Abstract: PO0950
Circulating MicroRNAs Associated with Hyperglycemia and Their Effects on Renal Function Decline in Type 2 Diabetes: Global miRNome Analysis
Session Information
- Diabetic Kidney Disease: Clinical - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 602 Diabetic Kidney Disease: Clinical
Authors
- Kobayashi, Hiroki, Joslin Diabetes Center, Boston, Massachusetts, United States
- Satake, Eiichiro, Joslin Diabetes Center, Boston, Massachusetts, United States
- Md Dom, Zaipul I, Joslin Diabetes Center, Boston, Massachusetts, United States
- Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
Background
It has been reported that microRNAs (miRNAs) play an important role in the pathogenesis of diabetic complications. We aimed to search for circulating miRNAs that were associated with hyperglycemia in type 2 diabetes (T2D) and examine their effects on renal function decline.
Methods
Using the next-generation sequencing-based HTG EdgeSeq miRNA platform, a total of 2,083 miRNAs were measured in baseline plasma specimens obtained from 73 subjects with T2D and normal renal function (discovery panel), and 136 subjects with T2D and impaired renal function (replication panel). Subjects in both panels were followed for 6-12 years to determine eGFR decline.
Results
We identified 11 candidate miRNAs that were strongly associated with elevated levels of glycated hemoglobin (HbA1c) in both screening and replication panels. Using bioinformatics analyses, we found that the candidate miRNAs targeted proteins of 6 pathways (the Ras signaling pathway, Signaling pathways regulating pluripotency of stem cells, the MAPK pathway, Glutamatergic synapse, the Rap 1 signaling pathway, and the AMPK signaling pathway). Importantly, 4 of these 11 miRNAs were significantly associated with risk of renal function decline.
Conclusion
There were few previous reports about the association between circulating miRNAs, hyperglycemia, and diabetic kidney disease in T2D. The present study comprehensively examined and identified hyperglycemia-regulated miRNAs in human samples. Our findings are novel in that circulating miRNAs regulated by hyperglycemia are associated with risk of eGFR decline in T2D.
Funding
- Other NIH Support –