Abstract
Contractile dysfunction is underdiagnosed in early stages of diabetic cardiomyopathy. We evaluated the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers of subclinical cardiac abnormalities in type 2 diabetes. Forty-eight men with well-controlled type 2 diabetes and 12 healthy age-matched volunteers were enrolled in the study. Left ventricular (LV) parameters were measured by magnetic resonance imaging. A panel of lncRNAs was quantified in serum by RT-qPCR. No differences in expression levels of lncRNAs were observed between type 2 diabetes patients and healthy volunteers. In patients with type 2 diabetes, long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) was inversely associated with diastolic function, measured as E/A peak flow (P < 0.050 for all linear models). LIPCAR was positively associated with grade I diastolic dysfunction (P < 0.050 for all logistic models). Myocardial infarction-associated transcript (MIAT) and smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA (SENCR) were directly associated with LV mass to LV end-diastolic volume ratio, a marker of cardiac remodelling (P < 0.050 for all linear models). These findings were validated in a sample of 30 patients with well-controlled type 2 diabetes. LncRNAs are independent predictors of diastolic function and remodelling in patients with type 2 diabetes.
Highlights
Long non-coding RNAs are transcripts longer that 200 nucleotides that function as epigenetic regulators of gene expression[6]
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) levels were below the limit of detection in 65% and 75% of type 2 diabetes and control samples, respectively and this Long non-coding RNAs (lncRNAs) was excluded from further analyses
Time since diagnosis of diabetes, plasma fasting insulin, HDL-C and us-CRP, all of which were significantly associated with circulating Long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) levels in univariate analysis, and plasma fasting glucose, myocardial steatosis, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate, which have been previously associated with diastolic function[19], were separately entered as independent variables into model 1, in order to take into account the potential confounding effect of these variables on the associations observed
Summary
Long non-coding RNAs (lncRNAs) are transcripts longer that 200 nucleotides that function as epigenetic regulators of gene expression[6]. Type 2 diabetes patients showed a significant association between indices of LV diastolic function and lncRNA expression levels.
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