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1P-0142 Effects of type 2 diabetes mellitus and aging on regional arterial stiffness
Monday September 29, 2003: Poster Session Diabetic angiopathy 1P-0141
Estimation of atherogenic risk factors and complications in type 2 diabetic patients
S. Kobori, T. Takahashi, N. Ishi, R. Goto, K. Higashi. Department of Internal Medicine, Kumamoto National Hospital, Kumamoto, Japan
1P-0142
Effects of type 2 diabetes mellitus and aging on regional arterial stiffness
T. Shoji, E. Kimoto, K. Shinohara, M. Emoto, H. Koyama, Y. Nishizawa. Osaka City University Graduate School of Medicine, Osaka, Japan Background: Arterial stiffness affects cardiac function, peripheral circulation, and cardiovascular mortality. So far, however, little is known about regional difference in arterial stiffening. This study examined arterial stiffness in four different regions. Methods: The subjects were 161 patients with type 2 diabetes mellitus and 129 healthy controls. Regional arterial stiffness was evaluated by pulse wave velocity (PWV) measured simultaneously in the central (heartcarotid and heart-femoral segments) and peripheral arteries (heart-brachial and femoral-ankle segments) using an automatic device. Results: The diabetic patients had greater PWV than the healthy subjects in the four arterial regions, and the effect of diabetes on PWV was greater in the central than the peripheral arteries. PWV increased with age in the four arterial regions, and the effect of age on PWV was greater in the central than the peripheral arteries. In multiple regression analysis, age and systolic blood pressure had significant impacts on PWV of the four regions, whereas diabetes was significantly associated only with PWV of the central arteries. In contrast, sex was associated with PWV of the peripheral arteries. Conclusions: Type 2 diabetes and aging had greater impacts on stiffness of the central arteries, whereas sex-related difference was significant in peripheral arteries. Thus, different factors are involved in stiffness of different arterial regions. 1P-0143
Celiprolol hydrochloride, β1 antagonist, β2 agonist, retards progression of vascular lesions and restore endothelial dysfunction in type II diabetic rats complicated with NO dysfunction
T. Hayashi, J.R.P. Arockia, A. Miyazaki, A. Iguchi. Dept. of Geriatrics, Nagoya Univ. Graduate Sch. of Med., Japan Objective: We investigated the effect of Celiprolol hydrochloride, β1 antagonist, β2 agonist, on the development of vascular lesions and function after endothelial denudation in type II diabetic rats. Background: The effect of β1 antagonist in the diabetic vascular lesion is controversial. On the other hands, β2 agonist has been identified to improve endothelial function via enhancement of NO release. We investigated the effect of Celiprolol, of β1 antagonist, β2 agonist and Atenolol of β1 selective antagonist in the diabetic vascular lesion and vascular response. Methods and Results: Male OLETF (type II diabetic rats, 28 wks old) were divided into three groups. OLETF was fed regular chow w/wo Atenolol (25mg/kg/day) or Celiprolol (100mg/kg/day) treatment by oral gavage (Gp DM, Gp DM-a, Gp DM-c), and it was continued for five weeks. On day
3, endothelial cells of right inernal carotid artery were removed by balloon injury. Four weeks after balloon injury, the rats were evaluated. Plasma glucose, lipid levels and systolic blood pressure were not changed throughout the experimental period. Intimal thickening was observed in right carotid artery from Gp DM and DM-a, however, there was little in aortae from Gp DM-c. Tone-related basal NO release in carotid artery and plasma NOx (sum of NO− 2 and NO− 3 ) were higher in Gp DM-c than other groups. Acetylcholine-induced NO-dependent relaxation in carotid artery was improved in Gp DM-c compared with that in Gp DM and Gp DM-a. O− 2 from aorta and plasma TNF a was higher in Gp DM and DM-a, than in Gp DM-c. Conclusion: Celiprorol retards the progression of diabetic angiopathy after endothelial denudation in OLETF rats without changing plasma glucose. NO and O− 2 may play a role in important underlining mechanisms by decreasing TNF a levels. 1P-0144
Therapeutic effect of fidarestat, aldose reductase inhibitor, on an accelerated atherosclerosis with hyperglycemia in mice: Involvement of endothelial nitric oxide production
