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Alterations of glomerular levels of glutathione peroxidase in diabetic nephropathy
Track 2. Clinical Research
patients with normoalbumimnia(NOR; ~19mg/gCr)(ptO.OOl).Moreover, 22% of patients with NOR had higher type 4 collagen levels than a normal value. U4C levels were positively correlated with UA levels in all the patients with and without nephropathy (t=O.695). On the other hand, U4C values of non-diabetic LC patients whose serum type 4 collagen levels were abnormally high remained almost normal. Diabetic retinopathy was frequently found in those with positive U4C even in patients without albuminutia, indicating the presence of subclinical nephropathy. Conclusion: U4C is a useful marker of early diabetic nephropathy, probably even in the presence or absence of albuminuria.
Prevalence of Symptomes of the Metabolic Syndrome in Kidney ‘Ikansplant Recipients LASZLO GERC) I, Katalin Wldes 2, Istv&n Bama ’ , Adam Remport2, Et-m&et Maklllry ’ , Jeno Jaray 2, Ferenc Perner ‘, Rudolf deChate1’ ’
CKI.
Change
Zst
Dept. Med., Semmelweis Univ., Budapest, Hungary; 2 TranspUSurge~, Semmelweis, Budapest, Hungary Organ transplant
recipients have a 5-7-fold increased risk of vascular mortality. We examined the prevalence of glucose intolerance, dyslipidemia and hypertension among patients 6-36 months after a successful kidney transplantation. All patients had normal graft-function and received steroid-cyclosporin immunosuppression at the time of investigation. Of 370 such patients 85 were known to have diabetes. In the other 285 “non-diabetic” patients (fasting glucose ~7.0 mmol/l) a 75 g oGT identified overt diabetes in 29 (10.2%), and impaired glucose tolerance in 80 (28.1%) patients. C-peptide was detectable in all diabetic patients with a mean value being significantly higher (pt0.01) than that of 24 healthy controls. Fasting cholesterol levels were >5.2 mmohl in 76% and triglycerid z 1.7 mmolil in 61% of examined patients. Lp(a) levels showed a non-linear distribution with values 225 mg/dl in 26% of patients. A blood pressure level > 130/80 Hgmm was found in 70% of the patients. 24-h blood pressure monitoring showed nocturnal hypertension with dicreased systolic/diastolic diurnal indices: 0.02/3% vs. 1l/15% of 40 control persons. The frequency of reversed diurnal indices (absolute nocturnal hypertension) was 43/37% among these patients, 212% among the controls and 14/S% in 40 patients with essential hypertension (p
P1066 Rosiglitazone Added Tolerated in Patients Renal Impairment ARVJND AGRAWAL ’ SmithKline Beecham
was little difference between the adverse-event profile for those with renal impairment and those without for patients treated with SU+RSG. Symptoms of hypoglycemia were reported in 4.8% of patients with renal impairment (vs. 5.4% on SU+RSG normal renal function vs. 5.9% on SU alone), anemia in 2.8%. and edema in 2.8%. The cases of anemia or edema were not considered serious and did not lead to withdrawal from therapy.
N Baseline
Pm65
to a Sulphonylurea: Effective and Well with Qpe 2 Diabetes and Mild to Moderate ‘, Nigel P. Jones ‘, Maureen C. Sautter’.
Pharmaceuticals, ’ SmithKline Beecham Pharmaceuticals, of America
Ha&w, United Kingdom: Collegeville, PA, United States
Purpose: Patients with type 2 diabetes (T2D) who are inadequately controlled on a sulphonylurea (SU) and have renal impairment which precludes the addition of metformin have limited oral antidiabetic treatment alternatives. The efficacy of rosiglitazone (RSG), an insulin sensitizer and PPARy agonist, was evaluated in T2D patients with mild to moderate renal impairment taking high doses of SU using data from 3 studies. Methods: Data from the 3 double-blind studies of RSG added to a SU (glibenclamide, gliclazide, or glipizide) were pooled. Of the 803 patients receiving SU+RSG 4 mg or SU alone, 289 had mild to moderate renal impairment at baseline (creatinine clearance [Cr.Cl.] 30-SOml/min) and evaluable fasting plasma glucose (FPG); 5 14 had normal renal function. Results: RSG improved glycemia to a clinically important extent in patients with renal impairment and in those without (see Table). There
s257
& Care
>80
mumin
Cr.Cl. 30.80 mhin
su done
SUcRSG 4mg
SU
259
255
147
SU+RSG 4mg 142
11.9 * 0.2 +1.0 zk 0.2
12.1 f0.2 -1.6 i 0.2
11.5 zto.2 +0.5 It 0.2
11.2 f0.2 -2.1 f 0.2
Conelusions: Rosiglitazone is effective and well tolerated when added to patients with mild to moderate renal impairment who are inadequately controlled by SU monotherapy, offering a safe alternative to metformin.
