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- Title
The influence of the ACE (I/D) polymorphism on systemic and renal vascular responses to angiotensins in normotensive, normoalbuminuric Type 1 diabetes mellitus P.T. Luik et al.: ACE (I/D) genotype and renal haemodynamics in Type 1 diabetes mellitus.
- Authors
Luik, P. T.; Hoogenberg, K.; Kerstens, M. N.; Beusekamp, B. J.; de Jong, P. E.; Dullaart, R. P. F.; Navis, G. J.
- Abstract
Aim/hypothesis. The renin-angiotensin-aldosterone system is important in diabetic nephropathy, with the angiotensin-converting-enzyme DD-genotype being a renal risk factor. The D-allele is associated with higher ACE concentrations, but functional consequences in diabetes mellitus are not known. To analyse these consequences, we assessed renal and systemic responsiveness to angiotensin I infusion, with the response to angiotensin II as reference. Methods. Uncomplicated Type 1 (insulin-dependent) diabetic patients with contrasting genotypes (11 II and 11 DD) were studied, during low (50 mmol/24 h) and liberal (200 mmol/24 h) sodium diet, during a euglycaemic clamp. Angiotensin I was infused at 4 and 8 ng·kg-1·min-1, 1 h each, followed by infusions of angiotensin II after a 2-h wash-out period. Results. During low sodium, DD-homozygotes showed higher blood pressure sensitivity to angiotensin I (DD 21±5% vs II 15±5%, p<0.01). With liberal sodium, no differences in blood pressure were detected, whereas angiotensin I induced a higher response of ERPF (DD 40±5% vs II 35±4%, p<0.05) and RVR (DD 105±20% and II 89±16% p<0.05) in DD-homozygotes. Differences were not explained by altered angiotensin II sensitivity. Multiple-linear regression analysis showed that angiotensin I induced responses of blood pressure and renal haemodynamics are higher in subjects carrying the DD-genotype. The magnitude of the responses was modulated by sodium intake and long-term glycaemic control. Conclusion/interpretation. This study showed that responses of blood pressure and renal haemodynamics to angiotensin I are increased in diabetic subjects carrying the DD-genotype. Genotype-associated differences in ACE concentrations could, under certain circumstances, have functional consequenses in uncomplicated Type 1 diabetes mellitus.
- Subjects
ANGIOTENSINS; ANGIOTENSIN converting enzyme; BLOOD pressure; DIABETES complications; BLOOD circulation; KIDNEY diseases
- Publication
Diabetologia, 2003, Vol 46, Issue 8, p1131
- ISSN
0012-186X
- Publication type
Article
- DOI
10.1007/s00125-003-1149-x