STRENGTHS AND LIMITATIONS OF THIS STUDY
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The multicentre approach reduced site-specific biases and enhanced the generalisability of findings within the country.
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Clinical definitions of established atherosclerotic cardiovascular disease (ASCVD) and high ASCVD risk were based on widely accepted criteria.
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Cross-sectional design and chart review limit the ability to adjust for all potential confounders influencing ASCVD risk.
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Patients attending secondary care settings may have more severe disease or different characteristics than those in primary care settings.
Introduction
The substantial burden of type 2 diabetes mellitus (T2DM) has become more prominent in developing countries in recent years, a change presumed to be driven by trends of urbanisation, lifestyle modifications and inadequate prevention of non-communicable diseases.1 2 T2DM burden is primarily fuelled by its predisposition to a range of complications with greater health consequences, as well as its substantial economic burden on both individuals and healthcare systems.3 In the Middle East and Africa (MEA) region, the prevalence of diabetes and its associated complications has disproportionately increased compared with other regions.4–6 Consistently, the International Diabetes Federation (IDF) 2021 Atlas of Diabetes has reported an estimate of 10.9 million patients with diabetes in Egypt, positioning it as the 10th country with the most patients with diabetes in the world.4
Cardiovascular diseases (CVDs) are one of the main contributors to the T2DM burden. Patients with diabetes have an increased risk for CVD by 2–4 fold of the level observed for patients without diabetes7; additionally, a meta-analysis of 57 studies concluded that 32.2% of patients with diabetes have concurrent CVD.8 Among the different subtypes of CVD, atherosclerotic CVD (ASCVD), that is, coronary artery disease (CAD), cerebrovascular disease or peripheral artery disease (PAD), is particularly prevalent in this population, and it accounts for the largest proportion of mortality in people with T2DM.9 CVD mortality in middle-income countries is higher than in high-income countries and disproportionately affects individuals under the age of 60, especially in the Middle East and North Africa (MENA) region.5 10 The highest reported mortality per 10 000 adults for CVD for this region was in Lebanon (30.45), Tunisia (28.42) and Egypt (26.87).10
A recent decrease in the incidence of cardiovascular (CV) complications associated with T2DM was observed in high-income countries, which was attributed to efforts made to control CV modifiable risk factors, namely obesity, sedentary lifestyle, smoking, hypertension and dyslipidaemia, as well as better disease management.3 11 12 In contrast, the incidence and prevalence of CVD in populations with these risk factors are expected to increase substantially in developing countries, where the required lifestyle modifications are relatively less applicable, given the economic status.11
Currently, there is a lack of data on T2DM complications and risk factors, especially those relating to CVD, in low-income and middle-income countries.3 This data gap and the literature suggesting that the evolution of T2DM complications will potentially follow different courses in each country underscores the need for further research.11 This has previously prompted the conduct of the CAPTURE study that aimed to estimate the prevalence of CVD and characterise patient demographics in 13 countries; however, only two countries from the Middle East were included, and none from Africa.13 Hence, data from the MEA region are still limited. The PACT-MEA study primarily aimed to estimate the prevalence of established ASCVD (eASCVD) among people with T2DM across seven MEA countries: Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa and the United Arab Emirates. As a secondary objective, the study aimed to estimate the prevalence of high ASCVD risk in this population, among the population without eASCVD. Moreover, this study intended to report on the proportion of the T2DM population with either eASCVD or high ASCVD risk who are receiving antidiabetic medications with demonstrated CV benefit, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, that is, following the guidelines recommendations for pharmacological therapy for this population.9 14
The main findings from the PACT-MEA study were recently published.15 In this article, we report on the findings for Egypt’s cohort, describing different trends observed in the T2DM population to characterise patients’ profiles and elaborate on diabetes care status in Egypt.
Methodology and study design
Study design
This was a non-interventional, multicentre, cross-sectional, single-visit study that investigated the prevalence of eASCVD as well as the prevalence of high ASCVD risk in people with T2DM through medical chart review conducted between 12 April and 17 August 2022. Data were gathered from eight study sites to reduce site-specific biases, all of which were secondary care settings. These selected sites were capable of achieving recruitment targets by following data collection standards while considering local treatment guidelines, reimbursement criteria, referral flows and regulatory requirements. Adults diagnosed with T2DM at 180 days or more prior to the enrolment date were included. Patients presenting with a T1DM diagnosis, mental incapacity, unwillingness or language barriers, as well as patients with known congenital heart disease or malformation, were excluded. PACT-MEA was also registered (https://www.clinicaltrials.gov; unique identifier: NCT05317845). IQVIA was the contract research organisation responsible for data collection and management.
