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Clinical and metabolic predictors of silent myocardial ischemia in type 2 diabetic males
240
Wednesday 12 October 1994: Poster Abstracts Diabetes
predictors were respectively postprandial IDLC, postprandial plasma TG and postprandial plasma TG. These results suggest that exogenous hyperinsulinemia does not promote atherogenesis in cholesterol-fed rabbits, but that postprandial levels of IDL-C and/or TG may be involved in the promotion of atherosclerosis. Clinical and metabolic predictors of silent myocardlal ischemia in type 2 diabetic males kowski I, Tatdn J, Mamcarz A, Kuch J, Szczeklik 2, Braksator K, Walasik L, Kr61 J, Dept. of Int. Diseases and Diabetol. and
12291
Dept. of Cardiol.. Warsaw Med. Sch., Kondratowicza 8, 03242 Warsaw, Poland
atherosclerosis were male sex, serum LDL-C, age and cigarette smoking (R’ = 0.295, P c 0.001). These results show that NIDDM patients tend to have advanced atherosclerosis of their carotid and femoral arteries and there are different risk factors for carotid and femoral atherosclerosis. Augmented growth of vascular smooth muscle cells from rats treated with streptozotocin: overexpression of Ras farnesyl transferase Iruliy, Kawata S, Fukuda K, Maeda Y, Igura T, Nagase T, Yoshida S, Matsuzawa Y, 2nd Dept. of Int. Med., Osaka Univ. 12311
Med. Sch., 2-2 Yamadaoka, Suita 565, Japan
The appropriate clinical approach to silent myocardial ischemia in type 2 diabetics remains controversial. A two-step diagnostic algorithm based on clinical predictors and laboratory work-up seems a reasonable proposition. Our study aimed (a) to determine the prevalence of silent ischemia in 64 males with type 2 diabetes mellitus and in 50 males from a comparable control group without diabetes, (b) to assess the frequency of several clinical and metabolic parameters in groups of diabetics with and without a pattern of silent ischemia and in the control group without diabetes. All groups under study were similar with respect to age, lack of history of stenocardia and lifestyle. A standardized clinical observation, laboratory evaluation of carbohydrate and lipid metabolism, and non-invasive cardiology (exercise test, Holter ECG, echocardiography) were performed for each subject. Clinical factors significantly predicting the diagnosis of silent ischemia were: HbAlc, nephropathy, neuropathy both peripheral and autonomic, and arteriosclerosis obliterans. In addition, diabetics as a group were characterized by diastolic dysfunction of the heart and increased oxygen cost of exercise. Silent myocardial ischemia was demonstrated in 27% of tested diabetics and in 12% of controls. The probability of discovering silent heart ischemia was higher in those subgroups of diabetics who showed poor control or the presence of other angiopathic complications. We suggest that patients with elevated HbAlc who show symptoms of renal or nervous system impairment should be tested for silent heart ischemia as a priority.
The molecular chain constitutes one of the major signal tram+ duction pathways, ‘Ras pathway’, by which the messages carried by growth factors are. sent from the cell membrane to the cell interior. Ras p21 must be localized in the plasma membrane to function and to transform cells. This membrane localization is facilitated by a post-translational modification, famesylation of Ras. However, little is known about the contribution of Ras protein to the growth of vascular smooth muscle cells (SMC). The growth mechanism of SMC was studied from the viewpoint of farnesylation of Ras-protein. DM was induced by the injection of streptozotocin (STZ) in male rats. After 4 weeks, the thoracic aorta was removed and subsequently SMC from primary cultures were subcultured. DNA synthesis of SMC from rats with STZ-induced DM was 4 times that of controls. SMC from rats with STZ-induced DM expressed 5 times as much famesyl transferase (FT) mRNA as SMC from controls. The FT inhibitor manumycin (UCFl-C, Kyowa Hakko Co. Ltd, Tokyo, Japan), which crosses cell membranes, inhibited SMC proliferation. Conclusion: Overexpression of FI in SMC from rats with STZ-induced DM may contribute to the augmented growth due to increased Ras function. Induction of genetic expression and plasma activity of plasminogen activator inhibitor type 1 @‘AI-l) by proinsulin and insulin in vivo &&_J& Sawa H, Fujii S, Sobel BE, Dept. of Cardiol., Univ. of
12321
Different risk factor profiles for carotid and femoral atherosclerosis in NIDDM &nishi T, Nishizawa Y, Kawagishi T, Maekawa K, Emoto M, Ishimura E, Inaba M, Okuno Y, Morii H, 2nd Dept. of btt. Med.,
Heidelberg, Bergheimer Str. 58, 69115 Heidelberg, Germany; Washington Univ., St. Louis. MO; Univ. of Vermont, Burlington, VT, USA
Osaka City Univ. Med. Sch., l-5-7, Asahimachi Abeno-ku, Osaka 545, Japan
Causes of accelerated atherogenesis in non-insulin-dependent diabetes mellitus (NIDDM), a condition associated with increased plasma concentrations of proinsulin (P) and insulin (I) as well as with increased plasma activity of plasminogen activator inhibitor type 1 (PAI-l), remain enigmatic. Previously, we have found that P and I induce PAI- in cells in vitro (Nordt et al Circulation 1994; 89: 321-30). The objective of this study was to determine whether P and I directly induce PAI- in vivo. To simulate the hyper(pro)insulinemia of NIDDM, conscious rabbits (n = 53) maintained euglycemic were given iv. infusions (1 h) of I (1 III/kg), P, C-peptide (both equimolar to I), or placebo (all endotoxin-free). Plasma PAI- activity did not change with placebo (n = 16) or with C-peptide (n = 4). However, with I (P) plasma PAI- activity increased, peaking in 3 h at 3.7-(3S)fold (n = 17 (n = 16). P < 0.002 each). The induction was attributable to PAI- protein, as shown by reverse fibrin autography, and specific, as shown by unchanged activities of a2-antiplasmin and t-PA (also suggesting reduced net tibrinolytic activitv). PAIgene. expressio~(PAI~1 mRNA) in response to N (P) in&eased in 3 h bv 2.1- (2.1-)fold in aorta, bv 2.4 (19-)fold in liver (P < 0.05 eachi but not in’heart, lung, spleen and kidney, returning to baseline in 24 h (n = 4 each). The genetic induction of PAI- in aorta was localized to the endothelium by in situ hybridization.