M. Goto, M. Okuyama, K. Taniko, K. Ichikawa, N. Kato, Y. Nakayama. Institute of Developmental Research, Mie Research Laboratory, Sanwa Kagaku Kenkyusho Co., Mie, Japan Diabetes mellitus is associated with several cardiovascular complications, such as hypertension, atherosclerosis and thrombosis. The polyol pathway activated by hyperglycemia plays an important role for the initiation/progression of diabetic complications. Present experiments were disigned to investigate whether or not treatment of fidarestat, an aldose reductase inhibitor, affect the accelerated plaque formation with hyperglycemia in Apo E-deficient (Apo E-KO) mice. In order to accelerate plaque formation, we treated male Apo EKO mice with streptozotocin (STZ). Three weeks later, the STZ-treated mice received fidarestat (8mg/kg in diet) for 6 weeks. STZ-treated mice developed plasma total cholesterol and triglyceride levels compared to control mice. Plaque formation, which had been assessed histologically, in aortic sinus was accelerated by 3.8 fold with hyperglycemia. Fidarestat significantly improved the accelerated plaque formation without changes in plasma cholesterol, triglyceride, glucose, or insulin level. Sorbitol levels in red blood cells were increased with hyperglycemia and reduced by treatment of fidarestat below the normal level. Furthermore, fidarestat recovered the attenuated NO production in cultured endothelial cells under high glucose. These findings suggest that hyperglycemia lead to acceleration of atherosclerotic lesion formation, in part, resulting from impaired endothelial NO production by activation of polyol pathway, and fidarestat effectively prevents the accelerated atherosclerotic lesion formation with hyperglycemia. 1P-0145
Impact of diabetes mellitus on initial and long-term clinical results of long coronary lesions: Multicenter registry in Japan
S. Nakamura 1 , M. Hirose 1 , E. Saito 1 , T. Miyauchi 1 , A. Kanazawa 1 , K. Hozawa 2 , H. Nakamura 2 , K. Yamamoto 2 , N. Makishima 3 , S. Nakamura 4 , J. Koyama 4 . 1 Dept. of Cardiology, New Tokyo Hospital; 2 Dept. of Cardiology, Kasori Hospital; 3 Dept. of Cardiology, Kobari General Hospital; 4 Dept. of Cardiology, Secomedic Hospital, Japan Background: In patients undergoing percutaneous coronary interventions (PCI), diabetes mellitus (DM) is associated with poorer outcomes. On the other hand, the optimal PCI for the treatment of long lesions (>25mm) is still unknown. This study aimed to evaluate the influence of DM on the initial long-term clinical results of in the treatment of long lesions. Methods: We studied 778 patients underwent PCI for long coronary lesions, 264 (33.9%) with DM and 514 (66.9%) with non-DM. Stenting and rotational atherectomy were performed 612 patients (78.7%), 492 patients (53.2%), respectively.
In-hospital
6 months 1 year
Procedural success (%) Clinical success (%) MACE (%) Angiographic restenosis (%) TLR (%) Death (%) CABG (%) TLR (Re-PCI)(%) Any Events (%)
DM (n=264)
Non-DM (n=514)
p
98.5 98.1 0.8 40.2 34.8 0.8 2.3 39.4 42.4
98.8 98.6 0 27.2 23.3 0 0.2 24.5 24.7
NS NS NS p<0.01 p<0.01 NS NS p<0.01 p<0.01
XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan
MONDAY
To investigate prevalence of atherogenic risk factors and diabetic angiopathies on diabetes mellitus, a blood glucose control critical path was used in 258 type 2 diabetic patients who admitted for a blood glucose control and an diabetes education. prevalence of microangiopathies were 20% for diabetic retinopathy, 40% for diabetic nephropathy, 20% for neuropathy, respectively. There were significantly difference in blood glucose control between group with complications and without complication. On macroangiopathies, cerveral infarctions (almost lacunar infarctions), ischemic heart diseases and intimamedial hypertrophy were 34.9%, 24.5% and 67.6%, respectively. There were no difference in blood glucose control between two groups. On prevalences of atherogenic risk factors, hyperlipoproteinemia, hypertension and obesity were 58.9%, 45.2% and 41.6%, respectively. In a breakdown of hyperlipoproteinemia, Type IIa, IIb, IV and V were 10.9%, 24.0%, 23.3% 0.7%, respectively. On the other hand, an appearance rate of midband by lipoprotein electrophoresis was 60%. That rate of remnant showed 40% (22.9% hyperlipoproteinemia and 17.1% normolipoproteinemia) exclude for 20% hyperLp(a)nemia (more than 30mg/dL). Furthemore, high density lipoprotein-cholesterol level in patients with ischemic heart disease were significantly lower than that in those without ischemic heart disease. From these results, to prevente and treat diabetic macroangiopathies, it may be necessary not only to improve blood glucose control, but also to correct atherogenic risk factors excluding diabetes mellitus.
