International Journal of Medical Sciences And Clinical Research
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VOLUME
Vol.05 Issue03 2025
PAGE NO.
16-20
10.37547/ijmscr/Volume05Issue03-04
Relationship between insulin resistance and
hematological parameters in patients with metabolic
syndrome
Saydaliyev R.S.
Tashkent Medical Academy, Uzbekistan
Received:
23 January 2025;
Accepted:
26 February 2025;
Published:
25 March 2025
Abstract:
It has already been demonstrated that insulin resistance (IR) is associated with the stimulation of
erythroid progenitors and with increased levels of inflammation markers. Therefore, IR should also be associated
with increased red blood cell (RBC) and white blood cell (WBC) count. The aim of this study is to demonstrate that
IR is independently associated with altered hematological parameters in patients with metabolic syndrome. We
analyzed laboratorial exams from 275 subjects. All data on hematological parameters, insulin resistance
(Homeostasis Model Assessment [HOMA]) and lipid levels were included in the analysis. Demographic information
included age and gender. HOMA correlated positively with RBC (r= 0.17, p< 0.001), plasma hemoglobin
concentrations (r= 0.14, p< 0.001), hematocrit value (r= 0.15, p< 0.001) and WBC (r= 0.17, p< 0.01). Subjects in
the upper quartile of IR had higher levels of plasma glucose, fasting insulin, triglycerides, hematocrit, hemoglobin,
RBC and WBC count than those in the lower quartile. In conclusion, IR seems to be associated with alterations in
several hematological parameters. These hematological alterations may be considered an indirect feature of the
IR syndrome.
Keywords:
Insulin resistance, hyperinsulinemia, hemoglobin, red blood cells, white blood cells.
Introduction:
The metabolic syndrome (MS) is
currently described as the association of insulin
resistance with obesity (mainly visceral), hypertension,
and dyslipidemia (increased triglycerides and/or
decreased HDL-cholesterol). According to WHO criteria
[14], insulin resistance (IR) is the main determinant of
the syndrome and hyperinsulinemia, its major clinical
expression, is directly related to all other minor criteria.
Patients with MS are at increased risk for
cardiovascular death and hyperinsulinemia seems to be
an independent factor for a cardiovascular event [8].
The association between hyperinsulinemia and
cardiovascular disease is partially explained by the
effects of insulin on cell growth. Insulin has been shown
to promote growth of vascular cells and consequently
to induce atherosclerosis. Moreover, several authors
have already demonstrated that insulin also regulates
erythropoiesis in vitro [3,7]. Recently, it was suggested
that the effects of hyperinsulinemia in erythroid
progenitors could also lead to an increase in red blood
cell (RBC) count [2]. Therefore, the alterations in
hematological parameters could be included as a new
and indirect feature of the IR. We aimed at
demonstrating that IR is independently associated with
alterations
in
hematological
parameters
and
dyslipidemia in patients with metabolic syndrome.
METHODS
For the purpose of this study, we analyzed the results
of laboratorial exams from 275 subjects sequentially
selected between 18 and 80 years old. All patients had
a blood sample collected at the Republican scientific
center for emergency medical care laboratory to
perform exams for the evaluation of hematological
parameters, lipid profile and insulin resistance. Thirty-
two patients were excluded: 29 subjects because of
fasting glucose levels higher than 126 mg/dl (i.e.
Diabetes Mellitus) and 3 subjects becauseof insulin
levels higher than 100 μUI/ml. The final analysis
included 91 men and 152 women with a mean age of
43.8 ± 15.3 years old. Venous blood samples were
collected after a 12 hr fasting period. Blood glucose was
measured by an enzymatic colorimetric assay using
International Journal of Medical Sciences And Clinical Research
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
glucose oxidase method and plasma insulin by a
commercial
double-antidiv,
solid
phase
radioimmunoassay. Commercial enzymatic tests were
used for determining serum total- and HDL cholesterol
and triglyceride concentrations. Serum LDL cholesterol
concentrations were calculated by the Friedwald
formula [6]. Red blood cells (RBC) count, white blood
cells (WBC) count, hemoglobin concentration and
hematocrit
were
done
using
a
hematology
autoanalyzer. The estimate of insulin resistance by
homeostasis
model
assessment
(HOMA)
was
calculated with the formula: [fasting serum insulin
(uUI/ml) x fasting plasma glucose (mg/dl) x 0.0551] /
22.5 [10]. Statistical analysis was performed with
GraphPad In Stat 3.00 for Windows XP (GraphPad
Software, California, USA). The strength of the linear
relationship between two continuous variables was
evaluated by means of the Spearman's rank order
correlation coefficient. Multivariate linear regression
analysis was used to test the independent association
of age, gender and HOMA with the hematological
parameters. The level of statistical significance was 5%.