The largest feasible sample size was targeted for the PACT-MEA Egypt cohort population to ensure generalisability without a substantial decrease in precision (ie, ensuring a precision of ± 3%–5% points) as per the PACT-MEA study design.16 A final sample size of 550 allowed for a 4.2% precision level. Study design and detailed sample size calculations are described elsewhere.16
Study outcomes and variables
The primary outcome for this study was the prevalence of eASCVD in the studied population. eASCVD was defined as either
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CAD, subdivided into patients with a history of acute coronary syndrome, history of myocardial infarction (MI), past unstable angina, history of stable angina, past coronary revascularisation (percutaneous coronary intervention, coronary artery bypass graft), and unequivocally documented ASCVD on imaging (including plaque on coronary angiography or CT angiography).
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Cerebrovascular disease, presenting as a history of stroke or transient ischaemic attack (TIA) that is atherosclerotic in origin.
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PAD, including extracranial carotid artery disease (ie, unequivocally documented ASCVD on imaging including plaque on carotid ultrasound or CT angiography or past arterial revascularisation procedure), lower extremity arterial disease (LEAD) (ie, a history of claudication with an Ankle-Brachial Index ≤0.90, lesions documented on imaging, past arterial revascularisation or history of non-traumatic minor and major amputation), and other PADs (eg, aortic aneurysm, vertebral artery disease, atherosclerotic upper extremity artery disease, renal artery disease and mesenteric artery diseases).
The secondary outcome was the prevalence of high risk of ASCVD in people with T2DM, where high risk was defined as per the 2021 European Society of Cardiology (ESC) criteria,17 as presenting with either a T2DM disease duration of more than 10 years, or target organ damage (ie, retinopathy, nephropathy, neuropathy and left ventricular hypertrophy), or multiple ASCVD risk factors, with those being specified as an age of 55 years or more, hypertension, dyslipidaemia, smoking and obesity.
Exploratory outcomes for this study were the proportions of the T2DM population with either eASCVD or high ASCVD risk who were receiving GLP-1 analogues and/or SGLT2 inhibitors.
Statistical analysis
Normally distributed quantitative data were summarised using mean and SD, non-normally distributed quantitative variables were summarised using median and IQR, categorical variables were summarised using counts and percentages, and quantitative estimates were reported with 95% CI. To account for the proportion of the diabetes population in each country, weighted analysis was used for overall eASCVD prevalence and ESC risk category estimates. Missing pharmacotherapy and laboratory data were not imputed and were reported with descriptive statistics.
Patient and public involvement
Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this study.
Results
Patient disposition and demographics
A total of 550 patients were included in Egypt’s cohort of the PACT-MEA study. All patients recruited were treated in secondary care settings. The mean age (SD) of the enrolled patients was 54.5 (10.5) years, with a mean duration of diabetes of 9.3 (7.5) years; Egypt’s cohort results were lower than regional results (57.7 (11.6) and 10 (5–17), respectively) in both. Female patients constituted 62% of the study population, compared with only 47% in the overall PACT-MEA population. The predominance of female patients reflects the higher prevalence of T2DM among females compared with males in Egyptian.18 19 65% of enrolled patients were reported to have insurance; however, the type of insurance (ie, state insurance, private insurance) was not defined. The proportion of patients with a body mass index (BMI) of 30 kg/m2 or more was higher in Egypt’s cohort than that of the total PACT-MEA population (63% vs 52%). More data are presented in table 1.
Patients’ demographics, baseline characteristics and medical history
Patients’ characteristics and medical history
The prevalence of ASCVD risk factors in the Egyptian study population was comparable and/or slightly lower than that of PACT-MEA overall data; Egypt’s data matched PACT-MEA regional data in terms of diabetes complications, except for neuropathy (61% vs 25%). Further details on medical history are described in table 1.
