369 results on '"Mogensen Ce"'
Search Results
2. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes
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ADVANCE Collaborative Group, Patel, A, Macmahon, S, Chalmers, J, Neal, B, Billot, L, Woodward, M, Marre, M, Cooper, M, Glasziou, P, Grobbee, D, Hamet, P, Harrap, S, Heller, S, Liu, L, Mancia, G, Mogensen, Ce, Pan, C, Poulter, N, Rodgers, A, Williams, B, Bompoint, S, de Galan BE, Joshi, R, Travert, F, and DEL PRATO, Stefano
- Published
- 2008
3. Proteinuria and Progressive Renal Disease - June 1996 - Amsterdam, The Netherlands - Introduction
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de Jong, PE, deZeeuw, D, Mogensen, CE, and Groningen Kidney Center (GKC)
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- 1997
4. Efficacy and safety of routine blood pressure lowering in older patients with diabetes: results from the ADVANCE trial.
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Ninomiya T, Zoungas S, Neal B, Woodward M, Patel A, Perkovic V, Cass A, Cooper M, Grobbee D, Hamet P, Harrap S, Liu L, Mancia G, Mogensen CE, Poulter N, Rodgers A, Williams B, MacMahon S, Chalmers J, and ADVANCE Collaborative Group
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- 2010
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5. Risk of coronary artery disease associated with initial sulphonylurea treatment of patients with type 2 diabetes: a matched case-control study.
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Sadikot SM and Mogensen CE
- Abstract
AIMS: This study sought to assess the risk of developing coronary artery disease (CAD) associated with initial treatment of type 2 diabetes with different sulphonylureas. METHODS: In type 2 diabetic patients, cases who developed CAD were compared retrospectively with controls that did not. The 20-year risk of CAD at diagnosis of diabetes, using the UKPDS risk engine, was used to match cases with controls. RESULTS: The 76 cases of CAD were compared with 152 controls. The hazard of developing CAD (95% CI) associated with initial treatment increased by 2.4-fold (1.3-4.3, P=0.004) with glibenclamide; 2-fold (0.9-4.6, P=0.099) with glipizide; 2.9-fold (1.6-5.1, P=0.000) with either, and was unchanged with metformin. The hazard decreased 0.3-fold (0.7-1.7, P=0.385) with glimepiride, 0.4-fold (0.7-1.3, P=0.192) with gliclazide, and 0.4-fold (0.7-1.1, P=0.09) with either. CONCLUSIONS: Initiating treatment of type 2 diabetes with glibenclamide or glipizide is associated with increased risk of CAD in comparison to gliclazide or glimepiride. If confirmed, this may be important because most Indian patients receive the cheaper older sulphonylureas, and present guidelines do not distinguish between individual agents. [ABSTRACT FROM AUTHOR]
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- 2008
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6. Does albuminuria predict cardiovascular outcomes on treatment with losartan versus atenolol in patients with diabetes, hypertension, and left ventricular hypertrophy? The LIFE study.
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Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE, Dahlöf B, Snapinn SM, Wan Y, Lyle PA, Ibsen, Hans, Olsen, Michael H, Wachtell, Kristian, Borch-Johnsen, Knut, Lindholm, Lars H, Mogensen, Carl E, Dahlöf, Björn, Snapinn, Steven M, Wan, Ying, and Lyle, Paulette A
- Abstract
Objective: Our current aims were to investigate whether 1) baseline urinary albumin-to-creatinine ratio (UACR) predicted cardiovascular outcomes, 2) changes in UACR differed between treatments, 3) benefits of losartan were related to its influence on UACR, and 4) reduction in albuminuria reduced cardiovascular events.Research Design and Methods: In 1,063 patients with diabetes, hypertension, and left ventricular hypertrophy, UACR was measured for a mean of 4.7 years. The primary composite end point included cardiovascular death, myocardial infarction, and stroke. Cox models were run including and excluding baseline and time-varying UACR.Results: Increasing baseline albuminuria related to increased risk for cardiovascular events. Reductions in UACR at years 1 and 2 were approximately 33% for losartan vs. 15% for atenolol (P < 0.001). Benefits of losartan seem to be most prominent in patients with the highest level of baseline UACR, although treatment by albuminuria interaction was only significant for total mortality. Approximately one-fifth of the superiority of losartan was explained by the greater reduction of albuminuria. Risk of the primary end point was related to the in-treatment UACR.Conclusions: Lowering of albuminuria in patients with hypertension and diabetes appears to be beneficial and should be the subject of additional study in future clinical trials. [ABSTRACT FROM AUTHOR]- Published
- 2006
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7. Left ventricular dysfunction in hypertensive patients with Type 2 diabetes mellitus.
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Andersen NH, Poulsen SH, Poulsen PL, Knudsen ST, Helleberg K, Hansen KW, Berg TJ, Flyvbjerg A, and Mogensen CE
- Abstract
AIMS: To characterize left ventricular function in hypertensive patients with Type 2 diabetes and normal ejection fraction, and to relate these findings to pathogenic factors and clinical risk markers. METHODS: We examined 70 hypertensive patients with Type 2 diabetes mellitus with ejection fraction > 0.55 and fractional shortening > 0.25, all without any cardiac symptoms. Thirty-five non-diabetic subjects served as control subjects. Left ventricular longitudinal function was examined by tissue Doppler derived myocardial strain rate and peak systolic velocities. RESULTS: Hypertensive patients with diabetes had a significantly higher systolic strain rate (-1.1 +/- 0.3 s(-1) vs. -1.6 +/- 0.3 s(-1), P < 0.001) and lower systolic peak velocities (3.3 +/- 1.0 vs. 5.6 +/- 1.0 cm/s, P < 0.001) compared with control subjects. Myocardial systolic strain rate correlated significantly to left ventricular mass (r = 0.40, P < 0.01) and to both HbA1c (r = 0.43, P < 0.01), and fructosamine (r = 0.40, P < 0.01), but was not related to serum levels of carboxymethyllysine, albuminuria, blood pressure (dipping/non-dipping), or oral hypoglycaemic therapy. Patients with diastolic dysfunction had significantly higher levels of urine albumin [21.0 (5-2500) mg/l, vs. 9.5 (1-360), P < 0.01], heart rate (78 +/- 13 vs. 67 +/- 10 b.p.m., P < 0.005), and seated diastolic blood pressure (85 +/- 6 vs. 81 +/- 7 mmHg, P < 0.05) and non-dipping diastolic blood pressure was more frequent. CONCLUSIONS: Long axis left ventricular systolic function was significantly decreased in hypertensive patients with Type 2 diabetes mellitus, and is associated with hyperglycaemia and left ventricular hypertrophy. Diastolic dysfunction was closely related to increased diastolic blood pressure, non-dipping and increased urinary albumin excretion. [ABSTRACT FROM AUTHOR]
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- 2005
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8. NT-proBNP in normoalbuminuric patients with type 2 diabetes mellitus.
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Andersen NJ, Poulsen SH, Knudsen ST, Heickendorff L, and Mogensen CE
- Abstract
OBJECTIVE: To examine levels of NT-proBNP and its relation to hypertension, as well as diastolic function in normoalbuminuric patients with Type 2 diabetes. RESEARCH DESIGN AND METHODS: The study comprised 60 Type 2 diabetic patients without albuminuria. Thirty patients were normotensive and 30 had hypertension. Exclusion criteria were cardiac symptoms and an ejection fraction < 55%. Thirty age- and sex-matched normal subjects served as controls. Diastolic dysfunction was assessed with echocardiography, by means of mitral inflow and colour M-Mode flow propagation recordings. RESULTS: Overall NT-proBNP was significantly elevated in the Type 2 diabetes group, compared with the controls [54.5 pg/ml (5-162) vs. 32.7 pg/ml (5-74.3) P = 0.02]. NT-proBNP was significantly higher among hypertensive patients compared with both normotensive patients and controls but no difference was found between the normotensive patients and the controls [58.0 pg/ml (8.5-162), P < 0.05 vs. 50.8 pg/ml (5-131) P = 0.4]. Patients with concentric and eccentric hypertrophy had significantly higher NT-proBNP levels compared with the control group [81.0 pg/ml (5-147), P < 0.001 and 66.8 pg/ml (42-128), P < 0.001], whereas patients with left ventricular remodelling (enlarged relative wall diameter but normal left ventricular mass) were comparable with the control group [42.3 pg/ml (8.3-142) P = 0.55]. Patients with left atrial enlargement also had incremental NT-proBNP values. NT-proBNP was only moderately correlated to age (r = 0.33, P < 0.05) and left ventricular diastolic diameter (r = 0.41, P < 0.05), but unrelated to diastolic function. CONCLUSIONS: NT-proBNP is significantly increased in hypertensive, normoalbuminuric patients with Type 2 diabetes. These findings were related to left ventricular hypertrophy and increased left atrial and ventricular diameters. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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9. Long-term dual blockade with candesartan and lisinopril in hypertensive patients with diabetes: the CALM II study.
