Nghiên cứu mức độ biểu hiện của micro RNA 29a, micro RNA 146a và micro RNA 147b tự do huyết tương ở bệnh nhân đái tháo đường týp 2 TT TIENG ANH

MINISTRY OF EDUCATION

MINISTRY OF DEFENSE

AND TRAINING
VIETNAM MILITARY MEDICAL UNIVERSITY

PHAN THE DUNG

THE EXPRESSION OF CIRCULATING MICRO-RNA 29A,
MICRO-RNA 146A, AND MICRO-RNA 147B LEVELS IN
PLASMA OF PATIENTS WITH TYPE 2 DIABETES
MELLITUS

Specialization: Internal medicine
Code: 97.20.107

SUMMARY OF DOCTORAL DISSERTATION IN MEDICINE

HA NOI - 2021


The study was completed at:
VIETNAM MILITARY MEDICAL UNIVERSITY

Supervisors:
1. Assoc. Prof. Dr. Doan Van De
2. Prof. Dr. Nguyen Linh Toan
Reviewer 1: Dr Nguyen Van Do
Reviewer 2: Prof. Dr. Nong Van Hai
Reviewer 3: Assoc. Prof. Dr. Nguyen Minh Nui

The disseratation will be defended in front of the Board of
Dissertation Assessment, Vietnam Military Medical University
at ..........on ......... month ..... year .....

The dissertation could be found in:
1- Vietnam National Library
2- Library of Vietnam Military Medical University


THE PUBLISHED ARTICLES RELATED
TO THE DISSERTATION
1. Phan The Dung, Doan Van De, Nguyen Linh Toan, (2020).

The beta cell function disorder and insulin resistance status
in patients with type 2 diabetes mellitus. Vietnam Medical
Journal, 494(1):17-20
2. Phan The Dung, Doan Van De, Nguyen Linh Toan, (2020).

Plasma micro-RNA 29a, micro-RNA 146a and micro-RNA
147b expression level in patients with type 2 diabetes
melitus. Jounal of military pharmaco-medicine, 45(7):83-88


LIST OF ABBREVIATION IN THE THESIS
No

Abbreviation

Full text

1

β

Beta

2

BMI

Body Mass Index

3

cDNA

Complementary DNA

4

Ct

Threshold cycle

5

HOMA-β

Homeostasis Model Assessment

Beta cell function

6

HOMA-IR

Homeostasis Model Assessment Insulin
Resistance

7

HOMA-S

Homeostasis Model Assessment insulin
sensitivity

8

MiR

Micro-RNA

9

mRNA

Messenger RNA

10

RNA

Ribonucleic acid

11

RT-PCR

12

T2DM

Type 2 diabetes militus


1
INTRODUCTION
Diabetes mellitus is one of the non-communicable diseases
with a rapid growth rate. The pathogenesis of type 2 diabetes
mellitus (T2DM) is insulin resistance, impaired beta cell function.
Micro-RNAs (miRs) are RNAs with a molecular size of 19-24
nucleotide, non-protein-coding RNAs that regulate gene expression
at the post-transcriptional level by inhibiting transcription or
destroying messenger RNAs (mRNA). Extracellular miRs have been
reported to act as signaling molecules to mediate cell-to-cell
communication. Recent studies suggest that miRs are directly and
indirectly involved in the pathogenesis of T2DM and a potential
therapeutic approach for diabetes. Some recent studies show that
miR-29a, miR-146a participate in the pathogenesis of diabetes but
these have not been fully studied yet. Meanwhile, miR-147b has

been shown to be involved in programmed cell death and little
information is available about miR-147b studies in patients with
T2DM. In Vietnam, there are still no studies mentioning the role of
micro-RNAs, especially miR-29a, miR-146a and miR-147b in
plasma in T2DM. Therefore, we have conducted a research with
subject “The expression of circulating micro-RNA 29a, microRNA 146a and micro-RNA 147b levels in plasma of patients with
type 2 diabetes mellitus” including 2 goals:
1. Investigating the expression levels of micro-RNA 29a,
micro-RNA 146a, micro-RNA 147b in plasma in patients with type 2
diabetes mellitus.
2. Evaluating the relationship between the expression level of
micro-RNA 29a, micro-RNA 146a, micro-RNA 147b in plasma with
some clinical, subclinical, insulin resistance status in patients with
type 2 diabetes mellitus.


