Low-dose ramipril reduces microalbuminuria in type 1 diabetic patients without hypertension results of a randomized controlled trial - Results of a randomized controlled trial

被引:85
作者
O'Hare, JP [1 ]
Bilous, R [1 ]
Mitchell, T [1 ]
O'Callaghan, CJ [1 ]
Viberti, GC [1 ]
Willoughby, R [1 ]
Riley, J [1 ]
Robinson, AM [1 ]
Reckless, JP [1 ]
Havard, F [1 ]
Sampson, M [1 ]
Lloyd, A [1 ]
Williams, T [1 ]
Vora, J [1 ]
Chattington, P [1 ]
Hampson, K [1 ]
Ibrahim, H [1 ]
Borthwick, L [1 ]
Willoughby, R [1 ]
Viberti, G [1 ]
Russell, C [1 ]
Barnes, D [1 ]
Macklin, A [1 ]
Murphy, E [1 ]
Stephens, E [1 ]
Vincent, J [1 ]
Tindall, H [1 ]
Simpson, H [1 ]
Knowles, E [1 ]
Cunningham, B [1 ]
Simpson, E [1 ]
Bilous, R [1 ]
Bilous, M [1 ]
Mitchell, T [1 ]
O'Halloran, D [1 ]
Nugent, S [1 ]
Hadden, D [1 ]
Fetherstone, M [1 ]
McCarton, D [1 ]
McGurk, C [1 ]
Johnston, C [1 ]
Burton, J [1 ]
Harris, C [1 ]
Hempstead, H [1 ]
Baksi, A [1 ]
Bartlett, J [1 ]
Heaton, C [1 ]
Brown, K [1 ]
Arora, A [1 ]
Burke, J [1 ]
机构
[1] Univ Warwick, Sch Biol Sci, Sir Quentin Hazel Inst Mol Med, Coventry CV4 7AL, W Midlands, England
关键词
D O I
10.2337/diacare.23.12.1823
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE - To assess if low (1.25 mg) and/or standard (5 mg) doses of the ACE inhibitor ramipril could prevent progression of microalbuminuria (incipient diabetic nephropathy) in normotensive type 1 diabetic patients. RESEARCH DESIGN AND METHODS - This study, using a multicenter randomized placebo-controlled double-blind parallel group, was conducted over 2 years in 28 outpatient diabetic clinics in the U.K. and Ireland. We screened 334 type 1 diabetic patients with suspected microalbuminuria and normal blood pressure; of these, 140 patients 18-65 years of age with a diagnosis of type 1 diabetes and persistent microalbuminuria, defined as urinary albumin excretion rate (AER) of 20-200 mug/min, were enrolled in the study. RESULTS - The proportion of patients progressing to macroalbuminuria was reduced in the ramipril groups but did not reach statistical significance over 2 years. AER was significantly lower at year 2 in the combined ramipril-treated patients versus placebo (P = 0.013). More patients on ramipril regressed to normoalbuminuria (<20 <mu>g/min), with 11% for 1.25 mg ramipril, 20% for 5 mg ramipril, and 4% for placebo (P = 0.053). Blood pressure was significantly reduced to a similar extent with both 1.25 and 5 mg ramipril. Supine systolic blood pressure increased from 130 to 134 mmHg in the placebo group and fell in the 1.25 mg ramipril group (from 132 to 129 mmHg) and in the 5 mg ramipril group (from 134 to 130 mmHg) (P = 0.003, compared with placebo). No statistically significant changes were observed in glomerular filtration rate (GFR) between the placebo- and ramipril-treated groups during the 2-year period. CONCLUSIONS - Microalbuminuria is reduced significantly by ramipril treatment in type 1 diabetic patients without hypertension. Although the magnitude of the response was greater, there is no significant difference between responses to 1.25 or 5 mg ramipril. Small but highly significant reductions in systolic and mean arterial pressures occur in ramipril-treated patients. GFR is stable at this stage of the evolution of diabetic nephropathy and is unaffected by ramipril treatment for 2 years.
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页码:1823 / 1829
页数:7
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