Abstract

Hypertension and type 2 diabetes mellitus (T2DM) are powerful risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD), both of which are leading causes of morbidity and mortality worldwide. Research into the pathophysiology of CVD and CKD risk factors has identified salt sensitivity and insulin resistance as key elements underlying the relationship between hypertension and T2DM. Excess dietary salt and caloric intake, as commonly found in westernized diets, is linked not only to increased blood pressure, but also to defective insulin sensitivity and impaired glucose homeostasis. In this setting, activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS), as well as increased signaling through the mineralocorticoid receptor (MR), result in increased production of reactive oxygen species and oxidative stress, which in turn contribute to insulin resistance and impaired vascular function. In addition, insulin resistance is not limited to classic insulin-sensitive tissues such as skeletal muscle, but it also affects the cardiovascular system, where it participates in the development of CVD and CKD. Current clinical knowledge points towards an impact of salt restriction, RAAS blockade, and MR antagonism on cardiovascular and renal protection, but also on improved insulin sensitivity and glucose homeostasis.

Some interesting extracts from the review paper:

Salt and the cardiovascular system

Early studies have suggested that hypertension is, to a great extent, derived from the inability of the kidney to appropriately handle and excrete sodium in the setting of increased dietary salt intake, as commonly found in westernized diets.⁴ The average minimum daily requirement of sodium is approximately 400 mg per day; however, the estimated average sodium intake of a typical US citizen ranges from 6 g to 10 g per day.⁵ More recent epidemiological studies have confirmed a positive correlation between salt intake and elevated blood pressure in up to half of patients with hypertension.⁶ These effects of salt intake on the systemic blood pressure are observed in white, Hispanic, and African American individuals.⁷

The randomized, multicenter DASH (Dietary Approaches to Stop Hypertension) study⁸ has provided additional insights into the role of salt intake in hypertension. In a subgroup analysis (DASH-Sodium),⁹ adherence to the DASH diet, which includes several portions of fruits, vegetables, and low-fat dairy products, as well as reduction of dietary sodium intake (from approximately 150 mmol per day to 100 mmol per day), produced a significant reduction in systolic blood pressure (8.3 mmHg in patients with hypertension versus 5.6 mmHg in normotensive individuals).

Importantly, in some individuals, increased salt intake elicits a substantial rise in blood pressure that is consistent with enhanced blood-pressure sensitivity to salt, a feature known as ‘salt sensitivity’. Conversely, this concept also encompasses the tendency of blood pressure to be substantially reduced by dietary sodium restriction.¹⁰ Clinically, salt sensitivity has been defined in normotensive individuals as “a decrease in mean arterial pressure of at least 3 mmHg following the period of dietary salt restriction”.¹¹ Salt sensitivity seems to be multifactorial in origin, and has been linked to factors such as ethnicity, age, levels of sex steroids, dietary patterns, and adiposity.³ Salt sensitivity is also associated with diverse pathological conditions, in particular hypertension, the cardiometabolic syndrome, T2DM, obesity, and CKD.¹² Salt sensitivity seems to have a genetic predisposition, which would increase the risk of hypertension in genetically susceptible individuals.¹³

Salt, obesity, and insulin resistance

Obesity, a leading component of the cardiometabolic syndrome, has been related to salt sensitivity.¹⁵ In a study in adolescents, after switching from a 2-week high-salt diet (>250 mmol per day) to a low-salt diet (<30 mmol per day), the mean blood pressure reduction was significantly higher in obese individuals than in their nonobese counterparts (–12 ± 1 mmHg versus +1 mmHg ± 2mm Hg).¹⁵ Weight loss resulted in reduced sensitivity of blood pressure (reduced blood-pressure rises) in response to increased salt intake.

Read the complete paper:

Salt, aldosterone, and insulin resistance: impact on the cardiovascular system