Clinical Outcomes of Fetal Stem Cell Transplantation in Type 1 Diabetes Are Related to Alternations to Different Lymphocyte Populations.

Background: In patients with diabetes, transplantation of stem cells increases C-peptide levels and induces insulin independence for some period. Today, this positive therapeutic outcome is widely attributed to the well-documented immunomodulatory properties of stem cells. The aim of this study was to report alternations (the trend of increase or decrease) in different lymphocyte populations in a stem cell clinical trial performed in our institute. Methods: Recorded data of a clinical trial conducted on 72 patients with type 1 diabetes who had received fetal stem cell transplantation several years ago and were regularly monitored before and after the procedure in 1, 3, 6, 12, 24 months were analyzed. In these regular follow-up visits, insulin demand, HbA1c, C-peptide, and alternation to B cell and T cell populations were analyzed and recorded. For the purpose of the current study, patients were retrospectively divided into 2 groups, namely, those with the positive response to treatment and patients without such response. Temporary positive therapeutic response was defined by 2 different indicators, namely, plasma C-peptide levels and insulin dose-adjusted A1C (IDAA1c), which was calculated as A1C (percent) + (4 × insulin dose (units per kilogram per 24 h). Data analysis was performed by means of SPSS Version 18. Results: Besides the short-term therapeutic effect, we observed remarkably significant alternations to the populations of B and T lymphocytes in the recipients. When patients were retrospectively assigned to 2 different groups of patients with a positive therapeutic response (based on C-peptide changes) and those without it, it was observed that alternations to different populations of B-cells and T-cells were significantly different in these 2 groups. Conclusion: Our results demonstrated that transplantation of stem cells leads to significant positive therapeutic outcomes in one group of patients who showed totally distinct patterns of alternation to different groups of lymphocytes.

Iran in transition.

Being the second-largest country in the Middle East, Iran has a long history of civilisation during which several dynasties have been overthrown and established and health-related structures have been reorganised. Iran has had the replacement of traditional practices with modern medical treatments, emergence of multiple pioneer scientists and physicians with great contributions to the advancement of science, environmental and ecological changes in addition to large-scale natural disasters, epidemics of multiple communicable diseases, and the shift towards non-communicable diseases in recent decades. Given the lessons learnt from political instabilities in the past centuries and the approaches undertaken to overcome health challenges at the time, Iran has emerged as it is today. Iran is now a country with a population exceeding 80 million, mainly inhabiting urban regions, and has an increasing burden of non-communicable diseases, including cardiovascular diseases, hypertension, diabetes, malignancies, mental disorders, substance abuse, and road injuries.

Ramadan fasting and type 1 diabetes: a scoping review protocol.

INTRODUCTION: Ramadan fasting is globally observed and a great majority of the residents of Islamic countries and elsewhere fast during Ramadan all across the world every year. Many patients with type 1 diabetes fast during Ramadan according to (or against) medical and jurisprudence advice. Nonetheless, there is a paucity of scientific evidence regarding the risks patients with diabetes who fast may be confronted with. The current scoping review protocol aims at systematic analysis and mapping of existing literature in the field and highlighting scientific gaps. METHODS AND ANALYSES: This scoping review will be conducted based on the Arksey and O'Malley's methodological framework with consideration of later modifications and amendments. Three major scientific databases, namely PubMed, Scopus and Embase up to February 2022 will be systematically searched by expert researchers in collaboration with a medical librarian. Considering the fact that Ramadan Fasting is a cultural-dependent subject, which may be studied in the Middle Eastern and Islamic Countries in languages other than English, local Persian and Arabic Databases will also be included. Grey literature will be sought too, and unpublished works such as conference proceedings and academic degree dissertation will be considered. Subsequently, one author will screen and record all abstracts, and two reviewers will independently screen and retrieve eligible full texts. A third reviewer will then be designated to resolve potential discrepancies. Standardised data charts and forms will be used for information extraction and reporting of the outcomes. ETHICS AND DISSEMINATION: No ethical considerations apply to this research. Results will be published and presented in academic journals and scientific events.

