Could Ghrelin Expression Regulate Diastolic Cardiac Function in Type 2 Diabetic Obese Patients?

[AIMS] Adipose tissue expresses cytokines, sirtuin-1 (SIRT1), and microRNAs (miRs), regulating left ventricle (LV)-diastolic function (LV-DF). Ghrelin could modulate these pathways in patients with type 2 diabetes mellitus (T2DM) and obesity. We investigated ghrelin expression in T2DM obese patients after abdominal fat excision, and in those with LV-DF normalisation at 1 year of follow-up.

[MATERIALS AND METHODS] Two-hundred and two T2DM obese patients enroled for abdominoplastic surgery were divided into those with normal LV-DF (group 1: E/E' < 9, n 76) and those with altered LV-DF: group 2 (9 < E/E' < 14; n 96) and group 3 (E/E' > 14, n 28).

[RESULTS] Patients with LV-diastolic dysfunction had over-inflammation, lower SIRT1 and higher abdominal fat sodium-glucose-transporter-two (SGLT2) expression (p < 0.05). They did not differ for ghrelin expression (p > 0.05). They evidenced different tissue/serum expression of miR-21, miR-92 and miR-126 (p < 0.05). Group 2 versus group 1 over-expressed tissue inflammatory markers and SGLT2 (p < 0.05), with higher extent in group 3 versus group 1 (p < 0.01) and versus group 2 (p < 0.025). SIRT1 was downregulated in group 2 versus group 1 (p < 0.05), and versus group 3 (p < 0.01). At the follow-up end, patients with lower LV-diastolic dysfunction had lower inflammation and SGLT2, and higher serum ghrelin (p < 0.05). They increased miR-126, and reduced serum miR-21 and miR-92 expression. At the follow-up end, 50 patients experienced LV-DF normalisation, which was predicted by tissue miR-126 (HR 1.344, CI 95% 1.126-1.937), and ghrelin (HR 1.123, CI 95% 1.016-1.310).

[CONCLUSIONS] In T2DM obese patients, abdominal fat excision could reduce inflammation, up-regulating serum ghrelin and inducing miRs implied in LV-DF normalisation at 1 year of follow-up.

[CLINICAL RESEARCH TRIAL NUMBER] NCT05988346.