Left ventricular diastolic dysfunction in Type 1 Diabetes Mellitus: The potential nexus

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2258| International Journal of Pharmaceutical Research | Apr - Jun 2021 | Vol 13 | Issue 2
Research Article
Left ventricular diastolic dysfunction in Type 1 Diabetes
Mellitus: The potential nexus
DR. BASIM SAFI NAJI ALMGOTER1, HAYDER M. AL-KURAISHY2
1Assistant Professor in Medicine,M.B.ch,B, MRCP, Department of Medicine, College of Medicine,
University of Kerbala, IRAQ
2Professor in Department of clinical Pharmacology, medicine and therapeutic, Medical Faculty, College of
Medicine, Al-Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq, MBChB, MRCP,FRCP
*Corresponding Author
Email ID: Hayderm36@Yahoo.com
Received: 08.01.21, Revised: 07.02.21, Accepted: 06.03.21
ABSTRACT
Objectives: To assess the impact of long-lasting type 1 diabetes mellitus (TIDM) on the myocardial function.
Methods: The case-control study was conducted at the Department of Pharmacology, College of Medicine,
Mustansiriya University, Baghdad, Iraq, from July to October 2018 and involved forty T1DM patients compared
with forty healthy control subjects. Anthropometric and pressure profiles were evaluated. As well,
echocardiographic findings were estimated in both groups. SPSS version 20.00 was used for data analysis.
Results: No significant differences were noted in the parameter of the two groups (p>0.05). The duration of
their illness was (5-20) years (mean 11±3) years. The peak early basal annular velocity (E` wave) was reduced
in TIDM patients compared to the controls (P=0.00001). As well, other echogradiographic variables were
impaired in TIDM patients compared to the controls (P=0.00001) with exception of A (cm/s). Besides, LVEDD,
LVESD and EF were not significantly differed in TIDM patients compared to the controls (P>0.05). Moreover,
the effect of duration of T1DM on the left ventricular diastolic function by dividing those forty patient into two
subgroups, those with the disease duration of more than (10 years) which include (23) patient (57.5%) and
those with the disease duration of less than (10 years) and include (17) patient (42.5%), and comparing their
finding with that of the control group. However, in TIDM patients with duration <10 years only E (cm/s) was
differed which was lower in TIDM patients compared with the controls. Conclusion: T1DM induced-
myocardial dysfunction is duration dependent and linked with underlying diabetic complications.
Keywords: diabetic complications, type 1 diabetes mellitus, echogradiographic variables
INTRODUCTION
Diabetes mellitus (DM) refers to a group of
common metabolic disorders that share the
phenotype of hyperglycemia. 1 The overall
prevalence of DM in Iraq is 21.8 / 1000. Rates
are greater in urban than in rural areas and in
the South/Centre than in Kurdistan. The
prevalence of Type 1 DM (T1DM) appears low as
rates among 0-4- and 5–14-year-olds of diabetes
are negligible.2T1DM mainly affects lean children,
teenagers, and young adults. The disorder is
characterized by absolute insulin deficiency from
selective autoimmune destruction of insulin-
secreting pancreatic beta cells. After diagnosis,
residual insulin secretion can persist for several
months or even years. When there is enough
insulin to control blood glucose, a “honeymoon”
phase occurs during which the patient may
transiently be able to markedly reduce or even
eliminate insulin therapy. In T1DM, one or more
auto-antibodies directed against the beta cells or
their products can usually be detected.3 The
Framingham study demonstrated an increased
risk of heart failure in patients with diabetes and
that it has a greater impact on the incidence of
congestive heart failure, especially in women. 4 It
has been shown a 2-fold higher incidence of
heart failure in men with diabetes and a 5-fold
increase in women. Additional trials Studies of
Left Ventricular Dysfunction (SOLVD), the Heart
Outcomes Prevention Evaluation study (HOPE),
the Cardiovascular Health Study (CHS) and
nationwide case control study also identified
diabetes as a major risk factor for the
development of heart failure. 5 Hypertension and
coronary artery disease, known co-morbidities of
diabetes, are established causes of heart failure.
