Thiazolidinediones and the renal and hormonal response to water immersion-induced volume expansion in type 2 diabetes mellitus

Abstract

Thiazolidinediones cause sodium retention and edema by a direct effect on the kidneys. The aim of this study was to use the technique of head-out water immersion to investigate the effects of rosiglitazone on sodium and volume homeostasis in subjects with type 2 diabetes mellitus. The volume expansion response to water immersion was compared with the response on a non-immersion control day in 12 nondiabetic male subjects and 8 diet-controlled male type 2 diabetic subjects with hourly blood and urine sampling over a 4-h period. This was repeated after both groups had taken 4 mg of rosiglitazone daily for 7 days. Immersion produced a natriuresis in both groups (P < 0.001). An impairment of this natriuresis was seen in the diabetic subjects (P = 0.006). However, when rosiglitazone was taken, there was no significant difference in immersion-induced natriuresis compared with nondiabetic controls (P = 0.2). There was an immersion-induced rise in atrial natriuretic peptide (ANP) and urinary cyclic guanosine monophosphate (cGMP), in the healthy subjects (ANP P = 0.001, cGMP P = 0.043), which was not seen in the diabetic subjects (ANP P = 0.51, cGMP P = 0.74). Rosiglitazone restored the immersion-induced increase in cGMP excretion and rise of ANP in the diabetic group (ANP P = 0.048, cGMP P = 0.009). This study confirms that type 2 diabetic subjects have an impaired natriuretic response to acute volume expansion, which appears to be enhanced rather than diminished by rosiglitazone. This may be related to its effects in increasing natriuretic peptides and restoring the impaired cGMP excretion to volume expansion.

Pioglitazone does not modify ANP levels of type 2 diabetic patients

“…Our data seem to be in contrast with results found in a recent publication [35] showing that in type 2 diabetic subjects the impairment of ANP response to immersion was restored by rosiglitazone (after they had taken 4 mg of rosiglitazone every morning for 7 days prior to the study). However, the different type of TZD and the particular stimulus to cause volume expansion head-out water immersion) could explain the differences found in that study.…”

Effects of short-term heated water-based exercise training on systemic blood pressure in patients with resistant hypertension

“…Exercise training has been shown to decrease sympathetic and increase vagal nervous activity, and improve baroreceptor reflex sensitivity after exercise training [13]. These effects could result in decreased concentrations of renin, angiotensin II, aldosterone, reduction in renal sympathetic outflow, and increase in nitric oxide and atrial natriuretic peptide release, which have been observed previously in healthy individuals and in patients with heart failure [13,16,19]. These effects could result in decreased concentrations of renin, angiotensin II, aldosterone, reduction in renal sympathetic outflow, and increase in nitric oxide and atrial natriuretic peptide release, which have been observed previously in healthy individuals and in patients with heart failure [13,16,19].…”

“…Additional effects attributed to exercise being performed specifically in heated water are arterial vasodilatation and reduction in volemia [14,16]. However, changes in neurohormonal secretion, peripheral resistance, and diuresis reported as the result of heated water-based exercise were not associated with reduction in BP in healthy individuals and patients with heart failure [13,14,19]. However, changes in neurohormonal secretion, peripheral resistance, and diuresis reported as the result of heated water-based exercise were not associated with reduction in BP in healthy individuals and patients with heart failure [13,14,19].…”

From history to reality: sodium glucose co‐transporter 2 inhibitors – a novel therapy for type 2 diabetes mellitus

“…This makes them a potential future therapeutic option in patients with type 2 diabetes who are overweight or obese. Subjects with type 2 diabetes have been shown to have a higher exchangeable body sodium, and this propensity to retain sodium may contribute to the pathophysiology of the high prevalence of hypertension in diabetes 42. Therefore, one can argue that potentially the urinary sodium loss resulting from inhibition of SGLT‐2 and the osmotic diuretic effect caused by glycosuria produced by these drugs, may have some advantages in patients with type 2 diabetes, particularly in those who also have hypertension.…”