Microvascular and C-Fiber Function in Diabetic Charcot Neuroarthropathy and Diabetic Peripheral Neuropathy

Abstract

OBJECTIVE -Sympathetic denervation and hyperemia are implicated in the pathogenesis of Charcot neuroarthropathy (CN) but are also features of diabetic peripheral neuropathy (DPN). Differences in these physiological parameters were sought by determining C-fiber function (laser Doppler imager [LDI]flare technique) and maximum microvascular hyperemia (MMH) in 13 subjects with diabetic CN (DCN), 10 subjects with DPN, and 10 healthy control subjects. Additionally, unaffected limbs of the nine DCN subjects with unilateral CN (UCN) were studied to determine whether any observed differences precede CN.RESULTS -LDIflare area was reduced in DPN (mean Ϯ SD 1.41 Ϯ 0.51 cm 2 ) and DCN (1.42 Ϯ 0.37) groups compared with the healthy control group (5.24 Ϯ 1.33; P Ͻ 0.0001). MMH was higher in DCN (432 Ϯ 88 PU [perfusion units]) than in DPN (262 Ϯ 71; P ϭ 0.001) subjects but lower than in the control group (564 Ϯ 112; P Ͻ 0.01). LDIflare area and MMH were similar in the UCN and DCN groups.CONCLUSIONS -C-fiber function is equally impaired in neuropathic patients with and without CN; however, a higher MMH distinguishes those with CN. Unaffected and affected limbs of those with unilateral CN have the same neurovascular abnormalities, suggesting that these abnormalities precede CN and are not a result of CN. Diabetes Care 30:3077-3079, 2007P eripheral sensory neuropathy and autonomic dysfunction are accepted prerequisites for the development of Charcot neuroarthropathy (CN) but are also features of diabetic peripheral neuropathy (DPN) (1,2). CN is rare in comparison with DPN, suggesting that additional factors are involved in its pathogenesis. Small-fiber neuropathy, measured with quantitative sensory testing, has been implicated in its development (3,4). Moreover, a relatively higher maximum microvascular hyperemia (MMH) has been reported (3,4); however, whether this is a result of CN or preexisting is unknown. This study examines these features in greater detail. Small-fiber neuropathy was assessed using the laser Doppler imager (LDI)flare technique (5), a more sensitive test of small-fiber function than quantitative sensory testing. MMH was assessed using the LDImax technique (5). The unaffected foot in those with CN was also studied to determine whether any defects in these measures were preexisting, and therefore etiological, or consequential of CN. RESEARCH DESIGN AND METHODS -Four matched groupswere studied: the DPN group, 10 subjects with type 2 diabetes and neuropathy (aged 67.2 Ϯ 7.1 years, diabetes duration 19 Ϯ 8.1 years, vibration perception threshold [VPT] 30.3 Ϯ 6.0 V); the DCN group, 13 subjects with type 2 diabetes and quiescent CN (aged 65.5 Ϯ 8.7 years, diabetes duration 20 Ϯ 11.3 years, VPT 36.1 Ϯ 9.7 V) (4 with bilateral and 9 with unilateral CN); the unilateral CN (UCN) group, 9 subjects with UCN from the DCN group in whom the unaffected limb was studied (aged 64.7 Ϯ 10.2 years, diabetes duration 21 Ϯ 10.2 years, and VPT 33.5 Ϯ 8.1 V); and the control group, 10 healthy subjects (aged 61.4 Ϯ 9.7 years, VPT 8.0 Ϯ...

Pressure pain perception in the diabetic Charcot foot: facts and hypotheses

“…Subsequently, traumatic ‘first’ pain (A-delta nociception) is abolished, and so are the corresponding withdrawal reflexes at the spinal level. C-fiber function may be reduced but probably not abolished (according to axon reflex studies (14, 16, 17)). Accordingly the skin may be totally insensate to pinprick stimulation but sensitive to crude touch, whereas deep tissue may be sensitive to blunt pressure stimulation.…”

The Charcot Foot in Diabetes

“…Although it has been suggested that people with a Charcot foot may have particular patterns of sensory loss reflecting involvement of different fibers (5,6), this is not generally accepted. Nevertheless, three groups have shown that people who have had an acute Charcot foot exhibit retention of vasodilatory reflexes in contrast to diabetic individuals with distal symmetrical neuropathy without CN (7–9). …”

Foot bone density in diabetes may be unaffected by the presence of neuropathy

“…Microvascular flow rather than global blood flow may be a differentiating factor. Generally, the microvasculature in those with diabetic neuropathies has a reduced ability to dilate; however, this ability appears to be retained in those with Charcot foot (Baker, Green, Krishnan, & Rayman, 2007;Shapiro et al, 1998;Veves, Akbari, Primavera, Donaghue, et al, 1998). Such a retention in the ability to vasodilate may cause uncontrolled blood flow to bone leading to its demineralisation.…”

“…Increased fragility to bone caused by particular neural (Rix et al, 1999) and vascular factors (Baker et al, 2007) is proposed to precede and predispose to Charcot foot. This study did not find clinical neuropathy patterns or vascular reactivity to affect bone density in those with diabetes.…”