Angiotensin-converting enzyme inhibitors: Are there credible mechanisms for beneficial effects in diabetic neuropathy?

Abstract

Publisher Summary This chapter discusses that there is no treatment for diabetic neuropathy, and this lack of an effective therapy derives from three principal factors: (1) the complex etiology of the condition, (2) imperfect animal modeling and failure to accurately translate experimental findings to the clinical arena, and (3) imperfect drug candidates and flawed clinical trial design. Retrospective rationalization offers plausible explanations for the spectacular failures has been witnessed in clinical trials of human diabetic neuropathy. They include inappropriate selection of patients according to neuropathic severity, drug toxicity, inadequate drug potency, inappropriate measures of therapeutic efficacy, and inadequately short periods of study aimed to rapidly reverse a process, which has taken many years to develop. Angiotensin-converting enzyme (ACE) inhibitors have surpassed all predictions for their widespread use in clinical medicine. Initially deemed useful only in a select group of patients with renovascular hypertension, they constitute the panacea for the treatment of diabetes and its complications, ischemic heart and cerebrovascular disease, and nephropathy from a variety of causes. The pharmacology of ACE inhibition is complex and provides for a number of major interactions with pathogenetically relevant pathways resulting in human diabetic neuropathy.