RESULTS
In the whole group, HOMA was positively associated
with plasma concentrations of triglycerides (r= 0.36,
p<0.001), total cholesterol (r= 0.08, p= 0.01) and
negatively associated with concentrations of HDL-
cholesterol (r=-0.27, p< 0.001). After adjustment for
age, however, the association between HOMA and
total cholesterol was not significant (p=0.17). A positive
correlation between HOMA and the main
Table 1. Correlation between insulin risistance and the main hematological
parameters according to gender
HOMA and
RDCcout
08
R=0
P=0,19
R=0,13
P=0.01
HOMA
hemoglobin
and
06
R=0
P=0.32
R=0.078
P=0.038
HOMA and
hematocrid
12
R=0
P=0.07
R=0.10
P=0.007
HOMA and
WBC count
15
R=0
P=0.02
R=0.16
P<0.001
HOMA and
platelets
07
R=0
P=0.29
R=0.09
P=0.01
HOMA=Homeostatis Model Assesment; RBC=Red Blood Cell; WBC= White Blood
Cell
Table 2. Quartiles of insulin resistance.
1st
Quartile
(<1.44)
2nd
Quartile
(1.44 -
2.35)
3rd
Quartile
(2.35 -
3.90)
4th
Quartile
(>3.91)
IR (HOMA)
.3
0.93 ± 0.3 1.89 ± 0.2 3.09 ± 0
6.57 ± 2.83
Glucose
(mg/dl)
87.5 ± 9.4 92.0 ±
10.1
94.7 ± 1
99.1 ± 11.5
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
I
R=
Insmin’
ResisÍunce,
HOMA=Homeostasis
Model
:cnt;
I
I
I
I
R=
Insmin’
ResisÍunce,
HOMA=Homeostasis
Model
Assessm:cnt;
Chol.—
.Cholesterol;
Triglyc.=Trigl,v-cerides;
RBC=Red
Rlood
Count(
WBC-White
Blood
Count.
Dяta
are
meaпs
-ь
SD.
“P<0.01x1st
quartile;
‘p<0.01x2
nd
qua
rtile;
‘p<0.01x3rd
quartile.
hematological variables was also found. HOMA
correlated with RBC count (r= 0.17, p< 0.001), plasma
hemoglobin concentrations (r= 0.14, p< 0.001),
hematocrit value (r= 0.15, p< 0.001) and WBC count (r=
0.17, p< 0.01). All these associations were still
significant after adjustment for age (data not shown).
HOMA was not associated with the number of platelets
(r= 0.02, p= 0.52). Table 1 shows the correlation
between HOMA and the main hematological
parameters according to gender. By dividing subjects
into quartiles of HOMA, it was shown that subjects in
the upper quartile had higher levels of plasma glucose,
fasting insulin, triglycerides, hematocrit, hemoglobin,
RBC and WBC count than those in the lower quartile.
Levels of fasting insulin, triglycerides and RBC count
were found to be even higher than those in the third
quartile (table 2).
DISCUSSION
We investigated whether IR is associated with
dyslipidemia and hematological parameters. To reach
this goal, we systematically evaluated the results of
biochemical exams from 275 subjects. Our most
significant findings were the following: (1) IR presented
a positive correlation with all hematological
parameters (except platelets). especially in women;
and (2) patients at the higher quartile of IR had higher
levels of cardiovascular risk factors than those subjects
at the lower quartile. Hyperinsulinemia seems to exert
its effects in erythropoiesis through different
mechanisms. The presence of the insulin receptor (INS-
R) in human erythropoietic cells during all stages of
development suggests that insulin acts as a co-factor in
erythropoiesis [1]. Indeed, increased haematological
parameters (i.e. polycythaemia) observed in newborn
babies of diabetic mothers support the relationship of
hyperinsulinemia and erythropoiesis in vivo [12].
Furthermore, several authors have also demonstrated
the
growth-promoting
effects
of
insulin
in
erythropoietic
cells
in
vitro
[3,7].
Also,
hyperinsulinemia seems to increase concentrations of
hypoxia-inducible factor-1 alpha (HIF-1 alpha). HIF-1
alpha promotes the synthesis of erythropoietin and
may also mediate intestinal iron absorption [11]. Taken
Insulin
(μgU/ml)
4.3 ± 1.5
8.5 ± 1.4
13.5±2
27.2 ± 11.7
Chol.
(mg/dl) .2
195..4A44 192.6 ± 39 196.9 ±
34.4
198.8Z40.3
HDL-Chol.
(mg/dl) .8
60.4 ± 6
53.3 ±12.
52.5 ± 2
48.9 ± 12.2
Triglyc.