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Andersen NH, Poulsen PL, Knudsen ST, Poulsen SH, Eiskjær H, Hansen KW, Helleberg K, Mogensen CE, Andersen, Niels H, Poulsen, Per L, Knudsen, Søren T, Poulsen, Steen H, Eiskjaer, Hans, Hansen, Klavs W, Helleberg, Kjeld, and Mogensen, Carl E
- Abstract
Objective: To assess and compare the long-term effects of the combination of candesartan and lisinopril with high-dose lisinopril on systolic blood pressure in patients with hypertension and diabetes.Research Design and Methods: This was a prospective, randomized, parallel-group, double-blind, double-dummy study with a 12-month follow-up. Drug therapy was either lisinopril 40 mg once daily or dual-blockade treatment with candesartan 16 mg once daily and lisinopril 20 mg once daily. The study comprised 75 type 1 and type 2 diabetic patients aged 35-74 years. The main outcome measures were seated and 24-h ambulatory systolic blood pressure.Results: Reduction in systolic blood pressure (24-h systolic blood pressure) reduction was obtained in both treatment arms (mean reduction at final follow-up: dual blockade 6 mmHg vs. lisinopril 2 mmHg), but no significant difference was found between dual-blockade and lisinopril 40 mg once daily (P = 0.10). Both treatments were generally well tolerated, and similar low rates of side effects were found in the two groups.Conclusions: There was no statistically significant difference between lisinopril 40 mg once daily and lisinopril 20 mg in combination with candesartan 16 mg once daily in reducing systolic blood pressure in hypertensive patients with diabetes. [ABSTRACT FROM AUTHOR]- Published
- 2005
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10. Latin American consensus on diabetes mellitus and hypertension.
- Author
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Burlando G, Sánchez RA, Ramos FH, Mogensen CE, Zanchetti A, Latin American Experts Group, Burlando, Guillermo, Sánchez, Ramiro A, Ramos, Felipe H, Mogensen, Carl E, and Zanchetti, Alberto
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- 2004
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11. Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy.
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Ibsen H, Wachtell K, Olsen MH, Borch-Johnsen K, Lindholm LH, Mogensen CE, Dahlöf B, Devereux RB, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, Wan Y, Ibsen, Hans, Wachtell, Kristian, and Olsen, Michael H
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- 2004
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12. Microalbuminuria and hypertension with focus on type 1 and type 2 diabetes.
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Mogensen CE and Mogensen, C E
- Abstract
Unlabelled: Microalbuminuria and hypertension with Over the past decade, there has been considerable focus on the concept of microalbuminuria, not only because it predicts renal disease in type 1 and type 2 diabetes, but also because it relates to premature mortality in the diabetic and in the general population. More importantly, intervention at this stage is now possible with the perspective of preserving glomerular filtration rate (GFR) and ameliorating cardiovascular disease and ensuing strong end-points. INITIAL STUDIES: The concept of microalbuminuria was introduced about 20 years ago and since then there has been a multitude of studies and papers on this subject using the original definition, but not always, in the US. Before that time it was suggested, mainly from the US, that diabetic renal disease was an untreatable relentlessly progressive condition.Genetic Studies: There is an overwhelming number of studies on genetics and diabetes and also covering the genetics of diabetic complications including nephropathy. However, so far the results are extremely disappointing. Patients at risk cannot be identified and genetic analyses are of no value as a guide to treatment. The notion that the development of complications is controlled mainly by a special genetic pattern is increasingly doubtful. In genetic studies, it is rather phenotypic well-accepted risk factors that dominate. STRUCTURAL BASIS OF MICROALBUMINURIA: Patients with microalbuminuria have significant abnormalities in the kidney, including glomeruli. This is quite clear in patients with type 1 diabetes, but is also seen in type 2 diabetes, where on the other hand, other risk factors such as hypertension and dyslipidaemia also seem to be of importance, including loss of autoregulation. Renal biopsies are generally not indicated in the management of diabetic patients. MICROALBUMINURIA AND EARLY MORTALITY: It is quite clear that microalbuminuria predicts early mortality both in type 1 and type 2 diabetes. The association to other risk factors may partly explain this--but this does not account for the whole picture. Endothelial dysfunction as well as inflammatory and arteriosclerotic abnormalities in blood vessels may be a relevant hypothesis that needs to be further explored along with other possibilities. CLINICAL COURSE AND ASSOCIATED ABNORMALITIES: The risk factor for progression in normoalbuminuric patients to microalbuminuria is higher than normal albumin excretion (strongest factor), poor glycaemic control, elevated blood pressure, and to some extent smoking. The clinical course of microalbuminuria is usually progressive, but with the more effective intervention now available we encounter that the so-called natural history (without intervention) is increasingly difficult to study. Microalbuminuria is clearly associated with a number of abnormalities, almost in all organs, but GFR is generally well preserved in spite of more advanced structural lesions. Therefore, microalbuminuria is an important marker for more pronounced diabetic vascular disease in general as well as for nephropathy. Regression to normoalbuminuria only rarely occurs during standard unchanged nonintensive treatment. TREATMENT STRATEGIES: The best possible glycaemic control is important in preventing and ameliorating the course of normo- and micro-albuminuria. Another major treatment strategy, especially in microalbuminuric patients, is antihypertensive treatment including inhibition of the renal angiotensin aldosterone system. Numerous new studies are available, both in type 1 and type 2 diabetes, documenting that not only microalbuminuria but also renal and cardiovascular complications in these patient are also far better controlled by early detection and treatment. Therefore, screening for microalbuminuria should be a strategy in all diabetes management followed by effective intervention as outlined in this paper. [ABSTRACT FROM AUTHOR]- Published
- 2003
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13. Ramdomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study.
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Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, Cooper ME, and CALM Study Group
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- 2000
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14. Validity of rapid estimation of glomerular filtration rate in type 2 diabetic patients with normal renal function.
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Nielsen, S, Rehling, M, Schmitz, A, and Mogensen, CE
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Background.Rapid estimation of the renal function is widely used in clinical practice. [ABSTRACT FROM PUBLISHER]
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- 1999
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15. Prevention of diabetic renal disease with special reference to microalbuminuria.
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Mogensen CE, Keane WF, Bennett PH, Jerums G, Parving H, Passa P, Steffes MW, Striker GE, Viberti GC, Mogensen, C E, Keane, W F, Bennett, P H, Jerums, G, Parving, H H, Passa, P, Steffes, M W, Striker, G E, and Viberti, G C
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- 1995
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16. Abstracts. Proteinuria and progressive renal disease: towards preventing renal disease. Fourth International Symposium, 24-25 September 1997, Montreux, Switzerland.
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Burnier, M, Boner, G, Brunner, H, van Dijk, D, Donker, A, and Mogensen, CE
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- 1998
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17. Combination of enalapril and low-dose thiazide reduces normoalbuminuria in essential hypertension.
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Nielsen S, Dollerup J, Nielsen B, Mogensen CE, Nielsen, S, Dollerup, J, Nielsen, B, and Mogensen, C E
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- 1998
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18. The influence of age on renal and extrarenal effects of frusemide.
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Andreasen, F., Hansen, U., Husted, SE, Mogensen, CE, and Pedersen, EB
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The effect of frusemide 80 mg i.v. was compared during 24 h in 10 young and eight elderly healthy male volunteers following a 24 h control period in the ward. During the 30 min following the injection the increments in excretion of urine, sodium, potassium and frusemide were significantly smaller in the elderly. The 24 h increase in sodium excretion was significantly larger in the 0 young and eight elderly healthy male volunteers following a 24 h control period in the ward. During the 30 min following the injection the increments in excretion of urine, sodium, potassium and frusemide were significantly smaller in the elderly. The 24 h increase in sodium excretion was significantly larger in the 0 young and eight elderly healthy male volunteers following a 24 h control period in the ward. During the 30 min following the injection the increments in excretion of urine, sodium, potassium and frusemide were significantly smaller in the elderly. The 24 h increase in sodium excretion was significantly larger in the elderly. The endogenous 24 h creatinine clearance was reduced by 12% (P less than 0.01) in both age groups. The frusemide induced changes in the 8 h serum concentration curves for albumin differed significantly between the two groups (analysis of variance, P less than 0.01). The drug induced increase in albumin concentration became significant in the young 5 min after the injection. In the elderly it took more than 15 min before the increase in serum albumin reached significance. The average maximal increase in albumin concentration was 14.3% in the young and 9.7% in the elderly (P less than 0.05). No difference was seen between the two age groups in the significant frusemide induced increases in the 24 h albumin excretion but in the elderly a significantly larger decrease in the 24 h excretion of beta 2- microglobulin was observed (P less than 0.05). No significant age difference was observed in the initial significant increases in diastolic blood pressure observed in both age groups or between the later changes in systolic blood pressure which was significantly reduced in the young only. The slower haemoconcentration response in the elderly seemed associated with the slower secretion rate of frusemide to the tubular lumen. We found no evidence of an age related difference in tubular cell response to frusemide. It is emphasized that a maximal initial frusemide response in the elderly, in contrast to what was found in the young, probably was not achieved by the 80 mg i.v. [ABSTRACT FROM AUTHOR]
- Published
- 1984
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19. Albuminuria and 24-h ambulatory blood pressure in normoalbuminuric and microalbuminuric NIDDM patients. A longitudinal study.
