- Email: [email protected]
Effect of atorvastatin on lipids and lipoproteins in diabetic nephropathy
Posters 2. Diabetes - clinical research
54
Electron beam CT coronary artery scanning identifies asymptomatic persons with increased coronary plaque mass, as well as increased likelihood of obstructive coronary disease and future cardiovascular events, and may be used to ascertain coronary disease risk in persons with varying degrees of the insulin resistance syndrome. Methods: Electron beam CT-derived coronary artery calcium scores, metabolic and anthropometric parameters, and fasting and stimulated concentrations of glucose and insulin were measured in 1160 asymptomatic men and women screened for a population-based clinical trial. Summary of Results: In univariate analyses, coronary artery calcium scores correlated positively with fasting and two hour glucose and insulin, and with Homeostasis Model Assessment-derived insulin resistance. Coronary calcium scores correlated positively with intra-abdominal adiposity, age, the ratio of total cholesterol to HDL cholesterol, LDL cholesterol, triglycerides and blood pressure and Homeostasis Model beta cell timction and inversely with HDL cholesterol and triceps skin fold thickness. Most of these correlations remained significant for subjects with fasting blood glucose below 126 mg/dl or below 110 mg/dl. In a stepwise multivariate analysis, intra-abdominal adiposity was remained an independent predictor of coronary artcry calcium scores, preceded by age, gender and a family history of premature CAD and followed by LDL and smoking. Blood pressure, concentrations of HDL, triglycerides, glucose and insulin, and homeostatic model assessment insulin resistance or beta cell function did not independently correlate with coronary artery calcium scores. Conclusions: In asymptomatic non-diabetic individuals, coronary calcium scores are correlated with insulin resistance and with markers of the insulin resistance syndrome, in particular central obesity. This association persists even in the presence of only impaired glucose tolerance or even with normal fasting blood glucose. However beta cell function is positively correlated with coronary calcium scores so that impaired insulin secretion is not likely to be a cause of premature atherosclerosis as indicated by increased coronary calcification.
m
LDL SUBFRACTIONS IN TYPE 2 DL4BETICS ON HEMODWYSIS: PRELIMINARY BASELINE DATA FROM A PROSPECTIVE STUDY INVESTIGATING ATORVASTATIN IN HIGH RISK PATIENTS
K. Winkler, I. Friedrich, G. Ruf, M.W. Baumstark, E. Ritz, W. Miirz, C. Wanner. For the 40 Investigators: Department of Medicine, Divisions of Nephrologv, Sports Medicine and Clinical Chemistry, University of Freiburg, Heidelberg and Wiirzburg, and Pfizer AG Karlsruhe, Germany Rationale: The ‘Die Deutsche Diabetes Dialyse Studie’ (4D study) is a prospective randomized placebo-controlled trial investigating the effect of the HMG-CoA reductase inhibitor atorvastatin on the rate of cardiovascular mortality and of nonfatal myocardial infarction in patients with type 2 diabetes. The trial will enroll 1200 women and men who have been on hemodialysis treatment for no more than two years in 150 centers throughout Germany. Recruitment is expected to be completed by the end of the year 2001. We here report on the clinical characteristics, lipid metabolism and the distribution of LDL-subfractions at baseline of 152 patients having no prior lipid-lowering medication. Study Population: The data of 70 women and 82 men were evaluated. The average age and BMI were 66.6 (f8.6) years and 27.6 (f4.8) kg/mz, respectively, and HbAlc was 6.7 (f1.3) %. Due to impaired renal function, there was an increased creatinine of 6.9 (-+2.2) mg/dI. Hemoglobin was reduced to 10.8 (f1.3) g/dl. Total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol were 203 (f43.5) mg/dl, 245.5 (f161, median: 207.5) mg/dl, 87.6 (~t25.3) mg/dl, and 35.5 (f9.5) mg/d, respectively.
