The 2017 Banting Memorial Lecture The diabetic lower limb - a forty year journey: from clinical observation to clinical science.

A series of clinical research projects conducted over the past 40 years, all of which were informed by clinical observation or discussions with people with diabetes and staff colleagues are described in this review. A study of necrobiosis lipoidica diabeticorum confirmed that this rare skin complication occurs predominantly in young women with Type 1 diabetes and other microvascular complications. Biopsies of necrobiotic lesions showed destruction of superficial nerve fibres by inflammatory tissue, which likely causes the sensory loss in lesions that is pathognomonic of the condition. The development of corneal confocal microscopy as a new non-invasive surrogate marker of peripheral neuropathy in diabetes is described next and several small studies of the use of this new technique in clinical research are reported. The influence of blood glucose instability on the genesis of neuropathic pain is then explained, with results suggesting that the stability of glycaemic control may be more important than the level of control achieved. Lastly, in neuropathy, studies of gustatory sweating are discussed, including the observation that sweating in the head and neck region is more common in people with end-stage diabetic nephropathy than in those with neuropathy. The disappearance of gustatory sweating after renal transplantation suggests a metabolic cause and for those with troublesome sweating, use of the anticholinergic, anti-muscarinic, topical cream glycopyrrolate is confirmed in a randomized control trial. In the area of diabetic foot research, distended dorsal foot veins were observed to be a clinical sign of sympathetic autonomic neuropathy: raised venous Po and Doppler abnormalities of blood flow are highly suggestive of arteriovenous shunting. A series of studies of the abnormalities of pressures and loads under the neuropathic diabetic foot are described: high dynamic plantar pressures are highly predictive of subsequent ulceration in the neuropathic foot. Lastly, a number of recent studies on unsteadiness and gait abnormalities when climbing and descending stairs are described. It is hoped that the art of clinical observation survives in the highly technological 21st century.