(mg/dl)
94.0 ± 6.0 108.4 ± 62 129.2±76.7 156.5 ±
91.2
RBC
(10³/ml)
4.5 ± 0.4
4.6 ± 0.1
4.6 ± 0.4
4.7 ± 0.4
WBC
(10³/ml)
6.3 ± 1.8
6.3 ± 1.6
6.7 ± 1.9
7.0S10.7
Hemoglobin 13.6 ± 1.2 13.8 ± 1.3 13.9 ± 1
14.1 ± 1.4
Hematocrit
(%)
41.3 ± 3.3 41.8 ± 3.7 42.3 ± 3.
42.7 ± 3.9
Platelet
(10³/ml)
257.4650
250.3 ± 5
2
2G2.446
257.2 ±
63.2
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International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
together, these mechanisms may help to explain the
relation between IR and the erythropoietic parameters.
The increase in WBC and RBC count associated with IR
may contribute to the increased cardiovascular
mortality related to the MS. Blood viscosity is regulated
by several factors, including the number of both white
and red blood cells. The effects of insulin in
erythropoiesis may lead to an increase in blood
viscosity and to altered circulatory kinetics. Indeed,
blood viscosity has already been shown to be an
independent risk factor for stroke and myocardial
infarction [9]. It has been suggested that the MS
presents several features of an inflammatory disease.
Moreover, other inflammation markers, such as C
Reactive Protein, have recently been associated with
cardiovascular disease and cardiovascular mortality [5].
The association of IR with increased WBC count may
provide further evidence for all those who believe that
chronic inflammation is part of the MS. WBC are an
element necessary for plaque formation and growth.
Therefore,
increased
WBC
may
reflect
the
inflammatory activation related to the MS. Was In our
study, subjects in the higher quartile of IR showed
significantly higher levels of several independent
cardiovascular risk factors. Insulin resistance associated
with higher levels of triglycerides, RBC and WBC count,
hemoglobin, hematocrit and lower levels of HDL
cholesterol than subjects at the lowest quartile.
Although the relation among IR, dyslipidemia and
cardiovascular morbidity is widely accepted, the
inclusion of the hematological parameters as risk
factors strengths the necessity of a more detailed
approach of the patients with the MS. Further studies,
however, are necessary to clarify the independent
impact of the hematological parameters in
cardiovascular morbidity and mortality.
Our study has some limitations. First, we could not
include anthropometrical measurements (i.e. waist,
waist to-hip ratio, div mass index [BMI]) in the
statistical analysis. Therefore, we could not investigate
whether
the
hematological
parameters
were
influenced by weight excess instead of IR. However,
previously published reports demonstrated that the
relation between IR and the hematological parameters
persisted even after adjustment for waist and BMI
[2,4,13]. Second, we could not exclude patients who
were under treatment with drugs that might interfere
with erythropoiesis or with lipid levels. We believe that
the strength of the relation would not be changed with
the exclusion of these patients. Finally, it remains to be
determined the reason why the relationship between
IR and the hematological parameters (except for WBC
count) could not be demonstrated in men. We believe
that the small sample may be partially responsible for
these findings. Further studies are necessary to clarify
this issue. In conclusion, IR seems to be associated with
increased white and red cell count, hemoglobin and
hematocrit.
Hyperinsulinemia
may
increase
erythropoiesis and consequently increase blood
viscosity. The alterations in hematological parameters
induced by IR may be partly responsible for the
increased cardiovascular mortality. related to the MS.
Controlled studies are necessary to clarify the impact of
the treatment of IR in the hematological parameters.
REFERENCES
Aoki I, Taniyana M, Toyama K, Homori M, Ishikawa K.
Stimulatory effect of human insulin in erythroid
progenitors (CFU-E and BFU-E) in human CD34
separated bone marrow cells and the relationship
between insulin and erythropoetin. // Stem Cells 2010;
12:329-38.
Barbieri M, Ragno E, Benvenutti E, Zito GA, Corsi A,
Ferrucci L, et al. New aspects of the insulin resistance
syndrome: Impact in haematological parameters. //
Diabetologia 2011; 44:12327.
Bersch N, Groopman JE, Golde DW. Natural and
Biosynthetic insulin stimulates the growth of human
erythroid progenitors in vitro. // J Clin Endocrinol
Metab 2012; 55:1209-11.
Choi KM, Lee J, Kim YH, et al. Relation between insulin
resistance and hematological parameters in elderly
Koreans Southwest Seoul (SWS) Study. // Diabetes Res
Clin Pract 2003; 60:205-12.
Danesh J, Phil D, Wheeler JG, Hirschfield GM, Eda S.
Eiriksdottir G, et al. C-reactive protein and other
circulating markers of inflammation in the prediction of
coronary heart disease. // N Eng J Med 2004; 350:1387-
97.