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Nielsen S, Schmitz A, Poulsen PL, Hansen KW, Mogensen CE, Nielsen, S, Schmitz, A, Poulsen, P L, Hansen, K W, and Mogensen, C E
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- 1995
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20. How to protect the kidney in diabetic patients: with special reference to IDDM.
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Mogensen CE and Mogensen, C E
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- 1997
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21. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial.
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Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, Harrap S, Poulter N, Marre M, Cooper M, Glasziou P, Grobbee DE, Hamet P, Heller S, Liu LS, Mancia G, Mogensen CE, Pan CY, Rodgers A, and Williams B
- Abstract
Background: Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes, and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension. We assessed the effects of the routine administration of an angiotensin converting enzyme (ACE) inhibitor-diuretic combination on serious vascular events in patients with diabetes, irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs.Methods: The trial was done by 215 collaborating centres in 20 countries. After a 6-week active run-in period, 11 140 patients with type 2 diabetes were randomised to treatment with a fixed combination of perindopril and indapamide or matching placebo, in addition to current therapy. The primary endpoints were composites of major macrovascular and microvascular events, defined as death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction, and new or worsening renal or diabetic eye disease, and analysis was by intention-to-treat. The macrovascular and microvascular composites were analysed jointly and separately. This trial is registered with ClinicalTrials.gov, number NCT00145925.Findings: After a mean of 4.3 years of follow-up, 73% of those assigned active treatment and 74% of those assigned control remained on randomised treatment. Compared with patients assigned placebo, those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg. The relative risk of a major macrovascular or microvascular event was reduced by 9% (861 [15.5%] active vs 938 [16.8%] placebo; hazard ratio 0.91, 95% CI 0.83-1.00, p=0.04). The separate reductions in macrovascular and microvascular events were similar but were not independently significant (macrovascular 0.92; 0.81-1.04, p=0.16; microvascular 0.91; 0.80-1.04, p=0.16). The relative risk of death from cardiovascular disease was reduced by 18% (211 [3.8%] active vs 257 [4.6%] placebo; 0.82, 0.68-0.98, p=0.03) and death from any cause was reduced by 14% (408 [7.3%] active vs 471 [8.5%] placebo; 0.86, 0.75-0.98, p=0.03). There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline.Interpretation: Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events, including death. Although the confidence limits were wide, the results suggest that over 5 years, one death due to any cause would be averted among every 79 patients assigned active therapy. [ABSTRACT FROM AUTHOR]- Published
- 2007
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22. Increase in nocturnal blood pressure and progression to microalbuminuria in diabetes.
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Brotman DJ, Girod JP, Thomas S, Poulsen PL, Hansen KW, Mogensen CE, Caramori ML, Pecis M, Azevedo MJ, Marfella R, Esposito K, Giugliano D, Lurbe E, Redon J, and Batlle D
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- 2003
23. Non-proteinuric pathways in loss of renal function in patients with type 2 diabetes.
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Porrini E, Ruggenenti P, Mogensen CE, Barlovic DP, Praga M, Cruzado JM, Hojs R, Abbate M, and de Vries AP
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- Albuminuria complications, Albuminuria urine, Animals, Diabetes Mellitus, Type 2 complications, Diabetic Nephropathies complications, Disease Progression, Female, Glomerular Filtration Rate, Humans, Male, Phenotype, Risk Factors, Diabetes Mellitus, Type 2 physiopathology, Diabetic Nephropathies physiopathology
- Abstract
Largely on the basis of data from patients with type 1 diabetes, the natural history of diabetic renal disease has been classified as a sequence of three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Progressive decline of glomerular filtration rate (GFR) was thought to parallel the onset of macroalbuminuria (overt nephropathy), whereas glomerular hyperfiltration was deemed a hallmark of early disease. However, researchers have since shown that albuminuria is a continuum and that GFR can start to decline before progression to overt nephropathy. In addition to proteinuria, other risk factors might contribute to GFR deterioration including female sex, obesity, dyslipidaemia (in particular hypertriglyceridaemia), hypertension, and glomerular hyperfiltration, at least in a subgroup of patients. This phenomenon could explain why patients with type 2 diabetes can have renal insufficiency even before the onset of overt nephropathy, and might also suggest why the heterogeneous phenotype of type 2 diabetic renal disease does not necessarily associate with typical histological lesions of diabetic renal disease, unlike in type 1 diabetic renal disease. Patients with renal insufficiency but without albuminuria are usually excluded from randomised clinical trials in overt nephropathy, thus optimum treatment for this group of patients is unknown. The wide inter-patient variability of the disease probably needs individually tailored intervention., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
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- 2015
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24. Diabetic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes.
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Molitch ME, Adler AI, Flyvbjerg A, Nelson RG, So WY, Wanner C, Kasiske BL, Wheeler DC, de Zeeuw D, and Mogensen CE
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- Albuminuria etiology, Diabetic Nephropathies complications, Disease Progression, Humans, Hyperglycemia etiology, Hypertension etiology, Diabetic Nephropathies diagnosis, Diabetic Nephropathies therapy
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The incidence and prevalence of diabetes mellitus (DM) continue to grow markedly throughout the world, due primarily to the increase in type 2 DM (T2DM). Although improvements in DM and hypertension management have reduced the proportion of diabetic individuals who develop chronic kidney disease (CKD) and progress to end-stage renal disease (ESRD), the sheer increase in people developing DM will have a major impact on dialysis and transplant needs. This KDIGO conference addressed a number of controversial areas in the management of DM patients with CKD, including aspects of screening for CKD with measurements of albuminuria and estimated glomerular filtration rate (eGFR); defining treatment outcomes; glycemic management in both those developing CKD and those with ESRD; hypertension goals and management, including blockers of the renin-angiotensin-aldosterone system; and lipid management.
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- 2015
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25. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes.
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Zoungas S, Chalmers J, Neal B, Billot L, Li Q, Hirakawa Y, Arima H, Monaghan H, Joshi R, Colagiuri S, Cooper ME, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Lisheng L, Mancia G, Marre M, Matthews DR, Mogensen CE, Perkovic V, Poulter N, Rodgers A, Williams B, MacMahon S, Patel A, and Woodward M
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- Blood Glucose, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 mortality, Drug Combinations, Female, Follow-Up Studies, Glycated Hemoglobin analysis, Humans, Hypertension complications, Male, Middle Aged, Risk Factors, Antihypertensive Agents therapeutic use, Diabetes Mellitus, Type 2 drug therapy, Gliclazide administration & dosage, Hypertension drug therapy, Hypoglycemic Agents administration & dosage, Indapamide therapeutic use, Perindopril therapeutic use
- Abstract
Background: In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up., Methods: We invited surviving participants, who had previously been assigned to perindopril-indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events., Results: The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure-lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively., Conclusions: The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure-lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events. (Funded by the National Health and Medical Research Council of Australia and others; ADVANCE-ON ClinicalTrials.gov number, NCT00949286.).
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- 2014
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26. The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.
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Schernthaner G, Mogensen CE, and Schernthaner GH
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- Albuminuria etiology, Albuminuria prevention & control, Animals, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 diagnosis, Diabetic Nephropathies blood, Diabetic Nephropathies diagnosis, Diabetic Nephropathies etiology, Glucagon-Like Peptide 1 analogs & derivatives, Humans, Kidney enzymology, Risk Factors, Sodium-Glucose Transporter 2 metabolism, Treatment Outcome, Diabetes Mellitus, Type 2 drug therapy, Diabetic Nephropathies prevention & control, Dipeptidyl Peptidase 4 metabolism, Dipeptidyl-Peptidase IV Inhibitors therapeutic use, Glucagon-Like Peptide 1 therapeutic use, Kidney drug effects, Sodium-Glucose Transporter 2 Inhibitors
- Abstract
Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway., (© The Author(s) 2014.)
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- 2014
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27. Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease.
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de Vries AP, Ruggenenti P, Ruan XZ, Praga M, Cruzado JM, Bajema IM, D'Agati VD, Lamb HJ, Pongrac Barlovic D, Hojs R, Abbate M, Rodriquez R, Mogensen CE, and Porrini E
- Subjects
- Female, Humans, Male, Obesity pathology, Renal Insufficiency, Chronic pathology, Risk Factors, Lipid Metabolism, Obesity complications, Obesity metabolism, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic metabolism
- Abstract
The global increase in chronic kidney disease (CKD) parallels the obesity epidemic. Obesity conveys a gradual but independent risk of progression of CKD that seems irrespective of the underlying nephropathy. Obesity has been associated with a secondary focal segmental glomerulosclerosis coined obesity-related glomerulopathy (ORG). Pathways through which obesity might cause renal disease are not well understood, and early clinical biomarkers for incipient ORG or renal relevant obesity are currently lacking. Recent human and experimental studies have associated ectopic lipid accumulation in the kidney (fatty kidney) with obesity-related renal disease. There is enough growing insight that ectopic lipid--the accumulation of lipid in non-adipose tissue--is associated with structural and functional changes of mesangial cells, podocytes, and proximal tubular cells to propose the development of ORG as a maladaptive response to hyperfiltration and albuminuria. Recent advances in metabolic imaging might validate ectopic lipid as a biomarker and research aid, to help translate novel therapeutics from experimental models to patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
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- 2014
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28. Efficacy and safety of sitagliptin in patients with type 2 diabetes and ESRD receiving dialysis: a 54-week randomized trial.
