Relative preservation of the renin-angiotensin-aldosterone system response to active orthostatism in type 2 diabetic patients with autonomic neuropathy and postural hypotension

OBJECTIVE: The pathophysiological mechanisms involved in the progression of autonomic neuropathy (AN) and development of postural hypotension (PH) in type 2 diabetes (T2D) are largely unknown. The aim of this study was to address this issue by investigating the neurohormonal responses during active orthostatism (O) in T2D patients with and without PH. METHODS: Plasma noradrenaline (NA, pmol/L), adrenaline (A, pmol/L), plasma renin activity (PRA, angiotensin I, nmol/L/h) and aldosterone (ALD, pmol/L) were measured in the supine position (baseline) and after 2, 5, and 20 min O in 10 healthy subjects (C), 9 T2D patients without AN (D), 14 T2D patients with AN and without PH (DAN), and 7 T2D patients with AN and PH (DAN-PH). RESULTS: NA concentrations were significantly increased in the C. D and DAN groups during O. In the DAN-PH group, NA increased less markedly with no significant changes at 20 min O (+ 354 +/- 89 pmol/L at 2 min, p < 0.05; + 756 +/- 171 at 5 min, p < 0.05; + 656 +/- 295 at 20 min, p = NS). Absolute NA increments in the DAN-PH group were significantly lower than those in the C, D and DAN groups at 2 and 20 min. Concentrations of A increased significantly in the C and D groups whereas no significant changes were observed in the DAN (+ 27 +/- 27 pmol/L at 2 min, p = NS: + 22 +/- 22 at 5 min, p = NS; + 76 +/- 33 at 20 min, p = NS) and DAN-PH group (+ 16 +/- 11 pmol/L at 2 min, p = NS: + 71 +/- 27 at 5 min, p = NS; + 76 +/- 22 at 20 min, p = NS). Absolute A increments in the DAN and DAN-PH groups were significantly lower than those in controls at 2 and 20 min. By contrast, PRA and ALD increased significantly in all four groups. Absolute PRA increments were similar across the four groups, whereas ALD increments in the D, DAN and DAN-PH groups were significantly lower than those in the C group. CONCLUSIONS: In the DAN-PH group, the renin-angiotensin-aldosterone system response to O was relatively preserved compared with A and NA responses. The impairment of NA response was limited to the DAN-PH group, whereas the reduced A response was a feature of DAN regardless of PH.