Friedewald WT, Levy R, Fredricson DS. Estimation of
serum low-density lipoprotein without the use of a
preparative ultracentrifuge. // Clin Chem 2010; 18:499-
502.
Kurtz A, Selkmann W, Bauer C. Insulin stimulates
erythroid
colony
formation
independently
of
erythropoietin. // Br J Haematol 2013; 53:311-6.
Lakka HM, Lakka TA, Tuomilehto J, Sivenius J. Salonen
JT. Hyperinsulinemia and the risk of cardiovascular
death and acute coronary and cerebrovascular events
in men: the Kuopio Ischaemic Heart Disease Risk Factor
Study. // Arch Intern Med 2012; 24; 160:1160-88.
Lowe GD, Lee AJ, Rumley A, Price JF, Fowkes FG. Blood
viscosity and risk of cardiovascular events: the
Edinburgh Artery Study. // Br J Haematol 2007; 96:168-
73.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA,
International Journal of Medical Sciences And Clinical Research
20
https://theusajournals.com/index.php/ijmscr
International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)
Treacher DF, Turner RC. Homeostasis Model
assessment: Insulin resistance and beta-cell function
from fasting plasma glucose and insulin concentrations
in man. // Diabetologia 2012; 28:412-9.
McCarty MF. Hyperinsulinemia may boost both
hematocrit and iron absorption by up-regulating
activity of hypoxia-inducible factor-1 alpha. // Med
Hypotheses 2003; 61:567-73.
Perrini SP, Greene MF, Lee PDK, Cohen RA, Faller DV.
Insulin stimulates cord blood erythroid progenitor
growth: Evidence for an etiological role in neonatal
polycytemia. // Br J Haematol 2006; 64:503-11.
Tanigushi A, Fukushima M, Seino Y, et al. Platelet count
is independently associated with insulin resistance in
non-obese Japanese type 2 diabetic patients. //
Metabolism 2003: 52:1246-9.
World Health Organization. Definition, Diagnosis and
Classification
of
Diabetes
Mellitus
and
its
Complications. Part 1: Diagnosis and Classification of
Diabetes Mellitus, Department of Non Communicable
Disease
Surveillance,
WHO,
Geneva,
2013.
Метаболический синдром у женщин: особенности
терапии : научное издание // Medical express.
-
Т.,
2007,-
№2.
-
С. 14
-18.
Оганов Р.Г.,
Перова Н.В., Мамедов М.Н., Метельская
В.А. Сочетание компонентов метаболического
синдрома у лиц с артериальной гипертонией и их
связь
с
дислипидемией./
Российский
кардиологический журнал.
-
Москва, 2011.
-
№2.
-
С.
49-53.
Alberti K.G., Eckel R.N., Grundy S.M., Zimmet P.Z.,
Fruchart J-C., Smith S.C. Harmonizing the Metabolic
syndrome. Circulation.2009; 120: 1640-1645
Austin M.A., Hokanson J.E., Edwards K.L. 2008:81:7B
—
12B.
De Fronzo R.A., Ferrannini E. Insulin resistance: a
multifaceted syndrome responsible for N1DDM,
obesity, hyperten dyslipidemia and atherosclerotic
heart disease./Diabet 2003;14:173-194.
Haffner S.M., Valdez R.A., Hazuda H.R et al. Prospective
analyses of the insulin resistance syndrome (Syndrome
X)./ Diabetes.
—
2005; 41: 715
—
722.
Haffner S.M., Ferrannini E., Hazuda H. et al. Clustering
of
cardiovascular
risk
factors
in
confirmed
prehypertensive individuals. Hypertension 2006;20:38-
45.
Henefeld M„ Leonhardt W. Das inetabolische
Syndrome.
—
Deutsch. Ges. Wes.
—
2004;36:545-551.
Laakso M. How good a marker is insulin level for insulin
resistance? Am J Epidemiol 2005:137:959
—
965.
Reaven G.M. Role of insulin resistance in human
disease. / Diabetes.
—
2006; 37:1595-1607.
Reaven J.M. Banting lecture. Role of insulin insistence
in human disease./ Diabetes 2008: 37:1595-1607.
Taskinen M. R. Strategies for the diagnosis of metabolic
syndrome. Curr Opin Lipidol 2003;4:434-443.
Vanhala M., Kumpusalo E., Takala J. Metabolic
syndrome; a cluster of hypertension, dislipidemia and
hyper-inslinemia the association with obesity. //XVII
Congress of the European Sosiety of cardiology.
—
August, 20
—
24,2004. Amsterdam, Netherlands.CD
Conifer Information System.
—
P. 488.
Zavaroni L. Bonora E., Pagliara M. et al. Risk factors for
coronary artery disease in healthy persons with
hyperinsulinemia and normal glucosei tolerance. N Engl
J Med 2009:320:702-706.
