Circulating TGF-ß1-regulated miRNAs and the risk of rapid progression to ESRD in
type 1 diabetes.
Authors Pezzolesi MG, Satake E, McDonnell KP, Major M, Smiles AM, Krolewski AS
Submitted By Marcus Pezzolesi on 5/10/2015
Status Published
Journal Diabetes
Year 2015
Date Published 4/30/2015
Volume : Pages Not Specified : Not Specified
PubMed Reference 25931475
Abstract We investigated whether circulating TGF-ß1-regulated miRNAs detectable in plasma
are associated with the risk of rapid progression to end-stage renal disease
(ESRD) in a cohort of proteinuric patients with type 1 diabetes (T1D) and normal
eGFR. Plasma specimens obtained at entry to the study were examined in two
prospective sub-groups that were followed for 7-20 years (rapid progressors and
non-progressors), as well as a reference panel of normoalbuminuric T1D
patients.Of the 5 miRNAs examined in this study, let-7c-5p and miR-29a-3p were
significantly associated with protection against rapid progression and let-7b-5p
and miR-21-5p were significantly associated with the increased risk of ESRD. In
logistic analysis, controlling for HbA1c and other covariates, let-7c-5p and
miR-29a-3p were associated with more than a 50% reduction in the risk of rapid
progression (P = 0.001), while let-7b-5p and miR-21-5p were associated with a
>2.5-fold increase in the risk of ESRD (P = 0.005).This study is the first
prospective study to demonstrate that circulating TGF-ß1-regulated miRNAs are
deregulated early in T1D patients who are at risk of rapid progression to ESRD.

Investigators with authorship
Marcus PezzolesiUniversity of Utah