Can diabetic neuropathy be prevented by angiotensin-converting enzyme inhibitors?

The incidence of diabetes and its complications is increasing to staggering proportions. Presently the WHO estimates an overall prevalence of 130 million, but by 2025 there will be 300 million individuals with diabetes mellitus. The incidence of diabetic neuropathy approaches 50% in most diabetic populations; there is no treatment, and its consequences in the form of foot ulceration and amputation are financially punishing for health care providers. Attempts to develop treatments have faltered for want of an understanding of the aetiology of diabetic neuropathy. As a consequence, 1999 saw the demise of two further compounds: recombinant growth factor by Roche-Genentech and the aldose reductase inhibitor zopolrestat, by Pfizer, both had reached phase III clinical trials. They joined an impressive list of at least 30 other compounds which have reached phase III clinical trials and failed to establish efficacy. The need to establish a viable treatment for human diabetic neuropathy is absolutely paramount. To provide a rational answer as to whether angiotensin-converting enzyme (ACE) inhibitors can prevent human diabetic neuropathy, two major issues need addressing: 1) Does vascular dysfunction cause human diabetic neuropathy? 2) Can ACE inhibitors ameliorate diabetic vascular dysfunction and hence neuropathy? Epidemiological studies support a strong association between neuropathy, retinopathy and nephropathy. Microangiopathy is deemed as the root cause of both nephropathy, and retinopathy and mounting evidence provides support for a vascular basis of diabetic neuropathy. ACE inhibitors appear to correct many of the abnormalities associated with the vascular dysfunction found in diabetes. Thus effective ACE inhibition impacts very positively on cardiovascular outcomes in patients with ischaemic heart disease, particularly in diabetic patients. ACE inhibition also prevents the development and progression of incipient and established diabetic nephropathy and delays progression of background retinopathy. Quinapril improves measures of diabetic autonomic neuropathy. Our recent study has demonstrated a significant improvement in peripheral neuropathy following 12 months of treatment with the ACE inhibitor trandolapril.