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Hikaru Koide - One of the best experts on this subject based on the ideXlab platform.
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Effect of troglitazone on urinary albumin excretion and serum type IV collagen concentrations in Type 2 diabetic patients with Microalbuminuria or macroalbuminuria.
Diabetic Medicine, 2001Co-Authors: T. Nakamura, Chifuyu Ushiyama, Shigenobu Suzuki, N. Shimada, K. Sekizuka, L. Ebihara, Hikaru KoideAbstract:Summary Aims Troglitazone, a newly developed thiazolidinedione derivative, has been shown to ameliorate Microalbuminuria in diabetic animal model and in human diabetic nephropathy in short-term studies. The aim of the present study was to determine whether troglitazone or sulphonylurea affect micro- albuminuria, macroalbuminuria, or serum type IV collagen concentrations in patients with diabetic nephropathy. Methods We studied 32 normotensive patients with type 2 diabetes mellitus associated with Microalbuminuria (n = 16) or macroalbuminuria (n = 16) and 20 healthy controls. The patients were randomly assigned to one of two groups: those treated with glibenclamide (5.0 mg/day) (n = 8) and those treated with troglitazone (400 mg/day) (n = 8). They received the drug regimen for 12 months. Serum type IV collagen was measured with sandwich enzyme immunoassay. Results Type IV collagen concentrations in macroalbuminuric patients were higher than those in microalbuminuric patients (P
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effect of troglitazone on urinary albumin excretion and serum type iv collagen concentrations in type 2 diabetic patients with Microalbuminuria or macroalbuminuria
Diabetic Medicine, 2001Co-Authors: T. Nakamura, Chifuyu Ushiyama, Shigenobu Suzuki, N. Shimada, K. Sekizuka, L. Ebihara, Hikaru KoideAbstract:Summary Aims Troglitazone, a newly developed thiazolidinedione derivative, has been shown to ameliorate Microalbuminuria in diabetic animal model and in human diabetic nephropathy in short-term studies. The aim of the present study was to determine whether troglitazone or sulphonylurea affect micro- albuminuria, macroalbuminuria, or serum type IV collagen concentrations in patients with diabetic nephropathy. Methods We studied 32 normotensive patients with type 2 diabetes mellitus associated with Microalbuminuria (n = 16) or macroalbuminuria (n = 16) and 20 healthy controls. The patients were randomly assigned to one of two groups: those treated with glibenclamide (5.0 mg/day) (n = 8) and those treated with troglitazone (400 mg/day) (n = 8). They received the drug regimen for 12 months. Serum type IV collagen was measured with sandwich enzyme immunoassay. Results Type IV collagen concentrations in macroalbuminuric patients were higher than those in microalbuminuric patients (P < 0.05) and healthy controls (P < 0.01). Troglitazone reduced urinary albumin excretion (UAE) in micro- albuminuric patients from 126 μg/min (range 58–180 μg/min) to 42 μg/min (range 14–80 μg/min) (P < 0.01) and also reduced serum type IV collagen levels gradually at 3, 6 and 12 months after treatment (P < 0.05). However, glibenclamide did not affect UAE and type IV collagen levels in micro- albuminuric diabetes patients. In addition, neither troglitazone nor gliben- clamide changed UAE and type IV collagen levels in macroalbuminuric patients. Conclusions These data suggest that troglitazone is an effective treatment for renal injury in patients with early diabetic nephropathy.
Peter Rossing - One of the best experts on this subject based on the ideXlab platform.