Epidemiology of diabetes in Iran: A scoping review of studies published during 2015-2019.

Background: Proper synthesis of existing epidemiologic studies on diabetes in Iran can guide future research efforts. We aimed to conduct a comprehensive scoping review on all research articles that investigated any aspect of diabetes epidemiology in Iran during 2015-2019. Methods: This work was conducted as a part of the Iran Diabetes Research Roadmap and completed under Arksey and O'Malley's framework for scoping reviews. The Scopus and PubMed databases were searched on Feb 15th, 2020. Eligible document types on diabetes epidemiology in the Iranian population, in Persian or English, that published during the 2015-2019 period underwent eligibility assessment. A total of 315 relevant articles were included and further analysis was performed on the original studies (n = 268). Through classifying them into six domains: Diabetes incidence; the prevalence of diabetes and associated factors; the incidence/prevalence of complications/comorbid conditions; mortality/survival; burden; and prediction modeling. Results: In total, 64 (20.3%) papers were published in Q1 journals, and 40 (12.6%) were international collaborations. No clear annual trend was present in the number of published primary or secondary articles, the portion of papers published in Q1 journals, international collaborations or relative domain proportions. Few review articles were found on prediction modeling, mortality or burden (excluding global studies). Conclusions: Our findings show a minor portion of works on diabetic epidemiology in Iran meets the quality standards of Q1 journals. Researchers have neglected some critical subjects and have occasionally fallen for common pitfalls of epidemiologic research. In particular, adhering to established guidelines can help authors implement rigorous methods to develop, validate, and deploy practical clinical prediction models. Researchers should prioritize investigating longitudinally collected data that aid in measuring disease incidence and enable casual inference. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01094-0.

Immunopathology of Type 1 Diabetes and Immunomodulatory Effects of Stem Cells: A Narrative Review of the Literature.

Type 1 Diabetes (T1D) is a complex autoimmune disorder which occurs as a result of an intricate series of pathologic interactions between pancreatic ß-cells and a wide range of components of both the innate and the adaptive immune systems. Stem-cell therapy, a recently-emerged potentially therapeutic option for curative treatment of diabetes, is demonstrated to cause significant alternations to both different immune cells such as macrophages, natural killer (NK) cells, dendritic cells, T cells, and B cells and non-cellular elements, including serum cytokines and different components of the complement system. Although there exists overwhelming evidence indicating that the documented therapeutic effects of stem cells on patients with T1D are primarily due to their potential for immune regulation rather than pancreatic tissue regeneration, to date, the precise underlying mechanisms remain obscure. On the other hand, immune-mediated rejection of stem cells remains one of the main obstacles to regenerative medicine. Moreover, the consequences of efferocytosis of stem-cells by the recipients' lung-resident macrophages have recently emerged as a mechanism responsible for some immune-mediated therapeutic effects of stem-cells. This review focuses on the nature of the interactions amongst different compartments of the immune systems which are involved in the pathogenesis of T1D and provides an explanation as to how stem cell- based interventions can influence immune system and maintain the physiologic equilibrium.

Mapping evidence of Iran diabetes research: protocol for a scoping review.

Background: A considerable amount of research funding goes to diabetes management strategies to improve therapeutic goals and reduce the burden of diabetes. A vast amount of the budget is wasted due to unnecessary studies. A scoping review is a pivotal study to overview the available evidence and avoid research waste. In this review, we will try to find out the scope of available studies on diabetes management interventions, identify associated research gaps, and prioritize future studies. Method: We will carry out a study using Arksey and O'Malley's scoping review framework. We will search the Scopus and PubMed databases from 01/01/2015 till 01/01/2020. Only original articles related to pharmacological and non-pharmacological management interventions will be included. These interventional studies should be conducted on the Iranian population. After data extraction, a descriptive data analysis will be used to present information in different charts or tables. We will evaluate related published articles based on their document type, level of evidence, type of diabetes, subject area, interventions types, main findings and outcomes. Discussion: This study represents the first attempt to sum up available studies related to diabetes management interventions performed in Iran. The results of this study will be useful for all the stakeholders and policy-makers involved in diabetes research. It can help clinicians to be informed about studies on management interventions and can guide scientists eager to diabetes research to choose their future research plans based on diabetes research requirements and gaps.

