ECHOCARDIOGRAPHIC FINDINGS IN EGYPTIAN CHILDREN WITH TYPE 1 DIABETES MELLITUS By

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INTRODUCTION
In this study we aim to assess myocardial affection in Children with Type 1 Diabetes Mellitus using different modalities of Echocardiography.

Aims of the Work
The aim of the work is to assess cardiac function in children with type 1 Diabetes Mellitus using different modalities of Echocardiography.

Ethical considerations:
1.An informed consent was obtained from parents or legal guardians before getting involved in the study.
2. The study was done after approval of ethical committees of Pediatrics department & faculty of medicine for Al-Azhar University.
3. The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
4. All the data of the patients and results of the study are confidential and the patients have the right to keep it.
5. The parents have the right to withdraw from the study at any time without giving any reasons.
Financial disclosure/Funding: The author received no financial support for the research, authorship, and/or publication of this article.

Sample size calculation:
The sample size was calculated using Power and Sample size software version 3 (epi info).The sample size was calculated using the following formula:
• Both sexes will be included.

Exclusion criteria:
• Cardiac disease whether congenital or acquired.
• Thyroid disorder.TDI was obtained from the four chambers apical view, and tissue velocities were calculated.Using pulsed tissue velocity indices, the sample volumes were placed in the lateral sides of the mitral and tricuspid annuluses and the base of the interventricular septum (IVS).The peak systolic (S') and early and late diastolic velocities (E' and A', respectively) at these points were measured, and the E/E' ratio was calculated.The isovolumic relaxation time (IVRT) and isovolumic contraction time (IVCT) were both measured for both left ventricle (LV) and right ventricle (RV) lateral walls.

Calculation
of global myocardial performance index (MPI) was performed by pulsed tissue velocity imaging.For tissue Doppler, all interval measurements were performed within one cardiac cycle.The MPI was calculated a'-b'/b' where a' is the time interval from the end of A' wave to the onset of E' wave and b' the time from the onset to the end of the S' wave.
To reduce the effect of respiration on tissue velocities and as breath holding was not applicable in young children, three cardiac cycles were, recorded, and the average velocity was calculated.To reduce intra observer variability three different measurements for each tissue Doppler index was done and the average was taken.

Statistical Analysis of the data:
Data were statistically described in terms of mean ± standard deviation (SD), median and range, or frequencies (number of cases) and percentages when appropriate.The HbA1c (%), TG (mg/dL), LDL (mg/dL), HDL (mg/dL), and Microalbumin in urine were significantly higher in diabetic patients compared to controls (p value 0.000, 0.000, 0.000, 0.000, and 0.000, respectively).There was no significant difference between both groups regarding Cholesterol (mg/dL) (P value 0.217).The dimensions of aorta (AO), left ventricular internal diameter in diastole (LVIDd), left ventricular internal diameter in diastole (LVIDs), IVS, and left ventricular posterior wall (LVPW) were significantly higher in diabetic patients compared to controls (p value 0.001, 0.000, 0.000, 0.004, and 0.001, respectively).There was no statistically significant difference between the two groups regarding LA (p= 0.618), RV (p= 0.63), FS (%) (p= 0.107) or EF (%) (p= 0.073).The early diastolic inflow velocity (E), velocity during active atrial contraction (A), across the tricuspid valve, were significantly lower in diabetic patients compared to controls (p value 0.000, and 0.000, respectively).E to A wave (E/A) ratio, across the tricuspid valve was significantly higher in diabetic patients compared to controls (p value 0.006).There was no statistically significant difference between the two groups regarding DT (p value 0.091).The A' and E' velocities of the RV were significantly lower in diabetic patients compared to controls (p value0.016and 0.022, respectively).The ICT of the RV was significantly shorter in diabetic patients compared to controls (p value 0.007).The IRT of the RV was significantly longer in diabetic patients compared to controls (p value 0.000).The MPI of the RV of the patients was significantly higher than controls (p value 0.007).There was no statistically significant difference between the two groups regarding RV-S' (cm/sec) and RV-E/E' (p value 0.071 and 0.111 respectively).Regarding demographic characteristics among the two studied groups, there was no significant difference between both groups regarding age, body weight, height and BMI (P > 0.05).There was no significant difference between both groups in gender distribution as the Chisquared value was 0.81 (P > 0.05).None of our patients had cyanosis, palpitation or dyspnea at rest but there was 18 % with exercise intolerance.All patients had normal cardiac examination.There was positive family history of diabetes in 44 % of the patients.All the patients were receiving insulin.

Table (5): Comparison between Pulsed Wave echocardiography data of Tricuspid inflow of patients and controls
Regarding laboratory characteristics among the two studied groups, the HbA1c (%), TG (mg/dL), LDL (mg/dL), HDL (mg/dL), and Microalbumin in urine, were significantly higher in diabetic patients compared to controls (p value 0.000, 0.000, 0.000, 0.000, and 0.000, respectively).This could be explained by the nature of the disease.There was no significant difference between both groups regarding Cholesterol (mg/dL) (P value 0.217).

