Awareness of Stem Cell Therapy for Diabetes Among Type II Diabetic Patients in Makkah: A Cross-Sectional Study

Background Diabetes mellitus is a chronic disease that affects millions of people worldwide. Several studies have suggested using stem cells for diabetes treatment. However, there is a lack of research assessing the population’s awareness of stem cells. This study aimed to evaluate the level of awareness regarding the use of stem cell therapy for type 2 diabetes mellitus (T2DM). Methodology This study was conducted from December 2021 to April 2022 through an online survey that was distributed electronically via social media platforms. T2DM patients or their care providers who lived in Makkah were included. Patients aged less than 18 years and those with mental disabilities were excluded. Results Of the 316 participants included in the study, 56% were males, 33% had an age range of 46-55 years, and 76% were married. T2DM patients and their caregivers had a moderate level of awareness about stem cell therapy, with caregivers having higher awareness than diabetic patients. A non-significant relationship was found between educational level, income, diabetes control, time of diagnosis, and patients’ awareness. However, regarding the decision of treatment, participants aged less than 35 years were highly likely to decide to undergo stem cell treatment compared to other age groups. Conclusions There is a moderate level of awareness about stem cell therapy as a treatment option for T2DM among T2DM patients and caregivers in Makkah. Hence, there is a need to raise awareness by using online and in-person well-organized education programs in Makkah.


Introduction
Stem cells are unspecialized cells of the human body that can differentiate into any cell and have the ability to self-renewal. Stem cells exist both in embryos and adult cells. There are two major types of stem cells, namely, pluripotent stem cells which can differentiate into any cell type in the body, and multipotent stem cells which lack this trait and can only differentiate into a specific cell type. For example, multipotent cells derived from the gastrula's mesoderm go through a differentiation step that restricts them to becoming only muscle and connective tissue; however, further differentiation results in increased specialization to only connective tissue until the cells can give rise to only cartilage or only bone [1].
To overcome the ethical and immunological issues associated with the use of human embryonic stem cells, scientists have developed a technique to reprogram/transform adult stem cells back to a pluripotent state [2].
Diabetes mellitus is a global illness that has become much more prevalent in recent years and is a leading cause of premature mortality [3]. Several studies have shown that using stem cell therapy can be a treatment option for type 2 diabetes mellites (T2DM) [4]. According to the World Health Organization, Saudi Arabia has the second-highest prevalence of diabetes among Middle East countries and the seventh-highest prevalence in the world [5]. mesenchymal stem cells have been shown to have the ability to improve the function of pancreatic islet cells, thus reducing blood glucose [2,6]. Furthermore, these cells have effective therapeutic effects in T2DM, including reduction of daily insulin requirement, improvement in the level of glycosylated hemoglobin (HbA1C), and decrease the blood glucose level [6]. Autologous human bone marrow-derived mesenchymal stem cells have been shown to have a short-term therapeutic impact in lowering HbA1C and fasting blood sugar levels in patients with T2DM who have been diagnosed for less than 10 years and are not obese [7]. Bone marrow-derived mesenchymal stem cells also help in the recovery of damaged pancreatic islet cells to a near-normal level [8].
In diet-induced diabetic mice, the use of human embryonic stem cell therapy showed no improvement in weight nor fasting blood glucose level; however, HbA1c levels were reduced and insulin sensitivity was mildly increased. A combination of anti-diabetic drugs and stem cell therapy may be effective in treating other types of diabetes [9]. Other studies using bone marrow mononuclear stem cell [10] and autologous bone marrow-derived stem cell [11] transplantation to treat T2DM patients have shown a significant reduction in fasting blood glucose and HbA1C levels, as well as a reduction in the number of medications they needed, with no significant side effects. Stem cell transplantation is considered to be a safer type of transplantation therapy for diabetes mellitus compared to whole-organ and islet transplantation [12].
There is a lack of studies on the assessment of the level of awareness and understanding of using stem cell therapy as an optional treatment for T2DM patients in Makkah. Therefore, we aimed to evaluate the level of awareness regarding the use of stem cell therapy for T2DM and compare different demographic backgrounds and how that affects the population's knowledge.
This article was previously as a poster at the 1st Annual Saudi Medical Specialties Conference in Saudi German Hospitals, Makkah on March 18, 2023.

Study design
This community-based, cross-sectional, descriptive study was conducted in the region of Makkah, Kingdom of Saudi Arabia from December 2021 to April 2022. Study approval was obtained from the Biomedical Ethics Committee of Umm Al-Qura University (approval number: HAPO-02-K-012-2021-12-874).

Study population and sampling methodology
Adult residents of Makkah aged ≥18 years who were diagnosed with T2DM or their caregivers who agreed to participate were included in the study. Patients aged less than 18 years, those with mental disabilities, and those living outside Makkah were excluded.

Data collection
Data were collected through an original online questionnaire that was reviewed by a specialist. It was formulated in Arabic and English languages and completed using Google Forms. The questionnaire was distributed electronically via social media applications.
The questionnaire covered the following: participants' sociodemographic data, including age in years, gender, nationality, residence, education, marital status, total perceived monthly family income, occupation, knowledge of stem cell therapy, would the participant use stem cell therapy in the future and the reason for his/her choice, and the source of information about stem cell therapy in T2DM. For patients, a question about the current status of diabetes mellitus control was added.
For the No answer, a score of 1 was given, and for the Yes answer, a score of 2 was given. The awareness levels were classified as follows: a low level of awareness with a score of less than 2.66, a moderate level of awareness with a score from 2.67 to 3.33, and a high level of awareness with a score from 3.34 to 4.

