pleuro-amniotic shunting. Postnatally, a right-to-left shunt flow through a persistent ductus arteriosus was observed in 7.8% of the patients. The fetal lung lesion volume ratio (LVR) was significantly higher among these symptomatic patients (2.041.71 vs. 0.980.50, P<0.00071), and decreased to a greater degree in non-CCAM patients compared with CCAM patients during the late gestational period (from 1.371.28 to 1.140.84 in CCAM and from 1.080.47 to 0.460.64 in non-CCAM).An estimated 8-9% of prenatally diagnosed patients carry the highest risk of perinatal respiratory distress. Fetal LVR remaining at a high level during the late gestational period seems to predict a high risk.


Kawasaki R.,Yamagata University | Kawasaki R.,Royal Melbourne Hospital | Kawasaki R.,Osaka Medical Center for Health Science and Promotion | Tanaka S.,Kyoto University | And 9 more authors.
Ophthalmology | Year: 2013

Objective: Diabetic retinopathy (DR) is linked to cardiovascular risk in diabetic patients. This study examined whether mild-stage DR is associated with risk of coronary heart disease (CHD) and stroke in type 2 diabetic patients of the Japan Diabetes Complications Study (JDCS). Design: Prospective cohort study. Participants: In the JDCS, there were 2033 Japanese persons with type 2 diabetes free of cardiovascular diseases at baseline. Methods: Diabetic retinopathy was ascertained from clinical and photographic grading (70%) following the international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Incident CHD and stroke were followed up prospectively annually up to 8 years. Main Outcome Measures: Eight-year incidence of CHD and stroke compared between persons with or without DR. Results: After adjusting for traditional cardiovascular risk factors, persons with mild to moderate nonproliferative DR had a higher risk of CHD (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.17-2.97) and stroke (HR, 2.69; 95% CI, 1.03-4.86). Presence of retinal hemorrhages or microaneurysms was associated with risk of CHD (HR, 1.63; 95% CI, 1.04-2.56) but was not associated with stroke (P = 0.06). Presence of cotton-wool spots was associated with risk of incident stroke (HR, 2.39; 95% CI, 1.35-4.24) but was not associated with CHD (P = 0.66). When information about DR was added in the prediction models for CHD and stroke based on traditional cardiovascular risk factors, the area under the receiver operating curve improved from 0.682 to 0.692 and 0.640 to 0.677, and 9% and 13% of persons were reclassified correctly for CHD and stroke, respectively. Conclusions: Type 2 diabetic patients with even a mild stage of DR, such as dot hemorrhages, are already at higher risk of CHD and stroke independent of traditional risk factors. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2013 American Academy of Ophthalmology.


Sato S.,Tottori University | Fujiwara H.,Jichi Medical College | Oishi T.,Tottori University | Shimada M.,Tottori University | And 5 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2012

Purpose: Nedaplatin (NDP), a platinum derivative, has been developed to reduce nephrotoxicity and gastrointestinal toxicity of cisplatin. The pharmacokinetic profile of NDP is similar to that of carboplatin (CBDCA). The optimal dosing for CBDCA is determined by the area under the curve (AUC) using Calvert's formula. However, the administration dose of nedaplatin (NDP) is determined based on the body surface area in clinical treatment. Ishibashi et al. reported a formula for predicting NDP clearance based on renal function like Calvert's formula for CBDCA. We conducted the present study to evaluate the Ishibashi's formula. Methods: A total of 22 patients with cervical or ovarian cancer, who underwent chemotherapy consisting of NDP and irinotecan (CPT-11), were examined in this study. Blood samples were collected at 0, 1, 2, 4, and 6 h after the end of infusion of NDP (48-80 mg/m 2), and free platinum concentrations were measured. Observed AUCs were compared with predicted AUCs, which were calculated by the Ishibashi's formula. In addition, the relative reduction in platelets (PLTs) was assessed as a parameter of adverse effects. Results: The observed AUC of NDP ranged from 4 to 14 (μg h -1 ml -1) with large variation. The predicted AUC based on renal function was correlated with the observed AUC. There was a relationship between observed AUC and the decrease in PLTs. Conclusions: Ishibashi's formula would be predictable and useful for estimating the individual dose of NDP. © 2011 Springer-Verlag.


Shimada M.,Tottori University | Fujiwara H.,Jichi Medical College | Sato S.,Tottori University | Oishi T.,Tottori University | And 6 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2012

Purpose: Although the pharmacokinetic mechanism of nedaplatin (NDP) is similar to carboplatin, the dose of NDP is typically determined by body surface area and not by the area under the curve (AUC). We conducted a phase I study to determine the AUC-calculated optimal dosage of NDP used in combination chemotherapy with irinotecan (CPT-11) for gynecologic malignancies. Methods: A total of 15 patients who were to undergo combination chemotherapy consisting of NDP and CPT-11 were enrolled in this study. The dose of CPT-11 was administered at a fixed dose of 60 mg/m 2 and that of NDP was gradually increased from 8 to 12 μg h/mL (AUC). The individual dose of NDP was calculated based on cratinine clearance of the patient according following formula: Dose NDP = AUC × CL NDP, where CL NDP = 0.0738 × creatinine clearance + 4.47 (Ishibashi's formula). Results: One patient had dose-limiting toxicity (DLT) at level 1, and two patients suffered DLT at level 3. The dosage of NDP at AUC 12 was determined to be the maximum tolerated dose in combination chemotherapy with CPT-11, even though only two of the six patients showed DLT at level 3. Conclusions: The recommended dosage of NDP calculated by AUC with Ishibashi's fomula was set to AUC 10 in combination chemotherapy with CPT-11. © 2012 Springer-Verlag.


Sone H.,University of Tsukuba | Tanaka S.,Kyoto University | Iimuro S.,University of Tokyo | Ishibashi S.,Jichi Medical College | And 6 more authors.
Diabetes Care | Year: 2012

OBJECTIVE - To determine the best lipid variable to predict coronary heart disease (CHD) in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - Eligible Japanese men and women (1,771) aged 40-70 years with type 2 diabetes from59 institutes nationwide were followed for a planned 8-year period. The performance of eight conventional lipid variables, i.e., total cholesterol (TC), LDL-cholesterol (LDLC), HDL-cholesterol (HDLC), triglycerides (TGs), non-HDLC, TC/HDLC ratio, LDLC/HDLC ratio, and TG/HDLC ratio, as predictors of incident CHD were evaluated by four methods: hazard ratio (HR) per one SD increment by multivariate Cox analysis, χ 2 likelihood ratio test, area under the receiver operating characteristic curve (AUC), and tertile analysis. RESULTS - Although all variables significantly predicted CHD events inmen, non-HDLC (HR per one SD 1.78 [95% CI 1.43-2.21]; AUC 0.726) and TC/HDLC (HR 1.63 [1.36-1.95]; AUC 0.718) had the better predictive performances among the variables, including LDLC. In women, TGs (log-transformed; HR 1.72 [1.21-2.43]; AUC 0.708) were the best predictor according to results of tertile analysis (HR of the top tertile versus the bottom tertile 4.31 [1.53-12.16]). The associations with incident CHD were linear and continuous. CONCLUSIONS - For Japanese diabetic men, non-HDLC and TC/HDLC were the best predictors, whereas TGs were most predictive for women. These findings, which included prominent sex differences, should be considered among clinical approaches to risk reduction among East Asians with diabetes. © 2012 by the American Diabetes Association.

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