51
Estimation of atherogenic risk factors and complications in type 2 diabetic patients
S. Kobori, T. Takahashi, N. Ishi, R. Goto, K. Higashi. Department of Internal Medicine, Kumamoto National Hospital, Kumamoto, Japan
1P-0142
Effects of type 2 diabetes mellitus and aging on regional arterial stiffness
T. Shoji, E. Kimoto, K. Shinohara, M. Emoto, H. Koyama, Y. Nishizawa. Osaka City University Graduate School of Medicine, Osaka, Japan Background: Arterial stiffness affects cardiac function, peripheral circulation, and cardiovascular mortality. So far, however, little is known about regional difference in arterial stiffening. This study examined arterial stiffness in four different regions. Methods: The subjects were 161 patients with type 2 diabetes mellitus and 129 healthy controls. Regional arterial stiffness was evaluated by pulse wave velocity (PWV) measured simultaneously in the central (heartcarotid and heart-femoral segments) and peripheral arteries (heart-brachial and femoral-ankle segments) using an automatic device. Results: The diabetic patients had greater PWV than the healthy subjects in the four arterial regions, and the effect of diabetes on PWV was greater in the central than the peripheral arteries. PWV increased with age in the four arterial regions, and the effect of age on PWV was greater in the central than the peripheral arteries. In multiple regression analysis, age and systolic blood pressure had significant impacts on PWV of the four regions, whereas diabetes was significantly associated only with PWV of the central arteries. In contrast, sex was associated with PWV of the peripheral arteries. Conclusions: Type 2 diabetes and aging had greater impacts on stiffness of the central arteries, whereas sex-related difference was significant in peripheral arteries. Thus, different factors are involved in stiffness of different arterial regions. 1P-0143
Celiprolol hydrochloride, β1 antagonist, β2 agonist, retards progression of vascular lesions and restore endothelial dysfunction in type II diabetic rats complicated with NO dysfunction
T. Hayashi, J.R.P. Arockia, A. Miyazaki, A. Iguchi. Dept. of Geriatrics, Nagoya Univ. Graduate Sch. of Med., Japan Objective: We investigated the effect of Celiprolol hydrochloride, β1 antagonist, β2 agonist, on the development of vascular lesions and function after endothelial denudation in type II diabetic rats. Background: The effect of β1 antagonist in the diabetic vascular lesion is controversial. On the other hands, β2 agonist has been identified to improve endothelial function via enhancement of NO release. We investigated the effect of Celiprolol, of β1 antagonist, β2 agonist and Atenolol of β1 selective antagonist in the diabetic vascular lesion and vascular response. Methods and Results: Male OLETF (type II diabetic rats, 28 wks old) were divided into three groups. OLETF was fed regular chow w/wo Atenolol (25mg/kg/day) or Celiprolol (100mg/kg/day) treatment by oral gavage (Gp DM, Gp DM-a, Gp DM-c), and it was continued for five weeks. On day
3, endothelial cells of right inernal carotid artery were removed by balloon injury. Four weeks after balloon injury, the rats were evaluated. Plasma glucose, lipid levels and systolic blood pressure were not changed throughout the experimental period. Intimal thickening was observed in right carotid artery from Gp DM and DM-a, however, there was little in aortae from Gp DM-c. Tone-related basal NO release in carotid artery and plasma NOx (sum of NO− 2 and NO− 3 ) were higher in Gp DM-c than other groups. Acetylcholine-induced NO-dependent relaxation in carotid artery was improved in Gp DM-c compared with that in Gp DM and Gp DM-a. O− 2 from aorta and plasma TNF a was higher in Gp DM and DM-a, than in Gp DM-c. Conclusion: Celiprorol retards the progression of diabetic angiopathy after endothelial denudation in OLETF rats without changing plasma glucose. NO and O− 2 may play a role in important underlining mechanisms by decreasing TNF a levels. 1P-0144
Therapeutic effect of fidarestat, aldose reductase inhibitor, on an accelerated atherosclerosis with hyperglycemia in mice: Involvement of endothelial nitric oxide production