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Arjona Ferreira JC, Corry D, Mogensen CE, Sloan L, Xu L, Golm GT, Gonzalez EJ, Davies MJ, Kaufman KD, and Goldstein BJ
- Subjects
- Blood Glucose analysis, Diabetic Nephropathies therapy, Double-Blind Method, Glycated Hemoglobin, Humans, Kidney Failure, Chronic therapy, Renal Dialysis, Sitagliptin Phosphate, Diabetes Mellitus, Type 2 drug therapy, Diabetic Nephropathies drug therapy, Dipeptidyl-Peptidase IV Inhibitors therapeutic use, Pyrazines therapeutic use, Triazoles therapeutic use
- Abstract
Background: Treatment with oral antihyperglycemic agents has not been well characterized in patients with type 2 diabetes and end-stage renal disease (ESRD). The efficacy and safety of sitagliptin and glipizide monotherapy in patients with type 2 diabetes and ESRD on dialysis therapy were assessed in this study., Study Design: 54-week, randomized, double-blind, parallel-arm study., Setting & Participants: From 31 clinical sites in 12 countries, 129 patients 30 years or older with type 2 diabetes and ESRD who were on dialysis therapy and had a hemoglobin A1c (HbA1c) level of 7%-9% were randomly assigned 1:1 to treatment., Intervention: Monotherapy with sitagliptin, 25 mg daily or glipizide (initiated with 2.5 mg daily and titrated up to a potential maximum dose of 10 mg twice daily or down to avoid hypoglycemia)., Outcomes: Primary end points were 54-week change in HbA1c level from baseline and tolerability with sitagliptin. A secondary end point was the comparison of sitagliptin versus glipizide on the incidence of symptomatic hypoglycemia., Results: Of 129 patients randomly assigned, 64 were in the sitagliptin group (mean baseline age, 61 years; HbA1c, 7.9%) and 65 were in the glipizide group (mean baseline age, 59 years; HbA1c, 7.8%). After 54 weeks, the least squares mean change from baseline in HbA1c level was -0.72% (95% CI, -0.95% to -0.48%) with sitagliptin and -0.87% (95% CI, -1.11% to -0.63%) with glipizide, for a difference of 0.15% (95% CI, -0.18% to 0.49%). The incidences of symptomatic hypoglycemia and severe hypoglycemia were 6.3% versus 10.8% (between-group difference, -4.8% [95% CI, -15.7% to 5.6%]) and 0% versus 7.7% (between-group difference, -7.8% [95% CI, -17.1% to -1.9%]) in the sitagliptin and glipizide groups, respectively. Higher incidences (ie, 95% CI around between-treatment difference excluded 0) of cellulitis and headache were found with sitagliptin compared to glipizide (6.3% vs 0%, respectively, for both)., Limitations: Small sample size limits between-group comparisons., Conclusions: Treatment with sitagliptin or glipizide monotherapy was effective and well tolerated over 54 weeks in patients with type 2 diabetes and ESRD who were receiving dialysis., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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29. Intensive glucose control improves kidney outcomes in patients with type 2 diabetes.
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Perkovic V, Heerspink HL, Chalmers J, Woodward M, Jun M, Li Q, MacMahon S, Cooper ME, Hamet P, Marre M, Mogensen CE, Poulter N, Mancia G, Cass A, Patel A, and Zoungas S
- Subjects
- Aged, Albuminuria prevention & control, Diabetes Mellitus, Type 2 blood, Glomerular Filtration Rate, Glycated Hemoglobin analysis, Humans, Middle Aged, Blood Glucose analysis, Diabetes Mellitus, Type 2 drug therapy, Diabetic Nephropathies prevention & control, Kidney Failure, Chronic prevention & control
- Abstract
The effect of intensive glucose control on major kidney outcomes in type 2 diabetes remains unclear. To study this, the ADVANCE trial randomly assigned 11,140 participants to an intensive glucose-lowering strategy (hemoglobin A1c target 6.5% or less) or standard glucose control. Treatment effects on end-stage renal disease ((ESRD), requirement for dialysis or renal transplantation), total kidney events, renal death, doubling of creatinine to above 200 μmol/l, new-onset macroalbuminuria or microalbuminuria, and progression or regression of albuminuria, were then assessed. After a median of 5 years, the mean hemoglobin A1c level was 6.5% in the intensive group, and 7.3% in the standard group. Intensive glucose control significantly reduced the risk of ESRD by 65% (20 compared to 7 events), microalbuminuria by 9% (1298 compared to 1410 patients), and macroalbuminuria by 30% (162 compared to 231 patients). The progression of albuminuria was significantly reduced by 10% and its regression significantly increased by 15%. The results were almost identical in analyses taking account of potential competing risks. The number of participants needed to treat over 5 years to prevent one ESRD event ranged from 410 in the overall study to 41 participants with macroalbuminuria at baseline. Thus, improved glucose control will improve major kidney outcomes in patients with type 2 diabetes.
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- 2013
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30. Prediction of kidney-related outcomes in patients with type 2 diabetes.
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Jardine MJ, Hata J, Woodward M, Perkovic V, Ninomiya T, Arima H, Zoungas S, Cass A, Patel A, Marre M, Mancia G, Mogensen CE, Poulter N, and Chalmers J
- Subjects
- Aged, Albuminuria etiology, Female, Humans, Male, Prognosis, Randomized Controlled Trials as Topic, Risk Assessment, Diabetes Mellitus, Type 2 complications, Diabetic Nephropathies etiology, Kidney Diseases etiology
- Abstract
Background: Tools are needed to predict which individuals with diabetes will develop kidney disease and its complications., Study Design: An observational analysis of a randomized controlled trial., Setting & Participants: The ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) Study followed up 11,140 participants with type 2 diabetes for 5 years., Predictor: Readily available baseline demographic and clinical variables., Outcomes: (1) Major kidney-related events (doubling of serum creatinine to ≥2.26 mg/dL [≥200 μmol/L], renal replacement therapy, or renal death) in all participants, and (2) new-onset albuminuria in participants with baseline normoalbuminuria., Measurements: Cox proportional hazard regression models predicting the outcomes were used to generate risk scores. Discrimination of the risk prediction models was compared with that of models based on estimated glomerular filtration rate (eGFR) alone, urinary albumin-creatinine ratio (ACR) alone, and their combination., Results: Risk scores for major kidney-related events and new-onset albuminuria were derived from 7- and 8-variable models, respectively. Baseline eGFR and ACR were dominant although models based on the 2 factors, alone or combined, had less discrimination (P<0.05) than the risk prediction models containing additional variables (risk prediction model C statistics of 0.847 [95% CI, 0.815-0.880] for major kidney-related events, and 0.647 [95% CI, 0.637-0.658] for new-onset albuminuria). Novel risk factors for new-onset albuminuria included Asian ethnicity and greater waist circumference, and for major kidney-related events, less education. The risk prediction models had acceptable calibration for both outcomes (modified Hosmer-Lemeshow test, P=0.9 and P=0.06, respectively)., Limitations: The follow-up period was limited to 5 years. Results are applicable to people with type 2 diabetes at risk of vascular disease., Conclusions: Risk scores have been developed for early and late events in diabetic nephropathy. Although eGFR and urinary ACR are important components of the prediction models, the extra variables considered add significantly to discrimination and, in the case of new-onset albuminuria, are required to achieve satisfactory calibration., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)
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- 2012
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31. Effects of a fixed combination of perindopril and indapamide in patients with type 2 diabetes and chronic kidney disease.