Pm67 Alterations of Glomerular Levels of Glutathione Peroxidase in Diabetic Nephropathy HUNG-CHUN CHEN, Jinn-Yuh Guh, Shyi-Jang Shin, Yung-Hsiung Lai. Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Province of China
Glutathione peroxidase (GPX) is an important antioxidant which effectively scavenges hydrogen peroxide. Recent studies have revealed that plasma GPX activity is decreased in patients with chronic renal failure. However, there have been no reports on the GPX status in diabetic patients. Therefore, in this study we have measured the plasma and urinary GPX levels in patients with diabetic glomerulosclerosis (DGS), and measured the glomerular GPX immunostainingin patients and rats with diabetes, using the immunohistochemical method. The results showed that the plasma GPX level was significantly lower in DGS patients than in either diabetic patients without nephropathy (~~0.05) or normal controls (p
P1068 Diabetic Nephropathy Is Associated with the Z-2 Microsatellite Allele of the Aldose Reductase Gene in Chinese Subjects with ‘Qpe 2 Diabetes Y.F. LJU, N.M.S. Wat, S.S.M. Chung,K.S.L. Lam. Dept. ofMedicine; Institute of Molecular Biology, University of Hong Kong, Hong Kong, China The (A-Q dinucleotide repeat sequence upstream of the aldose reductase gene (5’~ALR2) has been shown to modulate its expression and the development of nephropathy in Caucasians with Type I diabetes. This study explores the hypothesis that this polymorphic sequence is also associated with diabetic nephropathy in Southern Chinese with Type 2 diabetes. In 265 unrelated Southern Chinese with Type 2 diabetes the 5’-ALR2 polymorphism was identified in genomic DNA using polymerase chain reaction with me sense primer being labelled with a fluorescent dye at the 5’-end. These subjects were classified as normoalbuminuric (n =128),
patients with normoalbumimnia(NOR; ~19mg/gCr)(ptO.OOl).Moreover, 22% of patients with NOR had higher type 4 collagen levels than a normal value. U4C levels were positively correlated with UA levels in all the patients with and without nephropathy (t=O.695). On the other hand, U4C values of non-diabetic LC patients whose serum type 4 collagen levels were abnormally high remained almost normal. Diabetic retinopathy was frequently found in those with positive U4C even in patients without albuminutia, indicating the presence of subclinical nephropathy. Conclusion: U4C is a useful marker of early diabetic nephropathy, probably even in the presence or absence of albuminuria.
Prevalence of Symptomes of the Metabolic Syndrome in Kidney ‘Ikansplant Recipients LASZLO GERC) I, Katalin Wldes 2, Istv&n Bama ’ , Adam Remport2, Et-m&et Maklllry ’ , Jeno Jaray 2, Ferenc Perner ‘, Rudolf deChate1’ ’
CKI.
Change
Zst
Dept. Med., Semmelweis Univ., Budapest, Hungary; 2 TranspUSurge~, Semmelweis, Budapest, Hungary Organ transplant
recipients have a 5-7-fold increased risk of vascular mortality. We examined the prevalence of glucose intolerance, dyslipidemia and hypertension among patients 6-36 months after a successful kidney transplantation. All patients had normal graft-function and received steroid-cyclosporin immunosuppression at the time of investigation. Of 370 such patients 85 were known to have diabetes. In the other 285 “non-diabetic” patients (fasting glucose ~7.0 mmol/l) a 75 g oGT identified overt diabetes in 29 (10.2%), and impaired glucose tolerance in 80 (28.1%) patients. C-peptide was detectable in all diabetic patients with a mean value being significantly higher (pt0.01) than that of 24 healthy controls. Fasting cholesterol levels were >5.2 mmohl in 76% and triglycerid z 1.7 mmolil in 61% of examined patients. Lp(a) levels showed a non-linear distribution with values 225 mg/dl in 26% of patients. A blood pressure level > 130/80 Hgmm was found in 70% of the patients. 24-h blood pressure monitoring showed nocturnal hypertension with dicreased systolic/diastolic diurnal indices: 0.02/3% vs. 1l/15% of 40 control persons. The frequency of reversed diurnal indices (absolute nocturnal hypertension) was 43/37% among these patients, 212% among the controls and 14/S% in 40 patients with essential hypertension (p
P1066 Rosiglitazone Added Tolerated in Patients Renal Impairment ARVJND AGRAWAL ’ SmithKline Beecham
was little difference between the adverse-event profile for those with renal impairment and those without for patients treated with SU+RSG. Symptoms of hypoglycemia were reported in 4.8% of patients with renal impairment (vs. 5.4% on SU+RSG normal renal function vs. 5.9% on SU alone), anemia in 2.8%. and edema in 2.8%. The cases of anemia or edema were not considered serious and did not lead to withdrawal from therapy.