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Microalbuminuria a parameter that has changed diabetes care
Diabetes Research and Clinical Practice, 2015Co-Authors: Peter Rossing, Hans-henrik Parving, Frederik PerssonAbstract:Diabetic nephropathy is characterised by persistent albuminuria, elevated blood pressure, relentless decline in GFR and enhanced fatal and nonfatal cardiovascular diseases. Microalbuminuria has been central to the development of clinical practise in prevention and treatment of diabetic nephropathy and cardiovascular disease. Treatment-induced and spontaneous remission of Microalbuminuria has been reported both in type 1 and type 2 diabetic patients, underlining the importance of sustained elevation of urinary albumin excretion. Recently many new biomarkers have been evaluated in diabetic patients, and apart from urinary proteomics, none has yet outperformed Harry Keen's discovery of Microalbuminuria as the best screening tool for diabetic nephropathy. Remission of Microalbuminuria preserves renal function. Microalbuminuria has also stood the test of time as a valid powerful independent predictor for fatal and nonfatal cardiovascular outcome in diabetes. Improved glycaemic control, blood pressure reduction, RAS blockade and multifactorial treatment of cardiovascular risk factors reduce the risk of development of micro-and macroalbuminuria, declining renal function and cardiovascular events.
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Serum amyloid A and C-reactive protein levels may predict Microalbuminuria and macroalbuminuria in newly diagnosed type 1 diabetic patients
Journal of Diabetes and Its Complications, 2012Co-Authors: Anne Julie Overgaard, Peter Rossing, Hans-henrik Parving, Peter Hovind, James N. Mcguire, Flemming PociotAbstract:Abstract Background In this study we evaluated the association of baseline levels of six different candidate proteins for the development of Microalbuminuria and macroalbuminuria in type 1 diabetic patients, who were followed for approximately 30 years. Two of the proteins are markers of inflammation: serum amyloid A (SAA) and C-reactive protein (CRP), three are involved in lipid metabolism: apolipoprotein A1, apolipoprotein E and adiponectin and the last protein, fibronectin, is related to structural changes. Methods A nested case control study population of 60 patients from an inception cohort of type 1 diabetic patients where 20 developed Microalbuminuria followed by macroalbuminuria and 40 stayed normoalbuminuric during approximately 30 years of follow-up time was used to evaluate baseline levels of the six candidate biomarkers. The proteins were quantified by multiplexed immunoassays. Results Log SAA levels were borderline predictor of Microalbuminuria, HR 2.31 (1–5.4) p = 0.053 in a univariate Cox regression model and predicted the development of macroalbuminuria HR 2.432 (1–6) p = 0.049, also univariate. When adjusting for covariates, log SAA predicted the development of Microalbuminuria with an HR 4.131 (1.1–15) p = 0.03. Log CRP predicted the development of Microalbuminuria, HR 2.928 (1.4–6.1) p = 0.004, and macroalbuminuria, HR 2.785 (1.3–5.8) p = 0.007 in univariate models. When adjusting for covariates, log CRP predicted the development of Microalbuminuria with an HR 5.882 (1.7–20.9) p = 0.006 and macroalbuminuria with an HR 3.233 (1.1–9.8) p = 0.038. Apolipoprotein A1, apolipoprotein E, fibronectin and adiponectin were not associated with development of elevated albumin excretion rate. Conclusions SAA and CRP baseline levels predicted development of micro- and macroalbuminuria during 30 years of follow up, supporting the theory that inflammation is involved in the progression of diabetic nephropathy. Further studies are needed to fully establish the two proteins’ potential as additional biomarkers for the development of diabetic nephropathy.