25
apoB
20 . ,..
tmgldl l
’ p < 0.01; ** p c 0.001
MELLITUS
ACTIVITY IN TYPE II DIABETES COMPLICATED BY RETINOPATW
B. Mackness, PN. Durrington, MI. Mackness. Uniuersity Department of Medicine, Manchester Royal Injrma~,
OxfoordRoad, Manchester,
UK
Human serum paraoxonase 1 (PONl) is located on high density lipoprotein and has been implicated in the detoxification of organophosphates and possibly in the prevention of low density lipoprotein lipid peroxidation. PONl has two genetic polymorphisms both due to amino acid substition, one involving glutamine (Q genotype) and arginine (R genotype) at position 192 and the other leucine (L genotype) and methionine (M genotype) at position 55. We investigated the effect of these polymorphisms and a polymorphism of the PON2 at position 3 10 (C + S) on serum PONl activity and concentration, plasma lipids and lipoproteins and glycaemic control in 93 type II individuals with no complications of diabetes and 101 with retinopathy. Serum PONl activity in the type II population with no complications (164.1 mnol/mim/ml(8.0-467.8)) was significantly higher than in the group with retinopathy (113.4 nmol/mim/ml (3.0-414.6)) (P < O.OOl),but PONl concentration was not different between the groups. The gene frequencies of the PONl-55 and 192 polymorphisms and PON2-310 polymorphism were not different between the study populations. The PONl-55 and 192 polymorphisms affected PONl activity in the way previously described in control and type II diabetes populations. The PON2-310 polymorphism also significantly affected serum PONl. PONl activity was significantly higher in the PON2 CC genotype in both type II populations and PONl concentration was significantly higher in PON2 CC homozygotes with no complications. Neither the PONl-55 or 192 polymorphisms were correlated with the serum lipid or lipoprotein concentrations in either population. In the group with retinopathy (but not the group with no complications) all three paraoxonase polymorphisms were correlated with glycaemic control, which was worse in the PONl-55 genotypes in the order MM > LM > LL (P = 0.0032), in the PONl-192 genotypes RR > QR > QQ (P = 0.011) and in the PON2-310 polymorphism CC > CS > SS (P = 0.010). Low serum PONl activity in retinopathy may be related to an increased tendency to lipid peroxidation. Our findings thus raise the possibility that in retinopathy the PON2 gene may influence PONl and that an interrelationship between the PONl and PGN2 genes may influence glycaemic control in subjects with type II diabetes complicated by retinopathy.
I
,~:....~II, 10 ,”
IP29 LOW PARAOXONASE
l
. ...... ,,............................ ...... . .. ....... ..... .. .
***
.......w................ .,.. .,.,....... . . ........ 5 I.... I oi
+ V'I
L-l L.2
1 I
male: n=82 L-3
L-4
L-5
L-6
Density Methods & Results: The distribution of LDL subfractions was determined by equilibrium density gradient ultracentrifugation. There was a significant gender difference in the LDL subfraction distribution. Female patients showed significantly increased concentrations of buoyant LDL, whereas male patients had increased dense LDL, although this was not significant (figure). Patients were assigned to either a low or a high density LDL-distribution profile according to their mean LDL density, with the median serving as cut-off value (d = 1.0379 kg/L). There was a consistent, although not statistically significant tendency towards cardiovascular complications like myocardial infarction, PTCA or CABG in patients presenting with denser LDL particles.
IP31 EFFECT
OF ATORVASTATIN LIPOPROTEINS IN DIABETIC
ON LIPIDS AND NEPHROPATHY
N -9 Joss’ M.J. Cash&e*, G. Stew&, C.J. Deighan’, J.M. Boulton-Jones’, C.J. Packard2. ‘Renal Unit; 2Department of Pathological Biochemistry, Glasgow Royal Injrmary UK
Cardiovascular morbidity and mortality are high in patients with diabetic nephropathy with dyslipidaemia being a strong risk factor. We evaluated the effect of atorvastatin on lipids and lipoproteins in patients with type 2 diabetes and diabetic nephropathy. 25 patients (25% female, mean age 62f8 y) were treated with atorvastatin 10 mgday for 6 months. VLDL and LDL subfractions were measured by density gradient ultracentrifugation in fasting EDTA plasma. At baseline TC was 5.4 f 0.8 mmol/l, TG 2.3fl.O mmol/I and HDL l.OztO.2 mmol/l, 64% of patients had atherogenic levels of LDL III (>lOO mg/dl). There were no significant changes in glycaemic control, BMI and renal timction (assessed by creatinine clearance and albumimuia) during follow up. Atorvastatin reduced TC by 31%, LDL-C by 38%, VLDL-C by 24% and TG by 22% (all p < O.Ol), with no change in HDL-C. There were significant reductions
72nd EAS Congress
Posters 2. Diabetes - clinical research (32-38%) in the concentrations of VLDLt, VLDL2 and IDL and significant decreases in the ratio of cholesterol ester to TG. The total LDL lipoprotein concentration fell by 34% (p = 0.004), with a reduction in the concentration of each subfraction: LDL I 23 mgdl to 14 mgdl (p = 0.053), LDL II 137 mgdl to 96 mg!dl (p = 0.006) LDL III 123 mg/dl to 73 mgdl (p = 0.02). There was no change in the relative distribution of the LDL subfractions, however, following treatment, only 8 patients had an LDL III > 100 mg/dl. Atorvastatin, at low doses, is an effective lipid lowering agent in patients with diabetic nepbropathy. Reductions were seen in the concentrations of all the apoB containing lipoproteins with favourable alterations in the core composition of the particles. As a consequence, the number of subjects with atherogenic levels of LDL III was halved.