SGLT2 inhibitors and GLP-1 analogues were extremely underused in T2DM therapy in the PACT-MEA Egypt cohort population in comparison to regional data (20% vs 36% and 3% versus 13%, respectively), whereas rates of use of other antidiabetics were in line with regional PACT-MEA findings. Similarly, the rates for use of CV therapy were slightly lower than those reported for the overall population. Details on medication use are also described in table 1. Baseline laboratory data for the Egyptian population were also comparable to that of the overall population; laboratory data are described in detail in table 2.
Prevalence of eASCVD and its subtypes
The prevalence of eASCVD of any type in the study population was estimated to be 19.6% (n=108, 95% CI 16.5 to 23.2), where CAD was of the highest prevalence (15.1%), followed by cerebrovascular disease (3.1%) and PAD (2.9%). Except for the latter, prevalence rates were consistently lower than those for the overall PACT-MEA study population (CAD: 21.2%; cerebrovascular disease: 3.6%; PAD: 2.1%); this difference was more profound on comparison to findings reported for secondary settings entries in the overall study data (13.6%, 2.5% and 2.0%, respectively) (figure 1).
Of the PACT-MEA, Egypt cohort population, 19.6% have established atherosclerotic cardiovascular disease (eASCVD). Coronary artery disease accounts for the highest proportion of eASCVD cases, with cerebrovascular disease and peripheral arterial disease occurring to a lesser extent. The overall PACT-MEA population exhibits a similar pattern of ASCVD distribution across different settings. Secondary settings show higher proportions of any eASCVD, as well as specific types such as coronary artery disease, cerebrovascular disease and peripheral arterial disease, compared with primary settings, with varying differences. MEA, Middle East and Africa; PACT-MEA, Prevalence and Clinical Management of Atherosclerotic Cardiovascular Diseases in Patients With Type 2 Diabetes Across Countries in the Middle East and Africa
Past coronary revascularisation and history of stable angina were the most reported CAD, with prevalence rates of 8.5% and 8.0%, respectively, while the least reported CAD was unequivocally documented ASCVD by imaging, with a prevalence of 1.5%.
For cerebrovascular disease, the prevalence of history of strokes with atherosclerotic origin was more than double that of the history of TIAs with atherosclerotic origin (2.7% vs 1.1%). The reported PAD in the study population was predominantly LEAD, with a higher prevalence than that reported in regional data (2.9% vs 1.7%). Detailed data are described in online supplemental file 1.
Prevalence of high risk of ASCVD and ESC CVD categories
Prevalence of high ASCVD risk among the population without eASCVD (n=442) was estimated to be 85.5% (n=378; 95% CI 81.9% to 88.5%), which is lower than the regional total prevalence of 89.4% and the regional prevalence in secondary settings of 90.0%. However, prevalence estimates of ESC-defined CVD high-risk patients across the seven participating countries, weighted to account for the size of the diabetes population of each country, resulted in Egypt having the highest estimate among the participating countries (figure 2). Stratifications of patients’ ASCVD categories by age, diabetes complications and risk factors are described in online supplemental file 2.
(a) The majority (85.5%) of the PACT-MEA, Egypt cohort population who do not have established atherosclerotic cardiovascular disease (eASCVD) are at high risk of developing ASCVD. At the regional level, the majority of participants without eASCVD in the overall PACT-MEA population are also at high risk of developing eASCVD, with a slightly higher percentage observed in secondary settings compared with primary settings. (b) This prevalence estimate of participants at high risk of ASCVD across the seven enrolled countries is calculated as a weighted estimate, accounting for the size of the diabetes population in each country. MEA, Middle East and Africa; PACT-MEA, Prevalence and Clinical Management of Atherosclerotic Cardiovascular Diseases in Patients With Type 2 Diabetes Across Countries in the Middle East and Africa; UAE, United Arab Emirates.
Weighted estimates of CVD risk categories have placed most of the study population (99.1% of 463 patients with available data) as either very high risk or high risk for CVD, as per the ESC risk classification (table 3).