2
* New contribution of the thesis
1. This is the first study on the expression levels, association
and diagnostic values of circulating miR-29a, miR-146a, miR-147b
in plasma of patients with T2DM in Vietnam. The results showed
that the expression of circulating miR-29a and miR-147b in plasma
significantly increased in patients with T2DM compared with healthy
people (p<0.001). Meanwhile, the expression of miR-146a had no
statistical difference in two groups (p>0.05).
2. There are positive correlation between plasma miR-29a and
miR-147b expression levels with glucose concentration, HbA1C, and
inversely correlated with C-peptide concentration and HOMA-β
indexes. The expression level of miR-146a was significantly lower
while that of miR-147b was significantly higher in patients with

T2DM with microalbuminuria in comparison to patients withous
microalbuminuria (p<0.05).The increased expression of miR-29a and
miR-147b are associated with impaired beta-cell function, which is
an important role in pathogenesis of T2DM. The expression levels of
miR-29a and miR-147b are valuable in diagnostics of beta-cell
dysfunction in patients with T2DM with area under the curve (AUC)
of 0.75 (sensitivity 85.9%, specificity 40%) and 0,75 (sensitivity
77.3%, specificity 67.1%). Respectively, in combination of miR-29a
and miR-147b, the are valuable in diagnostics is increased with the
AUC of 0,73 (sensitivity 74.3%, specificity 68.7%). Inconstrast, the
expression level of miR-146a is not valuable in diagnostics of betacell dysfunction in patients with T2DM. The study also confirms that
expression of these micro-RNAs are associated with insulin
resistance. There are important roles of circulating miR-29a, miR146a, miR-147b in pathogenesis of T2DM. From this study, it is
suggested that miR-29a and miR-147b can be used as markers to
diagnose beta cell dysfunction in patients with T2DM. In addition,


3
this study serves as a basis for further studies on the role of microRNA in diabetic patients.
* Thesis structure: the thesis has 126 pages (excluding
appendices and references): 2 pages of problem statement, 34 pages
of document overview, 25 pages of research objects and methods, 32
pages of research results, 31 pages of discussions, 3 pages of
conclusions and recommendations. The results of the study includes
24 tables, 39 figures. There are 149 references, including 17
Vietnamese documents, 132 English documents.
Chapter 1: OVERVIEW
1.1. Overview of type 2 diabetes mellitus
Diabetes mellitus is a chronic disorder, characterized by:
hyperglycemia, combined with abnormalities in carbohydrate, lipid

and protein metabolism, the disease is always associated with a
tendency to develop kidney, fundus, neurological and cardiovascular
diseases as a result of atherosclerosis.
Regarding the pathogenesis, there are currently many known
mechanisms causing hyperglycemia such as: beta-cell dysfunction,
insulin resistance, brain neurotransmission disorders, increased
glucagon secretion, incretin effect, increased glucose reabsorption in
the renal tubules, and insulin resistance and beta cell dysfunction are
key elements to the pathogenesis.
Insulin resistance: is a state of decreased biological response
of cells, occurring early in the progression of the disease. Insulin
resistance exists in the liver and peripheral tissues. At the cellular
level, abnormalities in insulin action at the cellular level are divided
into two levels: receptor defects and postreceptor defects. Postreceptor defects are characteristic of T2DM, where the binding of
insulin to the receptor remains normal. The main abnormality is a
disorder of the signaling system in the cell that leads to an impaired