P32 El
DEPENDENCE OF PREVALENCE OF DYSLIPIDEMIA AMONG PATIENTS WITH DIABETES MELLITUS TYPE 2 AND HYPERTENSION ON BODY MASS INDEX
K.M. Yafasov, S.I. Ismailov, N.Z. Sirozhiddinova, N.V Dubyanskaya, Yu.V Dubyanskaya. Institute of Endocrinology, Tashkent, Uzbekistan Purpose: Study of dependence of prevalence of dyslipidemia among patients with diabetes mellitus (DM) type II and hypertension on body mass index (BMI). Subject and Methods: 50 patients (16 men and 34 women, x63.2 y) with DM type 2 and hypertension were examined. The diagnosis of hypertension was made according to WHO (World Health Organization) criteria 1999. BMI was determined as the ratio of body mass in kg to height in m2 (kg/m*). The diagnosis of weight as normal was made when BMI was 2&24.9 kg/m2 (10 patients); as overweight, 25-29.9 kg/m* (13 patients); obesity, 3639.9 kp/m2 (27 uatients). The level of total cholesterol (TC). trislvcerides (TG), h&h de-n& lipoprotein cholesterol @L-C) was deter&&d by enzymatic analysis. Low density lipoprotein cholesterol (LDL-C) was calculated by W.T. Friedewald formula: LDL-C = TC - HDL-C - TG/2.2. Dyslipidemia was determined according to American Diabetes Association criteria 1999. Groups were adjusted for sex and age. Result: The frequency of dyslipidemia is depends on BMI. Comparison obesity vs overweight is characterized hyper TG 0, < 0.001) and low HDL-C level (p < 0.05).
CtiWiZ3
Group 1, Bhfl=
Group 2,
Group
20-24.9kgid BMI=25-29.9kg/m2 Bhfl=
3, 30-39.9kg/m2
55
criteria
Group
1,
GmP
BMI = 2b24.9
k&n2
2,
Group 3,
BMI = 25-29.9
k&n2
BMI = 3s39.9
TG > 2.3 mm01
8.3%
27.1%
LDL-C
> 2.6 mmolil
66.6%
83.3%
96%
HDL-C
< 1.1 mmol/l
25%
66.6%
68%
58.3%
12.2%
88%
Hypertension
kp/m2
48%
Conclusion: The present study indicates that BMI significantly correlate with prevalence of dyslipidemias and arterial hypertension in patients with DM type 2. CHOLESTERYL ESTER IP34 INSULIN DOWNREGULATES TRANSFER PROTEIN (CETP) EXPRESSION IN CETP TRANSGENIC MICE J.A. Berti, A.C. Casquero, E.J. Bighetti, E.C. de Faria, A.C. Boschero, H.C.F. Oliveira. Dept. of Physiology and Biophysics; Dept. of Clinical
Pathology, State University of Campinns, 131X33-970,SP, Brazil CETP mediates cholestetyl ester (CE) and triglycerides (TG) redistribution among plasma lipoprotein fractions. Altered CETP expression may lead to increased risk of atherosclerosis. The present study aimed at investigating whether insulin regulates the expression of CETI? Insulin deficiency (streptozotocin-treatment) or hyperinsulinemia were induced in transgenic mice expressing a human CETP minigene flanked by its natural up (3.4 Kb) and downstream (2.2 Kb) sequences. Plasma CETP activity was determined by isotopic assays using endogenous (whole plasma) and exogenous substrates. Results are expressed as percent of 3H-cholesteryl ester (CE) transferred from HDL to apoB containing lipoproteins, meanfSEM n:
Control 4.5i1.3
a: p < 0.05 us control, SC injection.
