Clinics in Endocrinology and Metabolism最新文献

The diabetic foot can be classified into the neuropathic foot, characterized by the neuropathic ulcer, the Charcot joint and neuropathic oedema associated with a good circulation, in which neuropathy predominates, and the ischaemic foot in which atherosclerosis is the dominant factor leading to a reduction in blood flow with absent pulses.

In the neuropathic foot, blood flow is increased, the vessels are still and dilated as a result of medial wall calcification and there is evidence for arteriovenous shunting.

The neuropathic ulcer characteristically develops on the plantar surface following inflammatory autolysis and haematoma formation under neglected callosities. Chiropody is therefore the mainstay of treatment and recurrence is prevented by redistribution of weight bearing forces by moulded insoles in special footwear. Charcot osteoarthropathy is often preceded by fracture which is a further complication of diabetic neuropathy and which precipitates the rapid bone and joint destruction of the Charcot joint. Neuropathic oedema responds to ephedrine with a reduction in peripheral flow and an increase in urinary sodium excretion.

The ischaemic foot is characterized by rest pain, ulceration and gangrene. Medical management can be successful in up to 72%, the remainder needing arteriography to assess suitability for arterial reconstruction or angioplasty. In the diabetic leg, atherosclerosis is predominant in the branches of the popliteal artery making arterial reconstruction difficult.

Optimum care of the diabetic foot is provided in a diabetic foot clinic where the skills of chiropodist, shoe-fitter and nurse receive full support from physician and surgeon. Many lesions of the diabetic foot are avoidable and thus patient education is the cornerstone of prevention.

Many of the diabetic neuropathic syndromes are characterized by painful symptoms with a sensation of burning and associated with troublesome hyperaesthesia. It is important to distinguish between the acute and chronic forms of peripheral sensory neuropathy; while the former carries an excellent prognosis for symptomatic improvement within one year, the latter may cause persistent symptoms for many years. In contrast to the acute form, in which symptoms are particularly severe but abnormal neurological signs are minimal, patchy stocking and glove sensory loss together with peripheral small muscle wasting are often present in chronic sensorimotor neuropathy. Peripheral polyneuropathies are more common in patients with poor metabolic control, although recent evidence implicates blood glucose flux as a possible contributory factor to neuropathic pain. It is possible that blood glucose flux or altered peripheral blood flow leads to increased spontaneous activity in nociceptive afferent fibres which are present in the axonal sprouts that characterize small fibre neuropathy. In the diagnosis of the neuropathies, exclusion of other aetiological factors is of paramount importance as there is no specific diagnostic test for diabetic nerve damage. If there is no symptomatic improvement after a period of stable and optimal metabolic control together with simple analgesics, then the tricyclic drugs should be regarded as first line therapy. The rapid effect of these drugs suggests a peripheral rather than central mode of action.

Diabetic glomerulopathy is characterized by a very slow development of basement membrane (BM) accumulation, manifested as thickening of the peripheral BM and increased volume of the mesangial BM-like material (BMLM) with mesangial expansion. The initiation of the process is probably at the onset of diabetes since the BM thickening is detectable after a few years. The BM accumulations at the two sites (PBM and BMLM) in the glomerular tuft are considered as two different expressions of a fundamental BM abnormality. The two locations present different conditions for quantitation, may have a different biochemical make-up, and immediate functional implications of the abnormalities may differ as well. In the long run, however, the two in concert lead to the ultimate solidification of the glomerular tuft with loss of capillary surface. The end-stage is glomerular closure, with elimination of glomerular function. A very close correlation has been found between the total remnant surface area of the glomerular capillaries and the level of GFR.

Along with the classical changes of the diabetic glomerulopathy, changes in glomerular size are detectable. In early diabetes during the stages of glomerular hyperfunction, hypertrophy develops acutely at the onset of diabetes, leading to an increase in capillary surface corresponding to the increase in filtration rate. In the advanced stages when glomerular closure involves a proportion of the nephrons compensatory hypertrophy develops, thereby probably helping to preserve capillary surface for a period of time.

The exact mechanisms that may influence these developments are not known, but underlying them all are the metabolic abnormalities of diabetes.