Kitakyūshū, Japan
Kitakyūshū, Japan

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Mori H.,University of Occupational and Environmental Health Japan | Okada Y.,University of Occupational and Environmental Health Japan | Kishikawa H.,Kishikawa Clinic | Inokuchi N.,Inokuchi Clinic | And 2 more authors.
Journal of Bone and Mineral Metabolism | Year: 2013

Evidence suggests that bone quality is poorer and fracture risk is higher in patients with diabetes, even those with normal bone mineral density. The aim of this study was to determine the effects of raloxifene on lipid, bone, and glucose metabolism in postmenopausal women with type 2 diabetes. The study subjects (144 postmenopausal women aged less than 80 years with type 2 diabetes) were randomly assigned into three groups: no medication, alfacalcidol 1 μg/day, or raloxifene hydrochloride 60 mg/day. The primary endpoint was the change in LDL-C at 6 months. Raloxifene significantly decreased the levels of bone metabolism markers NTX and BAP at 6 months in patients with diabetes. The primary endpoint, LDL-C at 6 months, was significantly lower in the raloxifene group than in the other two groups. However, percent changes in HDL-C were not significantly different among the three groups. Although glucose metabolism was unaffected, homocysteine, a bone quality marker, was significantly decreased at 6 months in the raloxifene group. The percent improvement in LDL-C did not correlate with percent improvement in any bone metabolism or bone quality markers. Raloxifene, unlike estrogen, improved LDL-C and decreased homocysteine, indicating that raloxifene can potentially improve LDL-C as well as bone quality in postmenopausal women with type 2 diabetes. © 2012 The Japanese Society for Bone and Mineral Research and Springer.


Oishi M.,Oishi Clinic | Yamazaki K.,Kawai Clinic | Okuguchi F.,Okuguchi Clinic | Sugimoto H.,Sugimoto Clinic | And 2 more authors.
Journal of Diabetes Investigation | Year: 2014

Aims/Introduction: Six kinds of oral antidiabetic drugs (OADs), including the new dipeptidyl peptidase 4 (DPP-4) inhibitors, are available. The present study aimed to define trends within the prescribing patterns of OADs, as well as changes in glycemic control in Japan over a 10-year period from 2002 to 2011. Materials and Methods: We carried out a cross-sectional study using data of type 2 diabetes mellitus patients from 24 clinics for 2002, 2005, 2008 and 2011. OAD use was analyzed combined with clinical data. Results: Sulfonylureas (SUs) were the most commonly used OAD, but their use for monotherapy markedly decreased over the study period. Biguanides (BGs) were the second most commonly used OAD, and their prescribing rate increased both for mono- and combination therapy. DPP-4 inhibitors (DPP-4I), released in 2009, were the third most commonly prescribed OAD in 2011 both for mono- and combination therapy. Among combination therapies, two OADs were mostly prescribed, but the use of three OADs and four OADs in 2011 was two- and 14.8-fold those in 2002. These trends were accompanied by an improvement in average glycated hemoglobin from 7.5 ± 1.2% in 2002 to 7.1 ± 0.9% in 2011. Conclusions: The OAD prescribing trend has moved away from monotherapy with SUs and toward combination therapies to achieve better glycemic control. Increased use of BGs and DPP-4I was predominant in 2011. These trends were accompanied by an improvement of the glycated hemoglobin level. © 2013 The Authors.


Yokoyama H.,Jiyugaoka Medical Clinic | Araki S.,Shiga University of Medical Science | Haneda M.,Asahikawa University | Matsushima M.,Jikei University School of Medicine | And 7 more authors.
Diabetologia | Year: 2012

