Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Renin-Angiotensin-Aldosterone System.

Sodium-glucose cotransporters inhibitors (SGLT2-i) and GLP-1 receptor agonists (GLP1-RA) are glucose-lowering drugs that are proved to reduce the cardiovascular (CV) risk in type 2 diabetes mellitus (T2DM). In this process, the renin-angiotensin-aldosterone system (RAAS) is assumed to play a role. The inhibition of SGLT2 improves hyperglycemia hampering urinary reabsorption of glucose and inducing glycosuria. This "hybrid" diuretic effect, which couples natriuresis with osmotic diuresis, potentially leads to systemic RAAS activation. However, the association between SGLT2-i and systemic RAAS activation is not straightforward. Available data indicate that SGLT2-i cause plasma renin activity (PRA) increase in the early phase of treatment, while PRA and aldosterone levels remain unchanged in chronic treated patients. Furthermore, emerging studies provide evidence that SGLT2-i might have an interfering effect on aldosterone/renin ratio (ARR) in patients with T2DM, due to their diuretic and sympathoinhibition effects. The cardio- and reno-protective effects of GLP-1-RA are at least in part related to the interaction with RAAS. In particular, GLP1-RA counteract the action of angiotensin II (ANG II) inhibiting its synthesis, increasing the inactivation of its circulating form and contrasting its action on target tissue like glomerular endothelial cells and cardiomyocytes. Furthermore, GLP1-RA stimulate natriuresis inhibiting Na+/H+ exchanger NHE-3, which is conversely activated by ANG II. Moreover, GLP1 infusion acutely reduces circulating aldosterone, but this effect does not seem to be chronically maintained in patients treated with GLP1-RA. In conclusion, both SGLT2-i and GLP1-RA seem to have several effects on RAAS, though additional studies are needed to clarify this relationship.

Serum zonulin in patients with inflammatory bowel disease: a pilot study.

BACKGROUND: In recent years it has been supposed that impaired intestinal permeability represents an early event preceding the onset of inflammatory bowel disease (IBD). Since zonulin has been proposed as a biomarker of intestinal permeability, we investigated its role in patients with IBD and the correlation between serum and fecal zonulin. METHODS: A total of 118 IBD patients (86 Crohn's disease [CD] and 32 ulcerative colitis [UC]) and 23 healthy controls (HC) were prospectively enrolled. A serum sample was collected for all the subjects included in the study. A stool specimen collected in the same day of blood drawing was available for a subgroup of 33 IBD patients. Serum and fecal zonulin were tested by ELISA. Non-parametric statistical tests were used for data analysis. RESULTS: Serum zonulin concentration was higher in IBD patients compared to HC (34.5 [26.5-43.9] ng/mL vs. 8.6 [6.5-12.0] ng/mL, P<0.001) showing an area under the curve of 0.98 for their discrimination. No difference in serum zonulin concentration was observed between patients with CD and those with UC (P=0.074). An inverse correlation was observed between serum zonulin concentration and disease duration (rs=-0.30, P=0.001); no correlation was observed between serum and fecal zonulin (rs=0.15, P=0.394). CONCLUSIONS: Serum zonulin is highly sensitive for the evaluation of intestinal permeability in IBD patients. There is no correlation between zonulin values in serum and feces.