M. Goto, M. Okuyama, K. Taniko, K. Ichikawa, N. Kato, Y. Nakayama. Institute of Developmental Research, Mie Research Laboratory, Sanwa Kagaku Kenkyusho Co., Mie, Japan Diabetes mellitus is associated with several cardiovascular complications, such as hypertension, atherosclerosis and thrombosis. The polyol pathway activated by hyperglycemia plays an important role for the initiation/progression of diabetic complications. Present experiments were disigned to investigate whether or not treatment of fidarestat, an aldose reductase inhibitor, affect the accelerated plaque formation with hyperglycemia in Apo E-deficient (Apo E-KO) mice. In order to accelerate plaque formation, we treated male Apo EKO mice with streptozotocin (STZ). Three weeks later, the STZ-treated mice received fidarestat (8mg/kg in diet) for 6 weeks. STZ-treated mice developed plasma total cholesterol and triglyceride levels compared to control mice. Plaque formation, which had been assessed histologically, in aortic sinus was accelerated by 3.8 fold with hyperglycemia. Fidarestat significantly improved the accelerated plaque formation without changes in plasma cholesterol, triglyceride, glucose, or insulin level. Sorbitol levels in red blood cells were increased with hyperglycemia and reduced by treatment of fidarestat below the normal level. Furthermore, fidarestat recovered the attenuated NO production in cultured endothelial cells under high glucose. These findings suggest that hyperglycemia lead to acceleration of atherosclerotic lesion formation, in part, resulting from impaired endothelial NO production by activation of polyol pathway, and fidarestat effectively prevents the accelerated atherosclerotic lesion formation with hyperglycemia. 1P-0145
Impact of diabetes mellitus on initial and long-term clinical results of long coronary lesions: Multicenter registry in Japan
S. Nakamura 1 , M. Hirose 1 , E. Saito 1 , T. Miyauchi 1 , A. Kanazawa 1 , K. Hozawa 2 , H. Nakamura 2 , K. Yamamoto 2 , N. Makishima 3 , S. Nakamura 4 , J. Koyama 4 . 1 Dept. of Cardiology, New Tokyo Hospital; 2 Dept. of Cardiology, Kasori Hospital; 3 Dept. of Cardiology, Kobari General Hospital; 4 Dept. of Cardiology, Secomedic Hospital, Japan Background: In patients undergoing percutaneous coronary interventions (PCI), diabetes mellitus (DM) is associated with poorer outcomes. On the other hand, the optimal PCI for the treatment of long lesions (>25mm) is still unknown. This study aimed to evaluate the influence of DM on the initial long-term clinical results of in the treatment of long lesions. Methods: We studied 778 patients underwent PCI for long coronary lesions, 264 (33.9%) with DM and 514 (66.9%) with non-DM. Stenting and rotational atherectomy were performed 612 patients (78.7%), 492 patients (53.2%), respectively.
In-hospital
6 months 1 year
Procedural success (%) Clinical success (%) MACE (%) Angiographic restenosis (%) TLR (%) Death (%) CABG (%) TLR (Re-PCI)(%) Any Events (%)
DM (n=264)
Non-DM (n=514)
p
98.5 98.1 0.8 40.2 34.8 0.8 2.3 39.4 42.4
98.8 98.6 0 27.2 23.3 0 0.2 24.5 24.7
NS NS NS p<0.01 p<0.01 NS NS p<0.01 p<0.01
XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan
MONDAY
To investigate prevalence of atherogenic risk factors and diabetic angiopathies on diabetes mellitus, a blood glucose control critical path was used in 258 type 2 diabetic patients who admitted for a blood glucose control and an diabetes education. prevalence of microangiopathies were 20% for diabetic retinopathy, 40% for diabetic nephropathy, 20% for neuropathy, respectively. There were significantly difference in blood glucose control between group with complications and without complication. On macroangiopathies, cerveral infarctions (almost lacunar infarctions), ischemic heart diseases and intimamedial hypertrophy were 34.9%, 24.5% and 67.6%, respectively. There were no difference in blood glucose control between two groups. On prevalences of atherogenic risk factors, hyperlipoproteinemia, hypertension and obesity were 58.9%, 45.2% and 41.6%, respectively. In a breakdown of hyperlipoproteinemia, Type IIa, IIb, IV and V were 10.9%, 24.0%, 23.3% 0.7%, respectively. On the other hand, an appearance rate of midband by lipoprotein electrophoresis was 60%. That rate of remnant showed 40% (22.9% hyperlipoproteinemia and 17.1% normolipoproteinemia) exclude for 20% hyperLp(a)nemia (more than 30mg/dL). Furthemore, high density lipoprotein-cholesterol level in patients with ischemic heart disease were significantly lower than that in those without ischemic heart disease. From these results, to prevente and treat diabetic macroangiopathies, it may be necessary not only to improve blood glucose control, but also to correct atherogenic risk factors excluding diabetes mellitus.
51