DIABETES, VOL. 47, AUGUST 1998 1347 Enhanced Responsiveness of Blood Pressure to Sodium Intake and to Angiotensin II Is Associated With Insulin Resistance in IDDM Patients With Microalbu m in u ria Roberto Trevisan, Daniela Bruttomesso, Monica Vedovato, Stefano Brocco, Alessandro Pianta, Cinzia Mazzon, Carlo Girardi, Elisabetta Jori, Andrea Semplicini, Antonio Tiengo, and Stefano Del Prato We assessed blood pressure ( BP) , body weight, renal hemodynamics, and insulin sensitivity ( by euglycemic- hyperinsulinemic clamp) in nine normoalbuminuric and seven microalbuminuric IDDM patients after 6 days on a low-sodium diet ( 20 mEq) and after 6 days on a high-sodium diet ( 250 mEq) . In microalbuminuric but not in normoalbuminuric IDDM patients, switching from a low to a high-sodium diet was associated with a significant increase in mean BP ( from 92 ± 3 to 101 ± 4 mmHg; P < 0.001) and in body weight (2.91 ± 0.63 vs. 1.47 ± 0.26 kg; P < 0.05). Moreover, under high-sodium conditions, angiotensin II infusion (3 ng · kg – 1 · min – 1 ) caused a greater increase in mean BP (14 ± 2 vs. 7.4 ± 1 mmHg; P < 0.05) and a smaller reduction in renal plasma flow (–122 ± 29 vs. –274 ± 41 ml · min – 1 · 1.73 m 2 ; P < 0.05) in microalbuminuric than in normoalbumin- uric IDDM patients. Under low sodium conditions, aldosterone increments after angiotensin II infusion were lower ( P < 0.05) in microalbuminuric than in nor- moalbuminuric IDDM patients. Insulin-mediated glu- cose disposal was not affected by sodium dietary con- tent, but it was lower in microalbuminuric ( P < 0.05) than in normoalbuminuric IDDM patients. The salt- induced changes in mean BP were related to insulin sensitivity ( r = –0.78; P < 0.001). In conclusion, in IDDM patients, microalbuminuria is associated with 1) an increased responsiveness of BP to salt intake and angiotensin II, 2) impaired modulation of renal blood f lo w, and 3 ) insulin resistance. Therefore, salt sensi- tivity in IDDM patients clusters with other factors that are likely to play an important role in the pathogene- sis of diabetic nephropathy and its cardiovascular com- plications. Diabetes 47:1347–1353, 1998 M icroalbuminuria, a powerful predictor of both renal failure and cardiovascular disease in IDDM patients (1,2), is associated with raised arterial blood pressure (BP), lipid abnormali- ties, abnormal cation transport activities, increased total exchangeable sodium, and impaired insulin sensitivity (3–5). Elevated exchangeable sodium and sodium retention have been described in IDDM patients even in the absence of dia- betic nephropathy or other signs of late diabetic complications (4,6). The elevation in total body exchangeable sodium is even higher in IDDM patients with clinical diabetic nephropa- thy (5). The positive correlation between BP values and total exchangeable sodium found in IDDM patients with incipient or clinical nephropathy (5) raises the possibility that sodium plays a central role in the pathogenesis of hypertension in IDDM patients. The reason for increased total body sodium content is not yet fully understood. Several studies have sug- gested that the antinatriuretic effect of insulin (7) may con- tribute to sodium retention in diabetic patients. An impaired capability to excrete an acute sodium load was demonstrated in IDDM patients without hypertension or nephropathy, and this abnormality has been reproduced in normal control sub- jects by acute insulin infusion (8,9) . These observations support the concept that diabetic patients retain sodium, and thus, they may be “sodium sen- sitive.” Nondiabetic subjects with or without essential hyper- tension exhibit a variety of BP responses to dietary salt intake (10). Those with a significant rise in mean BP in response to increased dietary sodium intake are defined as sodium-sensitive. A substantial subgroup of hypertensive patients, which includes ~40–50% of the normal- and high- renin essential hypertensive population, has also been described as non-modulators (11). In these patients, the nor- mal changes in renal blood flow associated with high dietary sodium intake and the normal response of plasma aldos- terone to exogenous angiotensin II on a low-salt diet are abolished (12,13). These patients gain more weight, due to a more positive sodium balance when shifted from a low to a high sodium intake, and, in parallel, exhibit higher BP values. The majority of these subjects are, apparently, salt sensitive. The association between reduced insulin action and salt sen- sitivity has prompted the hypothesis that hyperinsulinemia may be involved in the salt sensitivity of BP (14–16). From the Unit for Metabolic Disease, Department of Clinical and Experi- mental Medicine, University of Padua, Padua, Italy. Address correspondence and reprint requests to Dr. Roberto Tre vis an, MD, PhD, Cattedra di Malattie del Ricambio, Dipartimento di Medicina Clinica e Sperimentale, Via Giustiniani 2, 35128 Padova, Italy. Received fo r publicatio n 4 December 1997 and accepted in revised form 21 April 1998. AER, albumin excretion rate; BP, blood pressure; dBP, diastolic blood pressure; GFR, glomerular filtration rate; PAH, p -aminohippurate; RIA, radioimmunoassay; RPF, renal plasma flo w; sBP, systolic bloo d pressure.