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Heerspink HJ, Ninomiya T, Perkovic V, Woodward M, Zoungas S, Cass A, Cooper M, Grobbee DE, Mancia G, Mogensen CE, Neal B, and Chalmers J
- Subjects
- Antihypertensive Agents adverse effects, Drug Therapy, Combination, Female, Humans, Hypertension, Renovascular drug therapy, Indapamide adverse effects, Male, Middle Aged, Myocardial Infarction prevention & control, Perindopril adverse effects, Stroke prevention & control, Treatment Outcome, Antihypertensive Agents administration & dosage, Diabetes Mellitus, Type 2 drug therapy, Diabetic Nephropathies drug therapy, Indapamide administration & dosage, Perindopril administration & dosage, Renal Insufficiency, Chronic drug therapy
- Abstract
Aims: Individuals with diabetes and chronic kidney disease (CKD) are at high risk for cardiovascular disease. In these analyses of the ADVANCE trial, we assessed the effects of a fixed combination of perindopril-indapamide on renal and cardiovascular outcomes in patients with type 2 diabetes according to baseline CKD stage., Methods and Results: Patients with type 2 diabetes were randomized to perindopril-indapamide (4 mg/1.25 mg) or placebo. Treatment effects on cardiovascular (cardiovascular death, myocardial infarction, or stroke) and renal outcomes were compared in subgroups defined by baseline Kidney Disease Outcome Quality Initiative CKD stage. Homogeneity in treatment effect was tested by adding interaction terms to the relevant Cox models. The study included 10 640 participants with known CKD status, of whom 6125 did not have CKD, 2482 were classified as CKD stage 1 or 2, and 2033 as CKD stage ≥3. The relative treatment effects on major cardiovascular events were similar across all stages of CKD, with no heterogeneity in the magnitude of the effects for any outcome. In contrast, the absolute treatment effects approximately doubled in those with CKD stage ≥3 when compared to those with no CKD. For every 1000 patients with CKD stage ≥3 treated for 5 years, active treatment prevented 12 cardiovascular events when compared with six events per 1000 patients with no CKD., Conclusion: The treatment benefits of a routine administration of a fixed combination of perindopril-indapamide to patients with type 2 diabetes on cardiovascular and renal outcomes, and death, are consistent across all stages of CKD at baseline. Absolute risk reductions are larger in patients with CKD highlighting the importance of blood pressure-lowering in this population.
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- 2010
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32. Predictors of mortality of patients newly diagnosed with clinical type 2 diabetes: a 5-year follow up study.
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de Fine Olivarius N, Siersma V, Nielsen AB, Hansen LJ, Rosenvinge L, and Mogensen CE
- Abstract
Background: At diabetes diagnosis major decisions about life-style changes and treatments are made based on characteristics measured shortly after diagnosis. The predictive value for mortality of these early characteristics is widely unknown. We examined the predictive value of patient characteristics measured shortly after diabetes diagnosis for 5-year all-cause and cardiovascular mortality with special reference to self-rated general health., Methods: Data were from a population-based sample of 1,323 persons newly diagnosed with clinical diabetes and aged 40 years or over. Possible predictors of mortality were investigated in Cox regression models., Results: Multivariately patients who rated their health less than excellent experienced increased all-cause and cardiovascular mortality. These end-points also increased with sedentary life-style, relatively young age at diagnosis and presence of cardiovascular disease (CVD) at diagnosis. Further predictors of all-cause mortality were male sex, low body mass index and cancer, while cardiovascular mortality increased with urinary albumin concentration., Conclusions: We found that patients who rated their health as less than excellent had increased 5-year mortality, similar to that of patients with prevalent CVD, even when biochemical, clinical and life-style variables were controlled for. This finding could motivate doctors to discuss perceptions of health with newly diagnosed diabetic patients and be attentive to patients with suboptimal health ratings. Our findings also confirm that life-style changes and optimizing treatment are particularly relevant for relatively young and inactive patients and those who already have CVD or (micro)albuminuria at the time of diabetes diagnosis.
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- 2010
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33. Mistakes, misunderstandings and controversies in diabetes: A review and personal account.
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Mogensen CE
- Abstract
A number of controversies in diabetes have had too little attention. I discuss the following issues: (i) drug therapy; (ii) genetics; (iii) antihypertensive treatment in patients with normoalbuminuria and with abnormal albuminuria; (iv) insulin analogs; (v) cancer in diabetes; (vi) hypophysectomy; (vii) renal biopsy; (viii) low protein diet; and (ix) glycated hemoglobin. A closer look at these items is required in order to have a more realistic picture of diabetes research. A scheme of other controversies is also provided. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00012.x, 2010).
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- 2010
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34. Microalbuminuria and short-term prognosis in patients undergoing cardiac surgery.
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Mikkelsen MM, Andersen NH, Christensen TD, Hansen TK, Eiskjaer H, Mogensen CE, Hjortdal VE, and Johnsen SP
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- Adolescent, Adult, Aged, Aged, 80 and over, Albumins metabolism, Albuminuria mortality, Albuminuria urine, Atrial Fibrillation etiology, Biomarkers urine, Cardiac Surgical Procedures mortality, Creatine urine, Critical Care, Denmark epidemiology, Elective Surgical Procedures, Female, Follow-Up Studies, Heart Diseases complications, Heart Diseases mortality, Humans, Kaplan-Meier Estimate, Length of Stay, Male, Middle Aged, Myocardial Infarction etiology, Odds Ratio, Prospective Studies, Registries, Renal Insufficiency etiology, Reoperation, Risk Assessment, Risk Factors, Sepsis etiology, Stroke etiology, Surgical Wound Infection etiology, Time Factors, Treatment Outcome, Young Adult, Albuminuria complications, Cardiac Surgical Procedures adverse effects, Heart Diseases surgery
- Abstract
Objectives: To examine if preoperative microalbuminuria (MA) is associated with in increased risk of adverse outcomes in patients undergoing elective cardiothoracic surgery, and if adding information on MA could improve the accuracy of the additive EuroSCORE., Methods: In a follow-up study we included 962 patients undergoing elective cardiothoracic surgery from 1 April 2005 to 30 September 2007 at our department. MA (urine albumin/creatinine ratio between 2.5-25 mg/mmol) was assessed in a morning spot-urine sample. We used population-based medical registries for 30-day follow-up and compared the length of stay and adverse outcomes including (i) all-cause death, myocardial infarction, stroke, or atrial fibrillation, (ii) surgical reintervention, renal insufficiency, sternal wound infection, or septicaemia among patients with and without MA., Results: MA was found in 180 (18.7%) patients. The risk of both combined outcomes (adjusted odds ratios (ORs): 1.00 (95% confidence interval (CI): 0.77-1.30) and 1.18 (95% CI: 0.79-1.75), respectively) and most individual outcomes did not differ between the micro- and normoalbuminuric patients. The patients with MA and an additive EuroSCORE of 5 had a significantly prolonged median length of intensive care unit (ICU) stay (0.15 days [95% CI: 0.04-0.26]) and total hospital stay (0.5 days [95% CI: 0.04-0.96]). Patients with MA had a higher risk of postoperative septicaemia (OR: 12.1 [95% CI: 3.2-45.9]). Area under receiver operating characteristics curves of the EuroSCORE with regard to 30-day mortality was 0.86 both with and without MA., Conclusions: Preoperative MA in patients undergoing elective cardiothoracic surgery was not associated with most early adverse outcomes. However, risk of septicaemia was higher and patients with MA also had a marginally longer length of ICU and hospital stay. Information on preoperative MA did not improve the accuracy of the additive EuroSCORE.
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- 2009
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35. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes.
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Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, Patel A, Cass A, Neal B, Poulter N, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Macmahon S, and Chalmers J
- Subjects
- Aged, Cardiovascular Diseases epidemiology, Diabetes Mellitus, Type 2 epidemiology, Female, Glomerular Filtration Rate, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Renal Insufficiency epidemiology, Risk Factors, Albuminuria epidemiology, Cardiovascular Diseases etiology, Diabetes Mellitus, Type 2 complications, Diabetic Nephropathies epidemiology
- Abstract
There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR >300 mg/g and eGFR <60 ml/min per 1.73 m(2) at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors. In conclusion, high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes.
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- 2009
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36. Increased ambulatory arterial stiffness index and pulse pressure in microalbuminuric patients with type 1 diabetes.
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Laugesen E, Hansen KW, Knudsen ST, Erlandsen M, Ebbehøj E, Mogensen CE, and Poulsen PL
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- Adult, Elasticity, Female, Humans, Male, Middle Aged, Albuminuria physiopathology, Blood Pressure physiology, Blood Pressure Monitoring, Ambulatory, Diabetes Mellitus, Type 1 physiopathology, Vascular Resistance physiology
- Abstract
Background: Ambulatory arterial stiffness index (AASI) has been proposed as an indirect measure of arterial stiffness. The aims of this study were (i) to analyze AASI and pulse pressure (PP) in micro- and normoalbuminuric type 1 diabetes mellitus (T1DM) patients and healthy controls and (ii) to explore the relation between nocturnal blood pressure (BP) reduction, BP variability, and AASI., Methods: Ambulatory BP monitoring was performed in 34 micro- and 34 normoalbuminuric T1DM patients matched for gender, age, and diabetes duration and in 34 nondiabetic controls matched for gender and age. AASI and PP were calculated based on 24-h, day, and night BP recordings., Results: AASI increased from the control group (0.30 +/- 0.14) to the normo- (0.35 +/- 0.15) and microalbuminuric group (0.41 +/- 0.19; P < 0.05). After adjustment for nightly systolic BP reduction and systolic daytime BP variability (s.d.) in multivariate analysis, the association weakened and became nonsignificant (P = 0.078). No significant intergroup differences were found when AASI was calculated separately from day and night BP data. There was no significant difference between day and night AASI. The 24-h PP increased from the control group (48 +/- 7 mm Hg) to the normo- (50 +/- 6 mm Hg) and microalbuminuric group (54 +/- 9 mm Hg; P < 0.01). The association remained in the multivariate analysis. Day and night PPs were higher in microalbuminuric patients compared to healthy controls., Conclusions: AASI and PP are higher in microalbuminuric T1DM patients compared to healthy controls. The nocturnal BP reduction and systolic daytime BP variability are determinants of AASI. We propose these associations to reflect biological characteristics of arterial stiffness.