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Urinary Liver-Type Fatty Acid-Binding Protein Predicts Progression to Nephropathy in Type 1 Diabetic Patients
Diabetes Care, 2010Co-Authors: Stine E. Nielsen, Hans-henrik Parving, Peter Hovind, Takeshi Sugaya, Tsuneharu Baba, Peter RossingAbstract:OBJECTIVE Urinary liver-type fatty acid-binding protein (u-LFABP) is a marker of tubulointerstitial inflammation and has been shown to be increased in patients with type 1 diabetes and is further increased in patients who progress to micro- and macroalbuminuria. Our aim was to evaluate u-LFABP as a predictor of progression to micro- and macroalbuminuria in type 1 diabetes. RESEARCH DESIGN AND METHODS From an inception cohort of 277 patients, u-LFABP, adjusted for urinary creatinine (enzyme-linked immunosorbent assay), was measured in 24-h urine samples from 165 normoalbuminuric patients 9.6 ± 3.5 (mean ±SD) years after onset of type 1 diabetes. The outcome measured was development of persistent micro- or macroalbuminuria or death. RESULTS Patients were followed for a median of 18 (range 1–19) years; 39 progressed to Microalbuminuria, 8 of those progressed further to macroalbuminuria, and 24 died. In a Cox regression model, baseline log u-LFABP levels predicted the development of Microalbuminuria, adjusted for known risk factors (sex, age, A1C, systolic and diastolic blood pressure, albumin excretion rate, serum creatinine, and smoking) (hazard ratio [HR] 2.3 [95% CI 1.1–4.6]) and log u-LFABP predicted mortality (adjusted HR 3.0 [1.3–7.0]). u-LFABP (above versus below the median) predicted the development of macroalbuminuria (adjusted HR 2.6 [1.2–5.4]). As a continuous variable, u-LFABP tended to predict macroalbuminuria (HR 1.9, P = 0.2), but numbers were small. CONCLUSIONS High levels of the tubular inflammation marker u-LFABP predict the initiation and progression to diabetic nephropathy and all-cause mortality, independent of urinary albumin excretion rate and other established risk factors.
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Predictors for the development of Microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study.
BMJ, 2004Co-Authors: Peter Hovind, Peter Rossing, Lise Tarnow, Berit R. Jensen, Malene Graae, Inge Torp, C. Binder, Hans-henrik ParvingAbstract:Abstract Objective To evaluate baseline predictors for the development of persistent Microalbuminuria and macroalbuminuria prospectively in patients with type 1 diabetes. Design Prospective observational study of an inception cohort. Setting Outpatient diabetic clinic in a tertiary referral centre, Gentofte, Denmark. Participants 286 patients (216 adults) newly diagnosed with type 1 diabetes consecutively admitted to the clinic between 1 September 1979 and 31 August 1984. Main outcome measures Persistent Microalbuminuria and persistent macroalbuminuria. Results During the median follow up of 18.0 years (range 1.0-21.5 years), total of 4706 patient years of follow up, 79 of 277 (29%) patients developed persistent Microalbuminuria. 27 of 79 progressed further to persistent macroalbuminuria. The cumulative incidence of persistent Microalbuminuria and persistent macroalbuminuria was 33.6% (95% confidence interval 27.2% to 40.0%) and 14.6% (8.9% to 20.3%), respectively. Significant predictors for the development of persistent Microalbuminuria were a 10-fold increase in urinary albumin excretion rate (relative risk 3.78, 1.57 to 9.13), being male (2.41, 1.43 to 4.06), a 10 mm Hg increase in mean arterial blood pressure (1.38, 1.20 to 1.57), a 1% increase in haemoglobin A 1c (1.18, 1.04 to 1.32), and a 1 cm increase in height (0.96, 0.95 to 0.98). 28 patients with Microalbuminuria (35%) regressed to normoalbuminuria either transiently (n = 15) or permanently (n = 13). Conclusions Around one third of patients newly diagnosed with type 1 diabetes develop persistent Microalbuminuria within the first 20 years of diabetes. Several potentially modifiable risk factors predict the development of persistent microalbuminaria and persistent macroalbuminuria.
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Risk factors for development of incipient and overt diabetic nephropathy in type 1 diabetic patients: a 10-year prospective observational study.