4
ability to carry glucose. Recently, the role of genes involved in the
regulation of insulin resistance has been of interest.
Disorders of insulin secretion means pancreatic beta cells are
disrupted in their ability to produce insulin normally both
quantitatively and qualitatively to ensure normal glucose
metabolism.
1.2. Overview of micro-RNA
1.2.1. Molecular structure, mechanism of secretion and action of
miR
Micro-RNAs are short pieces of RNA between 19-24
nucleotides that are not involved in protein synthesis. MiR formation

takes place in the nucleus and in the cytoplasm. Many studies have
found that miRs exist in the extracellular fluid circulating in
biological fluids, such as plasma, cerebrospinal fluid, saliva, urine,
etc., but the mechanisms for releasing these miRs into the
extracellular environment are still unanswered. Two forms of
extracellular miR exist in body fluids: One is found in vesicles while
the other is associated with proteins, specifically AGO2. Many
studies have also demonstrated that extracellular miRs can act as
intercellular signaling molecules. In contrast to intracellular miRs,
extracellular miRs are more highly stable.
MiR molecules participate in the regulation of gene expression
by binding to the 3' non-translational region (3'UTR) of the mRNA,
causing mRNA to be degraded or transliterated on this mRNA
molecule lock up.
1.2.3. The role of micro-RNA in diabetes
Micro-RNA and pancreatic β-cells: Many important miRs
implicated in pancreatic β-cell dysfunction have been demonstrated.
Collectively, they affect cells through regulation of cell survival and
apoptosis, proliferation, cell differentiation, or function, especially


5
secretion. insulin.
MiR and insulin resistance: Insulin resistance is an important
pathogenesis of T2DM. In this process, the insulin signaling pathway
plays a central role. This process is initiated by insulin binding to the
insulin receptor on the cell surface, followed by the insulin receptor
substrate that initiates the intracellular signaling cascade. Evidence
suggests that insulin resistance is associated with insulin signaling
deficiencies and that miR may be involved in this process.

1.2.3.1. Origin and role of miR-29a in type 2 diabetes mellitus
MiR-29a can be find in human chromosome 7q32.3. The
study by Pullen et al (2011) showed that three isoforms of miR-29
are highly expressed in diabetic patients. The miR-29 acts on the
promoter region of the Mct1 gene and inhibits the expression of the
Mct-1 gene. This inhibits insulin secretion by pancreatic beta cells.
MiR-29 over expression promotes programmed cell death. The study
conducted by Bagge A. (2012) showed that increased miR-29a
expression in diabetic patients reduced insulin secretion by
pancreatic beta cells in response to hyperglycemia. By contrast,
attenuating miR-29a expression improved beta cell function.
Regarding the mechanism of insulin resistance in T2DM, a
recent analysis identified increased expression of miR-29 in muscle,
liver, and white adipose tissue in association with insulin resistance
in a mouse model of T2DM. Overall, aberrant expression of miR-29a
impairs insulin signaling and insulin-stimulated glucose uptake in
muscle cells through post-transcriptional inhibition of IRS.
1.2.3.2. Origin and role of miR-146a in T2DM
The gene for miR-146a is located on chromosome number
5q33.3. The role of miR-146a in the pathogenesis of T2DM is still
inconclusive. Some studies showed an increased expression, some
studies showed a decreased expression. The study of Rong et al


6
(2013) in patients with newly diagnosed T2DM showed that miR146a increased expression in patients with T2DM. The study of
Lovis (2008) showed an increased expression of miR-146a in
patients with T2DM. MIN6 beta cell line and induces decreased
insulin secretion. The study also showed that the increased miR-146a
expression did not affect insulin secretion but increased programmed