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- 2009
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37. Lowering blood pressure reduces renal events in type 2 diabetes.
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de Galan BE, Perkovic V, Ninomiya T, Pillai A, Patel A, Cass A, Neal B, Poulter N, Harrap S, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Glasziou P, Grobbee DE, MacMahon S, and Chalmers J
- Subjects
- Age of Onset, Aged, Albuminuria epidemiology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Antihypertensive Agents therapeutic use, Blood Pressure drug effects, Creatinine blood, Diastole drug effects, Diastole physiology, Drug Therapy, Combination, Female, Glomerular Filtration Rate, Humans, Male, Systole drug effects, Systole physiology, Blood Pressure physiology, Diabetes Mellitus physiopathology, Diabetes Mellitus, Type 2 physiopathology, Diabetic Nephropathies prevention & control, Hypertension prevention & control, Indapamide therapeutic use, Perindopril therapeutic use
- Abstract
BP is an important determinant of kidney disease among patients with diabetes. The recommended thresholds to initiate treatment to lower BP are 130/80 and 125/75 mmHg for people with diabetes and nephropathy, respectively. We sought to determine the effects of lowering BP below these currently recommended thresholds on renal outcomes among 11,140 patients who had type 2 diabetes and participated in the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. Patients were randomly assigned to fixed combination perindopril-indapamide or placebo, regardless of their BP at entry. During a mean follow-up of 4.3 yr, active treatment reduced the risk for renal events by 21% (P < 0.0001), which was driven by reduced risks for developing microalbuminuria and macroalbuminuria (both P < 0.003). Effects of active treatment were consistent across subgroups defined by baseline systolic or diastolic BP. Lower systolic BP levels during follow-up, even to <110 mmHg, was associated with progressively lower rates of renal events. In conclusion, BP-lowering treatment with perindopril-indapamide administered routinely to individuals with type 2 diabetes provides important renoprotection, even among those with initial BP <120/70 mmHg. We could not identify a BP threshold below which renal benefit is lost.
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- 2009
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38. Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients.
- Author
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Knudsen ST, Laugesen E, Hansen KW, Bek T, Mogensen CE, and Poulsen PL
- Subjects
- Age of Onset, Aged, Albuminuria, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Calcium Channel Blockers therapeutic use, Creatinine urine, Cross-Sectional Studies, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 urine, Disease Progression, Female, Humans, Hypoglycemic Agents therapeutic use, Male, Middle Aged, Monitoring, Ambulatory methods, Regression Analysis, Blood Pressure physiology, Circadian Rhythm, Diabetes Mellitus, Type 2 physiopathology, Diabetic Nephropathies physiopathology, Pulse
- Abstract
Aims/hypothesis: We followed type 2 diabetic patients over a long period to evaluate the predictive value of ambulatory pulse pressure (PP) and decreased nocturnal BP reduction (non-dipping) for nephropathy progression., Methods: Type 2 diabetic patients (n = 112) were followed for an average of 9.5 (range 0.5-14.5) years. At baseline, all patients underwent 24 h ambulatory BP measurement. Urinary albumin excretion rate was evaluated by three urinary albumin:creatinine ratio measurements at baseline and follow-up., Results: At baseline, patients who subsequently progressed to a more advanced nephropathy stage (n = 35) had reduced diastolic night/day BP variation and higher 24 h systolic BP and PP values; they also had more advanced nephropathy and were more likely to smoke than those with no progression of nephropathy (n = 77). In a Cox regression analysis, independent predictors of nephropathy progression were 24 h PP (p < 0.01), diastolic night:day BP ratio (p = 0.02) and smoking (p = 0.02). The adjusted hazards ratio (95% CI) for each mmHg increment in 24 h PP was 1.04 (1.01-1.07), whereas the adjusted hazards ratio (95% CI) for each 1% increase in diastolic night:day BP ratio was 1.06 (1.01-1.11). Only one of 33 patients (3.0%) with both a diastolic night:day BP ratio and a 24 h PP below the median progressed, whereas 17 of 32 patients (53.1%) with both a diastolic night:day BP ratio and a 24 h PP equal to or above the median progressed to a more advanced nephropathy stage (p < 0.001)., Conclusions/interpretation: Ambulatory PP, impaired nocturnal BP decline and smoking are strong, independent predictors of nephropathy progression in type 2 diabetic patients.
- Published
- 2009
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39. Twelve shifting paradigms in diabetic renal disease and hypertension.
- Author
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Mogensen CE
- Subjects
- Albuminuria, Humans, Prognosis, Diabetic Nephropathies complications, Hypertension diagnosis
- Abstract
In the last 30 years we have seen considerable progress in the management of patients with diabetes, in particular with diabetic renal disease. A number of paradigms have been broken down, namely the following, as a consequence, clinical care has improved dramatically. . Significant renal involvement and albuminuria is rare in patients with essential hypertension. 2. High GFR is good for prognosis. 3. Only proteinuric diabetic patients have a poor prognosis. 4. Microalbuminuria only predicts renal disease. 5. Reducing blood pressure may cause low perfusion in the kidney and other organs with long-term negative effect, especially on the glomerular filtration rate. 6. Only in the presence of high blood pressure, should microalbuminuric patients receive anti-hypertensive treatment, including blockade of the RAS. 7. Only reducing blood pressure by blocking RAS in diabetes is relevant and justified. 8. Normoalbuminuria as indicated in the present definition is 'normal'. 9. ACE-I or ARB can only be used separately. 10. Diastolic blood pressure and later systolic pulse pressure are the best parameters for blood pressure recording. 11. Microalbuminuria is the strongest risk marker in patients with type 1 diabetes. 12. Screening for microalbuminuria is relevant, but follow-up was not proposed (also regarding microalbuminuria). In the present situation, it is well-known that patients with essential hypertension may sometimes have microalbuminuria, and it is known that it predicts a poor prognosis. Interestingly, in type 1 diabetes, hyperfiltration is a marker for poor prognosis related to metabolic control. Thus hyperfiltration is a marker for bad development, but microalbuminuria (below the proteinuric level) is also associated with a poor prognosis. It was originally believed that microalbuminuria only predicts renal disease. However, surprisingly it predicts as well cardiovascular disease and early mortality. The story about blood pressure and progression of renal disease is interesting, because it was earlier believed that a certain high blood pressure was mandatory for preservation of the renal function. This appeared to be a completely wrong concept. The data regarding microalbuminuria suggest that patients with microalbuminuria should receive anti-hypertensive treatment, even patients with so-called normal blood pressure. This was confirmed in several trials and also included in the guidelines. Reducing blood pressure is important, but it appeared to be especially beneficial to block the renin-angiontensin system, and it is clear that albuminuria is a continuous variable and is also a risk factor. Earlier it was suggested to use ACE-inhibitors or ARBs. Now it is clear that it is possible to use a combination, with good theoretical background. In the history of hypertension, it was earlier believed that diastolic blood pressure was most important, but later on it was generally accepted that systolic is a better predictor and the goal for treatment and pulse pressure may be even better. Not only is microalbuminuria an important risk marker, but it is as well clear that regression of microalbuminuria is a good marker for a better prognosis in patients. Microalbuminuria is believed to be the strongest risk factor, but new studies actually suggest that a simple parameter such as self-rated health is crucial along with other factors. Regarding new developments, it is clear that new studies have led to several advancements in management in patients, for instance the Steno II study shows positive effect on mortality by multifactorial intervention. Similarly, the ADVANCE study also showed positive effect on mortality by more intensified anti-hypertensive treatment with an ACE-inhibitor. We are eagerly awaiting the results from glucose arm in the ADVANCE study, especially in the light of the ACCORD study showing increased mortality with too strict glycemic control with a goal of 6% in HbA1c.
- Published
- 2008
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40. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients with left ventricular hypertrophy and diabetes.