The most prominent risk factor for heart failure in
diabetic patients is prior history of coronary artery
disease. 6 Furthermore, heart failure is more
frequent in diabetic than in non-diabetic patients
with myocardial ischemic injury; however,
evidence of diabetic cardiomyopathy was found
in diabetic patients even in the absence of other
co-morbidities .7 The evidence of a clinical impact
of diabetic cardiomyopathy on myocardial
function has increased in recent years, mainly
because of refined echocardiographic methods
ISSN 0975-2366
DOI: https://doi.org/10.31838/ijpr/2021.13.02.302

Dr. Basim Safi Naji Almgoter et al / Left ventricular diastolic dysfunction in Type 1 Diabetes Mellitus:
The potential nexus
2259| International Journal of Pharmaceutical Research | Apr - Jun 2021 | Vol 13 | Issue 2
such as tissue Doppler techniques. In a large
population-based study, tissue Doppler imaging
revealed impaired systolic and diastolic function
in persons with DM and several other
observational studies of populations without any
apparent heart diseases have found similar
results. 7 Several studies have shown a correlation
between glycemic control and LVDD, with
associated improvement in cardiac function after
adequate treatment. 8 Therefore, the aim of the
present study was to assess the impact of long-
lasting TIDM on the myocardial function.
MATERIALS AND METHODS
This case-control study was done in the
Department of Clinical Pharmacology and
Internal Medicine , College of Medicine, AL-
Mustansiriya University, in cooperation with the
Al-Yarmouk Teaching Hospital, Baghdad-Iraq
from July to October 2018. This study was
approved by Scientific and Ethical Committee
Editorial Board, College of Medicine, AL-
Mustansiriya University. This case-control study
involved forty T1DM patients with long-lasting
diabetes mellitus (mean 11±3years), aged (32±6
years), and forty healthy control subjects, matched
in terms of gender, age, and body mass index
(BMI). T1DM patients were recruited from the
outpatient diabetic departments. Exclusion
criteria: Any patients having renal failure, heart
failure, liver failure, thyroid disease, malignancy,
head trauma, cerebral hemorrhage, pregnancy,
lactation, psychiatric, cardiac arrhythmias,
congenital or acquired valvular heart disease,
chronic renal failure and poor echocardiographic
window and mental disorders were excluded.
Anthropometric profiles: Weight and height of
every patient was measured by means of the
weight and height measuring scale for the
purpose of measuring Body Mass Index (BMI);
BMI= BW (kg) /Ht (m2).9 Blood pressure profile,
including; systolic blood pressure (SBP) and
diastolic blood pressure (DBP) were measured by
automated digital sphygmomanometer.
Echocardiographic examination: All the patients
were underwent echocardiographic examination
by using pulsed Doppler at the tip of mitral valve,
the peak early transmitral flow velocity (E wave),
the peak late (atrial) transmitral flow velocity (A
wave), the (E wave) deceleration time and the
ratio between (E wave) and (A wave) were
registered. The tissue Doppler (non-preload
dependent) was used to assess the basal medial
mitral valve annular velocities, the peak early
basal annular velocity (E` wave) and E/E` ratio
were assessed , E/A<1, E DT >220 ms, E/E`<12
were considered as criteria for diagnosing
impaired relaxation, while the pseudonormalised
patients that can`t be caught by transmitral flow
Doppler alone were unmasked by combining the
flow Doppler criteria together with tissue Doppler
criteria thus, E/A>1, E DT<220 ms, E/E`>12
were the criteria for the pseudonormal LV filling
pattern., EF was used to report the systolic
function hence EF>50% was considered
indicators of normal systolic function. The LVDF
was divided in to two groups (LVDD positive and
LVDD negative), another classification was used
also in which LVDF was classified in to (normal,
impaired relaxation, pseudonormal). The duration
of DM was grouped as <10 years and >10
years, then compared to LVDD, with the mean
duration was assessed for the LVDF groups. All
had normal ECG and normal renal function tests
(blood urea ˂40mg/dl and serum creatinine ˂
1.2 mg/dl). Data was analyzed using SPSS 20,
and presented as mean ± standard deviation (SD)
and the variables were tested by using unpaired
student t-test between the controls and the treated
groups. One way analysis of variance (ANOVA)
with post-hoc test was used to scrutinize the
significance of differences among the groups.
Level of significance was set at p<0.05.
RESULT
The clinical characteristics of diabetic patient and
the results of their investigation were summarized
in the (table-1). Forty patients including twenty
male (50%) and forty control subjects including
twenty male (50%) were well matched for age,
gender , height ,weight and blood pressure. No
significant differences were noted in the
parameter of the two groups (p>0.05). The
duration of their illness was (5-20) years (mean
11±3) years. Among the forty T1DM patients
their mean fasting blood glucose (FBG) was
135±30 mg/dl and random blood glucose (RBG)
was 243±49 mg/dl.
