Nonmodulation as the Mechanism for Salt Sensitivity of Blood Pressure in Individuals with Hypertension and Type 2 Diabetes Mellitus

Context: It is assumed that in individuals with type 2 diabetes mellitus (T2DM), blood pressure sensitivity to salt intake and the frequency of a low renin state are both increased compared with the nondiabetic population. However, studies supporting these assumptions may have been confounded by participant inclusion criteria, and study results may reflect target organ damage. Objective: The objective of this study was to examine in a cohort of T2DM 1) the frequency of salt sensitivity of blood pressure and 2) whether alterations of the renin-angiotensin-aldosterone system (RAAS) contribute to salt sensitivity in this population. Design, Patients, and Methods: Within participants of the HyperPATH cohort, four groups were analyzed: 1) T2DM with hypertension (HTN), n = 51; 2) T2DM without HTN, n = 30; 3) HTN only, n = 451; and 4) normotensive, n = 209. Phenotype studies were conducted after participants completed two dietary phases: liberal sodium (200 mmol/d) and low sodium (10 mmol/d) for 7 d each. Participants were admitted overnight to a clinical research center after each diet, and supine measurements of the RAAS before and after a 60-min angiotensin II infusion (3 ng/kg . min) were obtained. Results: Multivariate regression analysis demonstrated that T2DM status (all individuals with T2DM vs. individuals without T2DM) was not associated with the change in mean arterial pressure between the low and liberal sodium diets after accounting for age, gender, body mass index, race, and baseline blood pressure (T2DM status, P = 0.5). Furthermore, two intermediate phenotypes of altered RAAS, low renin, and nonmodulation (NMOD), were associated with salt-sensitive blood pressure but occurred at different frequencies in the T2DM-HTN and HTN groups (low renin, 12% T2DM-HTN vs. 29% HTN; NMOD, 41% T2DM-HTN vs. 27% HTN; P = 0.01). Conclusion: The frequency of NMOD in participants with T2DM was significantly higher compared with HTN, suggesting that the salt sensitivity often seen in T2DM is driven by NMOD. (J Clin Endocrinol Metab 97: 3775-3782, 2012)