GLUC:
STZ (7)
15.0*3.0
(7)E
22.Ozkl.O (9)
31.ozt2.0
(9)E
Control
GLUC
6.8zkl.O (8)
7.5il.3
21.6h2.6
37.0f3.0
(8)
ws (9) (10)
‘: p < 0.10 and c: p < 0.01 us GLW!.
14 days of 5% glucose
as drinking
solution,
+ GLUC
4.4io.9 21.3i1.7
(7)b (8)’
STZ: 7 days after streptozotocin INS:
14 days of daily imulii
SC
mjections.
2.3mmoL'l
30%
31%
LDL-C
> 2.6 mm&l
60%
92%
92%
HDL-c
Q 1.1 mmov1
30%
69%
78%
TG>
14%
Conclusion: Prevalence of dyslipidemia among patients with DM type 2 and hypertension increases when BMI increase; it reaches the highest expression in patients with obesity, i.e. BMI >= 30 kg/m2.
P33 El
Both, plasma triglycerides and free fatty acids levels were significantly increased in STZ and decreased in GLUC and INS + GLUC as compared to the control groups. Considering that exogenous assay is indicative of CETP mass while the endogenous represents the amount of CETP plus substrates, these results show that insulin deficiency increases plasma CETP activity and mass while hyperinsulinemia downregulates the glucose stimulated CETP expression, [p35_1 POSTPRANDIAL
BODY MASS INDEX AND CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH DIABETES MELLITUS TYPE 2
LIPAEMIA
IN DIABETICS
TYPE 2
Z. Jankovec, M. Jandova, Z. RuSav$, P. TeSinslj. Department of Medicine I, Charles University Hospital, Pilsen, Czech Republic
K.M. Yafasov, S.I. Ismailov, N.Z. Sirozhiddinova, N.V Dubyanskaya, Yu.V Dubyanskaya. Institute of Endocrinology, Tashkent, Uzbekistan Purpose: The present study aimed at analyzing the relationship between body mass index (BMI) and cardiovascular risk factors in patients with diabetes mellitus (DM) type 2. Subjects and Methods: We evaluated the BMI and assess serum lipids and blood pressure by 55 patients with DM II type: 27 men and 28 women, average age - 60 years. BMI was determined as the ratio of body mass in kg to height in m2 (kg/m2). The diagnosis of weight as normal was made when BMI was 20-24.9 kg/m2 (25 patients); as overweight, 25-29.9 kg/m2 (18 patients); obesity, 30-39.9 kg/m2 (25 patients). Dyslipidemia was determined-according to American Diabetes Association 1999, TG > 2.3 mmol/l, LDL-C 2 2.6 mmobl, HDL-C < 1.1 mmol/l. Groups were adjusted for sex and age. Summary of Re8Ult8:Obesity is characterized of increase of prevalence high level of TG, LDL-C (p < 0.001) and low level antiatherogenic HDL-C @ < 0.01).
