thy, and 24-h blood pressure (BP) pattern in insulin-dependent diabetes ... simultaneously measured 24-h BP and urinary albumin excretion rate (UAE) on urine ...
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Relationship Between Autonomic Neuropathy, 24-h Blood Pressure Profile, and Nephropathy in Normotensive IDDM Patients VLNCENZA SPALLONE, MD, PHD SERGIO GAMBARDELLA, MD MARIA R. MAIELLO, MD
ANGELA BARINI, MD SlMONA FRONTONI, MD GUIDO MENZINGER, MD
O B J E C T I V E — To evaluate the relationship between autonomic neuropathy, nephropathy, and 24-h blood pressure (BP) pattern in insulin-dependent diabetes mellitus (IDDM).
RESEARCH DESIGN A N D METHODS — We studied 30 normotensive IDDM patients without overt nephropathy, divided into two groups and matched for age, duration of diabetes, and HbA^ according to the presence of cardiovascular autonomic neuropathy. We simultaneously measured 24-h BP and urinary albumin excretion rate (UAE) on urine collections timed overnight and at 2-h intervals during the day. R E S U L T S — Mean day and night systolic and diastolic BP values did not significantly differ between the groups. Mean night albuminuria was significantly higher in patients with autonomic neuropathy than in those without (61.4 ± 104.6 [mean ± SD] vs. 16 ± 25.2 ju,g/min, P < 0.04). The percentages day-night changes in systolic BP, diastolic BP, and UAE were significantly lower in neuropathic patients (systolic BP: 2.4 ± 7.7 vs. 9.6 ± 4.2%, P < 0.001; diastolic BP: 8.4 ± 6.9 vs. 15.5 ± 5.4%, P < 0.002; UAE: - 8 ± 99.4 vs. 49.3 ± 29.4%, P < 0.02) and were inversely related to autonomic score, index of autonomic neuropathy degree (r = —0.54, P < 0.002; r = -0.58, P < 0.001; and r = -0.53, P < 0.005, respectively). In patients with autonomic neuropathy, 2-h day periods and day and night UAE were more strongly related, respectively, to mean 2-h day periods (r = 0.58, P < 0.0001), day systolic BP (r = 0.67, P < 0.04), and night systolic BP (r = 0.69, P < 0.04) than in patients without autonomic neuropathy (2-h day periods: r = 0.32, P < 0.001; day: r = 0.37, NS; night: r = 0.35, NS). C O N C L U S I O N S — Autonomic neuropathy in IDDM patients is associated with reduced nocturnal falls in BP and UAE and with a stronger relationship of UAE to systolic BP. We suggest a pathogenetic role of autonomic neuropathy in the development of diabetic nephropathy through changes in nocturnal glomerular function and by enhanced kidney vulnerability to hemodynamic effects of BP.
From the Department of Internal Medicine, Endocrinology (V.S., S.G., M.R.M., S.F., G.M.), Tor Vergata University, Rome, Italy; and the Institute of Biochemistry (A.B.), Catholic University, Rome, Italy. Address correspondence and reprint requests to Vincenza Spallone, MD, PhD, Dipartimento di Medicina Interna, Universita di Tor Vergata, Complesso Integrato Columbus, via della Pineta Sacchetti 506, 00168 Rome, Italy. Received for publication 12 August 1993 and accepted in revised form 20 January 1994. IDDM, insulin-dependent diabetes mellitus; BP, blood pressure; ABPM, ambulatory 24-h blood-pressure monitoring; UAE, urinary albumin excretion.
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linical and epidemiological studies have shown an association between autonomic neuropathy and nephropathy in insulin-dependent diabetes mellitus (IDDM) (1-4). This rinding is of prognostic interest, because both of these diabetic complications are associated with a higher mortality rate (5-9). A pathogenetic significance of the association between diabetic neuropathy and nephropathy has been proposed preliminarily by some authors (4,10,11) and supported by the knowledge of a rich innervation of the kidney and of a neural control of renal function (12-16). Moreover, abnormalities in kidney function have also been described in conditions of autonomic failure other than diabetic neuropathy (17,18). The pathogenesis of diabetic nephropathy is not wholly understood, and the temporal link between hypertension and nephropathy is still under debate. Ambulatory 24-h blood-pressure monitoring (ABPM) has been proved to be a useful tool for recording blood pressure (BP). Compared to casual BP, ABPM is both more strongly related to target organ damage of hypertension and to albuminuria and more sensitive in detecting an early increase in BP load in diabetic patients (19-21). Moreover, ABPM has allowed us to detect in diabetic patients unsuspected abnormalities of the BP circadian rhythm and to relate them to autonomic (22-24) or renal dysfunction (21,25). More information on the relationship between autonomic neuropathy, BP, and nephropathy might lead to a better pathogenetic understanding of hemodynamic changes of diabetic nephropathy. We performed this study to evaluate in normotensive IDDM patients without clinical nephropathy the relationship between autonomic neuropathy, nephropathy assessed by albuminuria, and the 24-h BP pattern. RESEARCH DESIGN A N D M E T H O D S — Thirty subjects with IDDM participated in the study. Informed
DIABETES CARE, VOLUME 17,
NUMBER 6, J U N E
1994
Spallone and Associates
Table 1—Clinical parameters and cardiovascular reflex tests of IDDM patients without and with autonomic neuropathy (AN) IDDM patients n Age (years) Sex (M/F) Diabetes duration (years) Body mass index (kg/m2) Insulin (U/day) HbA, (%) Serum creatinine (JUM) Retinopathy (absent/background/ proliferative) Casual systolic BP (mmHg) Casual diastolic BP (mmHg) Deep breathing (breaths/min) Lying to standing Valsalva ratio Postural hypotension (mmHg) Autonomic score
Without AN 18 39.3 ± 8.9 9/9 16 ± 9 . 1 23.1 ± 2 . 7 43.2 ± 14 8.2 ± 1.8 73.2 ± 20.9 11/6/1 116.16 ± 13.84 72.11 ± 5 . 6 3 22.19 ± 7.37 1.15 ± 0 . 1 0 1.46 ± 0.35 3.62 ± 7.27 0.67 ± 0.69
With AN 12 41.5 ± 12.7 7/5 18.5 ± 8.2 22.9 ± 3.5 39.4 ± 12.5 9.2 ± 1.9 73.1 ± 20.9 4/6/2 114.66 72.27 7.68 0.97 1.21 17.85 4.75
± 13.73 ± 10.36 ± 7.23 ± 0.05 ± 0.2 ± 14.18 ± 1.66
P value NS NS NS NS NS NS NS NS NS NS 0.0001 0.0001 0.02 0.001 0.0001
Data are means ± SD.
consent was obtained from all partici- ±11.1 years of age) for 24-h BP monitorpants. They were consecutively recruited ing. from the diabetic clinic of the University Autonomic function was explored of Rome Tor Vergata. Inclusion criteria by deep breathing, lying to standing, Valwere
