Non-insulin-dependent diabetes mellitus, nephropathy, and the renin system.
Renal protective effects in diabetic patients. Blocking the renin-angiotensin system slows the progression of nephropathy and end-stage renal disease in diabetes mellitus. While substantial evidence exists for the renal protective effects of angiotensin converting enzyme (ACE) inhibitors in patients with insulin-dependent diabetes mellitus (IDDM), the role of renin-angiotensin system blockade in non-insulin-dependent diabetes mellitus (NIDDM) is less clear. The evidence regarding ACE inhibitors has been attained through the traditional channels of evidence-based medicine: observational studies, trials in animal models, preliminary human analyses, and large, randomized trials. While a sound approach, these pathways to elucidating therapeutic effects require the expenditure of substantial time and resources. Accelerated trials with angiotensin II receptor antagonists have relied on the proven effects of ACE inhibitors in the diabetic patient, as well as on pharmacologic principles dictating that renin-angiotensin blockade is more complete when the system is interrupted at the rate-limiting or receptor level. Irbesartan and creatinine clearance in NIDDM patients. The Collaborative Study pilot trial has already shown that the angiotensin II receptor antagonist irbesartan is significantly more effective than the calcium antagonist amlodipine on creatinine clearance in hypertensive NIDDM patients. Subsequent to this trial, a large, randomized study of over 1600 hypertensive patients with NIDDM has been initiated. Other trials have indicated that the response to blocking angiotensin II receptors with irbesartan in patients with NIDDM is substantially larger than it is in healthy humans.
Hollenberg
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Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D000077405:Irbesartan; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D013777:Tetrazoles; D003404:Creatinine; D000077405:Irbesartan