Categories of cardiovascular risk in diabetes across the entire population as per the ESC guidelines (17) (weighted)
Pharmacotherapy data
On stratifying antidiabetic medications with proven CV benefits use in each of the study categories (ie, eASCVD, high risk, no eASCVD no high risk), Results have shown that only 27% (n=29) of patients with eASCVD were receiving SGLT2 inhibitors, and only 1% (n=1) was receiving GLP-1 analogues. Estimates have shown an extreme underuse of these two drug classes in Egypt’s study population in comparison to overall study data, where 43% and 10% of the overall eASCVD population were receiving SGLT2 inhibitors and GLP-1 analogues, respectively. Full data on the use of different T2DM medications stratified by ASCVD status are available in online supplemental file 1.
Achievement of the guidelines’ recommendations
Results for reaching recommended targets for patients with CVD risk (ie, patients fulfilling the criteria for ESC very high risk or high risk) in the study population were consistently lower than those for PACT-MEA overall population, where only 27% achieved an HbA1c of less than 7% in the study population, 23% maintained a BP of less than 130/80 mm Hg and 16% maintained low-density lipoprotein (LDL) levels of less than 1.8 mmol/L (70 mg/dL), 20% were using GLP-1 analogues or SGLT2 inhibitors and 14% had a BMI below 25 kg/m2, while in the overall PACT-MEA population, 37%, 30%, 30%, 43% and 15% achieved these targets, respectively. In contrast, 21% of ESC very high-risk and high-risk patients have reported regularly exercising 5 days per week in Egypt’s cohort versus only 16% in the overall study population. No patients were found to achieve all the guidelines-recommended criteria for this population. More data are available in online supplemental file 1.
Discussion
The burden of the steady increase in prevalence of diabetes in the Egyptian population is mirrored by the greater burden of pervasive diabetes complications. ASCVD represents the most alarming complication, given its possible grave outcomes and greatest rates of mortality in people with T2DM.9
The prevalence of eASCVD in people with T2DM in Egypt has not been systematically estimated prior to our study; however, a study on the T2DM population in Upper Egypt has reported that 55.75% of the study population (n=800) had established CVD.20 Interestingly, a recent study has estimated a prevalence of 9.8% for macrovascular complications in an Egyptian T2DM population (n=583), with the most common macrovascular complication being CAD (7.5%). The authors interpreted these results as an underestimation that is attributable to the lack of resources, allowing regular screening for CV complications.21 Our study estimated a prevalence of 19.6% for eASCVD in Egypt’s T2DM population, which was also lower than the average pooled estimated prevalence of 24.4% reported for the PACT-MEA study overall population. Regional prevalence of eASCVD retrieved from secondary care settings was also significantly higher than that of primary care settings (27.5% vs 15.9%), which goes in line with patients tending to seek secondary care settings in case of advanced conditions, which was previously reported in similar studies.22
In a 2015 observational study conducted on 2000 patients with DM in Egypt, of which 96.75% presented with T2DM, a prevalence of 21.05% for CAD was reported23; moreover, the National Hypertension Project has estimated a prevalence of 8.3% for CAD in the general Egyptian population in 2003, with a higher prevalence of 19.5% in hypertensive patients.24 25 The estimates of our study for CAD (15.1%) suggest an increased rate of undetected CAD in our studied population. This potential underestimation was more prominent in some of the CAD subcategories, where a history of MI was reported in 3.3% of the Egyptian population compared with 11.5% in the regional secondary care population. The prevalence of ASCVD, equivocally documented by imaging, was disproportionally low (1.5% vs 10.5%). Such underdiagnosis trends can be attributed to the lack of well-established screening programmes, limited availability of diagnostic facilities and lower awareness among both patients and healthcare providers regarding CAD symptoms and risk factors.26 Given the increased CV risk faced by patients with diabetes and the wide prevalence of some of the risk factors, such as obesity and hypertension, in the Egyptian population, more efforts should be directed towards establishing timely screening and follow-up guidance for people with T2DM with multiple risk factors.27 28 On the other hand, PAD estimates for the study population were higher than that of the regional total (2.9% vs 2.1%), which can be attributed to the recent increase in regular screening practices for LEAD, driven by the American Diabetes Association (ADA) guidelines, as well as the recent foundation of Diabetes Foot Care Centres in different localities in Egypt. Other PAD subcategories (extracranial carotid artery disease and other PAD of atherosclerotic origin) most likely remain underdiagnosed, given the lack of similar initiatives, where a previous study has estimated a prevalence of 11% for PAD in the Egyptian DM population.23 Evidently, this calls for the generalisation of screening initiatives to allow for earlier intervention.
