Small vessel disease in progressive diabetic neuropathy associated with good metabolic control.

Abstract

SUMMARY Clinical, electrophysiological, and electron microscopical data are presented on 10 diabetic patients with severe progressive neuropathy, predominantly motor in type, in the presence of good blood glucose control, and for one patient with painful neuropathy and third cranial nerve palsy. Endothelial cell hyperplasia was seen in small vessels in all cases, and seven patients showed plugging of the vascular lumen by degenerate cellular material and electron dense protein. It is suggested that these cells desquamate and occlude smaller peripheral vessels at a point of narrowing. In one case the lumen of a vessel was occluded by thrombus. Electron microscopical examination showed a vessel occluded by degranulated platelets.Electrophysiological studies showed a pattern of denervation that was asymmetrical and distally predominant in some patients, suggesting that the neuropathy, at least in part, relates to multiple small infarcts.Peripheral nerves in diabetes sustain widespread damage consisting of segmental demyelination' and axonal degeneration.2 Various clinical syndromes occur as a result, and it is now customary to refer to "diabetic neuropathies" rather than to the single entity of diabetic neuropathy. The aetiology of diabetic neuropathy is still under question, and the relative importance of metabolic and vascular factors is uncertain.Many of the syndromes of diabetic neuropathies manifest diffuse sensory or motor features, suggesting a metabolic effect; it is possible, however, that diffuse small vessel disease could also result in symmetrical abnormalities of nerve function. In 1959 Fagerberg described "vascular lesions in peripheral nerve in the form of hyalinisation, caliber reduction and thickening of the wall which were more common in patients with diabetic neuropathy than in other groups."3 He attributed such change to progressive degenerative disease and assumed that they were responsible for the structural damage to the myelin sheath in diabetic patients. Timperley et al described plugging of small blood vessels with fibrin or thrombus, and also focal areas of necrosis and loss of nerve fibre.4 Similarly, Williams et al, in an electron microscopical study, described thrombi and hyperplasia of vascular endothelial cells sufficient to occlude the lumen of small vessels.5 They suggested Accepted for publication 15 May 1985 that hyperplasia of endothelial cells could result in profound alterations of local blood flow and might account for a symmetrical form of neuropathy. Material and methodsWe studied 11 patients with diabetes ( Table 1). Nine of these had type II diabetes and two type I. The age range of the patients was 31-77 (mean 58.2) years with a duration of diabetes of one to 25 (mean 6.2) years. The duration of the neuropathic syndrome was relatively short at two to 24 (mean 12) months. All but one patient had a range of random blood glucose concentrations consistently below 9 mmol/l (162 mg/100 ml). The glycosylated haemoglobin values in the patients were near to the normal range (m...

Thrombomodulin Deficiency in Human Diabetic Nerve Microvasculature

“…Peripheral neuropathy is the most prevalent neurological sequelae, present in ϳ60% of individuals with non-insulin-dependent diabetes (2). Although the precise mechanisms underlying human diabetic neuropathy remain controversial, a consensus of research indicates that microvascular ischemia is a final common pathological event (3,4). Despite the established importance of microangiopathy, no prior studies have investigated the role of impaired native thrombomodulin (TM)-protein C antithrombotic mechanisms in the pathogenesis of diabetic neuropathy.…”

Impaired blood flow and arterio-venous shunting in human diabetic neuropathy: a novel technique of nerve photography and fluorescein angiography

“…In man, nerve biopsy studies have shown that when there is significant diabetic neuropathy, severe microvascular abnormalities [4][5][6][7][8][9][10] are present. In addition, the degree of vessel disease correlates with the severity of nerve damage [6,10] and the multifocal pattern of nerve fibre loss suggests ischaemia [8,9].…”

An Update On Rodent Model Studies In Diabetic Neuropathy: A Brief Communication

“…It can be assumed that, depending on the severity and duration of diabetes, it is the degree of spinal reorganization, due to the degeneration of small afferents, for example, which leads to the deafferentation of spinal neurons and the abnormal branching of A-b fibers. [16,45,47] Moreover, the anatomical framework of the spinal cord allows the transfer of specific inputs to localized subsets of dorsal horn neurons. This allows the separation in signal transduction pathways for low-intensity stimuli and noxious stimuli.…”

“…[15] The best predictor of T2DM macrovascular complications is the preceding presence of microvascular complications, particularly diabetic polyneuropathy (DPN) and diabetic nephropathy (DN). [2] DPN consists of demyelization and axonal degeneration of peripheral nerves, [16], leading to slowing of nerve conduction velocity and reduction of the amplitude of the compound muscle and sensory nerve action potentials. [16,23] These features of diabetic polyneuropathy are observed in human diabetes [16,24] and in experimentally induced diabetic animals.…”

“…[2] DPN consists of demyelization and axonal degeneration of peripheral nerves, [16], leading to slowing of nerve conduction velocity and reduction of the amplitude of the compound muscle and sensory nerve action potentials. [16,23] These features of diabetic polyneuropathy are observed in human diabetes [16,24] and in experimentally induced diabetic animals. [17][18][19][20][21][22][23] DPN is one of the main complications of diabetes, which may impair the peripheral nerve regeneration.…”