)230)
Non-insulin-dependent diabetes mellitus (NIDDM) is an important risk factor for peripheral atberial disease. But little is known about the risk factors for early femoral atherosclerosis in NIDDM. The aim of this study was to investigate the risk factors for femoral atherosclerosis and to compare the impact of the major coronary risk factors on e&y atherosclerosis in carotid and femoral arteries in patients with NIDDM. B-mode ultrasound imaging was conducted to determine noninvasively the mean maximal intima-media thickness (IMT) in the far wall of the common carotid (CA) and femoral (FA) arteries in 300 NIDDM patients and 161 age-matched control subjects without hyperlipidemia or hypertension. The results showed greater IMTs of both arteries in NIDDM patients than in subject (CA, 1.14 + 0.03 mm vs 0.71 rt0.2 mm, FA, 1.62 kO.06 mm vs 1.08 f 0.04 mm, mean f SE, P < 0.01). There was a significant but weak relationship between the carotid and femoral IMT in all subjects (R* = 0.162, P < 0.001). Multiple regression analysis showed that age, male sex and serum LDL-cholesterol were independent risk factors for carotid atherosclerosis in NIDDM patients (R*= 0.323, PcO.001). On the other hand, those for femoral
Atherosclerosis X, Montreal, October 1994
Wednesday 12 October 1994: Poster Abstracts Diabetes
predictors were respectively postprandial IDLC, postprandial plasma TG and postprandial plasma TG. These results suggest that exogenous hyperinsulinemia does not promote atherogenesis in cholesterol-fed rabbits, but that postprandial levels of IDL-C and/or TG may be involved in the promotion of atherosclerosis. Clinical and metabolic predictors of silent myocardlal ischemia in type 2 diabetic males kowski I, Tatdn J, Mamcarz A, Kuch J, Szczeklik 2, Braksator K, Walasik L, Kr61 J, Dept. of Int. Diseases and Diabetol. and
12291
Dept. of Cardiol.. Warsaw Med. Sch., Kondratowicza 8, 03242 Warsaw, Poland
atherosclerosis were male sex, serum LDL-C, age and cigarette smoking (R’ = 0.295, P c 0.001). These results show that NIDDM patients tend to have advanced atherosclerosis of their carotid and femoral arteries and there are different risk factors for carotid and femoral atherosclerosis. Augmented growth of vascular smooth muscle cells from rats treated with streptozotocin: overexpression of Ras farnesyl transferase Iruliy, Kawata S, Fukuda K, Maeda Y, Igura T, Nagase T, Yoshida S, Matsuzawa Y, 2nd Dept. of Int. Med., Osaka Univ. 12311
Med. Sch., 2-2 Yamadaoka, Suita 565, Japan
The appropriate clinical approach to silent myocardial ischemia in type 2 diabetics remains controversial. A two-step diagnostic algorithm based on clinical predictors and laboratory work-up seems a reasonable proposition. Our study aimed (a) to determine the prevalence of silent ischemia in 64 males with type 2 diabetes mellitus and in 50 males from a comparable control group without diabetes, (b) to assess the frequency of several clinical and metabolic parameters in groups of diabetics with and without a pattern of silent ischemia and in the control group without diabetes. All groups under study were similar with respect to age, lack of history of stenocardia and lifestyle. A standardized clinical observation, laboratory evaluation of carbohydrate and lipid metabolism, and non-invasive cardiology (exercise test, Holter ECG, echocardiography) were performed for each subject. Clinical factors significantly predicting the diagnosis of silent ischemia were: HbAlc, nephropathy, neuropathy both peripheral and autonomic, and arteriosclerosis obliterans. In addition, diabetics as a group were characterized by diastolic dysfunction of the heart and increased oxygen cost of exercise. Silent myocardial ischemia was demonstrated in 27% of tested diabetics and in 12% of controls. The probability of discovering silent heart ischemia was higher in those subgroups of diabetics who showed poor control or the presence of other angiopathic complications. We suggest that patients with elevated HbAlc who show symptoms of renal or nervous system impairment should be tested for silent heart ischemia as a priority.
