Micro-RNA as Novel

Biomarker for Diabetes

Mellitus
Muhammad Attique
Manager Clinical Laboratories
Micro-RNAs
Micro-RNAs
MicroRNAs (miRNAs) are small non-coding RNA molecules that act as translational
repressors by pairing with target messenger RNAs.

They were first discovered in Caenorhabditis elegans (Round Worm) and have since been
found in vertebrates and plants.

The human genome encodes over 1600 miRNA precursors, generating up to 2237 mature
miRNAs.

MiRNAs are major regulators of gene expression and key controllers of biological and
pathological processes.
Biogenesis of
Micro-RNAs
Role of miRNAs
in Diabetes
Pathogenesis
Alteration in miRNAs

Expression of a set of miRNAs, including miR-375, regulates

hormone secretion and β-cell mass expansion in response to insulin
resistance.

These miRNAs are altered in both type-1 and type-2 Diabetes

Mellitus, contributing to impaired tissue function.
Non-obese Pre-diabetic model

In non-obese, pre-diabetic mice, miRNAs like miR-21, -34a, -29,

and -146a have deleterious impacts on β-cell functions leading to
development of diabetes mellitus.
Obesity Models

In obesity models, miRNAs like miR-143, miR-802, and miR-103

and -107 are dysregulated, possibly contributing to insulin
resistance.

MiRNA changes related to diabetes have also been reported in

human tissues, with over sixty differentially expressed miRNAs
detected in human skeletal muscle biopsies from T2D patients.
Gestational Diabetes

Three miRNAs (miR-29a, -122, and -132) deregulated in gestational

diabetes women before blood glucose levels were detectable.
This suggests that gestational diabetes may lead to changes in
blood miRNAs that differ from those of type 1 or type 2 diabetes.
miRNAs as
Biomarkers in
Diabetes Mellitus
To predict development and progression of Diabetes Mellitus
Circulating miRNAs, found in blood and body fluids, may play a role in gene
regulation. In vitro studies suggest that miRNAs can be transferred to
recipient cells through exosomes or high-density lipoprotein.

These small RNA molecules are stable and resistant to harsh conditions,
making them suitable biomarkers.

Circulating miRNAs can be detected using sensitive PCR methods and are
evolutionary conserved, making them useful for translating in vivo animal
studies to human healthcare.

Their homogenous and constant serum profiles make them a valuable

biomarker.
A group of researchers identified a characteristic blood miRNA
expression profile related to Type 2 Diabetes Mellitus (T2DM) in
their prospective study, analyzing blood samples of over 800
individuals from the Bruneck cohort.

The level of these miRNAs was already modified years before the
onset of the disease, providing initial evidence for the usefulness
of circulating miRNAs as early predictors of T2DM and its
vascular complications.

(Zampetaki et al 2010)
Another study revealed that there is an increase in the expression of
seven diabetes-related miRNAs in T2DM patients compared to
pre-diabetic or T2DM susceptible subjects.

However, no differences were observed between normal glucose

tolerant and pre-diabetic individuals, indicating that the level of
these miRNAs is not suitable to predict T2DM susceptibility.

(Kong et al 2011)
Another study measured the miRNAs present in the blood and in
exosomes of 265 patients with different health conditions
associated with metabolic syndrome and observed a strong
correlation between elevated fasting glucose concentrations and
the alteration of miR-27a and miR-320a levels in T2DM
individuals.

(Karolina et al 2012)
Prediction of
Complications of
Diabetes Mellitus
Diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are
linked to long-term micro- and macrovascular complications,
impacting life quality and expectancy.

Identifying biomarkers for these long-term complications could help

tailor therapeutic approaches and minimize the disease's impact.
Cardiovascular complications
Cardiovascular complications account for up to 80% of premature mortality
in diabetic patients, are a major concern.

MiRNAs like miR-126, miR-503, and miR-126 have been identified as

potential biomarkers for monitoring diabetic vascular complications.

Circulating miRNAs have also been suggested as diagnostic markers for

various cardiovascular diseases, but their use in predicting or monitoring
these complications in diabetic patients remains to be investigated.
Renal Complications

Circulating miRNAs could also be used to monitor renal failure in

diabetic patients, as they are not eliminated by hemodialysis and
have been tested in various renal diseases.

Large-scale prospective studies focusing on diabetic patients

undergoing renal failure are needed to identify specific miRNA
profiles in plasma or urine.
References
• Zampetaki, A. et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other
microRNAs in type 2 diabetes. Circ Res 107, 810-7 (2010).

• Kong, L. et al. Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2
diabetes: a clinical study. Acta Diabetol 48, 61-9 (2011)..

• Karolina, D.S. et al. Circulating miRNA Profiles in Patients with Metabolic Syndrome. J Clin
Endocrinol Metab 97, E2271-6 (2012).
Thank You