Aims/hypothesis: In type 2 diabetic patients at low risk for cardiovascular disease (CVD), the relationship between the clinical course of nephropathy by stage of chronic kidney disease (CKD) and onset of CVD remains unclear. Clarification of this relationship is important for clinical decision-making for both low-and high-risk diabetic patients. Methods: This 4 year prospective study enrolled 2,954 type 2 diabetic patients with no prevalent CVD, and serum creatinine <176.8 μmol/l. The risk for CVD onset (non-fatal and fatal CVD and stroke, and peripheral arterial disease) was assessed according to CKD stage categorised by urinary albumin-to-creatinine ratio (ACR; mg/mmol) and estimated GFR (eGFR; ml min-1 1.73 m-2). Association of progression from žno CKD' stage (ACR <3.5 mg/mmol and eGFR ≥90 ml min 1.73 m-2) with risk for CVD onset was also evaluated. Results: During follow-up (median 3.8 years), 89 CVD events occurred. Compared with patients with žno CKD' as reference, those with ACR≥35.0 mg/mmol with coexisting eGFR 60-89 ml min-1 1.73 m-2 or <60 ml min-1 1.73 m-2 showed increased risk for CVD onset, whereas those with eGFR ≥90 ml min1- 1.73 m-2 did not. Those with ACR ≤3.5 mg/mmol and eGFR ≤60 ml min-1 1.73 m -2 did not show any increased risk. Among patients with žno CKD' stage at baseline, those who progressed to ACR ≥3.5 mg/mmol during follow-up showed an increased risk compared with those who did not, whereas those who progressed to eGFR ≥90 ml min-1 1.73 m-2 did not have increased risk. Conclusions/interpretation: The risk for CVD was associated with progression of albuminuria stage rather than eGFR stage in type 2 diabetic patients at relatively low risk for CVD. © Springer-Verlag 2012.


Yokoyama H.,Jiyugaoka Medical Clinic | Matsushima M.,Jikei University School of Medicine | Kawai K.,Kawai Clinic | Hirao K.,HEC Science Clinic | And 6 more authors.
Diabetic Medicine | Year: 2011

Aims To investigate whether a reduced incidence of cardiovascular disease in Type2 diabetes can be achieved in a newly recruited cohort following the recently advanced concept of multifactorial treatment and followed in primary care settings as compared with earlier cohorts. Methods A prospective study was performed in primary care settings at multiple clinics nationwide in the Japan Diabetes Clinical Data Management (JDDM) study group. Subjects were 2984 patients with Type2 diabetes without prevalent cardiovascular disease. The main outcome measure was the first event of non-fatal or fatal coronary heart disease, ischaemic stroke or peripheral artery disease, and the incidence was compared with other representative cohorts. Results There were 90 cardiovascular events over 10827 person-years of follow-up with a dropout rate of 6%. The incidences (per 1000 person-years, 95% confidence interval) of composite, coronary heart disease, ischaemic stroke and peripheral artery disease in the JDDM study were 8.3 (6.6-10.0), 4.4 (3.2-5.6), 3.1 (2.1-4.2), and 0.7 (0.2-1.2), respectively. Each incidence was lowest in the JDDM study compared with other cohorts (P<0.01 vs. each cohort). In the JDDM study, significant variables predictive of the occurrence of a cardiovascular event were age, duration of diabetes, HbA 1c, HDL cholesterol and urinary albumin. Conclusion The novel finding of low cardiovascular disease occurrence in this study may be conferred by the feasibility at primary care settings for providing patients with Type2 diabetes with favourable control of blood glucose, blood pressure and lipids, coupled with unique ethnicity/country factors. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.


PubMed | HEC Science Clinic, Oishi Clinic, Kurihara Clinic, Shiga University of Medical Science and 5 more.
Type: Journal Article | Journal: BMJ open diabetes research & care | Year: 2016

