What is the clinical evidence from this study?

Study design: Observational. Population: Type 2 diabetes (n=90). Intervention: Circulating long non-coding RNAs (LIPCAR, MIAT, SENCR) vs. Healthy volunteers / lower expression levels. Primary outcome: Grade I diastolic dysfunction (OR 1.053, 95% CI 1.007-1.101, p=0.023).

November 22, 2016Open Access

Circulating long-non coding RNAs as biomarkers of left ventricular diastolic function and remodelling in patients with well-controlled type 2 diabetes

Key Result

In men with well-controlled type 2 diabetes, circulating levels of the long non-coding RNA LIPCAR independently predicted grade I diastolic dysfunction (OR 1.053), while MIAT and SENCR predicted left ventricular remodelling.

Study Design

Type

Observational (n=90)

Multicenter

Yes

Structured PICO

Are circulating long non-coding RNAs associated with left ventricular diastolic function and remodeling in patients with well-controlled type 2 diabetes?

Population

48 men with well-controlled type 2 diabetes and 12 healthy age-matched volunteers, with a validation cohort of 30 patients with well-controlled type 2 diabetes.

Intervention

Quantification of a panel of circulating long non-coding RNAs (lncRNAs) in serum by RT-qPCR

Comparator

Healthy age-matched volunteers (for baseline expression) and internal correlation with MRI-derived LV parameters

Outcome

Association of lncRNAs with left ventricular diastolic function (E/A peak flow) and cardiac remodeling (LV mass to LV end-diastolic volume ratio)surrogate

Circulating lncRNAs such as LIPCAR, MIAT, and SENCR may serve as independent biomarkers for subclinical diastolic dysfunction and cardiac remodeling in patients with well-controlled type 2 diabetes.

Main Result

Effect estimate: OR 1.053 (95% CI 1.007-1.101)

p-value: p=0.023

Limitations

Study population was restricted to men with well-controlled disease and no significant comorbidities, limiting generalizability.
The panel of lncRNAs examined was biased by subjective selection.
Small sample size.
Inability to determine causal relationships.
Tissue origin of circulating lncRNAs could not be identified.
Biological role of these lncRNAs in cardiac physiology or pathology remains unknown.
Lack of accepted internal standards for extracellular non-coding RNAs.

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.

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