Data analysis
Data were analyzed using the SPSS® software for Mac, version 26 (IBM Corp., Armonk, NY, USA). For numerical variables, data were expressed as mean and standard deviation (mean ± SD). The t-test and analysis of variance test were used for data analysis. Spearman correlation was used to evaluate relationships involving ordinal variables. A p-value <0.05 was considered statistically significant.

Results
A total of 316 participants fulfilled the inclusion criteria and were either diabetic patients or caregivers. Overall, 56% were males, 33% were aged from 46 to 55 years, and 76% were married. Further, 44% had a fulltime job, 40% had a bachelor's degree, and 34% had an income of less than 5,000 SR per month. Most patients 79% had children ( Table 1). The mean body mass index of the participants was 28.7 ± 6.11 kg/m 2 , and the mean age of the youngest sibling was 34.5 ± 6.36 years.

Level of awareness about treatment options and stem cell therapy
As shown in Table 2, the mean awareness of all participants was 2.67, indicating that T2DM patients in Makkah had moderate awareness of stem cell therapy.  There was a non-significant association between the time of diabetes mellitus diagnosis, education level, income status, and diabetes control and participants' awareness level (p ≥ 0.05).

Differences in awareness between specific groups
The results showed that there was a significant difference in the awareness between diabetics and caregivers (p = 0.002), with caregivers having more awareness of stem cell therapy than diabetic patients.

Factors affecting the choices of treatment
The relationship between how seriously a complication impacted the choice of treatment was not significant (p = 0.357). When we evaluated the relationship between the patient's preferences for stem cell therapy and their family history of morbidity, the result was non-significant (p = 0.113).
There was a difference between age groups and the decision of treatment of the patients which was statistically significant (p = 0.001). Table 3 illustrates which age groups were different from the others and shows that the age group (less than 35 years old) was mainly different.  Gender and the level of awareness were examined, and the results showed no significant correlation with a p-value of 0.290.
The impact of the age of the youngest sibling on their parents' choices regarding therapeutic options was assessed, and the result showed that it was non-significant (p = 0.082).

Discussion
In this study, we aimed to identify the level of awareness regarding stem cell therapy for diabetes among T2DM patients in Makkah, Saudi Arabia.
This study found that T2DM patients and their caregivers in Makkah have moderate awareness of stem cell therapy. An insufficient knowledge level was also reported in a previous Saudi study which aimed to assess the knowledge, attitude, and practice of doctors and medical students toward stem cells in diabetes mellitus management in Tabuk City. The study found that knowledge was poor in 21%, fair in 76.5%, and good in 2.5% of the participants [13].
In the Jouf region of Saudi Arabia, a study found a medium-to-high level of knowledge among the majority of students from healthcare sciences colleges, and a high attitude score was also noted toward stem cells [14]. The same poor knowledge was observed in a previous Malaysian study. This poor knowledge could be explained by a lack of exposure to stem cell therapy in our region [15].
A non-significant gender difference was found for awareness about stem cell treatment in this study. At the same time, this study found a non-significant relationship between the participants' awareness and their income or educational level. Therefore, this study reveals that socioeconomic status does not have a significant effect on the awareness level regarding stem cell therapy for T2DM.
There is a lack of previous studies assessing the correlation between socioeconomic status and the awareness level of stem cell therapy in T2DM patients. The reason for this is that in Saudi Arabia, the Internet and social media are fairly accessible as they are affordable, available to everyone, and not dependent on monthly income. Moreover, the Ministry of Health organizes numerous free educational and awareness campaigns regarding any updated information. A study done in Saudi Arabia in Tabuk City found a non-significant relationship between knowledge level about stem cell treatment and participants' demographics [13].
The current study also found that caregivers had a greater level of awareness compared to diabetic patients. A previous study found a similar result, where caregivers who lived with patients had a greater knowledge of diabetes in general [16].
This study found a non-significant association between the time of diabetes mellitus diagnosis, education level, income status, and diabetes control and participants' awareness level. Due to a lack of studies assessing diabetic patients' awareness of stem cells, it was difficult to find studies to compare our findings.
This study assessed if severe complications affect decisions regarding stem cell treatment in patients with T2DM. The study found a non-significant relationship between having diabetes-related comorbidities and the patient considering stem cell therapy. Although several treatments improve diabetes and help in delaying its complications, to date, there are no treatment options that completely cure diabetes [17]. This makes patients seek other treatments and encourages researchers to discover a curable medicine. Recently, extensive research on the use of mesenchymal stem cell (MSC) therapy to treat diabetes mellitus complications in pre-clinical animal studies has been conducted, and the majority of studies have shown effective outcomes for diabetic complications [18,19]. MSCs are anticipated to become effective therapeutic agents due to their potential for immunomodulatory ability, self-renewal, and differentiation [20].

Study limitations
A limitation of the present study was the use of a self-reporting questionnaire that could have a recall bias. In addition, the lack of research that addresses diabetic patients' awareness of stem cells hindered the comparison between our study results with other studies. Finally, as the study was restricted to patients from Makkah, the results cannot be generalized, for which a country-wide sample is needed.

Conclusions
This study demonstrates a moderate level of awareness about stem cell therapy among patients with T2DM and their caregivers in Makkah. The results showed that there is no significant association between the awareness about using stem cell therapy and the time of diagnosis, education level, income status, HbA1C level, and gender. On the other hand, the study found that caregivers were more aware of stem cell therapy.
The results revealed that severe complications, having children, dietary habits, and a family history of complications did not affect patients' decision of using stem cell therapy. It was only affected by age as we found that patients aged less than 35 years had a higher possibility of deciding compared to the other age groups.

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