- Email: [email protected]
Impaired circadian blood pressure variation and plasma homocysteine in type 2 diabetes mellitus patients
Track 2. Clinical Research
P531 SerumPromnin Levels Determined by Newly Developed Direct Method in Diabetic Patients SHINYA MINAGAWA ‘, Shoji Kawazu ’ , Yasuo Imai ’ , Eiji Ohmura ’ , Masako Yazawa ’ , Atsuko Tsuchida ’ , Chika Ihara ’ , Fukashi Matsuzaki ’ , Hiroshi Tanakaz, Yuichi Ishidaz. ’ 1stDepartment ofInternal Medicine, Saitama Medical Centez Saitama Medical Shoal, Kawagoe, Saitama, Japan; 2 Tokiwa Chemical Industries Co.Ltd., Toshima-ku, Tokyo, Japan Purpose: F’rorenin, a precursor of renin, is thought to be produced not only in kidneys but also in a variety of organs including endothelial cells. It has been reported that large molecular inactive renin (so-called prorenin) increase in sera of diabetic patients, especially in the presence of microvascular complications such as nephropathy. However, there are no studies on the evaluation of circulating intact prorenin. In this study, we measured specifically serum prorenin by a newly developed assay method (Antibody-activating direct-prorenin [AAD-PR] assay method). Methods: Sera from diabetic patients and control subjects were frozen at -30” and assayed within two months. The 1st step of this assay is composed of specific activation of prorenin by anti-prorenin-profragmentpeptide (N-terminal) antibody fixed on microplates (Suzuki F et al: Biosci. Biotechnol. Biochem. 63550, 1999). The 2nd step is an ELISA of angiotensin 1 converted from recombinant-sheep-angiotensinogen as substrate. This method has a specific reactivity to intact human prorenin and has enough reproducibility. Results: In diabetic patients, the concentrations of AAD-PR were apparently higher than those of normal controls (p
P532 Impaired Circadian Blood Pressure Variation and Plasma Homocysteine in Type 2 Diabetes Mellitus Patients JOZEF DRZEWOSKI ‘, Leszek Czuprynisk’, Edward Bald*. ‘Department of Metabolic Diseases and Gastmentemlogy, Medical University of L.odz, Ladz, Poland: ‘Department Chemistry, University of Lod& L.odz, Poland
of Environmental
It has been recently suggested that high fasting plasma total homocysteine level(tHcy), an independent risk factor for atherosclerosis and cardiovascular disease, is related to arterial hypertension. The aim of our study was to assess fasting plasma homocysteine in type 2 diabetes patients with impaired circadian blood pressure (BP) variation (i.e. not manifesting nocturnal blood pressure fall by at least 10%). The study subjects were 24 well-controlled orally-treated normotensive normoalbuminuric type 2 diabetes patients (11 men, 13 women, mean age 64.6f4.7 yrs, body mass index 27.6f5.2 kg/m*, duration of diabetes 9.0f4.8 yrs, HbAi, 7.lf1.61) with impaired BP variation (‘non-dippers’). The control group consisted of 16 well-matched normotensive type 2 diabetes subjects (8 men, 8 women, mean age 64.3f6.2 yrs, body mass index 26.9f4.3 kg/m’, duration of diabetes 9.5f5.6 yrs, HbAt, 7.3f1.48) with normal BP rhythm. Day/night blood pressure variation was examined using ABP-Monitor Mobil-O-Graph (I.E.M., Stolberg, Germany). Recordings were made at 20-minute intervals during the day and 30-minute inter-
& Care
S129
vals during the night. Impaired circadian BP variation was defined as night-to-day blood pressure loss being less than 10% in systolic and/or diastolic pressure. Fasting plasma tHcy was assessed by high-performance liquid chromatography. Results: Type 2 diabetes subjects with disturbed BP rhythm had significantly higher - although still in the normal range (4-15 @mol/l) - plasma homocysteine concentrations than control subjects (table). In conclusion, well-controlled normotensive type 2 diabetes patients with impaired circadian BP variation have significantly higher fasting plasma total homocysteine concentrations than patients with normal BP profile.
