Abstract 4085: Altered Homeostatic Response to Postural Change and Loss of Capillary Autoregulation in Diabetic (type 1) Nephropathy
Objective Capillary hypertension and altered autonomic neural function are well known features in DM type 1 patients with microalbuminuria (DN). In order to investigate loss capillary autoregulation, we studied changes in arterial hemodynamics and its consequences for the resulting capillary fluid shift during postural change.
Methods The data were collected in control subjects (C, n=8), normoalbuminuric (DM, n=8) and DN (n=8), matched for age and duration of diabetes. The patients did not use antihypertensive medication and did not have clinical apparent autonomic neuropathy as assessed by five standard cardiovascular reflex tests. The parameters studied were blood pressure, heart rate, femoral blood flow (duplex doppler ultrasonography), capillary fluid shift (changes of bioelectrical impedance), autonomic neural function (spectral analysis of heart rate variability), and levels of norepinephrine and epinephrine.
Results Vascular resistance and sympatico-neural activity were higher in rest in DN. After postural change, mean arterial blood pressure, heart rate, and vascular resistance increased in C and DM, while only heart rate increased in DN. Norepinephrine levels were lower after postural change in DN. Capillary fluid shift and blood flow after standing did not differ between the three groups. A relation between systemic and capillary circulation was exclusively found in DN: capillary fluid shift correlated with the change of femoral blood flow (r=−0.79, p=0.018) and, intriguingly, with baseline vascular resistance (r=−0.95, p=0.0003).
Conclusion Patients with DN have an altered homeostatic response to postural change due loss of capillary autoregulation. We propose that lost capillary autoregulation, probably in concert with capillary rarefaction, results in significant changes in hemodynamics including an increase of vascular resistance. Capillary dysfunction is thus readily related to key processes involved in arterial hypertension, the major risk factor for progression of diabetic nephropathy and cardiovascular mortality.