- Author
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Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, and Mogensen CE
- Subjects
- Albuminuria complications, Albuminuria physiopathology, Angiotensin II Type 1 Receptor Blockers therapeutic use, Denmark epidemiology, Diabetes Mellitus, Type 2 metabolism, Follow-Up Studies, Glomerular Filtration Rate, Humans, Hypertension drug therapy, Hypertension metabolism, Hypertrophy, Left Ventricular metabolism, Losartan therapeutic use, Morbidity trends, Myocardial Infarction etiology, Prognosis, Risk Factors, Stroke etiology, Survival Rate trends, Time Factors, Albuminuria urine, Creatinine urine, Diabetes Mellitus, Type 2 complications, Hypertension complications, Hypertrophy, Left Ventricular complications, Myocardial Infarction epidemiology, Stroke epidemiology
- Abstract
In type 2 diabetes the degree of albuminuria is strongly related to progression of diabetic renal disease, as well as to the risk for cardiovascular complications. If normoalbuminuria is maintained, the risk of diabetic nephropathy is very low. In individuals with microalbuminuria, the rate of decline in glomerular filtration rate is closely related to the degree of albuminuria, and regression to normoalbuminuria slows down the rate of decline in renal function. Data from the LIFE-diabetes subgroup showed that levels of albuminuria well below what is usually defined as microalbuminuria, strongly predicted risk for cardiovascular complications. This indicates that when albuminuria is used as a risk predictor for cardiovascular events, so called normal values should be redefined. Traditional values for normo-micro-macroalbuminuria are primarily defined as predictors for the risk of development of diabetic nephropathy. In the LIFE-diabetes subgroup we found that reduction in albuminuria was more pronounced in losartan-based as compared with atenolol-based treatment. The benefit in favor of losartan was partly related to its major influence on albuminuria. Individuals with the highest baseline values of albuminuria had the greatest benefit in terms of reduction in cardiovascular morbidity and mortality on losartan as compared with atenolol. The level of albuminuria during treatment was closely related to the risk for cardiovascular events. We conclude that tiny amounts of albuminuria, well below traditional levels for microalbuminuria, predict cardiovascular morbidity and mortality. Reduction in albuminuria during treatment translates to reduction in cardiovascular events. Monitoring of albuminuria should be an integrated part of management of hypertension in diabetic as well as nondiabetic patients.
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- 2008
41. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.
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Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, and Travert F
- Subjects
- Aged, Blood Glucose analysis, Cardiovascular Diseases epidemiology, Cardiovascular Diseases mortality, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 mortality, Diabetic Angiopathies epidemiology, Diabetic Angiopathies prevention & control, Diabetic Nephropathies epidemiology, Diabetic Nephropathies prevention & control, Drug Therapy, Combination, Female, Follow-Up Studies, Gliclazide adverse effects, Humans, Hypoglycemia chemically induced, Hypoglycemic Agents adverse effects, Male, Middle Aged, Proportional Hazards Models, Risk Factors, Diabetes Mellitus, Type 2 drug therapy, Gliclazide administration & dosage, Glycated Hemoglobin analysis, Hypoglycemic Agents administration & dosage
- Abstract
Background: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain., Methods: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately., Results: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001)., Conclusions: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.), (2008 Massachusetts Medical Society)
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- 2008
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42. Pulse pressure lowering effect of dual blockade with candesartan and lisinopril vs. high-dose ACE inhibition in hypertensive type 2 diabetic subjects: a CALM II study post-hoc analysis.
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Knudsen ST, Andersen NH, Poulsen SH, Eiskjaer H, Hansen KW, Helleberg K, Poulsen PL, and Mogensen CE
- Subjects
- Aged, Albuminuria complications, Biphenyl Compounds, Blood Pressure drug effects, Blood Pressure Monitoring, Ambulatory, Drug Therapy, Combination, Female, Humans, Hypertension complications, Hypertension diagnosis, Male, Middle Aged, Treatment Outcome, Angiotensin II Type 1 Receptor Blockers therapeutic use, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Benzimidazoles therapeutic use, Diabetes Mellitus, Type 2 complications, Hypertension drug therapy, Lisinopril therapeutic use, Tetrazoles therapeutic use
- Abstract
Background: Elevated pulse pressure (PP) is strongly associated with micro- and macrovascular complications in type 2 diabetic patients. We examined the effect of 12 months of dual blockade with candesartan and lisinopril vs. high-dose lisinopril monotherapy on ambulatory PP in hypertensive type 2 diabetic patients from the CALM (Candesartan and Lisinopril Microalbuminuria Trial) II study., Methods: The CALM II study was a 12-month prospective, randomized, parallel-group, double-masked study that included 75 type 1 and type 2 diabetic subjects with hypertension. Participants were randomized for treatment with either high-dose lisinopril (40 mg once daily (o.d.)) or for dual blockade treatment with candesartan (16 mg o.d.) and lisinopril (20 mg o.d.). In this article, we present data from the post-hoc subgroup of 51 type 2 diabetic subjects who completed the full 12-month study period with successful ambulatory blood pressure (BP) measurements at both baseline and follow-up visits., Results: Baseline 24-h BP values were similar in the two groups (24-h systolic BP (SBP) 130 +/- 12 vs. 127 +/- 9, 24-h diastolic BP (DBP) 77 +/- 8 vs. 74 +/- 7, and 24-h PP 53 +/- 8 vs. 53 +/- 7 mm Hg, for the lisinopril and dual blockade groups, respectively, P > 0.2 for all). Compared with lisinopril monotherapy, dual blockade treatment caused a highly significant reduction in 24-h PP levels (-5 +/- 5 mm Hg, P = 0.003), albeit the difference in the BP lowering effect between the treatment groups did not differ significantly for 24-h systolic (P = 0.21) or diastolic (P = 0.49) BP. Dual blockade treatment significantly lowered 24-h SBP (-5 +/- 11 mm Hg, P = 0.03), but not 24-h DBP (-2 +/- 7 mm Hg, P = 0.29), whereas in the lisinopril group, the opposite effect was observed (24-h SBP -1 +/- 9 mm Hg, P = 0.45, 24-h SBP -3 +/- 7 mm Hg, P = 0.03)., Conclusions: Twelve months of dual blockade with candesartan and lisinopril significantly reduced PP when compared with high-dose monotherapy with lisinopril. Larger studies are needed to confirm this observation, and to evaluate whether this effect translates into a greater degree of end-organ protection from dual blockade treatment than from conventional angiotensin-converting enzyme (ACE) inhibition.
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- 2008
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43. The management of the type 2 diabetic patient with hypertension - too late and too little: suggested improvements.
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Rydén L, Waeber B, Ruilope LM, Mancia G, Volpe M, Holzgreve H, Mogensen CE, and Laurent S
- Subjects
- Diabetes Complications prevention & control, Diabetes Mellitus, Type 2 physiopathology, Disease Management, Drug Therapy, Combination, Humans, Renin-Angiotensin System drug effects, Treatment Outcome, Antihypertensive Agents therapeutic use, Diabetes Mellitus, Type 2 complications, Hypertension drug therapy
- Abstract
Patients with comorbid hypertension and type 2 diabetes are common, have a greatly increased risk of premature cardiovascular and renal morbidity and mortality, and are likely to increase substantially in number over the next 10-15 years. We suggest the need for more aggressive management strategies for these patients, regardless of their baseline blood pressure, including the early use of combination therapy with blockers of the renin-angiotensin system.
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- 2008
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44. Simvastatin reduces plasma osteoprotegerin in type 2 diabetic patients with microalbuminuria.
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Nellemann B, Gormsen LC, Dollerup J, Schmitz O, Mogensen CE, Rasmussen LM, and Nielsen S
- Subjects
- Albuminuria blood, Atherosclerosis prevention & control, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 urine, Diabetic Angiopathies prevention & control, Diabetic Nephropathies blood, Diabetic Nephropathies drug therapy, Double-Blind Method, Enzyme-Linked Immunosorbent Assay, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Male, Diabetes Mellitus, Type 2 drug therapy, Osteoprotegerin blood, Simvastatin therapeutic use
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- 2007
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45. Endothelial dysfunction, ambulatory pulse pressure and albuminuria are associated in Type 2 diabetic subjects.
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Knudsen ST, Jeppesen P, Frederiksen CA, Andersen NH, Bek T, Ingerslev J, Mogensen CE, and Poulsen PL
- Subjects
- Aged, Blood Pressure Monitoring, Ambulatory methods, Endothelium, Vascular physiopathology, Female, Humans, Male, Middle Aged, von Willebrand Factor analysis, Albuminuria physiopathology, Blood Pressure physiology, Cardiovascular Diseases physiopathology, Diabetes Mellitus, Type 2 physiopathology, Diabetic Angiopathies physiopathology
- Abstract
Aim: Elevated pulse pressure (PP) is associated with microvascular complications in Type 2 diabetic patients. In non-diabetic subjects, elevated PP has been associated with endothelial dysfunction. The relation between endothelial dysfunction and PP in diabetic subjects has not previously been examined. We examined the relation between PP, markers of endothelial activation and albuminuria in Type 2 diabetic patients., Methods: In 46 Type 2 diabetic patients and 19 non-diabetic subjects, we performed 24-h ambulatory blood pressure (AMBP) monitoring. Urinary albumin excretion rate was measured as three urinary albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma., Results: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or macroalbuminuria (group A). PP levels increased in a stepwise manner from the control group (group C) to group N and group A; night PP 43 +/- 5, 48 +/- 10 and 59 +/- 12 mmHg (groups C, N and A, respectively, P < 0.001). Likewise, plasma levels of vWF, fibrinogen, E-selectin and ICAM-1 increased from group C to group A; e.g. ICAM-1 [median (interquartile range)] 191 (160-217), 213 (189-262) and 316 (260-417) ng/ml, groups C, N and A, respectively, P < 0.001). In diabetic patients, night PP and plasma levels of E-selectin and ICAM-1 correlated (r = 0.38, P < 0.01 and r = 0.37, P = 0.01, night PP with E-selectin and ICAM-1, respectively)., Conclusion: Increased PP is associated with endothelial activation and albuminuria in Type 2 diabetic patients. Thus, endothelial dysfunction may represent a pathophysiological link between an elevated PP and microvascular complications in these subjects. Prospective studies are needed to further elucidate these associations.