P533 Zh-BG Is a Better Predictor for All Cause Mortality Than Either HbAlc or FPG QING QIAO’, Femmie de Vegt*, Giel Nijpels’, Francois Everhard3, Aulikki Nissinen4, Jaakko Tuomilehto’, Jacqueline M. Dekker*, Robert J. Heine’. ‘Diabetesand Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland; 2 The Hoom Study Research Group, Vrije Vniversiteit, Amsterdam, Netherlands; 3 Novartis Pharmo AG, Basel, Switzerland: 4 University of ffiopio, Kuopio, Finland
Background: Several publications have shown that 2h-blood glucose (2h-BG) is an independent risk factor for mortality and a better predictor than fasting plasma glucose (FPG). However, these analyses have not accounted for HbAlc. This analysis quantifies the relative contribution of Zh-BG, FIG and HbAlc to mortality. Study populations: 1276 women without known diabetes from the Hoom study and 1412 men from the Hoom and East and West Finland studies. Methods: Multivariate Cox-regression models were analysed for FIG, Zh-BG and HbAlc after adjustment for age, sex, study centm, smoking status, body mass index, systolic blood pressure and total cholesterol. Differences in log-likelihoods between regression models were assessed for the statistical significance of incremental information contributed by glucose variables alone and in combination. Relative risk (RR) estimates were compared on the basis of one unit increases in the respective parameters. Results: 256 deaths were observed in men and 98 deaths in women. Mortality increased with HbAlc, FPG and 2h-BG alone. The multivariate analyses showed, that the inclusion FPG and 2h-BG improved the prediction of HbAlc alone. Neither FPG (p=O.47) nor HbAlc (p&42) added statistically significant information once 2h-BG was included in the model. Conversely, the addition of Zh-BG to HbAlc (p=O.OOl) or FPG (p=O.O2) significant improved the prediction. In a model including all three variables simultaneously, the RR 95% CI for a 1% increase in HbAlc was 1.0484 (0.8719; 1.2605). for a 1 mmol/l increase in FPG was 1.0253 (.8887; 1.1829) and for a 1 mmol/l increase in Zh-BG was 1.0581 (1.009; 1.1100). Conclusion: 2h-BG is a better predictor for all-cause mortality than FPG or HbAlc.
P534 Role of Growth Hormone, IGF-1 and IGFBP3 System in Diabetic Micmangopathy ALY A. ABBASSY ‘, Soheir S. Kamel’, Aida S. Said*, Ahmed A. el masry 3, Gamal E. El basiony ’ . I Endocmology, Alexandria University, Alexandria, Egypt; 2 Clinicalpathology, Alexandria University, Alexandria, Egypt; 3 Ophalmology, Alexandria University, Alexandria, Egypt
Night-to-day systolic BP fall (W) Study group CO~tKdS Mean valuesfSD
5.6i3.5’ 15.5f6.1 x p
* p
“S controls
Night-to-day diastolic BP fall(S)
Mcy (cLmoW
2.6f1.6’ 11.5f6.1
11.9f3.93# 7.6zk3.2
It’s currently uncertain whether growth hormone (GH) and IGF-1 play a role in diabetic complications or not. The close relationship between glucose homeostasis and GH, IGF-1 and IGFBP3 system has encouraged us to study this system in type 1 and type 2 diabetic patients with microangiopathy. The study was carried out on 80 patients, 40 type1 (groupI)
P531 SerumPromnin Levels Determined by Newly Developed Direct Method in Diabetic Patients SHINYA MINAGAWA ‘, Shoji Kawazu ’ , Yasuo Imai ’ , Eiji Ohmura ’ , Masako Yazawa ’ , Atsuko Tsuchida ’ , Chika Ihara ’ , Fukashi Matsuzaki ’ , Hiroshi Tanakaz, Yuichi Ishidaz. ’ 1stDepartment ofInternal Medicine, Saitama Medical Centez Saitama Medical Shoal, Kawagoe, Saitama, Japan; 2 Tokiwa Chemical Industries Co.Ltd., Toshima-ku, Tokyo, Japan Purpose: F’rorenin, a precursor of renin, is thought to be produced not only in kidneys but also in a variety of organs including endothelial cells. It has been reported that large molecular inactive renin (so-called prorenin) increase in sera of diabetic patients, especially in the presence of microvascular complications such as nephropathy. However, there are no studies on the evaluation of circulating intact prorenin. In this study, we measured specifically serum prorenin by a newly developed assay method (Antibody-activating direct-prorenin [AAD-PR] assay method). Methods: Sera from diabetic patients and control subjects were frozen at -30” and assayed within two months. The 1st step of this assay is composed of specific activation of prorenin by anti-prorenin-profragmentpeptide (N-terminal) antibody fixed on microplates (Suzuki F et al: Biosci. Biotechnol. Biochem. 63550, 1999). The 2nd step is an ELISA of angiotensin 1 converted from recombinant-sheep-angiotensinogen as substrate. This method has a specific reactivity to intact human prorenin and has enough reproducibility. Results: In diabetic patients, the concentrations of AAD-PR were apparently higher than those of normal controls (p
P532 Impaired Circadian Blood Pressure Variation and Plasma Homocysteine in Type 2 Diabetes Mellitus Patients JOZEF DRZEWOSKI ‘, Leszek Czuprynisk’, Edward Bald*. ‘Department of Metabolic Diseases and Gastmentemlogy, Medical University of L.odz, Ladz, Poland: ‘Department Chemistry, University of Lod& L.odz, Poland