The fact that population with type 2 diabetes mellitus and bodyweight of patients are increasing but diabetes care is improving makes it important to explore the up-to-date rates of achieving treatment targets and prevalence of complications. We investigated the prevalence of microvascular/macrovascular complications and rates of achieving treatment targets through a large-scale multicenter-based cohort.A cross-sectional nationwide survey was performed on 9956 subjects with type 2 diabetes mellitus who consecutively attended primary care clinics. The prevalence of nephropathy, retinopathy, neuropathy, and macrovascular complications and rates of achieving targets of glycated hemoglobin (HbA1c) <7.0%, blood pressure <130/80mmHg, and lipids of low-density/high-density lipoprotein cholesterol <3.1/1.0mmol/L and non-high-density lipoprotein cholesterol <3.8mmol/L were investigated.The rates of achieving targets for HbA1c, blood pressure, and lipids were 52.9%, 46.8% and 65.5%, respectively. The prevalence of microvascular complications was 28% each, 6.4% of which had all microvascular complications, while that of macrovascular complications was 12.6%. With an increasing duration of diabetes, the rate of achieving target HbA1c decreased and the prevalence of each complication increased despite increased use of diabetes medication. The prevalence of each complication decreased according to the number achieving the 3 treatment targets and was lower in subjects without macrovascular complications than those with. Adjustments for considerable covariates exhibited that each complication was closely inter-related, and the achievement of each target was significantly associated with being free of each complication.Almost half of the subjects examined did not meet the recommended targets. The risk of each complication was significantly affected by 1 on-target treatment (inversely) and the concomitance of another complication (directly). Total diabetes care including one-by-one management of modifiable risk factors and complications may be important for high-quality care. The future studies including more subjects and clinics with precise complication status are needed.


PubMed | HEC Science Clinic, Oishi Clinic, Shiga University of Medical Science, Niigata University and 3 more.
Type: Journal Article | Journal: Diabetes research and clinical practice | Year: 2015

The protective association of pioglitazone with cardiovascular events and death was investigated over 6-years in large-scale type 2 diabetic subjects without established cardiovascular disease in a primary care setting.A six-year observational cohort study including 2864 subjects with type 2 diabetes without established cardiovascular disease was performed. The primary endpoint was a composite of first occurrence of cardiovascular disease or death. The effect of pioglitazone use at a baseline year with a Cox proportional hazard model and the time-dependent use in each one-year examination interval with a pooled logistic regression model were analyzed.Baseline use of pioglitazone (n=493) did not show a statistically protective effect on the primary endpoint (n=175), although it tended to reduce the risk (adjusted hazard ratio 0.67 [95% CI: 0.43-1.05]). However, pooled logistic regression analysis indicated a significant protective association of pioglitazone with the primary endpoint (0.58 [0.38 to 0.87] and cardiovascular disease (0.54 [0.33-0.88]), independent of concurrent levels of blood glucose, blood pressure, lipids, albuminuria, and renal function. In particular, this protective association was observed in those with diabetic nephropathy regardless of the daily dose of pioglitazone. Among a total of 898 subjects who took pioglitazone during the period, 43% experienced a discontinuation at least once; however, serious adverse effects were rare.This observational study indicated a protective association of pioglitazone with cardiovascular disease and death in type 2 diabetic subjects without established vascular disease, particularly those with nephropathy.


Masuda D.,Osaka University | Sakai N.,Sakai Clinic | Sugimoto T.,Sugimoto Clinic | Kitazume-Taneike R.,Osaka University | And 15 more authors.
Journal of Atherosclerosis and Thrombosis | Year: 2011

Aim: Postprandial hyperlipidemia (PH) is thought to be caused by the impaired postprandial metabolism of triglycerides (TG)-rich lipoproteins in both endogenous and exogenous pathways; however, there is no consensus. It is difficult to estimate the presence of PH without performing a time-consuming oral fat loading (OFL) test, so postprandial lipoprotein metabolism was analyzed by measuring the postprandial levels of apolipoprotein (apo) B-48 and apo B-100, and the correlation between postprandial TG increase and fasting apoB-48 levels was assessed to establish a good marker of PH without performing an OFL test. Methods: Ten male normolipidemic subjects were loaded with a high-fat (HF, 1045 kcal) or standard (ST, 566 kcal) meal, and the lipids, apolipoproteins and lipoprotein profiles were analyzed after each meal. Results: TG, apo B-48, remnant-like particles (RLP)-cholesterol and RLP-TG levels were increased and their levels were significantly higher after intake of the HF meal than the ST meal; however, there was no postprandial increase in apo B-100 and LDL-C levels. Postprandial increases in TG levels of CM, VLDL, LDL and HDL were significantly higher after intake of the HF meal than the ST meal. Fasting apo B-48 levels were strongly correlated with the incremental area under the curve of TG after intake of the HF meal, but not the ST meal. Conclusion: Postprandial TG increase was mainly due to increased CM and CM-R, but not VLDL. Measurement of fasting serum apo B-48 may be a simple and useful method for assessment of the existence of PH.


