Diabetic neuropathy: are we still barking up the wrong tree and is change finally in sight?

Excerpt

To the Editor: I read with interest the review article by Callaghan et al on diabetic neuropathy that was recently published in Diabetologia [1]. One seemingly relentless problem with this elusive diabetes complication is that recommended diagnostic methods [2] are much more applicable to research rather than to everyday clinical practice. As a result, diagnostic guidelines for diabetic neuropathy within diabetes clinic settings remain widely variable. Its heterogeneous presentation and insidious natural history render diabetic neuropathy research equally problematic. Clinical trials investigating a therapeutic role for protein kinase C β (PKCβ) inhibition, nerve growth factor (NGF) and aldose reductase inhibition [3] in established neuropathy using robust diagnostic criteria have been largely disappointing, and effective licensed treatments are still unavailable. The role of metabolic factors, such as lipids and sphingolipids, in the aetiology of neuropathy is discussed in some detail in the review by Callaghan and colleagues [1]. Although of novel scientific interest, further research in this area is realistically unlikely to influence clinical practice. Despite observed associations between dyslipidaemia and neuropathy, the limited outcome studies on lipid-lowering therapies in diabetic neuropathy are both unconvincing and conflicting [4]. The interventional research studies targeting obesity that are proposed by Callaghan et al [1] may show an interesting positive effect on neural function but, in the real world, weight loss and lifestyle modification remain a key strategic measure in diabetes irrespective of their effect on neuropathy. As prediabetes (impaired fasting glucose and impaired glucose tolerance), which is often related to obesity, is related to early complications, including neuropathy [5], investment in diabetes prevention programmes would seem a much safer direction. After all, the past has taught us with some conviction that prevention of neuropathy (as shown by the DCCT and, to a lesser extent, by the UK Prospective Diabetes Study [UKPDS]), is a much more reliable option than treatment. …