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 mill ion, but by 2025 there will be 300 million individuals with diabetes mellit us. The incidence of diabetic neuropathy approaches 50% in most diabetic po pulations; there is no treatment, and its consequences in the form of foot ulceration and amputation are financially punishing for health care: provid ers. Attempts to develop treatments have faltered for want of an understand ing of the aetiology of diabetic neuropathy. As a consequence, 1999 saw the demise of two further compounds: recombinant growth factor by Roche-Genent ech and the aldose reductase inhibitor zopolrestat, by Pfizer, both had rea ched 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 d iabetic neuropathy is absolutely paramount. To provide a rational answer as to whether angiotensin-converting enzyme (ACE) inhibitors can prevent huma n diabetic neuropathy, two major issues need addressing: 1) Does vascular d ysfunction cause human diabetic neuropathy? 2) Can ACE inhibitors ameliorat e diabetic vascular dysfunction and hence neuropathy? Epidemiological studi es support a strong association between neuropathy, retinopathy and nephrop athy. 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 abnormali ties associated with the vascular dysfunction found in diabetes. Thus effec tive ACE inhibition impacts very positively on cardiovascular outcomes in p atients with ischaemic heart disease, particularly in diabetic patients. AC E inhibition also prevents the development and progression of incipient and established diabetic nephropathy and delays progression of background reti nopathy, Quinapril improves measures of diabetic autonomic neuropathy. Our recent study has demonstrated a significant improvement in peripheral neuro pathy following 12 months of treatment with the ACE inhibitor trandolapril.