Masuda D.,Osaka University | Sugimoto T.,Sugimoto Clinic | Tsujii K.-I.,Tsujii Clinic | Inagaki M.,Osaka University | And 11 more authors.
European Journal of Clinical Investigation | Year: 2012

Background Postprandial hyperlipidemia partially refers to the postprandial accumulation of chylomicrons and chylomicron remnants (CM-R). Many in vitro studies have shown that CM-R has highly atherogenic properties, but consensus is lacking on whether CM-R accumulation correlates with the development of atherosclerotic cardiovascular diseases. We investigated the correlation between CM-R accumulation and the prevalence of coronary artery disease (CAD). Design Subjects who received a coronary angiography and did not take any lipid-lowering drugs (n=189) were enrolled. Subjects with coronary artery stenosis (≥75%) were diagnosed as CAD. Biochemical markers for glucose and lipid metabolism including fasting apolipoprotein (apo) B-48 concentration were compared between CAD patients (n=96) and age-, sex-, and body mass index (BMI)-matched non-CAD subjects without overt coronary stenosis (<75%) (n=67). We tried to determine which metabolic parameters were correlated with the prevalence of CAD by multiple logistic regression analysis, and whether or not the combination of high apo B-48 and other coronary risk factors (high triglyceride, low HDL-C, high HbA1c or low adiponectin levels) increased the prevalence of CAD. Results Fasting serum apo B-48 levels were significantly higher in CAD patients than in non-CAD subjects (3·9±2·4 vs. 6·9±2·6μg/mL, P<0·0001) and had the most significant correlation with the existence of CAD. The clustering of high fasting apo B-48 levels (>4·34μg/mL, the cut-off value) and other coronary risk factors were found to be associated with a stronger risk of CAD compared with single high fasting apo B-48 levels. Conclusion Fasting serum apo B-48 levels significantly correlated with the prevalence of CAD. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.


Nakatani K.,Osaka University | Sugimoto T.,Sugimoto Clinic | Masuda D.,Osaka University | Okano R.,Osaka Police Hospital Dock | And 13 more authors.
Atherosclerosis | Year: 2011

Background: Postprandial hyperlipidemia (PPHL) is an independent risk factor for coronary heart disease (CHD) which is based on the accumulation of chylomicrons (CM) and CM remnants containing apolipoprotein B-48 (apoB-48). Since atherosclerotic cardiovascular diseases are frequently observed even in subjects with normal serum triglyceride (TG) level, the correlation between fasting apoB-48 containing lipoproteins and carotid intima-media thickness (IMT) was analyzed in subjects with normal TG levels. Methods: From subjects who took their annual health check at the Osaka Police Hospital (n=245, male), one-hundred and sixty-four male subjects were selected to take part in this study; the excluding factors were: systolic blood pressure ≥140. mmHg, intake of antihypertensive or antihyperlipidemic drugs, or age >65 years. The association between biochemical markers and IMT was analyzed and independent predictors of max-IMT were determined by multiple regression analysis in all subjects and in groups N-1 (TG < 100 mg/dl, n=58), N-2 (100 ≤ TG < 150. mg/dl, n=53) and H (150 ≤ TG mg/dl, n=53), respectively. Results: Fasting total cholesterol, LDL-cholesterol, HDL-cholesterol, apoB-100 and ln. RemL-C (remnant lipoprotein-cholesterol) levels were not correlated with max-IMT, but ln. TG and ln. apoB-48 were significantly correlated with max-IMT in all subjects. Ln. apoB-48 and apoB-48/TG ratio were significantly correlated with max-IMT in group N-2. By multiple regression analysis, age and ln. apoB-48 were independent variables associated with max-IMT in group N-2. Conclusion: Serum apoB-48 level might be a good marker for the detection of early atherosclerosis in middle-aged subjects with normal-range levels of blood pressure and TG. © 2011 Elsevier Ireland Ltd.

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