Table 1: Clinical characteristics of studied patients and control subjects
Clinical features
T1DM patients
Control
P
Age (years)
32 6
30 6-5
0.28
Height (cm)
161 14
167 8
0.76
Weight (Kg)
66 12
69 11
0.26
BMI
24.99±2.03
25.78±1.92
0.08
SBP
1205
1205
0.68

Dr. Basim Safi Naji Almgoter et al / Left ventricular diastolic dysfunction in Type 1 Diabetes Mellitus:
The potential nexus
2260| International Journal of Pharmaceutical Research | Apr - Jun 2021 | Vol 13 | Issue 2
DBP
80 10
75 10
0.38
Duration (years)
11 3
--------------
--------------
Data are presented as mean ±SD, BMI: body
mass index; SBP: systolic blood pressure; DBP:
diastolic blood pressure; PP: pulse pressure. The
peak early basal annular velocity (E` wave) was
reduced in TIDM patients compared to the
controls (P=0.00001). As well, other
echogradiographic variables were impaired in
TIDM patients compared to the controls
(P=0.00001) with exception of A (cm/s). Besides,
LVEDD, LVESD and EF were not significantly
differed in TIDM patients compared to the
controls (P>0.05), (Table-2).
Table 2: Echocardiographic findings of T1DM patients compared to the control group
Measurement
T1DM patients (n=40)
Control (n=40)
P
E (cm/s)
75.22 13.11
101.03 7.67
0.00001*
A (cm/s)
70.55 13.87
65.05 4.98
0.62
E/A(ratio)
1.22 0.32
1.54 0.08
0.00006*
DT
167.44±5.55
216±6.64
0.0001*
E/E´
13.74±2.82
6.89±0.90
0.0001*
LVEDD (cm)
45.22 4.66
44.98 0.42
0.85
LVESD (cm)
31.25 3.34
29.35 5.11
0.21
EF (%)
60.42 5.11
63.04 5.11
0.52
Data are presented as mean ±SD, LVEDD: left
end-diastolic dysfunction, LVESD: left end-systolic
dysfunction. Moreover, the effect of duration of
T1DM on the left ventricular diastolic function by
dividing those forty-patient into two subgroups,
those with the disease duration of more than (10
years) which include (23) patient (57.5%) and
those with the disease duration of less than (10
years) and include (17) patient (42.5%), and
comparing their finding with that of the control
group, (Table-3).
Table 3: Doppler echocardiography of T1DM patients (≥ 10 years) with the control subjects.
Measurement
T1DM (n=23)
Control (n=40)
P
E (cm/s)
72.32 13.91
101.03 7.67
0.00001*
A (cm/s)
71.57 13.55
65.05 4.98
0.58
E/A(ratio)
1.06 0.77
1.54 0.08
0.00001*
DT
169±9.88
216.89±6.64
0.0001*
E/E´
13.29±2.01
6.74±0.13
0.0001*
LVEDD (cm)
43.28 4.39
44.98 0.42
0.84
LVESD (cm)
30.35 3.64
29.35 5.11
0.04*
EF (%)
59.42 5.96
63.04 5.11
0.04*
Data are presented as mean ±SD, LVEDD: left
end-diastolic dysfunction, LVESD: left end-systolic
dysfunction. However, in TIDM patients with
duration <10 years only E (cm/s) was differed
which was lower in TIDM patients compared with
the controls (Table-4).