beta cell death.
Some other studies showed that the miR-146a decreased
expression in patients with T2DM. Decreased expression of miR146a is related to inflammatory factor, promoting inflammatory
process causing damage in tissues. The study of Balasubramanyam
M. (2011) on 20 patients with T2DM showed that miR-146a was
significantly reduced in expression in peripheral blood mono nuclear
cells and was negatively correlated with HbA1C, TRAF6, TNF, IL-6
mRNA, insulin resistance. Most of the studies suggested that the role
of miR-146a is related to inflammatory and proinflammatory
factors , causing chronic complications in diabetes.
1.2.5.5. Origin and role of plasma miR-147b in T2DM
MiR-147b is located on chromosome 15q21.1. There are not
many current studies on miR-147b . Several recent reports suggest a
role for miR-147b in breast and ovarian cancers and are considered
as potential biomarkers for these cancers. In the study of Xu et al
(2016) in an obese mouse model with diabetes, the results of study
showed that miR-147 is upregulated, which over-activates the
inflammatory properties of macrophages, thereby increasing the
inflammatory process that contributes to inflammation. Periodontitis
in diabetic rats. Another report has shown that miR-147b can
promote programmed cell death of ovarian cancer cells and inhibit
proliferation. However, studies on the role of miR-147b in diabetic
patients are currently limited.


7
1.2.4. Quantitative method of micro-RNA
There are two ways to quantify the target agent based on the
quantitative purpose of interest to the experimenter: absolute
quantification and relative quantification. The quantification usually

shows expression of genes.
Chapter 2: RESEARCH SUBJECTS AND METHODS
2.1. Research subjects
The study was conducted on 198 people who came for health
check- up and treatment at Nghe An Endocrinology Hospital, then
they are divided into 2 groups:
Group of diseases: 105 patients were diagnosed with T2DM;
Control group: 93 healthy people.
2.1.1. Selection criteria
- Disease group: Aged from 40 to 70, diagnosed with T2DM
and agreed to participate in the study.
Control group: Healthy people who came for health check-up,
did not have diabetes or pre-diabetes, aged from 40 to 70, agreed to
participate in the study.
2.1.2. Exclusion criteria
Disease group:
- Being diagnosed with type 1 diabetes, gestational diabetes,
diabetes with a cause.
- Suffering from severe acute infections, respiratory failure,
cancer. Patients with severe complications, history of exposure to
radioactive substances, Agent Orange. Have comorbidities affecting
glucose metabolism.
- Patients with alcoholism and tobacco addiction were
excluded from the study.
Control group:
Are suffering from acute infections, cancer. These patients


8
have been using some drugs that affect glucose metabolism within 1

month. Patients with alcohol abuse, smoking addiction, history of
exposure to radioactive substances, Agent Orange.
2.2. RESEARCH METHODS
2.2.1. Research design
The study describes a cross-sectional, controlled comparison.
2.2.2. Place and time of study
The study was carried out at Nghe An Endocrinology Hospital,
Military Medical Academy, 108 Military Central Hospital. The study
period lasted from September 2016 to June 2019.
2.2.3. Sample size and sampling method
- Sample size: n=198 in which control group n=93, patient
group n=105.
- Sampling method: convenient sampling.
2.2.4.4. Quantitative method for plasma micro-RNA
Quantification of miR-29a, miR-146a, miR-147b by Real-time
reverse transcription PCR (Real-time reverse transcription PCR)
through two stages: Stage 1: Performing reverse transcription
reaction (Reverse transcription) converts single-stranded RNA into
double-stranded cDNA (complementary DNA). Stage 2: Real-time
PCR reaction using the sample is the cDNA product of phase 1.
Implementation process
Step 1: Extraction and purification of RNA
- Put 250 μl of plasma in a 1.5ml tube. Add 5 μl miR-39 as a
reference gene for 5 pm concentration, 750 μl of Trizol/RNA fluid to
each tube and votex for 15 seconds. Add 200 μl of Cloroform
solution to each gently shaker tube, centrifuge 12000 rounds for 15
minutes at 40C. Gently suck the upper phase (upper floating fluid)
(500μl) to the new 1.5ml tube. Isopropanol supplementation (500μl)
is equivalent to the translation part that has just been transferred.