of Environmental
It has been recently suggested that high fasting plasma total homocysteine level(tHcy), an independent risk factor for atherosclerosis and cardiovascular disease, is related to arterial hypertension. The aim of our study was to assess fasting plasma homocysteine in type 2 diabetes patients with impaired circadian blood pressure (BP) variation (i.e. not manifesting nocturnal blood pressure fall by at least 10%). The study subjects were 24 well-controlled orally-treated normotensive normoalbuminuric type 2 diabetes patients (11 men, 13 women, mean age 64.6f4.7 yrs, body mass index 27.6f5.2 kg/m*, duration of diabetes 9.0f4.8 yrs, HbAi, 7.lf1.61) with impaired BP variation (‘non-dippers’). The control group consisted of 16 well-matched normotensive type 2 diabetes subjects (8 men, 8 women, mean age 64.3f6.2 yrs, body mass index 26.9f4.3 kg/m’, duration of diabetes 9.5f5.6 yrs, HbAt, 7.3f1.48) with normal BP rhythm. Day/night blood pressure variation was examined using ABP-Monitor Mobil-O-Graph (I.E.M., Stolberg, Germany). Recordings were made at 20-minute intervals during the day and 30-minute inter-
& Care
S129
vals during the night. Impaired circadian BP variation was defined as night-to-day blood pressure loss being less than 10% in systolic and/or diastolic pressure. Fasting plasma tHcy was assessed by high-performance liquid chromatography. Results: Type 2 diabetes subjects with disturbed BP rhythm had significantly higher - although still in the normal range (4-15 @mol/l) - plasma homocysteine concentrations than control subjects (table). In conclusion, well-controlled normotensive type 2 diabetes patients with impaired circadian BP variation have significantly higher fasting plasma total homocysteine concentrations than patients with normal BP profile.
P533 Zh-BG Is a Better Predictor for All Cause Mortality Than Either HbAlc or FPG QING QIAO’, Femmie de Vegt*, Giel Nijpels’, Francois Everhard3, Aulikki Nissinen4, Jaakko Tuomilehto’, Jacqueline M. Dekker*, Robert J. Heine’. ‘Diabetesand Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland; 2 The Hoom Study Research Group, Vrije Vniversiteit, Amsterdam, Netherlands; 3 Novartis Pharmo AG, Basel, Switzerland: 4 University of ffiopio, Kuopio, Finland
Background: Several publications have shown that 2h-blood glucose (2h-BG) is an independent risk factor for mortality and a better predictor than fasting plasma glucose (FPG). However, these analyses have not accounted for HbAlc. This analysis quantifies the relative contribution of Zh-BG, FIG and HbAlc to mortality. Study populations: 1276 women without known diabetes from the Hoom study and 1412 men from the Hoom and East and West Finland studies. Methods: Multivariate Cox-regression models were analysed for FIG, Zh-BG and HbAlc after adjustment for age, sex, study centm, smoking status, body mass index, systolic blood pressure and total cholesterol. Differences in log-likelihoods between regression models were assessed for the statistical significance of incremental information contributed by glucose variables alone and in combination. Relative risk (RR) estimates were compared on the basis of one unit increases in the respective parameters. Results: 256 deaths were observed in men and 98 deaths in women. Mortality increased with HbAlc, FPG and 2h-BG alone. The multivariate analyses showed, that the inclusion FPG and 2h-BG improved the prediction of HbAlc alone. Neither FPG (p=O.47) nor HbAlc (p&42) added statistically significant information once 2h-BG was included in the model. Conversely, the addition of Zh-BG to HbAlc (p=O.OOl) or FPG (p=O.O2) significant improved the prediction. In a model including all three variables simultaneously, the RR 95% CI for a 1% increase in HbAlc was 1.0484 (0.8719; 1.2605). for a 1 mmol/l increase in FPG was 1.0253 (.8887; 1.1829) and for a 1 mmol/l increase in Zh-BG was 1.0581 (1.009; 1.1100). Conclusion: 2h-BG is a better predictor for all-cause mortality than FPG or HbAlc.
P534 Role of Growth Hormone, IGF-1 and IGFBP3 System in Diabetic Micmangopathy ALY A. ABBASSY ‘, Soheir S. Kamel’, Aida S. Said*, Ahmed A. el masry 3, Gamal E. El basiony ’ . I Endocmology, Alexandria University, Alexandria, Egypt; 2 Clinicalpathology, Alexandria University, Alexandria, Egypt; 3 Ophalmology, Alexandria University, Alexandria, Egypt
Night-to-day systolic BP fall (W) Study group CO~tKdS Mean valuesfSD
5.6i3.5’ 15.5f6.1 x p
* p
“S controls
Night-to-day diastolic BP fall(S)
Mcy (cLmoW
2.6f1.6’ 11.5f6.1
11.9f3.93# 7.6zk3.2
It’s currently uncertain whether growth hormone (GH) and IGF-1 play a role in diabetic complications or not. The close relationship between glucose homeostasis and GH, IGF-1 and IGFBP3 system has encouraged us to study this system in type 1 and type 2 diabetic patients with microangiopathy. The study was carried out on 80 patients, 40 type1 (groupI)