N Baseline
Pm65
to a Sulphonylurea: Effective and Well with Qpe 2 Diabetes and Mild to Moderate ‘, Nigel P. Jones ‘, Maureen C. Sautter’.
Pharmaceuticals, ’ SmithKline Beecham Pharmaceuticals, of America
Ha&w, United Kingdom: Collegeville, PA, United States
Purpose: Patients with type 2 diabetes (T2D) who are inadequately controlled on a sulphonylurea (SU) and have renal impairment which precludes the addition of metformin have limited oral antidiabetic treatment alternatives. The efficacy of rosiglitazone (RSG), an insulin sensitizer and PPARy agonist, was evaluated in T2D patients with mild to moderate renal impairment taking high doses of SU using data from 3 studies. Methods: Data from the 3 double-blind studies of RSG added to a SU (glibenclamide, gliclazide, or glipizide) were pooled. Of the 803 patients receiving SU+RSG 4 mg or SU alone, 289 had mild to moderate renal impairment at baseline (creatinine clearance [Cr.Cl.] 30-SOml/min) and evaluable fasting plasma glucose (FPG); 5 14 had normal renal function. Results: RSG improved glycemia to a clinically important extent in patients with renal impairment and in those without (see Table). There
s257
& Care
>80
mumin
Cr.Cl. 30.80 mhin
su done
SUcRSG 4mg
SU
259
255
147
SU+RSG 4mg 142
11.9 * 0.2 +1.0 zk 0.2
12.1 f0.2 -1.6 i 0.2
11.5 zto.2 +0.5 It 0.2
11.2 f0.2 -2.1 f 0.2
Conelusions: Rosiglitazone is effective and well tolerated when added to patients with mild to moderate renal impairment who are inadequately controlled by SU monotherapy, offering a safe alternative to metformin.
Pm67 Alterations of Glomerular Levels of Glutathione Peroxidase in Diabetic Nephropathy HUNG-CHUN CHEN, Jinn-Yuh Guh, Shyi-Jang Shin, Yung-Hsiung Lai. Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Province of China
Glutathione peroxidase (GPX) is an important antioxidant which effectively scavenges hydrogen peroxide. Recent studies have revealed that plasma GPX activity is decreased in patients with chronic renal failure. However, there have been no reports on the GPX status in diabetic patients. Therefore, in this study we have measured the plasma and urinary GPX levels in patients with diabetic glomerulosclerosis (DGS), and measured the glomerular GPX immunostainingin patients and rats with diabetes, using the immunohistochemical method. The results showed that the plasma GPX level was significantly lower in DGS patients than in either diabetic patients without nephropathy (~~0.05) or normal controls (p
P1068 Diabetic Nephropathy Is Associated with the Z-2 Microsatellite Allele of the Aldose Reductase Gene in Chinese Subjects with ‘Qpe 2 Diabetes Y.F. LJU, N.M.S. Wat, S.S.M. Chung,K.S.L. Lam. Dept. ofMedicine; Institute of Molecular Biology, University of Hong Kong, Hong Kong, China The (A-Q dinucleotide repeat sequence upstream of the aldose reductase gene (5’~ALR2) has been shown to modulate its expression and the development of nephropathy in Caucasians with Type I diabetes. This study explores the hypothesis that this polymorphic sequence is also associated with diabetic nephropathy in Southern Chinese with Type 2 diabetes. In 265 unrelated Southern Chinese with Type 2 diabetes the 5’-ALR2 polymorphism was identified in genomic DNA using polymerase chain reaction with me sense primer being labelled with a fluorescent dye at the 5’-end. These subjects were classified as normoalbuminuric (n =128),