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Obihiro, Japan

Katakami N.,Osaka University | Mita T.,Juntendo University | Yoshii H.,Juntendo University | Onuma T.,Juntendo University | And 12 more authors.
Journal of Atherosclerosis and Thrombosis

Aim: Alogliptin, an efficacious inhibitor of DPP-4 that improves glycemic control, as well as the pancreatic beta-cell function, is now increasingly used to accomplish glycemic targets in type 2 diabetic patients. Interestingly, recent experimental studies have shown that alogliptin exerts anti-atherosclerotic effects in GLP-1-dependent and -independent manners. The aim of the present ongoing study is to investigate the preventive effects of alogliptin on the progression of atherosclerosis in type 2 diabetic subjects using the carotid intima-media thickness (IMT), an established marker of cardiovascular disease. Methods and Results: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A) is a prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study. Between March 2011 and March 2012, 341 participants were recruited at 11 clinical sites, and were randomly allocated either to an alogliptin treatment group (172 patients) or a conventional treatment group (169 patients). The primary outcomes are the changes in the maximum and mean IMT of the common carotid artery during a 24-month treatment period, as measured by carotid arterial echography. The secondary outcomes include the changes in glycemic control, parameters related to beta-cell function and diabetic nephropathy, the occurrence of cardiovascular events and adverse events and biochemical measurements reflecting vascular function. Conclusions: This is the first study to address the effects of DPP-4 inhibitors on the progression of changes in the carotid IMT, with the patients without DPP-4 inhibitor treatment serving as a control group. The results will be available soon, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent cardiovascular disease. Source

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.

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. Source

Otani T.,Saitama Memorial Hospital | Otani T.,Tokyo Womens Medical University | Yokoyama H.,Jiyugaoka Medical Clinic | Uchigata Y.,Tokyo Womens Medical University
Diabetes Research and Clinical Practice

Aims: We investigated changes in vital prognosis according to the year at diagnosis of type 1 diabetes mellitus (T1DM) in a hospital-based survey. Methods: Of 1054 Japanese subjects diagnosed as T1DM between 1952 and 1999 before the age of 30 and consulted the diabetes center between 1962 and 1999, the survival status up to 2010 or 20 years of follow-up was investigated. Subjects were divided by the year at diagnosis of T1DM: before 1979 (Group A: n=. 359), 1980 to 1989 (Group B: n=. 400), and 1990 to 1999 (Group C: n=. 295). The mortality (/100,000 person years) and standardized mortality ratio (SMR) were calculated, and the effect of year at diagnosis of T1DM was explored by the Cox proportional hazard model. Results: The survival status was confirmed in 90.0%. The mortality rate (95%CI) and age and sex adjusted SMR (95%CI) were 457 (288-627) and 3.0 (1.9-4.2) in Group A, 265 (143-387) and 2.2 (1.2-3.2) in Group B, and 144 (29-259) and 1.6 (0.3-2.9) in Group C, respectively. The cumulative survival rate was significantly different according to the year at diagnosis of T1DM (. p=. 0.0239). Cox's proportional hazard model revealed that Groups B and C had significantly lower risks of death than Group A after adjustment for gender and age at diagnosis of T1DM (HR 0.48 [95%CI 0.26-0.87] for Group B and HR 0.25 [95%CI 0.09-0.60] for Group C). Conclusion: This study indicated that vital prognosis is improving according to the year at diagnosis of T1DM and suggested the need of a nationwide survey. © 2015 Elsevier Ireland Ltd. Source

Mita T.,Juntendo University | Katakami N.,Osaka University | Shiraiwa T.,Shiraiwa Medical Clinic | Yoshii H.,Juntendo Tokyo Koto Geriatric Medical Center | And 13 more authors.
Diabetes Care

Objective The effect of additional treatment with oral hypoglycemic agents on the progression of atherosclerosis remains unknown in insulin-treated patients with type 2 diabetes mellitus (T2DM). We assessed the effects of sitagliptin, a dipeptidyl peptidase 4 inhibitor, on carotid intima-media thickness (IMT) in T2DM. Research Design and Methods This prospective, randomized, open-label, blinded end point, multicenter, parallelgroup, comparative study included 282 insulin-treated patients with T2DM free of a history of apparent cardiovascular diseases who were recruited at 12 clinical units and randomly allocated to either the sitagliptin group (n = 142) or the control group (n = 140). The primary outcomes were changes in mean and maximum IMT of the common carotid artery measured by echography at the end of a 104-week treatment period. Results Sitagliptin had a more potent glucose-lowering effect compared with the conventional treatment (20.5 ± 1.0% vs. 20.2 ± 0.9%; P = 0.004), without increasing hypoglycemic episodes or body weight. Changes in the mean and left maximum IMT, but not right maximum IMT, of the common carotid arteries were significantly greater after sitagliptin treatment compared with conventional treatment (20.029 [SE 0.013] vs. 0.024 [0.013] mm [P = 0.005]; 20.065 [0.027] vs. 0.022 [0.026] mm [P = 0.021]; 20.007 [0.031] vs. 0.027 [0.031] mm [P = 0.45], respectively). Over 104 weeks, sitagliptin, but not conventional treatment, significantly reduced the mean IMT and left maximumIMT of common carotid arteries relative to the baseline. Conclusions Sitagliptin attenuated the progression of carotid IMT in insulin-treated patients with T2DM free of apparent cardiovascular disease compared with conventional treatment. © 2016 by the American Diabetes Association. Source

Mikada A.,Akita University | Mikada A.,Gastroenterology and Diabetes Unit | Narita T.,Akita University | Yokoyama H.,Jiyugaoka Medical Clinic | And 5 more authors.
Diabetes Research and Clinical Practice

Aim: To assess changes in circulating incretin levels and body fat compositions with initial combination therapy with α-glucosidase inhibitor and dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes (T2D). Methods: In this multicenter open-label 24-week trial, Japanese over-weight (BMI≥25kg/m2) patients with T2D not taking medication or taking metformin and/or sulfonylurea were randomly assigned to receive either 50mg of miglitol three times a day (M, n=14), 50mg of sitagliptin once a day (S, n=14), or a combination of both (M+S, n=13). Changes in plasma incretin levels during a meal tolerance test (MTT) and body fat composition with impedance method were evaluated. Results: During MTT, postprandial plasma glucose levels decreased more after M. +. S than after M or S, and postprandial serum insulin levels decreased significantly after M and M. +. S whereas they increased after S. After M, active gastric inhibitory polypeptide (aGIP) decreased significantly at 30. min despite a significant increase at 120. min. After S, aGIP levels increased significantly throughout the MTT. After M. +. S, aGIP increased significantly at 0 and 120. min despite of significant decrease at 30. min. M. +. S further enhanced postprandial active glucagon-like peptide-1 levels during MTT than S did. Total body fat mass decreased significantly after M and M. +. S. Visceral fat mass decreased significantly only after M. +. S. Serum adiponectin increased significantly only after M. +. S. Conclusions: In over-weight patients with T2D, M. +. S may have a beneficial effect on adiposity with relation to these different effects on two incretins. © 2014 Elsevier Ireland Ltd. Source

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