Diabetes Care, 2002Co-Authors: Peter Rossing, Philip Hougaard, Hans-henrik ParvingAbstract:OBJECTIVE—To evaluate prospectively putative risk factors for development of Microalbuminuria and macroalbuminuria in type 1 diabetes. RESEARCH DESIGN AND METHODS—Prospective observational study of a cohort of type 1 diabetic patients followed in the outpatient clinic at Steno Diabetes Center for ≤10 years (median 9 years). We followed 537 patients aged ≥18 years with type 1 diabetes, with duration of diabetes ≥5 years, with normoalbuminuria (urinary albumin excretion rate ≤30 mg/24 h), and who were not taking antihypertensive medication. Risk factors for development of Microalbuminuria and macroalbuminuria were evaluated. RESULTS—The mean progression of urinary albumin excretion rate was 7.6% (SE 0.8) per year. During follow-up, 134 patients (25%) progressed to persistent Microalbuminuria or macroalbuminuria (>30 mg/24 h in two of three consecutive urine samples). Cox multiple regression analysis using baseline values of putative predictors of progression showed the following significant predictors of progression from normoalbuminuria to Microalbuminuria or macroalbuminuria: baseline log urinary albumin excretion rate 2.63 (relative risk; 95% CI 1.65–4.19), HbA1c 1.13% (1.04–1.23), presence of any retinopathy 1.90 (1.26–2.88), and smoking 1.61 (1.11–2.33). Sex, duration of diabetes, arterial blood pressure, serum creatinine, height, and social class were not risk factors. CONCLUSIONS—Our study suggests that several potentially modifiable risk factors predict the development of Microalbuminuria and macroalbuminuria in type 1 diabetic patients.
T. Nakamura - One of the best experts on this subject based on the ideXlab platform.
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Effect of troglitazone on urinary albumin excretion and serum type IV collagen concentrations in Type 2 diabetic patients with Microalbuminuria or macroalbuminuria.
Diabetic Medicine, 2001Co-Authors: T. Nakamura, Chifuyu Ushiyama, Shigenobu Suzuki, N. Shimada, K. Sekizuka, L. Ebihara, Hikaru KoideAbstract:Summary Aims Troglitazone, a newly developed thiazolidinedione derivative, has been shown to ameliorate Microalbuminuria in diabetic animal model and in human diabetic nephropathy in short-term studies. The aim of the present study was to determine whether troglitazone or sulphonylurea affect micro- albuminuria, macroalbuminuria, or serum type IV collagen concentrations in patients with diabetic nephropathy. Methods We studied 32 normotensive patients with type 2 diabetes mellitus associated with Microalbuminuria (n = 16) or macroalbuminuria (n = 16) and 20 healthy controls. The patients were randomly assigned to one of two groups: those treated with glibenclamide (5.0 mg/day) (n = 8) and those treated with troglitazone (400 mg/day) (n = 8). They received the drug regimen for 12 months. Serum type IV collagen was measured with sandwich enzyme immunoassay. Results Type IV collagen concentrations in macroalbuminuric patients were higher than those in microalbuminuric patients (P
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effect of troglitazone on urinary albumin excretion and serum type iv collagen concentrations in type 2 diabetic patients with Microalbuminuria or macroalbuminuria
Diabetic Medicine, 2001Co-Authors: T. Nakamura, Chifuyu Ushiyama, Shigenobu Suzuki, N. Shimada, K. Sekizuka, L. Ebihara, Hikaru KoideAbstract:Summary Aims Troglitazone, a newly developed thiazolidinedione derivative, has been shown to ameliorate Microalbuminuria in diabetic animal model and in human diabetic nephropathy in short-term studies. The aim of the present study was to determine whether troglitazone or sulphonylurea affect micro- albuminuria, macroalbuminuria, or serum type IV collagen concentrations in patients with diabetic nephropathy. Methods We studied 32 normotensive patients with type 2 diabetes mellitus associated with Microalbuminuria (n = 16) or macroalbuminuria (n = 16) and 20 healthy controls. The patients were randomly assigned to one of two groups: those treated with glibenclamide (5.0 mg/day) (n = 8) and those treated with troglitazone (400 mg/day) (n = 8). They received the drug regimen for 12 months. Serum type IV collagen was measured with sandwich enzyme immunoassay. Results Type IV collagen concentrations in macroalbuminuric patients were higher than those in microalbuminuric patients (P < 0.05) and healthy controls (P < 0.01). Troglitazone reduced urinary albumin excretion (UAE) in micro- albuminuric patients from 126 μg/min (range 58–180 μg/min) to 42 μg/min (range 14–80 μg/min) (P < 0.01) and also reduced serum type IV collagen levels gradually at 3, 6 and 12 months after treatment (P < 0.05). However, glibenclamide did not affect UAE and type IV collagen levels in micro- albuminuric diabetes patients. In addition, neither troglitazone nor gliben- clamide changed UAE and type IV collagen levels in macroalbuminuric patients. Conclusions These data suggest that troglitazone is an effective treatment for renal injury in patients with early diabetic nephropathy.
