Asymptomatic peripheral nerve dysfunction and vascular reactivity in IDDM patients with and without microalbuminuria

Abstract

SummaryAbnormal vascular reactivity has been implicated in the aetiology of diabetic microvascular disease and we have previously demonstrated enhanced contractility of hand veins to noradrenaline in insulin-dependent diabetic (IDDM) patients with microalbuminuria. We have now assessed the possible contribution of subclinical peripheral nerve dysfunction to exaggerated vascular reactivity in microalbuminuric patients. Twenty-five IDDM patients (15 with microalbuminuria), none of whom had symptomatic neuropathy, and 10 control subjects were studied. Vasoconstrictor responses were measured in dorsal hand veins using noradrenaline and phenylephrine. Conduction in median, peroneal and sural nerves was assessed using electrophysiology, and autonomic function using standard cardiovascular reflex tests. The noradrenaline dose causing 50 % vasoconstriction was significantly lower in the microalbuminuric diabetic subjects compared with normoalbuminuric (3.6(1.7) mean (SEM) ng/min vs 20.1(6.0) ng/min, p = 0.0002) and non-diabetic subjects (35.1(5.0) ng/min; p < 0.0001). However, reactivity to phenylephrine did not differ between the groups. Median nerve motor conduction velocity was significantly slower in microalbuminuric (48.4(1.4) m/s) than in normoalbuminuric (52.7(1.2) m/s, p = 0.04) and non-diabetic subjects (56.7(0.9) m/s, p = 0.0001). In the diabetic group overall, there was a strongly positive linear correlation between vascular response to noradrenaline and conduction velocity in both the median nerve (r = 0.62, p = 0.0009) and peroneal nerve (r = 0.53, p = 0.006). There was no correlation between phenylephrine-induced responses and motor conduction velocity in either nerve, nor were indices of autonomic function correlated with vascular reactivity to either agent. Enhanced vascular reactivity to noradrenaline ((x 1-and a2-agonist), but not phenylephrine (ch-agonist only), in subclinical neuropathy is correlated with severity of nerve damage. This suggests that damage to presynaptic inhibitory a2-adrenoceptors is in part responsible for the exaggerated vascular responses found in microalbuminuric subjects. [Diabetologia (1994) Vascular tone is determined by neural and hormonal influences, including noradrenaline (NA) [1], which acts on vascular smooth muscle (x-adrenoceptors to cause vasoconstriction. These receptors can be stimulated by NA released locally from sympathetic nerve endings, and into the circulation from nerve endings and the adrenal medulla. We have previously reported that vascular reactivity to NA is exaggerated in normotensive insulin-dependent diabetic (IDDM) patients with incipient nephropathy [2]. We measured vascular responses in veins on the dorsum of

Ocular and systemic reactivity to isoprenaline in patients with insulin‐dependent diabetes mellitus

“…Moreover, it has been shown that large artery capacitance, which is defined as change in volume per change in pressure is reduced in patients with diabetes mellitus [8][9][10]. Increased aortic stiffness in IDDM patients was suggested from post-mortem experiments [11], whereas in vivo studies showed this only in diabetic women [12].…”