SALT-SENSITIVE BLOOD PRESSURE RISE IN TYPE 1 DIABETES IS ACCOMPANIED BY INCAPACITY FOR VASODILATION – A RANDOMIZED EXPERIMENTAL CROSS-OVER STUDY

Abstract

Objective: Diabetes mellitus type 1 (DM1) is suggested to be associated with salt sensitivity. However, strong evidence to support this is scarce, and the pathophysiology is not known. For a long time, the volume-regulating function of the kidney was thought to be the only important factor in salt-sensitive hypertension. Due to insufficient sodium excretion by the kidney, sodium excess was considered to increase extracellular fluid volume (ECFV) and cardiac output (CO), resulting in a blood pressure (BP) rise. However, recent publications put forward that systemic vascular resistance (SVR) might be central in BP regulation. We hypothesized that in salt-sensitive hypertension in DM1, vasodysfunction rather than increases in ECFV and CO plays a role.Design and method: We included 8 DM1 patients and 12 age-matched healthy controls (HC), with normal BP, body mass index, and kidney function. All subjects adhered to an 8-day low salt diet (LSD) and an 8-day high salt diet (HSD), in randomized order. After each diet, hemodynamic measurements included BP (Omron) and CO (Nexfin™), and SVR was calculated accordingly. To assess volume-dependent changes, ECFV, interstitial fluid volume (IFV) and plasma volume (PV) were calculated by the use of iohexol and 125I-albumin distribution. HC were divided in two subgroups: those with versus those without a BP increase after HSD. Results: After HSD, patients with DM1 showed a BP increase (mean arterial pressure HSD vs LSD (85 (5) mmHg vs. 80 (3) mmHg; P = 0.03) while BP in HC did not rise (78 (5) mmHg vs. 78 (5) mmHg; P = 0.85). The difference in BP response was not accompanied by differences in urinary sodium excretion between the DM1 patients and HC (Figure 1) nor by differences in CO, ECFV or ICF (Table 1). HC without a BP increase after HSD (n = 5) showed a SVR reduction after HSD, while this reduction was not present in the HC with a BP increase after HSD (n = 7) or in the DM1 patients (Figure 2, Table 1). Conclusions: DM1 is associated with increased salt sensitivity compared to HC, coinciding with incapacity for vasodilation.