Table 4: Doppler echocardiography of T1DM patients (< 10 years) with the control subjects
Measurement
T1DM patients Mean + SD n= 17
Control Mean + SD n=40
P
E (cm/s)
76.66 11.75
101.03 7. 67
0.00001*
A (cm/s)
68.59 6.95
65.05 4.98
0.52
E/A(ratio)
1.46 0.34
1.54 0.08
0.12
DT
215.5±0.77
216.89±6.64
0.5
E/E´
6.98±0.25
6.74±0.13
0.6
LVEDD (cm)
44.33±3.87
44.98±0.42
0.65
LVESD (cm)
31.45±3.62
29.35±5.11
0.64
EF (%)
64.72±5.45
63.04±5.11
0.31
Data are presented as mean ±SD, LVEDD: left end-diastolic dysfunction, LVESD: left end-systolic
dysfunction
DISCUSSION

Dr. Basim Safi Naji Almgoter et al / Left ventricular diastolic dysfunction in Type 1 Diabetes Mellitus:
The potential nexus
2261| International Journal of Pharmaceutical Research | Apr - Jun 2021 | Vol 13 | Issue 2
Reports about the prevalence of diastolic
dysfunction in diabetes have been largely
variable, due to the differences in methodology
and criteria used to diagnose it. Several earlier
studies that reported a lower frequency of
diastolic dysfunction in diabetes 10 were not taking
into account the pseudonormal pattern which
reflects an intermediate stage in the progression
of the abnormalities in LV relaxation and filling. 11
That’s why we tried to reveal this hidden portion
of the diastolic dysfunction by using two different
means of evaluation of the diastolic function, the
flow Doppler and tissue Doppler. As against the
high prevalence of diastolic dysfunction noted in
the present study, LV systolic function was within
normal limits supporting the existence of a
primary diabetic cardiomyopathy of
predominantly diastolic nature as diastolic
dysfunction may occur early in T1DM and its
recognition may provide a window of opportunity
for early therapeutic intervention to prevent its
progression to heart failure. 12 The reported LVDD
among our patients was related to the duration of
the diabetes, and this found to be in accordance
with that reported by a previous study. 13 It has
been suggested that LVDD is secondary to
microvascular disease because an association
with triopathy (retinopathy, nephropathy and
neuropathy) has been reported; a suggestion that
could be attributed to the same shared
pathophysiologic mechanisms.14 Only recently
have clinical and epidemiologic data
demonstrated the incidence, prevalence,
and prognosis of heart failure in patients with
diabetes. To date, heart failure has been
described as heart failure with preserved ejection
fraction (HFpEF) or heart failure with reduced
ejection fraction (HFrEF), according to left
ventricular function.15 To dichotomize heart failure
into these 2 entities has certain limitations and
probably does not cover an intermediate stage
that the most recent guidelines of the European
Society of Cardiology (ESC) termed heart failure
with a mid-range ejection fraction (HFmrEF;
ejection fraction 40%-49%).16This extended
definition is a first step to better phenotyping and
an improved taxonomy of heart failure.
Nevertheless, clinical and epidemiologic data, as
well as experimental data, have only focused
on HFrEF and HFpEF. Imaging studies have
revealed left ventricular concentric remodeling as
a relevant characteristic of diabetic myocardium,
which may be associated with impaired
myocardial energetics and reduced systolic strain.
17 Hypertrophy of the diabetic heart is the
consequence of myocardial triglyceride deposition
and/or increased extracellular volume as an
indicator for collagen deposition and fibrosis, with
the increased extracellular volume being
predictive for mortality and heart failure in this
population. 18 In addition, hyperinsulinemia due
to insulin resistance is also thought to directly
promote myocardial hypertrophy. Others have
found direct association among myocardial tissue
perfusion, oxygen supply, energetic substrate
availability, and myocardial function in patients
with diabetes, suggesting microcirculatory
damage as a contributing cause for diabetic
cardiomyopathy.19 Deposition of advanced
glycation end products constitutes a driving factor
for microvascular damage in diabetes and has
been associated with cardiomyocyte stiffness and
myocardial collagen deposition. 20 Advanced
glycation end products are created by
nonenzymatic reactions of glucose and other
glycating compounds with lipid and protein
moieties, causing structural and functional
modifications. 21 Glycated molecules are
identified by a pattern recognition receptor of the
immune globulin family termed receptor for
advanced glycation end product, which initiates
inflammatory signaling and
propagates apoptosis, fibrotic remodeling, and
immune cell infiltration.22 The consequential
increase in myocardial stiffness translates
to diastolic dysfunction, reduced myocardial
strain, and atrial enlargement, which has been
associated with an increased prevalence of atrial
fibrillation in patients with diabetes. 23
CONCLUSION
T1DM induced-myocardial dysfunction is duration
dependent and linked with underlying diabetic
complications.
Acknowledgment: We are grateful to Prof. Dr.
Sadiq M. Al-Hamash for his great support.
Disclaimer: None.
Conflicts of Interest: None.
Source of Support: None.
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The potential nexus
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