9
Leave the natural cupboard at room temperature for 10 minutes.
Centrifuge 12000 rounds in 15 minutes at 4 0C. Remove all floating
fluid, collect residue.
- Washing the precipitate (residue) for the first time: Adding
1000 µl alcohol 750 . Centrifuging 7,500 rounds in 5 minutes at 40C
before discarding the supernatant.
- Washing the precipitate for the second time: Adding 1000 μl
alcohol 700 and then centrifuging 7,500 laps in 5 minutes at 40C.
Next, removing the supernatant, and then drying the residue with a
vacuum cleaner for 10 minutes. Dissolve the residue in 50 µl of
DNAase/RNAse-free solution (DEPC-DW). Store RNA samples at
-800C until use.
Step 2: OD measurement RNA quality test
The concentration and purity of RNA is determined by the
NanoPhotometer™ Pearl (Implen GmbH).
Use 1 μl of undiluted RNA samples and measure at wavelengths of
260 mm and 280 nm.
- The concentration of RNA is calculated automatically by
the machine according to the formula A260 x dilution coefficient x
40 = μg RNA / μl. Cleanness calculated in the ratio of A260 / A280
from 1.8 to 2 is calculated as clean.
- Store the RNA sample at - 800C until use.
Step 3: cDNA Synthesis
To assess the level of expression of miR-29a, miR-146a,
miR-147b, miR-39, single-strand RNA must be converted into
double-fiber cDNA by reacting to RT-PCR reverse transcript
transcriptation.
- Phase 1: Reverse transcript reaction:

RevertAid First Strand cDNA Synthesis Kit.
Synchronously put the following substances into the same


10
tube eppendorf 1.5ml: 200μl.
Ingredient
Volume (μl)
5x Reaction Buffer
4
RiboLock RNase Inhibitor (20U/μl)
1
dNTP Mix (10 mM)
2
RevertAid M-MuLV RT (200 U/μL)
1
Stem-loop RT primer (50 nM)
1
RNA
11
Amount
20
- Run the reaction heat cycle
After the end of the reverse transcriptive heat cycle obtains
cDNA. The cDNA sample is diluted in a ratio of 1:5 with
Invitrogen™ UltraPure™ DNase/RNase-Free Distilled Water
(Brand: Invitrogen™ 10977035) solution into each tube.
- Store the cDNA sample at - 200C until cDNA is used.
Step 4: Implement a Real-time PCR reaction
Phase 2: Real-time PCR Reaction

Using the sample is cDNA obtained from step 2, (phase 1), semidosing miR using real-time PCR technique on the AriaMx Real-time PCR
system (USA) using fluorescent DNA dye SYBR GreenI.
 Quantitative principles
Mechanism of action of SYBR Green I: (1) When there is no
amplification product, the secondary tube does not emit light when
receiving stimulating light, (2) But in the presence of the
amplification product, SYBR I inserts and attaches to the DNA
molecule, causing the reaction tube to fluoresce when receiving
stimulating light.
 Specific bait sequence for micro-RNA
MiR amplified specific bait and probe design uses miR-bymiR
reference
sequences
from
ncbi
gene
bank
( and uses advanced NTI 11.0 vector


11
software.

21

Amplif
ication
Lengt
h (bp)
66

22

66

19

66

22

66

MiR code Down-prey
Bait
on gene sequence
(5'-... length
bank
-3')
(bp)

MiR
name
miR-29a

MIMAT0
000086
MIMAT0
004608
MIMAT0

004928
MIMAT0
000010

miR146a
miR147b
CelmiR-39



TGGGGTAGCAC
CATCTGAAAT
GGTGTGCCTCT
GAAATTCAGTT
GTGTTGTGCGG
AAATGC
TGTGTTTCACC
GGGTGTAAATC
Reverse
bait
sequence for all 4
miR
gtgcagggtccgaggt
RT-PCR reaction component

