VPB0373 - Alteration of circulating platelet-related and diabetes-related microRNAs in individuals with type 2 diabetes: Results from a stepwise hypoglycaemic clamp study

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

CE

Ceren Eyileten

Senior Researcher
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland

Co-Author(s)

Zofia Wicik, PhD

Senior Researcher
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland
DK

Disha Keshwani

Student
1. Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Center for Preclinical Research and Technology CEPT, 02-091 Warsaw, Poland
Warsaw, Mazowieckie, Poland
AN

Anna Nowak

PhD candidate
Medical University of Warsaw
Warsaw, Mazowieckie, Poland
FA

Faisal Aziz

Assistant Prof
Medical University of Graz
Graz, Steiermark, Austria
FA

Felix Aberer

Prof
Medical University of Graz
Graz, Steiermark, Austria
PP

Peter Pferschy

Prof
Medical University of Graz
Graz, Steiermark, Austria
NT

Norbert Tripolt

Prof
Medical University of Graz
Graz, Steiermark, Austria
CS

Caren Sourij

Prof
Medical University of Graz
Graz, Steiermark, Austria
BP

Barbara Prietl

Dr
Medical University of Graz
Graz, Steiermark, Austria
FP

Florian Prüller

Prof
Medical University of Graz
Graz, Steiermark, Austria
DV

Dirk Von Lewinski

Prof
Medical University of Graz
Graz, Steiermark, Austria
JS

Jolanta M. Siller-Matula

Professor
Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna,1090 Vienna, Austria
Vienna, Wien, Austria
MP

Marek Postula

Prof
Medical University of Warsaw
Warsaw, Mazowieckie, Poland
HS

Harald Sourij

Prof
Medical University of Graz
Graz, Steiermark, Austria

Background: Platelet function impairs in T2DM patients and hypoglycemia could increase the risk of cardiovascular complications. No study aimed to analyze the miRNA expression related to platelets in response to acute hypoglycemia in T2DM.

Aims: We aimed to investigate the influence of hypoglycemia on several selected miRNAs (based on bioinformatic analysis-hsa-miR-16-1, hsa-miR-34a, hsa-miR-129-2, hsa-miR-15a, hsa-miR-15b, hsa-miR-106a) in subjects at an early stage of T2DM on metformin monotherapy, without established CVD and antiplatelet therapy during a stepwise hypoglycemic clamp experiment and a follow-up seven days after the clamp event.

Methods: 14 patients with T2DM were included, all participants were on metformin monotherapy and they underwent a hyperinsulinemic-euglycemic and subsequently a hyperinsulinaemic-hypoglycaemia clamp experiment. Platelet activity, coagulation, endothelial function and inflammatory markers were determine and miRNAs expressions were analyzed.

Results: MiR-106a-5p, miR-15b, miR-15a, miR-16-5p, miR-223 and miR-126 showed significant increasing trend after euglycaemic clamp followed by hypoglycaemic clamp. MiR-16-5p was negatively correlated with interleukin (IL)-6, intercellular adheasion molecule (ICAM) and vascular cell adheasion molecule (VCAM) (p=0.002, p< 0.001, p=0.016, respectively), whereas miR-126 was positively correlated with VCAM (p < 0.001). There were negative correlations between miR-16-5p, miR-126 and coagulation factors, including factor VIII and vWF. MiR-126, miR-129-2-3p and miR-15b showed correlation with platelet function. Disease enrichment analysis showed that targets present in platelets of all analyzed miRNAs are associated with cancer related phenotypes

Conclusion(s): Our study found that acute hypoglycemia could modulate miRNAs expression during an hyperinsulinaemic-hypoglycaemic clamp experiment. It is worth noticing that up to this day, only a few studies have directly investigated the impact of hypoglycemia on thrombotic parameters, platelet function, and inflammatory biomarkers. In the first stage, applying bioinformatics analysis tools, we associated crucial biological function and signaling pathways related to the miRNAs with the most prominent differential expression pattern in T2DM associated with glucose metabolism, inflammation, thrombosis, and platelet function.