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胃饥饿素表达是否能调节2型糖尿病肥胖患者的心脏舒张功能?

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

作者信息

Sardu Celestino, D'Onofrio Nunzia, Trotta Maria Consiglia, Balestrieri Maria Luisa, Nicoletti Giovanni Francesco, D'Amico Giovanbattista, Fumagalli Carlo, Contaldi Carla, Pacileo Giuseppe, Scisciola Lucia, Nicoletti Maddalena, Marfella Ludovica Vittoria, Sbriscia Matilde, Sasso Ferdinando Carlo, Signoriello Giuseppe, Paolisso Giuseppe, Marfella Raffaele

机构信息

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

出版信息

Diabetes Metab Res Rev. 2025 May;41(4):e70049. doi: 10.1002/dmrr.70049.

Abstract

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.

摘要

目的

脂肪组织表达细胞因子、沉默调节蛋白-1(SIRT1)和微小RNA(miR),调节左心室(LV)舒张功能(LV-DF)。胃饥饿素可调节2型糖尿病(T2DM)和肥胖患者的这些通路。我们研究了腹部脂肪切除术后T2DM肥胖患者以及随访1年时LV-DF恢复正常患者的胃饥饿素表达情况。

材料与方法

202例接受腹部整形手术的T2DM肥胖患者被分为LV-DF正常组(第1组:E/E' < 9,n = 76)和LV-DF异常组:第2组(9 < E/E' < 14;n = 96)和第3组(E/E' > 14,n = 28)。

结果

LV舒张功能障碍患者存在过度炎症反应,SIRT1水平较低,腹部脂肪钠-葡萄糖协同转运蛋白2(SGLT2)表达较高(p < 0.05)。他们的胃饥饿素表达无差异(p > 0.05)。他们的miR-21、miR-92和miR-126的组织/血清表达存在差异(p < 0.05)。第2组与第1组相比,组织炎症标志物和SGLT2过度表达(p < 0.05),第3组与第1组相比程度更高(p < 0.01),与第2组相比(p < 0.025)。第2组与第1组相比SIRT1下调(p < 0.05),与第3组相比(p < 0.01)。在随访结束时,LV舒张功能障碍较轻的患者炎症和SGLT2水平较低,血清胃饥饿素较高(p < 0.05)。他们的miR-126增加,血清miR-21和miR-92表达降低。在随访结束时,50例患者的LV-DF恢复正常,这可由组织miR-126(HR 1.344,95%CI 1.126 - 1.937)和胃饥饿素(HR 1.123,95%CI 1.016 - 1.310)预测。

结论

在T2DM肥胖患者中,腹部脂肪切除可减轻炎症,上调血清胃饥饿素,并在随访1年时诱导与LV-DF恢复正常相关的miR。

临床研究试验编号

NCT05988346。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c0e/12051781/e87cb4185f7a/DMRR-41-e70049-g003.jpg

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