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- 2007
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46. Response of retinal arteriole diameter to increased blood pressure during acute hyperglycaemia.
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Jeppesen P, Knudsen ST, Poulsen PL, Mogensen CE, Schmitz O, and Bek T
- Subjects
- Acute Disease, Adult, Arterioles physiology, Blood Glucose metabolism, Cross-Over Studies, Double-Blind Method, Exercise physiology, Humans, Male, Muscle, Smooth, Vascular, Ophthalmic Artery physiology, Ophthalmodynamometry, Somatostatin administration & dosage, Tomography, Optical Coherence, Vasoconstriction physiology, Blood Pressure physiology, Hyperglycemia physiopathology, Retinal Artery physiology
- Abstract
Purpose: To study retinal response in terms of arteriole diameter and retinal thickness secondary to an increase in arterial blood pressure during acute hyperglycaemia., Methods: In a randomized, double-blinded, cross-over study, nine healthy persons were subjected to clamping of blood glucose to either 5 mmol/l or 15 mmol/l using somatostatin to control endogenous insulin secretion. The response of retinal arterioles in terms of diameter as determined with the retinal vessel analyser (RVA) and retinal thickness as assessed by optical coherence tomography (OCT) were measured after an increase in arterial blood pressure induced by isometric exercise. Arterial feeding pressure in the eye was assessed from the ophthalmic artery pressure and pulse amplitude measured by ophthalmodynamometry., Results: Isometric exercise induced a significant increase in mean arterial blood pressure and a significant contraction of the retinal arterioles. An acute increase in blood glucose from 5 mmol/l to 15 mmol/l did not affect either the diameter of retinal vessels or retinal thickness., Conclusions: Acute hyperglycaemia per se does not change isometric exercise-induced retinal arteriolar contraction. Metabolic factors other than blood glucose are suspected to be involved in the impairment of retinal autoregulation as seen in hyperglycaemia induced by oral glucose intake.
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- 2007
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47. Endothelial perturbation: a link between non-dipping and retinopathy in type 2 diabetes?
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Knudsen ST, Jeppesen P, Frederiksen CA, Andersen NH, Bek T, Ingerslev J, Mogensen CE, and Poulsen PL
- Abstract
Reduced diurnal blood pressure (BP) variation ("non-dipping") is associated with both micro- and macrovascular complications in patients with type 2 diabetes. The relation between endothelial perturbation and diurnal BP variation in diabetic subjects has not previously been studied. Seventy-six subjects, stratified to 4 gender-, age-, and duration-matched groups of 19 subjects each, were studied (group A: non-diabetic subjects; group B to D, type 2 diabetic subjects; group B: no retinopathy; group C: minimal background retinopathy; group D: diabetic maculopathy). All subjects underwent a 24-hour ambulatory BP monitoring. von Willebrand factor (vWF), fibrinogen, E-selectin, and intercellular adhesion molecule-1 were measured in plasma. Systolic night/day BP ratio increased gradually in groups A to D: 85.2 +/- 5%, 85.7 +/- 7%, 88.5 +/- 6%, and 90.5 +/- 7%, respectively, P < .05. Among diabetic patients, non-dippers had significantly higher plasma levels of vWF and fibrinogen than dippers (median/interquartile range 1.7/1.4 to 2.1 vs. 1.2/0.9 to 1.5 U/mL, P < .01 and 3.6/3.6 to 3.7 vs. 2.9/2.5 to 3.6 g/L, P = .01). Non-dipping is associated with elevated plasma levels of proteins related to endothelial cell activation as well as with retinopathy in subjects with type 2 diabetes. This finding suggests a possible mechanism linking non-dipping with microvascular complications in these subjects.
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- 2007
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48. Plasma concentrations of osteoprotegerin during normo- and hyperglycaemic clamping.
- Author
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Knudsen ST, Jeppesen P, Poulsen PL, Andersen NH, Bek T, Schmitz O, Mogensen CE, and Rasmussen LM
- Subjects
- Adult, Cross-Over Studies, Humans, Insulin blood, Insulin pharmacology, Male, Single-Blind Method, Somatostatin pharmacology, Blood Glucose analysis, Glucose Clamp Technique methods, Osteoprotegerin blood
- Abstract
Objective: Plasma levels of osteoprotegerin (OPG) are elevated in subjects with diabetes as well as in non-diabetic subjects with cardiovascular disease. In previous studies a positive correlation was found between plasma levels of OPG and markers of glycaemic control in diabetic subjects. The aim of the present study was to examine the effect of acute hyperglycaemia on plasma levels of OPG in non-diabetic subjects., Material and Methods: Nine healthy, lean, male subjects were examined in a randomized, blinded, cross-over study design during hyperglycaemic (plasma glucose = 15 mmol/L, study H) as well as during euglycaemic (plasma glucose = 5 mmol/L, study E) conditions. Blood samples were collected at baseline and at t=240 min., Results: Plasma OPG decreased slightly during study H (1.26+/-0.39 versus 1.19+/-0.35 ng/mL, p<0.05), whereas the level did not change significantly during study E (1.40+/-0.46 ng/mL versus 1.57+/-0.50 ng/mL, NS). The decrease in plasma OPG during hyperglycaemia did not correlate with the change in plasma glucose but correlated significantly with changes in serum insulin (r=-0.70, p=0.038)., Conclusions: Acute hyperglycaemia does not seem to increase plasma levels of OPG in non-diabetic subjects, whereas hyperinsulinaemia may suppress plasma levels of OPG. This finding indicates that the elevated plasma levels of OPG observed in diabetic subjects with poor metabolic control cannot be ascribed to hyperglycaemia per se.
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- 2007
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49. The blood pressure-induced diameter response of retinal arterioles decreases with increasing diabetic maculopathy.
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Frederiksen CA, Jeppesen P, Knudsen ST, Poulsen PL, Mogensen CE, and Bek T
- Subjects
- Arterioles physiopathology, Diabetes Mellitus, Type 2 physiopathology, Exercise physiology, Homeostasis, Humans, Middle Aged, Retina pathology, Tomography, Optical Coherence, Vasodilation, Blood Pressure physiology, Diabetic Retinopathy physiopathology, Macular Edema physiopathology, Retinal Artery physiopathology
- Abstract
Background: The aim of the study was to compare the diameter response of retinal arterioles and retinal thickness in patients with different stages of diabetic maculopathy during an increase in the arterial blood pressure., Methods: Four groups each consisting of 19 individuals were studied. Group A consisted of normal individuals and groups B-D consisted of type 2 diabetic patients matched for diabetes duration, age, and gender, and characterized by: Group B no retinopathy, Group C mild retinopathy, Group D maculopathy not requiring laser treatment. The diameter changes of a large retinal arteriole were measured using the Retinal Vessel Analyzer (RVA, Imedos, Germany) before, during, and after an increase in the blood pressure induced by isometric exercise. Additionally, the retinal thickness was measured using optical coherence tomography scanning., Results: The arterioles contracted during isometric exercise in normal persons (diameter response: -0.70+/-0.48%) and in patients with no retinopathy (-1.15+/-0.44%), but dilated in patients with mild retinopathy (0.41+/-0.49%) and diabetic maculopathy (0.54+/-0.44%), p=0.01. Retinal thickness was normal in Group A (260+/-5.0 microm), Group B (257+/-4.5 microm), and Group C (253+/-4.4 microm), but was significantly (p=0.006) increased in Group D (279+/-5.3 microm)., Conclusions: The diameter response was reduced in type 2 diabetic patients with retinopathy, whereas retinal thickness was increased in patients with diabetic maculopathy. This suggests that impairment of diameter response in retinal arterioles precedes the development of diabetic macular edema.
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- 2006
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50. Ambulatory pulse pressure and progression of albuminuria in type 2 diabetes: evidence provided, new questions emerge.
- Author
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Knudsen ST, Andersen NH, and Mogensen CE
- Subjects
- Albuminuria complications, Cross-Sectional Studies, Diabetes Mellitus, Type 2 complications, Disease Progression, Follow-Up Studies, Humans, Hypertension drug therapy, Middle Aged, New York, Predictive Value of Tests, Prospective Studies, Risk Factors, Telemedicine, Albuminuria physiopathology, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Diabetes Mellitus, Type 2 physiopathology, Hypertension physiopathology
- Published
- 2006
- Full Text
- View/download PDF
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