Purpose of the Study: The aim was to compare levels of postprandial lipaemia during oral fat tolerance test (OFTT) in patients with diabetes mellitus type 2 in stage of macrovascular complications. The postprandial hyperlipaemia is generally interpreted as an important risk factor of atherosclerosis progression. Fasting levels of triglycerides concentrations (TG) are in course of day greatly variable and they are determined by a number of different impacts. The past studies demonstrated a close relationship of basal and postprandial TG. Diabetes mellitus type 2 is characterized by elevation of TG, small LDL, nonesterified fatty acids (NEFA), decrease of HDL concentration and postprandial hyperlipaemia. All these changes are closely linked with insulin resistance and multiple cardiovascular mortality in comparison with nondiabetics. Methods: For examination of postprandial lipaemia we used the OFTT with experimental breakfast (700 kcaFm2): fat 81%, carbohydrates 14%, proteins 5%. Venous blood samples for assessment of glycaemia and TG were taken at time 0, 2,4, 6 and 8 hours after the test breakfast. Summary of Results: We investigated 18 males (age 59.7hl2.03 years, body mass index 28.9h4.56 kg/m2) with evident atherosclerotic handicap
72nd EAS Congress
54
Electron beam CT coronary artery scanning identifies asymptomatic persons with increased coronary plaque mass, as well as increased likelihood of obstructive coronary disease and future cardiovascular events, and may be used to ascertain coronary disease risk in persons with varying degrees of the insulin resistance syndrome. Methods: Electron beam CT-derived coronary artery calcium scores, metabolic and anthropometric parameters, and fasting and stimulated concentrations of glucose and insulin were measured in 1160 asymptomatic men and women screened for a population-based clinical trial. Summary of Results: In univariate analyses, coronary artery calcium scores correlated positively with fasting and two hour glucose and insulin, and with Homeostasis Model Assessment-derived insulin resistance. Coronary calcium scores correlated positively with intra-abdominal adiposity, age, the ratio of total cholesterol to HDL cholesterol, LDL cholesterol, triglycerides and blood pressure and Homeostasis Model beta cell timction and inversely with HDL cholesterol and triceps skin fold thickness. Most of these correlations remained significant for subjects with fasting blood glucose below 126 mg/dl or below 110 mg/dl. In a stepwise multivariate analysis, intra-abdominal adiposity was remained an independent predictor of coronary artcry calcium scores, preceded by age, gender and a family history of premature CAD and followed by LDL and smoking. Blood pressure, concentrations of HDL, triglycerides, glucose and insulin, and homeostatic model assessment insulin resistance or beta cell function did not independently correlate with coronary artery calcium scores. Conclusions: In asymptomatic non-diabetic individuals, coronary calcium scores are correlated with insulin resistance and with markers of the insulin resistance syndrome, in particular central obesity. This association persists even in the presence of only impaired glucose tolerance or even with normal fasting blood glucose. However beta cell function is positively correlated with coronary calcium scores so that impaired insulin secretion is not likely to be a cause of premature atherosclerosis as indicated by increased coronary calcification.
m
LDL SUBFRACTIONS IN TYPE 2 DL4BETICS ON HEMODWYSIS: PRELIMINARY BASELINE DATA FROM A PROSPECTIVE STUDY INVESTIGATING ATORVASTATIN IN HIGH RISK PATIENTS
K. Winkler, I. Friedrich, G. Ruf, M.W. Baumstark, E. Ritz, W. Miirz, C. Wanner. For the 40 Investigators: Department of Medicine, Divisions of Nephrologv, Sports Medicine and Clinical Chemistry, University of Freiburg, Heidelberg and Wiirzburg, and Pfizer AG Karlsruhe, Germany Rationale: The ‘Die Deutsche Diabetes Dialyse Studie’ (4D study) is a prospective randomized placebo-controlled trial investigating the effect of the HMG-CoA reductase inhibitor atorvastatin on the rate of cardiovascular mortality and of nonfatal myocardial infarction in patients with type 2 diabetes. The trial will enroll 1200 women and men who have been on hemodialysis treatment for no more than two years in 150 centers throughout Germany. Recruitment is expected to be completed by the end of the year 2001. We here report on the clinical characteristics, lipid metabolism and the distribution of LDL-subfractions at baseline of 152 patients having no prior lipid-lowering medication. Study Population: The data of 70 women and 82 men were evaluated. The average age and BMI were 66.6 (f8.6) years and 27.6 (f4.8) kg/mz, respectively, and HbAlc was 6.7 (f1.3) %. Due to impaired renal function, there was an increased creatinine of 6.9 (-+2.2) mg/dI. Hemoglobin was reduced to 10.8 (f1.3) g/dl. Total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol were 203 (f43.5) mg/dl, 245.5 (f161, median: 207.5) mg/dl, 87.6 (~t25.3) mg/dl, and 35.5 (f9.5) mg/d, respectively.