G. Pagano - One of the best experts on this subject based on the ideXlab platform.
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apolipoprotein h is increased in type 2 diabetic patients with Microalbuminuria
Nutrition Metabolism and Cardiovascular Diseases, 2000Co-Authors: Paolo Cavallo Perin, Roberto Gambino, Maurizio Cassader, Gabriella Gruden, Sara Giunti, L Arnaldi, G. PaganoAbstract:BACKGROUND AND AIM: Serum apolipoprotein H (Apo H) levels are increased in hyperlipidemic subjects and type 2 diabetics, but unknown in Microalbuminuria, another disorder with an increased cardiovascular risk. We looked to see whether increased Apo H levels are associated with Microalbuminuria in type 2 diabetes. METHODS AND RESULTS: Serum Apo H was calculated in 20 normoalbuminuric and 17 microalbuminuric type 2 diabetics matched for age, sex, body mass index (BMI), glycosylated haemoglobin, plasma lipids and duration of diabetes, and also compared with 20 non-diabetic controls matched for age, sex, BMI and plasma lipids. Mean serum Apo H was significantly higher in the microalbuminuric patients (31.12 +/- 1.58 SEM vs 25.25 +/- 1.52 and 24.72 +/- 0.99 mg/dL, p = 0.003). CONCLUSION: Serum apo H levels are increased in type 2 diabetics with Microalbuminuria.
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prothrombin fragment 1 2 and antithrombin iii thrombin complex in microalbuminuric type 2 diabetic patients
Diabetic Medicine, 1994Co-Authors: Gabriella Gruden, P Cavalloperin, Renato Romagnoli, Claudia Olivetti, D Frezet, G. PaganoAbstract:: In Microalbuminuria there is an increased cardiovascular risk not fully explained by the excess of conventional risk factors. To investigate whether or not Microalbuminuria is associated with haemostatic abnormalities in Type 2 diabetic patients, we measured the prothrombin fragment 1 + 2, a marker of thrombin generation, and the thrombin-antithrombin complex, a marker of thrombin neutralization. Plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin complex were assayed in 17 microalbuminuric patients (albumin excretion rate, AER 20-200 micrograms min-1) and in 17 comparable normoalbuminuric (AER < 20 micrograms min-1) Type 2 diabetic patients. Plasma prothrombin fragment 1 + 2 was significantly higher in microalbuminuric than in normoalbuminuric patients (1.09 +/- 0.06 vs 0.86 +/- 0.04 nM, p = 0.003). Individual values of F1 + 2 were above the upper limit of the normal range in 8/17 microalbuminuric and in none of the normoalbuminuric Type 2 diabetic patients. Plasma thrombin-antithrombin complex values were not significantly different in the two groups and were not correlated with AER. These results suggest that Microalbuminuria is associated with a prethrombotic state and a relatively defective thrombin neutralization. Coagulation abnormalities might be part of the cardiovascular risk in microalbuminuric patients.
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Prothrombin fragment 1 + 2 and antithrombin III-thrombin complex in microalbuminuric type 2 diabetic patients.
Diabetic Medicine, 1994Co-Authors: Gabriella Gruden, Renato Romagnoli, Claudia Olivetti, D Frezet, Paolo Cavallo-perin, G. PaganoAbstract:: In Microalbuminuria there is an increased cardiovascular risk not fully explained by the excess of conventional risk factors. To investigate whether or not Microalbuminuria is associated with haemostatic abnormalities in Type 2 diabetic patients, we measured the prothrombin fragment 1 + 2, a marker of thrombin generation, and the thrombin-antithrombin complex, a marker of thrombin neutralization. Plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin complex were assayed in 17 microalbuminuric patients (albumin excretion rate, AER 20-200 micrograms min-1) and in 17 comparable normoalbuminuric (AER < 20 micrograms min-1) Type 2 diabetic patients. Plasma prothrombin fragment 1 + 2 was significantly higher in microalbuminuric than in normoalbuminuric patients (1.09 +/- 0.06 vs 0.86 +/- 0.04 nM, p = 0.003). Individual values of F1 + 2 were above the upper limit of the normal range in 8/17 microalbuminuric and in none of the normoalbuminuric Type 2 diabetic patients. Plasma thrombin-antithrombin complex values were not significantly different in the two groups and were not correlated with AER. These results suggest that Microalbuminuria is associated with a prethrombotic state and a relatively defective thrombin neutralization. Coagulation abnormalities might be part of the cardiovascular risk in microalbuminuric patients.