Our
study showed that regarding comparison between the studied groups.
Pulsed Wave echocardiography revealed that our patients had significantly lower mitral and tricuspid E and A waves velocity (p value 0.000, 0.001, 0.000, and 0.000, respectively).
Our results come in agreement with the study of (F et al. 2017), who demonstrated that, the patients had significantly lower E and A waves velocity across both the mitral valve and the tricuspid valve than controls (p value 0.019, 0.054, 0.023, and 0.006, respectively).Furthermore, Our results come in agreement with (Salem et al., 2009), who found that, both mitral and tricuspid (E) wave velocities were lower in diabetics, but without statistical significance, however; the (A) wave velocities of both the mitral valve and the tricuspid valve were significantly higher in diabetics (P < 0.05, P < 0.05) respectively, with a consequently significant lower E/A ratio (P < 0.05, P < 0.05) respectively compared to controls.Also, our results come in agreement with the study of (Labombarda et al., 2014), who found that, the mitral A wave and E/A ratio were lower than the healthy group but without statistical significance (p value 0.76, and 0.08, respectively), whereas the (E) wave velocity of the mitral valve was significantly lower in diabetics (p value 0.025).
In contrary, our results come in disagreement with the study of (Gökşen et al., 2013), who found that, tricuspid A-wave velocity was significantly higher (p value 0.000), whereas E/A ratio was significantly lower (p value 0.000) in patients compared with controls.
Tricuspid E-wave velocity, mitral E and A velocities and mitral E/A ratio had no significant differences between patients and control.

Tissue
Doppler echocardiography revealed that our patients had significantly lower A' and E' velocities of the RV (p value 0.016 and 0.022, respectively), whereas the A' and E' velocities of the LV were lower in diabetics, but without statistical significance (p value 0.907, and 0.097, respectively).The S' velocity of the LV was significantly lower in comparison to the controls (p value 0.006), whereas the S' velocity of the RV was lower in diabetics, but without statistical significance.(p-value 0.071).
Our results come in agreement with the study of (F et al., 2017), who found that, the E' and A' velocities of both LV and RV, were lower in diabetics, but without statistical significance (p value 0.200, 0.963, 0.097 and 0.185, respectively).The S' velocity of LV was significantly lower in comparison to the controls (p value 0.041), whereas the S' velocity of the RV was lower in diabetics, but without statistical significance.(p-value 0.172).Also, our results come in agreement with the study of (Hensel et al., 2016), who found that, the E', A' and S' velocities of the LV were lower in diabetics, but without statistical significance.
In contrary, our results come in disagreement with the study of (Salem et al., 2009), who found that, the A' and S' velocities of both RV and LV were higher in diabetics, but without statistical significance.(p value ˃ 0.05).Also, our results come in disagreement with the study of (Rakha et al., 2019), who found that, the A' and S' velocities of the LV were higher in diabetics, but without statistical significance (p value 0.968 and 0.764, respectively).
The mitral annular or basal LV velocities reflect the long axis mitral motion of the ventricle, which is an important component of LV systolic and diastolic function.The peak systolic velocity is also a sensitive marker of mildly impaired LV systolic function, even in those with a normal LV ejection fraction or apparently preserved LV systolic function, such as diastolic heart failure or in diabetic subjects without overt heart disease Other findings which support the presence of subtle diastolic dysfunction were significantly longer IRT (p value 0.000), and significantly higher MPI of the RV (p value 0.007) in our patients.The IRT and MPI of the LV showed no significant differences between the two groups.
It is important to emphasize that the diastolic dysfunction was more prominent in the RV parameters.These changes reflect early changes in myocardial relaxation.
Our results come in agreement with the study of (F et al., 2017), who demonstrated that, there were significantly longer IRT (p value 0.001), and significantly higher MPI (p value 0.049) of the RV, whereas the IRT and MPI of the LV showed no significant differences between the two groups.
Diabetes mellitus significantly increases the risk of heart disease.Diabetic heart disease is a conglomeration of coronary artery disease (CAD), cardiac autonomic neuropathy (CAN), and diabetic cardiomyopathy (DCM) (Rajbhandari et al., 2021).Diabetic cardiomyopathy has been defined as ventricular systolic or diastolic dysfunction in a patient with DM without other recognized cause (such as CAD or hypertension) (Dunlay et al., 2021).The high incidence of such diastolic dysfunction and its association with HF and with mortality underscore the existence of diabetic cardiomyopathy as a very serious clinical condition (From et al., 2010).Even if these complications affect predominantly the adult diabetic patient, the process of vascular changes starts much earlier.Autopsies have shown that the atherosclerotic processes at the endothelial level begin in childhood and progress rapidly in the presence of risk factors (Dalla Pozza et al., 2011).Thus, children with diabetes mellitus are considered as highrisk patients and special attention to vascular health has been recommended (Nesto et al., 2020).Echocardiography has become the most important non-invasive technique for the diagnosis and follow-up of heart disease in children.It will add important information about the effect of chronic hyperglycemia in type 1 diabetic children on the cardiac functions.Highly informative subcostal windows often yield a structural diagnosis within the first few minutes of imaging.Echocardiography also permits detailed assessment of ventricular size and function (McLeod et al., 2018).
The critical value that divides the central 95% of the Z distribution from the 5% in the tail.Zβ =The critical value that separates the lower 20% of the Z distribution from the upper 80%.σ = The estimate of the standard deviation of the children with diastolic dysfunction in the lowest quartile.µ1 = mean children with diastolic dysfunction in the lowest quartile.µ2 = mean children with diastolic dysfunction in the other quartiles follow up.By calculation, the sample size will be equal to 70 in total.This case control study was conducted on 70 children attending the Outpatient pediatric clinic, and Clinics of Pediatric cardiology and endocrinology, Al-Hussein University Hospital in Cairo, in the period from the beginning of July 2021 to the end of November 2021.The recruited children were randomly assigned into two groups: Al Hussein University hospital.Children who fulfilled the inclusion criteria were only considered for the study.

Table ( 1): Demographic characteristics of the subjects in the patient and control groups
NA: not applicable, NS: not significant, S: significant.

Table ( 3): Laboratory characteristics of the subjects in the patient and control groups
NS: not significant, S: significant.

Table ( 4): Comparison between patient group and control group regarding systolic functions
NS: not significant, S: significant.

Table ( 7): Comparison between patient group and control group regarding right ventricle diastolic functions
NS: not significant, S: significant.