SGLT2-inhibitors modulate the Cardiac Autonomic Neuropathy and reduce the vaso-vagal syncope recurrence in patients with type 2 diabetes mellitus: the SCAN study

Abstract

Background: In patients with type 2 diabetes mellitus (T2DM) the vaso-vagal syncope (VVS) recurrence could be due to the alteration of autonomic system function, evaluated by heart rate variability (HRV), and by 123I-metaiodobenzylguanidine (123I-mIBG) myocardial scintigraphy indexes: Heart to Mediastinum ratio (H/Mlate), and Washout rate (WR). The SGLT2-I could modulate/reduce autonomic dysfunction in T2DM patients with VVS. This effect could reduce the VVS recurrence in T2DM patients. Methods: In a prospective multicenter study, we studied a population of 607 T2DM patients affected by VVS, as SGLT2-I-users (n 161) vs. Non-SGLT2-I users (n 446). Thus, in SGLT2-I-users vs. Non-SGLT2-I users, we investigated the HRV and 123I-MIBG modifications and VVS recurrence at 12 months of follow-up. Results: At baseline, and follow-up end Non-SGLT2-I users vs. SGLT2-I-users over-expressed the inflammatory markers and norepinephrine, with worse glucose homeostasis and significant difference of HRV parameters, H/Mlate, and the WR (p<0.05). Non-SGLT2-I users vs. SGLT2-I-users had higher recurrence of all causes VVS, and of vasodepressor, and mixed VVS (p<0.05). The Cox regression analysis showed that the H/Mlate (0.710, CI 95% [0.481-0.985]; p 0.024), and SGLT2-I (0.550, CI 95% [0.324-0.934]; p 0.027) predicted all VVS recurrence. Conclusions: Non-SGLT2-I users vs. SGLT2-I-users had alterations of the autonomic nervous system, with a higher rate of VVS recurrence at 1 year of follow-up. The indexes of cardiac denervation predicted the VVS recurrence, while the SGLT2-I reduced the risk of VVS recurrence. Clinical trial registration number: NCT03717207.

The Outcomes of Sodium-Glucose Co-transporter 2 Inhibitors (SGLT2I) on Diabetes-Associated Neuropathy: A Systematic Review and meta-Analysis

“…The wash-out ratio difference between the SGLT2I and control groups was reported in two studies, including 651 patients ( Shimizu et al, 2020 ; Sardu et al, 2022 ). In the random-effects model ( I 2 = 93%, p = 0.0002), the two groups were not statistically different (MD 2.13; 95% −8.48, 12.75; p = 0.69) ( Figure 3 ).…”

“…Three of the four studies ( Shimizu et al, 2020 ; Mehta et al, 2021 ; Liao et al, 2022 ) showed a low risk of attribution bias, and one study ( Jordan et al, 2017 ) showed a high risk. The NIH quality assessment tool revealed that two studies ( Wang et al, 2019 ; Sardu et al, 2022 ) were good quality ( Figure 2 and Table 1 ).…”

“…Two studies ( Jordan et al, 2017 ; Sardu et al, 2022 ), including 645 patients, assessed the difference in heart rate between SGLT2I and control groups. In the random-effects model ( I 2 = 81%, p = 0.02), the difference between the two groups was not statistically significant (MD -4.51; 95% −10.05, 1.04; p = 0.11) ( Figure 3 ).…”

“…Two studies ( Shimizu et al, 2020 ; Sardu et al, 2022 ), including 653 patients, reported the mean heart-to-mediastinum ratio in patients treated with SGLT2I and the control group. The mean heart-to-mediastinum ratio was significantly higher in the SGLT2I group (MD 0.41; 95% 0.17, 0.64; p = 0.0006) in the random-effects model ( I 2 = 61%, p = 0.11) ( Figure 3 ).…”

Hyperreactivity of Salivary Alpha-Amylase to Acute Psychosocial Stress and Norepinephrine Infusion in Essential Hypertension

“…Indeed, previous research revealed that sAA is among the protein biomarkers associated with new-onset of atherosclerotic cardiovascular disease [ 46 ]. Moreover, given the role of the sympathetic over-activity in potential consequences of hypertension progression [ 47 ] such as proteinuria and kidney disease [ 48 , 49 , 50 ] but also cardiac damage and future cardiovascular prognosis [ 51 , 52 , 53 ], sAA reactivity could also serve as risk indicator at later cardiovascular disease stages. Currently, salivary biomarkers, but not sAA, are increasingly employed in screening, diagnosis, and monitoring of kidney functioning [ 54 ].…”