25
apoB
20 . ,..
tmgldl l
’ p < 0.01; ** p c 0.001
MELLITUS
ACTIVITY IN TYPE II DIABETES COMPLICATED BY RETINOPATW
B. Mackness, PN. Durrington, MI. Mackness. Uniuersity Department of Medicine, Manchester Royal Injrma~,
OxfoordRoad, Manchester,
UK
Human serum paraoxonase 1 (PONl) is located on high density lipoprotein and has been implicated in the detoxification of organophosphates and possibly in the prevention of low density lipoprotein lipid peroxidation. PONl has two genetic polymorphisms both due to amino acid substition, one involving glutamine (Q genotype) and arginine (R genotype) at position 192 and the other leucine (L genotype) and methionine (M genotype) at position 55. We investigated the effect of these polymorphisms and a polymorphism of the PON2 at position 3 10 (C + S) on serum PONl activity and concentration, plasma lipids and lipoproteins and glycaemic control in 93 type II individuals with no complications of diabetes and 101 with retinopathy. Serum PONl activity in the type II population with no complications (164.1 mnol/mim/ml(8.0-467.8)) was significantly higher than in the group with retinopathy (113.4 nmol/mim/ml (3.0-414.6)) (P < O.OOl),but PONl concentration was not different between the groups. The gene frequencies of the PONl-55 and 192 polymorphisms and PON2-310 polymorphism were not different between the study populations. The PONl-55 and 192 polymorphisms affected PONl activity in the way previously described in control and type II diabetes populations. The PON2-310 polymorphism also significantly affected serum PONl. PONl activity was significantly higher in the PON2 CC genotype in both type II populations and PONl concentration was significantly higher in PON2 CC homozygotes with no complications. Neither the PONl-55 or 192 polymorphisms were correlated with the serum lipid or lipoprotein concentrations in either population. In the group with retinopathy (but not the group with no complications) all three paraoxonase polymorphisms were correlated with glycaemic control, which was worse in the PONl-55 genotypes in the order MM > LM > LL (P = 0.0032), in the PONl-192 genotypes RR > QR > QQ (P = 0.011) and in the PON2-310 polymorphism CC > CS > SS (P = 0.010). Low serum PONl activity in retinopathy may be related to an increased tendency to lipid peroxidation. Our findings thus raise the possibility that in retinopathy the PON2 gene may influence PONl and that an interrelationship between the PONl and PGN2 genes may influence glycaemic control in subjects with type II diabetes complicated by retinopathy.
I
,~:....~II, 10 ,”
IP29 LOW PARAOXONASE
l
. ...... ,,............................ ...... . .. ....... ..... .. .
***
.......w................ .,.. .,.,....... . . ........ 5 I.... I oi
+ V'I
L-l L.2
1 I
male: n=82 L-3
L-4
L-5
L-6
Density Methods & Results: The distribution of LDL subfractions was determined by equilibrium density gradient ultracentrifugation. There was a significant gender difference in the LDL subfraction distribution. Female patients showed significantly increased concentrations of buoyant LDL, whereas male patients had increased dense LDL, although this was not significant (figure). Patients were assigned to either a low or a high density LDL-distribution profile according to their mean LDL density, with the median serving as cut-off value (d = 1.0379 kg/L). There was a consistent, although not statistically significant tendency towards cardiovascular complications like myocardial infarction, PTCA or CABG in patients presenting with denser LDL particles.
IP31 EFFECT
OF ATORVASTATIN LIPOPROTEINS IN DIABETIC
ON LIPIDS AND NEPHROPATHY
N -9 Joss’ M.J. Cash&e*, G. Stew&, C.J. Deighan’, J.M. Boulton-Jones’, C.J. Packard2. ‘Renal Unit; 2Department of Pathological Biochemistry, Glasgow Royal Injrmary UK
Cardiovascular morbidity and mortality are high in patients with diabetic nephropathy with dyslipidaemia being a strong risk factor. We evaluated the effect of atorvastatin on lipids and lipoproteins in patients with type 2 diabetes and diabetic nephropathy. 25 patients (25% female, mean age 62f8 y) were treated with atorvastatin 10 mgday for 6 months. VLDL and LDL subfractions were measured by density gradient ultracentrifugation in fasting EDTA plasma. At baseline TC was 5.4 f 0.8 mmol/l, TG 2.3fl.O mmol/I and HDL l.OztO.2 mmol/l, 64% of patients had atherogenic levels of LDL III (>lOO mg/dl). There were no significant changes in glycaemic control, BMI and renal timction (assessed by creatinine clearance and albumimuia) during follow up. Atorvastatin reduced TC by 31%, LDL-C by 38%, VLDL-C by 24% and TG by 22% (all p < O.Ol), with no change in HDL-C. There were significant reductions
72nd EAS Congress
Posters 2. Diabetes - clinical research (32-38%) in the concentrations of VLDLt, VLDL2 and IDL and significant decreases in the ratio of cholesterol ester to TG. The total LDL lipoprotein concentration fell by 34% (p = 0.004), with a reduction in the concentration of each subfraction: LDL I 23 mgdl to 14 mgdl (p = 0.053), LDL II 137 mgdl to 96 mg!dl (p = 0.006) LDL III 123 mg/dl to 73 mgdl (p = 0.02). There was no change in the relative distribution of the LDL subfractions, however, following treatment, only 8 patients had an LDL III > 100 mg/dl. Atorvastatin, at low doses, is an effective lipid lowering agent in patients with diabetic nepbropathy. Reductions were seen in the concentrations of all the apoB containing lipoproteins with favourable alterations in the core composition of the particles. As a consequence, the number of subjects with atherogenic levels of LDL III was halved.