Chifuyu Ushiyama - One of the best experts on this subject based on the ideXlab platform.
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Effect of troglitazone on urinary albumin excretion and serum type IV collagen concentrations in Type 2 diabetic patients with Microalbuminuria or macroalbuminuria.
Diabetic Medicine, 2001Co-Authors: T. Nakamura, Chifuyu Ushiyama, Shigenobu Suzuki, N. Shimada, K. Sekizuka, L. Ebihara, Hikaru KoideAbstract:Summary Aims Troglitazone, a newly developed thiazolidinedione derivative, has been shown to ameliorate Microalbuminuria in diabetic animal model and in human diabetic nephropathy in short-term studies. The aim of the present study was to determine whether troglitazone or sulphonylurea affect micro- albuminuria, macroalbuminuria, or serum type IV collagen concentrations in patients with diabetic nephropathy. Methods We studied 32 normotensive patients with type 2 diabetes mellitus associated with Microalbuminuria (n = 16) or macroalbuminuria (n = 16) and 20 healthy controls. The patients were randomly assigned to one of two groups: those treated with glibenclamide (5.0 mg/day) (n = 8) and those treated with troglitazone (400 mg/day) (n = 8). They received the drug regimen for 12 months. Serum type IV collagen was measured with sandwich enzyme immunoassay. Results Type IV collagen concentrations in macroalbuminuric patients were higher than those in microalbuminuric patients (P
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effect of troglitazone on urinary albumin excretion and serum type iv collagen concentrations in type 2 diabetic patients with Microalbuminuria or macroalbuminuria
Diabetic Medicine, 2001Co-Authors: T. Nakamura, Chifuyu Ushiyama, Shigenobu Suzuki, N. Shimada, K. Sekizuka, L. Ebihara, Hikaru KoideAbstract:Summary Aims Troglitazone, a newly developed thiazolidinedione derivative, has been shown to ameliorate Microalbuminuria in diabetic animal model and in human diabetic nephropathy in short-term studies. The aim of the present study was to determine whether troglitazone or sulphonylurea affect micro- albuminuria, macroalbuminuria, or serum type IV collagen concentrations in patients with diabetic nephropathy. Methods We studied 32 normotensive patients with type 2 diabetes mellitus associated with Microalbuminuria (n = 16) or macroalbuminuria (n = 16) and 20 healthy controls. The patients were randomly assigned to one of two groups: those treated with glibenclamide (5.0 mg/day) (n = 8) and those treated with troglitazone (400 mg/day) (n = 8). They received the drug regimen for 12 months. Serum type IV collagen was measured with sandwich enzyme immunoassay. Results Type IV collagen concentrations in macroalbuminuric patients were higher than those in microalbuminuric patients (P < 0.05) and healthy controls (P < 0.01). Troglitazone reduced urinary albumin excretion (UAE) in micro- albuminuric patients from 126 μg/min (range 58–180 μg/min) to 42 μg/min (range 14–80 μg/min) (P < 0.01) and also reduced serum type IV collagen levels gradually at 3, 6 and 12 months after treatment (P < 0.05). However, glibenclamide did not affect UAE and type IV collagen levels in micro- albuminuric diabetes patients. In addition, neither troglitazone nor gliben- clamide changed UAE and type IV collagen levels in macroalbuminuric patients. Conclusions These data suggest that troglitazone is an effective treatment for renal injury in patients with early diabetic nephropathy.