16

Reaction component
PowerUp™ SYBR™ Green Master Mix (Cat A25742,
Applied Biosystems)

Specific down prey for miR-39 reference/miR29a/miR-146a/miR-147b (50 nM)/ Common specific
reverse bait for all 4 miR (50 nM)
cDNA is synthesized from step 3
Amount
 Reference gene used in NC

Tm°
C

CG%

65.7

47.6

64.6

45.5

65.8

52.6

65.9

45.5

63.1

68.8

Volume
1
reaction (μl)
5
1
4
10

To minimize the fluctuation in the amount of miR between
NC samples, the level of expression of the target miR is normalized
"normalised" with a reference miR. The degree of expression of miR
versus reference gene (miR-39) is calculated according to the
formula of Schmittgen T. D. and cs: Expression of miR = 2 -ΔCt. In
which ΔCt = Ct (target miR) - Ct (miR reference)


12
2.5. DATA PROCESSING METHODS
- The study data were processed using SPSS 22.0 software.
Chapter 3: RESULTS
3.1. GENERAL CHARACTERISTICS OF SUBJECTS
3.1.1. Clinical characteristics of research subjects
- The study was performed on 105 patients with T2DM: The
average age is 55.85 ± 8.35, which is not different from the control
group (54.03 ± 8.36). Male gender accounted for 49.5%, not different
from the control group. The mean time of disease detection was 2.08
± 3.28 years. Patients with newly diagnosed diabetes for the first
time without treatment intervention were 52 people (49.5%).
- In the study group: BMI was 23.49 ± 3.23 not different from

the control group 22.9 ± 3.36 (p>0.05), the rate of hypertension
accounted for 47.6%. The average blood glucose concentration was
9.47 ± 2.67 mmol/l, HbA1C 8.2 ± 1.99 %, insulin 10.07 ± 5.53
µU/ml. The rate of patients with microalbuminuria (+) was 66.7%.
The researchers had HOMA-IR 1.61 ± 0.59 ,which is higher
than the control group 1.45 ± 0.42 (p<0.05), HOMA-β 41.84 ± 20.54
is lower than the control group 111.69 ± 25.53 (p<0.001), HOMA-S
70.52 ± 24.94 were not statistically different from the control group
74.74 ± 21.24 (p>0.05).
3.2. EXPRESSION LEVELS OF MIR-29A, MIR-146A, MIR147B IN PLASMA IN TYPE 2 DIABETES MELLITUS
- The expression of miR-29a in the group of patients with
T2DM was higher than that of the control group in which the rate of
increased expression accounted for 49.5%. MiR-29a expression in
newly diagnosed T2DM was higher than in T2DM with treatment
intervention (p<0.05).
- The expression of miR-146a in type 2 diabetic patients was
not statistically different from the control group (p=0.083). The miR-


13
146a expression rate at normal level was 70.5%. The expression of
plasma miR-146a in the group of newly diagnosed T2DM patients
who have not been treated yet had no statistical difference compared
to the control group and the treated group of T2DM (p>0.05).
- The expression of miR-147b in plasma in the group of
patients with T2DM was higher than that of the control group
(p<0.001), in which increased expression accounted for 72.4%. The
expression of plasma miR-147b in the group of newly diagnosed
T2DM and treated T2DM was higher than that in the control group
(p<0.001).

3.3. THE RELATIONSHIP BETWEEN THE EXPRESSION OF
MIR-29a, MIR-146a, MIR-147b IN PLASMA WITH SOME
CLINICAL AND PARACLINICAL FEATURES IN PATIENTS
WITH TYPE 2 DIABETES MELLITUS
3.3.1. The relationship of plasma miR-29a, miR-146a, miR-147b
expression levels with some clinical and subclinical
characteristics
- There was no statistical difference between the expression
levels of miR-29a, miR-146a, miR-147b in plasma between men and
women, obesity and hypertension in patients with T2DM (p>0.05).
- The expression levels of miR-29a, miR-146a, miR-147b in
plasma in the group of T2DM patients with metabolic syndrome and
the group without metabolic syndrome had no statistical difference
(p>0.05).
- The expression level of miR-146a in plasma in the group of
patients with T2DM with microalbuminuria was lower, while the
expression of miR-147b was higher than the figure for the group
without microalbuminuria (p<0.05).
3.3.2. Correlation of plasma miR-29a, miR-146a, miR-147b
expression levels with some clinical and subclinical