Our findings underline the extensive prevalence of CV risk factors in the Egyptian T2DM population, where 85.5% of the enrolled population presented with high risk for ASCVD; furthermore, approximately 74% of them had two or more risk factors for CV. These results align with data from Upper Egypt, where 84% of the population was reported to present with two or more CV risk factors.20
On stratification by age, Egypt’s cohort findings reflected an earlier incidence of both eASCVD and high risk for ASCVD, where the mean age for the eASCVD patient group was 57.7 (8.8) years, while that for the overall study population was 63.2 (10.1) years (online supplemental file 2). The prevalence of eASCVD and high risk of ASCVD in all age groups under 65 years was significantly higher in Egyptian’s population. This trend is widely observed for CVD in the Egyptian population.29 Moreover, early incidence of CVD, that is, at the working age, highly influences productivity, which certainly reflects on the socioeconomic burden of the disease in the country.30 Additionally, evidence from literature suggests that the increase in healthcare expenditure observed for CVD complications in the age group of 45–64 years is far higher than that in older age groups in populations with diabetes.31 Immediate intervention is needed to overcome this increase in CVD morbidity in this age group, where nationwide initiatives are needed to increase preventive cardioprotective measures in the Egyptian diabetes care system.
Currently, both the ADA and ESC guidelines recommend SGLT2 inhibitors and GLP-1 analogues for patients with T2DM with CV risk factors9 14; accordingly, the immense underuse of both drug classes documented in the present study is worrisome. One of the factors contributing to this issue is financial considerations, where GLP-1 is not yet included in the medical insurance coverage provided in the study sites. Medication availability also plays an important role in physicians’ prescription patterns. In light of the patients’ profile presented in our study findings, initiatives to amplify SGLT2 inhibitors and GLP-1 analogues use in people with T2DM, of whom 99% are considered either very high risk or high risk for CV complications, should be adopted and encouraged by decision-makers and healthcare entities. Studies investigating healthcare utilisation costs, as well as cost-effectiveness studies, have highlighted the massive increase in costs associated with ASCVD in people with T2DM.32 33 Therefore, increasing the utilisation of agents with dual impact on both glycaemic control and CVD prevention is expected to reduce overall costs.
Our findings highlight the gaps resulting from inadequate diabetes care, where only 27% of the population fulfilling ESC very high-risk and high-risk criteria were found to have met the international guidelines of a glycaemic target of HbA1c less than 7%. The suboptimal glycaemic control was also investigated in the International Diabetes Management Practices Study cohort study of 180 Egyptian subjects with T2DM, where it was reported that only 17.4% of the patients had achieved this target at the time of enrolment.34 This suggests that including patients treated in primary care settings may uncover higher rates of suboptimal diabetes control. Different studies have reported inadequate diabetes care in relation to CV risks and complications in Egypt, where a study of 100 patients with T2DM in 2016 reported that 78% of the patients were not adequately managed in terms of CVD prevention.35 Another study that included 360 patients treated in the largest three diabetes care centres in Alexandria in 2008 found that 49.2% of the patients had poor diabetes control, defined as two fasting blood glucose readings of more than 120 mg/dL in the two consecutive visits before enrolment.36 Glycaemic control is reported to be associated with a lower incidence of major CV events,37 which necessitates directing more efforts towards active glycaemic control, given the proportion of CVD risk observed in our study population.