P32 El
DEPENDENCE OF PREVALENCE OF DYSLIPIDEMIA AMONG PATIENTS WITH DIABETES MELLITUS TYPE 2 AND HYPERTENSION ON BODY MASS INDEX
K.M. Yafasov, S.I. Ismailov, N.Z. Sirozhiddinova, N.V Dubyanskaya, Yu.V Dubyanskaya. Institute of Endocrinology, Tashkent, Uzbekistan Purpose: Study of dependence of prevalence of dyslipidemia among patients with diabetes mellitus (DM) type II and hypertension on body mass index (BMI). Subject and Methods: 50 patients (16 men and 34 women, x63.2 y) with DM type 2 and hypertension were examined. The diagnosis of hypertension was made according to WHO (World Health Organization) criteria 1999. BMI was determined as the ratio of body mass in kg to height in m2 (kg/m*). The diagnosis of weight as normal was made when BMI was 2&24.9 kg/m2 (10 patients); as overweight, 25-29.9 kg/m* (13 patients); obesity, 3639.9 kp/m2 (27 uatients). The level of total cholesterol (TC). trislvcerides (TG), h&h de-n& lipoprotein cholesterol @L-C) was deter&&d by enzymatic analysis. Low density lipoprotein cholesterol (LDL-C) was calculated by W.T. Friedewald formula: LDL-C = TC - HDL-C - TG/2.2. Dyslipidemia was determined according to American Diabetes Association criteria 1999. Groups were adjusted for sex and age. Result: The frequency of dyslipidemia is depends on BMI. Comparison obesity vs overweight is characterized hyper TG 0, < 0.001) and low HDL-C level (p < 0.05).
CtiWiZ3
Group 1, Bhfl=
Group 2,
Group
20-24.9kgid BMI=25-29.9kg/m2 Bhfl=
3, 30-39.9kg/m2
55
criteria
Group
1,
GmP
BMI = 2b24.9
k&n2
2,
Group 3,
BMI = 25-29.9
k&n2
BMI = 3s39.9
TG > 2.3 mm01
8.3%
27.1%
LDL-C
> 2.6 mmolil
66.6%
83.3%
96%
HDL-C
< 1.1 mmol/l
25%
66.6%
68%
58.3%
12.2%
88%
Hypertension
kp/m2
48%
Conclusion: The present study indicates that BMI significantly correlate with prevalence of dyslipidemias and arterial hypertension in patients with DM type 2. CHOLESTERYL ESTER IP34 INSULIN DOWNREGULATES TRANSFER PROTEIN (CETP) EXPRESSION IN CETP TRANSGENIC MICE J.A. Berti, A.C. Casquero, E.J. Bighetti, E.C. de Faria, A.C. Boschero, H.C.F. Oliveira. Dept. of Physiology and Biophysics; Dept. of Clinical
Pathology, State University of Campinns, 131X33-970,SP, Brazil CETP mediates cholestetyl ester (CE) and triglycerides (TG) redistribution among plasma lipoprotein fractions. Altered CETP expression may lead to increased risk of atherosclerosis. The present study aimed at investigating whether insulin regulates the expression of CETI? Insulin deficiency (streptozotocin-treatment) or hyperinsulinemia were induced in transgenic mice expressing a human CETP minigene flanked by its natural up (3.4 Kb) and downstream (2.2 Kb) sequences. Plasma CETP activity was determined by isotopic assays using endogenous (whole plasma) and exogenous substrates. Results are expressed as percent of 3H-cholesteryl ester (CE) transferred from HDL to apoB containing lipoproteins, meanfSEM n:
Control 4.5i1.3
a: p < 0.05 us control, SC injection.