The molecular chain constitutes one of the major signal tram+ duction pathways, ‘Ras pathway’, by which the messages carried by growth factors are. sent from the cell membrane to the cell interior. Ras p21 must be localized in the plasma membrane to function and to transform cells. This membrane localization is facilitated by a post-translational modification, famesylation of Ras. However, little is known about the contribution of Ras protein to the growth of vascular smooth muscle cells (SMC). The growth mechanism of SMC was studied from the viewpoint of farnesylation of Ras-protein. DM was induced by the injection of streptozotocin (STZ) in male rats. After 4 weeks, the thoracic aorta was removed and subsequently SMC from primary cultures were subcultured. DNA synthesis of SMC from rats with STZ-induced DM was 4 times that of controls. SMC from rats with STZ-induced DM expressed 5 times as much famesyl transferase (FT) mRNA as SMC from controls. The FT inhibitor manumycin (UCFl-C, Kyowa Hakko Co. Ltd, Tokyo, Japan), which crosses cell membranes, inhibited SMC proliferation. Conclusion: Overexpression of FI in SMC from rats with STZ-induced DM may contribute to the augmented growth due to increased Ras function. Induction of genetic expression and plasma activity of plasminogen activator inhibitor type 1 @‘AI-l) by proinsulin and insulin in vivo &&_J& Sawa H, Fujii S, Sobel BE, Dept. of Cardiol., Univ. of
12321
Different risk factor profiles for carotid and femoral atherosclerosis in NIDDM &nishi T, Nishizawa Y, Kawagishi T, Maekawa K, Emoto M, Ishimura E, Inaba M, Okuno Y, Morii H, 2nd Dept. of btt. Med.,
Heidelberg, Bergheimer Str. 58, 69115 Heidelberg, Germany; Washington Univ., St. Louis. MO; Univ. of Vermont, Burlington, VT, USA
Osaka City Univ. Med. Sch., l-5-7, Asahimachi Abeno-ku, Osaka 545, Japan
Causes of accelerated atherogenesis in non-insulin-dependent diabetes mellitus (NIDDM), a condition associated with increased plasma concentrations of proinsulin (P) and insulin (I) as well as with increased plasma activity of plasminogen activator inhibitor type 1 (PAI-l), remain enigmatic. Previously, we have found that P and I induce PAI- in cells in vitro (Nordt et al Circulation 1994; 89: 321-30). The objective of this study was to determine whether P and I directly induce PAI- in vivo. To simulate the hyper(pro)insulinemia of NIDDM, conscious rabbits (n = 53) maintained euglycemic were given iv. infusions (1 h) of I (1 III/kg), P, C-peptide (both equimolar to I), or placebo (all endotoxin-free). Plasma PAI- activity did not change with placebo (n = 16) or with C-peptide (n = 4). However, with I (P) plasma PAI- activity increased, peaking in 3 h at 3.7-(3S)fold (n = 17 (n = 16). P < 0.002 each). The induction was attributable to PAI- protein, as shown by reverse fibrin autography, and specific, as shown by unchanged activities of a2-antiplasmin and t-PA (also suggesting reduced net tibrinolytic activitv). PAIgene. expressio~(PAI~1 mRNA) in response to N (P) in&eased in 3 h bv 2.1- (2.1-)fold in aorta, bv 2.4 (19-)fold in liver (P < 0.05 eachi but not in’heart, lung, spleen and kidney, returning to baseline in 24 h (n = 4 each). The genetic induction of PAI- in aorta was localized to the endothelium by in situ hybridization.
)230)
Non-insulin-dependent diabetes mellitus (NIDDM) is an important risk factor for peripheral atberial disease. But little is known about the risk factors for early femoral atherosclerosis in NIDDM. The aim of this study was to investigate the risk factors for femoral atherosclerosis and to compare the impact of the major coronary risk factors on e&y atherosclerosis in carotid and femoral arteries in patients with NIDDM. B-mode ultrasound imaging was conducted to determine noninvasively the mean maximal intima-media thickness (IMT) in the far wall of the common carotid (CA) and femoral (FA) arteries in 300 NIDDM patients and 161 age-matched control subjects without hyperlipidemia or hypertension. The results showed greater IMTs of both arteries in NIDDM patients than in subject (CA, 1.14 + 0.03 mm vs 0.71 rt0.2 mm, FA, 1.62 kO.06 mm vs 1.08 f 0.04 mm, mean f SE, P < 0.01). There was a significant but weak relationship between the carotid and femoral IMT in all subjects (R* = 0.162, P < 0.001). Multiple regression analysis showed that age, male sex and serum LDL-cholesterol were independent risk factors for carotid atherosclerosis in NIDDM patients (R*= 0.323, PcO.001). On the other hand, those for femoral
Atherosclerosis X, Montreal, October 1994