Regarding LDL targets, our findings showed more inadequate control than those observed in the 2013 DYSlipidemia International Study-Egyptian, where 70.1% of 1240 very high-risk patients were reported to have above target LDL levels,38 while in the current study, approximately 82% of the very high-risk population were not at the target LDL level of 1.8 mmol/L (70 mg/dL). In contrast, our study has reported higher rates of regular exercise for Egypt’s population than that reported for the overall study population, where 21% of the population fulfilling ESC very high-risk and high-risk criteria have reported to exercise 5 days per week; this relatively increased adherence to guidelines can be accounted for by the inclusion of patients from rural backgrounds, where the rural lifestyle necessitates physical activity. This can be further confirmed by observations from previous studies, where a large study that included more than 9000 subjects, with two-thirds of them residing in rural areas, has reported a regular exercise rate of 48%.19 For the general population in Egypt, the 2017 WHO STEPwise survey has reported that 25% of Egyptian are exposed to less than 150 min of moderate activity per week.39
The findings of this study illustrate the wide prevalence of CV complications and risk factors in the Egyptian T2DM population, and how this trend is accompanied by suboptimal management and prevention approaches. Accordingly, this study proposes a call for action to improve multiple aspects of T2DM care, through increasing awareness of different healthcare practitioners on CV complications prevention and management, enhancing accessibility and utilisation of guideline-recommended pharmacological therapies, and introducing population-centred initiatives calling for necessary lifestyle modifications to reduce susceptibility to CV complications. Our study has the limitation of relying solely on chart reviews, which may have subjected the findings to a degree of inaccuracy; for instance, neuropathy in our studied population was reported to be of a prevalence of 61%, compared with only 25% for the overall study population (online supplemental file 2). This may be interpreted as an extreme overestimation resulting from patients’ misconceptions of neuropathy signs and symptoms, where a previous study from 2009 reported neuropathy prevalence of only 29.3% in a population of 2000 patients (96.75% had T2DM), defined as sensory neuropathy.23 Our study also had the limitation of the relatively limited sample size; however, a sample size of 550 was deemed sufficient to ensure generalisability without significantly compromising precision.16 Although cross-sectional data collection was challenging in a single visit, which has affected the collection of some details, including statin intensity and laboratory values, our data demonstrates real-world clinical practice with some limited interpretations. Moreover, no primary care settings were included owing to logistical issues.16 These limitations warrant further assessment of rates of ASCVD and CV comorbidities in the Egyptian population.
Conclusions
This study revealed a concerning prevalence of eASCVD in the general T2DM population, and a high risk of developing ASCVD in most of the T2DM population without eASCVD in Egypt. Additionally, our study identified an underutilisation of pharmacological treatments with CV benefits among patients with T2D in Egypt. Moreover, only a minority of studied patients achieved the recommended targets for patients with CVD risk. Based on these findings, it is evident that there is a pressing need to optimise care for people with T2DM in Egypt. The importance of implementing comprehensive strategies, involving decision-makers, healthcare authorities and healthcare professionals, to control CV risk in this population is necessary. Modifications to the diabetes care in Egypt should be guided by the identified gaps in management and prevention reflected in real-world data.
Data availability statement
Data are available on reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
Each of the study sites obtained approval from the local institutional review board/ethics committee, as follows: the Ethics Committee of the Faculty of Medicine, Alexandria University on 17 February 2022 (040431) and 17 March 2022 (040431), the Medical Research Ethics Committee of the Faculty of Medicine, Mansoura University on 21 May 2022 (R.22.04.169), the Research Ethics Committee at Faculty of Medicine, Ain Shams University on 28 May 2022 (FMASU P 13/2022) (FMASU P 14/2022), the Ethics Committee of the Faculty of Medicine, Menoufia University on 12 June 2022 (12/06/20222). Additionally, the Research Ethics Committee of the General Organization for Teaching Hospitals and Institutions approved the study protocol on 31 August 2022 (IDE00291). All patients provided written informed consent before commencing any study-related procedures, and anonymity and confidentiality of patients’ data were strictly ensured throughout the study.
Acknowledgments
Medical writing and editorial support were provided by Nada Talaat on behalf of DataClin CRO and were funded by Novo Nordisk Egypt. The authors would like to thank the study investigators; Mona Abd El Motleb, National Institute of Diabetes and Endocrinology (NIDE); Maysa Marwan, NIDE; Athar Reda, NIDE; Heba Ramadan, NIDE; Sherihan Abo El Yazeed, Ain Shams University; Ahmed El Behery, Mansoura University; Amr El Feky, Alexandria University; Hytham Badr, Menoufia University; Shaimaa Zewain, Menoufia University; Mohamed Zendan, Ain Shams University; Noha Gaber, Alexandria University; and Nehad Sabry, Alexandria University, for their valuable efforts throughout the study period.