MiRNA and associated inflammatory changes from baseline to hypoglycemia in type 2 diabetes

Manjunath Ramanjaneya, Ruth Priyanka, Milin Bensila, Jayakumar Jerobin, Krunal Pawar, Thozhukat Sathyapalan, Abdul Badi Abou-Samra, Najeeb M Halabi, Abu Saleh Md Moin, Stephen L Atkin, Alexandra E Butler, Manjunath Ramanjaneya, Ruth Priyanka, Milin Bensila, Jayakumar Jerobin, Krunal Pawar, Thozhukat Sathyapalan, Abdul Badi Abou-Samra, Najeeb M Halabi, Abu Saleh Md Moin, Stephen L Atkin, Alexandra E Butler

Abstract

Objective: Hypoglycemia in type 2 diabetes (T2D) increases morbidity and mortality but the underlying physiological response is still not fully understood, though physiological changes are still apparent 24 hours after the event. Small noncoding microRNA (miRNA) have multiple downstream biological effects that may respond rapidly to stress. We hypothesized that hypoglycemia would induce rapid miRNA changes; therefore, this pilot exploratory study was undertaken.

Methods: A pilot prospective, parallel study in T2D (n=23) and controls (n=23). Insulin-induced hypoglycemia (2mmol/l: 36mg/dl) was induced and blood sampling performed at baseline and hypoglycemia. Initial profiling of miRNA was undertaken on pooled samples identified 96 miRNA that were differentially regulated, followed by validation on a custom designed 112 miRNA panel.

Results: Nine miRNAs differed from baseline to hypoglycemia in control subjects; eight were upregulated: miR-1303, miR-let-7e-5p, miR-1267, miR-30a-5p, miR-571, miR-661, miR-770-5p, miR-892b and one was downregulated: miR-652-3p. None of the miRNAs differed from baseline in T2D subjects.

Conclusion: A rapid miRNA response reflecting protective pathways was seen in control subjects that appeared to be lost in T2D, suggesting that mitigating responses to hypoglycemia with blunting of the counter-regulatory response in T2D occurs even in patients with short duration of disease.

Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT03102801?term=NCT03102801&draw=2&rank=1, identifier NCT03102801.

Keywords: Type 2 diabetes; hypoglycemia; metabolic pathways; miRNA; proteomics.

Conflict of interest statement

Authors MR, RP, MB,JJ and AA-S were employed by Hamad Medical Corporation The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Ramanjaneya, Priyanka, Bensila, Jerobin, Pawar, Sathyapalan, Abou-Samra, Halabi, Moin, Atkin and Butler.

Figures

Figure 1
Figure 1
The top 10 miRNAs that changed from baseline to hypoglycemia in control subjects. RQ, mean relative quantification.
Figure 2
Figure 2
The top 10 miRNAs that changed from baseline to hypoglycemia in type 2 diabetes subjects. RQ, mean relative quantification.
Figure 3
Figure 3
Ingenuity pathway analysis of top 10 miRNA that showed differential expression in control subjects in response to hypoglycemia.
Figure 4
Figure 4
Ingenuity pathway analysis of top 10 miRNA that showed differential expression in type 2 diabetic subjects in response to hypoglycemia.

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