14
characteristics
- The expression level of plasma mir-29a is negatively
correlated with the time of disease detection (r = -0.28; p = 0.004),
there is no correlation with other clinical indicators such as weight,
BMI, waist circumference, Hip circumference, WRH, blood
pressure.
- The expression of miR-146a was negatively correlated with

patient age (r= -0.2; p=0.04), not correlated with other clinical
indicators.
- The expression level of plasma miR-147b did not correlate
with the clinical parameters of research subjects.
Table 3.26. Correlation between miR-29a expression level and
some blood biochemical indices, HOMA in patients with T2DM.
Newly diagnosed T2DM
T2DM (n=105)
(n=52)
Index
Correlation
Correlation
P
p
coefficient (r)
coefficient (r)
Glucose
0,39
<0,001
0,03
0,83
(mmol/l)
HbA1C (%)
0,33
0,001
0,024
0,87
Insulin (%)
0,06
0,52

-0,13
0,73
C-peptide
-0,12
0,22
-0,26
0,07
(ng/ml)
HOMA-IR
-0,016
0,87
-0,268
0,05
HOMA-S
-0,02
0,85
0,273
0,05
HOMA-β
-0,35
<0,001
-0,12
0,39
MiR-146a
0,2
0,045
0,26
0,06
MiR-147b
0,47

<0,001
0,45
0,001
The expression of plasma miR-29a is positively correlated
with blood glucose levels, HbA1C, miR-146a, expression of miR147b, moderately inversely correlated with HOMA- β; not correlated
with:
insulin
concentration,
C-peptide,
blood
lipids,
Microalbuminuria, HOMA-IR, HOMA-S.


15
Table 3.27. Correlation between plasma miR-146a expression
level and blood biochemical index and HOMA in patients with
T2DM.
T2DM (n=105)
Index
Microalbuminuria
(mg/l)
MiR-147b

Newly diagnosed
T2DM (n=52)
Correlation
p
coefficient (r)

Correlation
coefficient (r)

p

-0,21

0,03

-0,28

0,045

-0,29

0,003

-0,29

0,04

Plasma miR-146a expression is inversely correlated with
plasma miR-147b expression, microalbuminuria; Not correlated with
indexes: glucose, insulin, HbA1c, C-peptide, blood lipids,
microalbuminuria, HOMA-IR, HOMA-S, HOMA-β.
Table 3.28. Correlation between plasma miR-147b expression
level and blood biochemical index, HOMA in patients with
T2DM.
T2DM (n=105)
Index

Glucose (mmol/l)
HbA1C (%)
C-peptide (ng/ml)
HOMA-IR
HOMA-S
HOMA-β
Microalbuminuria

Correlation
coefficient (r)
0,34
0,23
-0,21
-0,09
0,09
-0,35
0,29

p
<0,001
0,02
0,03
0,36
0,35
<0,001
0,003

Newly diagnosed T2DM
(n=52)
Correlation

p
coefficient (r)
0,48
<0,001
0,14
0,34
-0,38
0,006
-0,18
0,21
0,23
0,1
-0,52
<0,001
0,13
0,37

The expression of miR-147b in plasma is positively correlated
with glucose concentration (r=0.34; p<0.001), HbA1C (r=0.23;
p=0.02), microalbuminuria (r=0.29). ; p=0.003), negatively
correlated with C-peptide (r=-0.21; p=0.03) and HOMA- β (r=-0.35;
p<0.001); not correlated with insulin, C-peptide, blood lipids,