GLUC:
STZ (7)
15.0*3.0
(7)E
22.Ozkl.O (9)
31.ozt2.0
(9)E
Control
GLUC
6.8zkl.O (8)
7.5il.3
21.6h2.6
37.0f3.0
(8)
ws (9) (10)
‘: p < 0.10 and c: p < 0.01 us GLW!.
14 days of 5% glucose
as drinking
solution,
+ GLUC
4.4io.9 21.3i1.7
(7)b (8)’
STZ: 7 days after streptozotocin INS:
14 days of daily imulii
SC
mjections.
2.3mmoL'l
30%
31%
LDL-C
> 2.6 mm&l
60%
92%
92%
HDL-c
Q 1.1 mmov1
30%
69%
78%
TG>
14%
Conclusion: Prevalence of dyslipidemia among patients with DM type 2 and hypertension increases when BMI increase; it reaches the highest expression in patients with obesity, i.e. BMI >= 30 kg/m2.
P33 El
Both, plasma triglycerides and free fatty acids levels were significantly increased in STZ and decreased in GLUC and INS + GLUC as compared to the control groups. Considering that exogenous assay is indicative of CETP mass while the endogenous represents the amount of CETP plus substrates, these results show that insulin deficiency increases plasma CETP activity and mass while hyperinsulinemia downregulates the glucose stimulated CETP expression, [p35_1 POSTPRANDIAL
BODY MASS INDEX AND CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH DIABETES MELLITUS TYPE 2
LIPAEMIA
IN DIABETICS
TYPE 2
Z. Jankovec, M. Jandova, Z. RuSav$, P. TeSinslj. Department of Medicine I, Charles University Hospital, Pilsen, Czech Republic
K.M. Yafasov, S.I. Ismailov, N.Z. Sirozhiddinova, N.V Dubyanskaya, Yu.V Dubyanskaya. Institute of Endocrinology, Tashkent, Uzbekistan Purpose: The present study aimed at analyzing the relationship between body mass index (BMI) and cardiovascular risk factors in patients with diabetes mellitus (DM) type 2. Subjects and Methods: We evaluated the BMI and assess serum lipids and blood pressure by 55 patients with DM II type: 27 men and 28 women, average age - 60 years. BMI was determined as the ratio of body mass in kg to height in m2 (kg/m2). The diagnosis of weight as normal was made when BMI was 20-24.9 kg/m2 (25 patients); as overweight, 25-29.9 kg/m2 (18 patients); obesity, 30-39.9 kg/m2 (25 patients). Dyslipidemia was determined-according to American Diabetes Association 1999, TG > 2.3 mmol/l, LDL-C 2 2.6 mmobl, HDL-C < 1.1 mmol/l. Groups were adjusted for sex and age. Summary of Re8Ult8:Obesity is characterized of increase of prevalence high level of TG, LDL-C (p < 0.001) and low level antiatherogenic HDL-C @ < 0.01).
Purpose of the Study: The aim was to compare levels of postprandial lipaemia during oral fat tolerance test (OFTT) in patients with diabetes mellitus type 2 in stage of macrovascular complications. The postprandial hyperlipaemia is generally interpreted as an important risk factor of atherosclerosis progression. Fasting levels of triglycerides concentrations (TG) are in course of day greatly variable and they are determined by a number of different impacts. The past studies demonstrated a close relationship of basal and postprandial TG. Diabetes mellitus type 2 is characterized by elevation of TG, small LDL, nonesterified fatty acids (NEFA), decrease of HDL concentration and postprandial hyperlipaemia. All these changes are closely linked with insulin resistance and multiple cardiovascular mortality in comparison with nondiabetics. Methods: For examination of postprandial lipaemia we used the OFTT with experimental breakfast (700 kcaFm2): fat 81%, carbohydrates 14%, proteins 5%. Venous blood samples for assessment of glycaemia and TG were taken at time 0, 2,4, 6 and 8 hours after the test breakfast. Summary of Results: We investigated 18 males (age 59.7hl2.03 years, body mass index 28.9h4.56 kg/m2) with evident atherosclerotic handicap
72nd EAS Congress