Knowledge gaps in diabetes research: an evidence mapping of the literature.

Background: Mapping the available evidence can be used to inform current diabetes research, identify relevant gaps, and prioritize future research. In this regard, we mapped diabetes research performed in Iran. Method: We searched the Scopus and PubMed databases from 01/01/2015 till 01/01/2020 using keywords such as diabetes and Iran. The included articles were classified according to their document types, level of evidence, and subject areas. Results: The majority of the included articles (53%) were related to diabetes types, followed by complications (28%). Most of the documents were original articles (82%), and reviews were 18% of the publications. Systematic reviews constitute only 6% of the total documents. Observational studies were the most common types of study designs (26%), followed by clinical trials (20%). Moreover, topics on control and management of diabetes were the most prevalent subject areas (58%), and fewer studies were on preventive strategies (6%). In diabetes management studies, less attention has been paid to evaluate psychological (10%), educational (9%), and physical activity-related (7%) interventions. There was a shortage of secondary studies related to physical activity, psychology, diagnostic, and screening-related studies. Conclusion: To fill diabetes research gaps, more investment in cost-effectiveness interventions, such as preventive strategies and behavioral self-management programs, need. Moreover, we need to pay more attention on applied sciences and real world evidence to bridge translational gaps from bench to bedside. In this regard, further data synthesis can be helpful in evaluating the effectiveness of the available studies and avoiding unnecessary investigations.

Ramadan fasting and diabetes, latest evidence and technological advancements: 2021 update.

Development of updated guidelines for management of diabetes in Ramadan Fasting is of paramount importance. Nonetheless, evidence-based guidelines in the field of Ramadan Fasting and Diabetes are scarce. Moreover, findings of some recent research such as effects of Ramadan fasting on microbiota, genetics and epigenetics, hormonal changes (such as adiponectin, leptin, testosterone…), and alternations in circadian rhythm should also be reviewed and included on a yearly basis. It is documented that self-monitoring of blood glucose (SMBG) is of vital importance for patients with type 1 diabetes who fast, and advantages of continuous glucose monitoring (CGM) or flash glucose monitoring (FGM) techniques should be highlighted. Moreover, the recent findings about applications of advanced insulin delivery technology in patients with diabetes who fast in Ramadan should also considered in the annual updates of the guidelines.

Ramadan fasting and diabetes, latest evidence and technological advancements: 2021 update.

Development of updated guidelines for management of diabetes in Ramadan Fasting is of paramount importance. Nonetheless, evidence-based guidelines in the field of Ramadan Fasting and Diabetes are scarce. Moreover, findings of some recent research such as effects of Ramadan fasting on microbiota, genetics and epigenetics, hormonal changes (such as adiponectin, leptin, testosterone…), and alternations in circadian rhythm should also be reviewed and included on a yearly basis. It is documented that self-monitoring of blood glucose (SMBG) is of vital importance for patients with type 1 diabetes who fast, and advantages of continuous glucose monitoring (CGM) or flash glucose monitoring (FGM) techniques should be highlighted. Moreover, the recent findings about applications of advanced insulin delivery technology in patients with diabetes who fast in Ramadan should also considered in the annual updates of the guidelines.

Assessment of immune-alternations and their correlations with therapeutic outcomes of transplantation of autologous Mesenchymal and Allogenic fetal stem cells in patients with type 1 diabetes: a study protocol.

INTRODUCTION: Stem-cell therapy, which has recently emerged as a potentially therapeutic option for diabetes, is demonstrated to significantly alter both cellular and non-cellular elements of the immune system. In addition, it is demonstrated that allogenic stem-cells, once considered immune-privileged, can be rejected by the host immune system almost similar to any other somatic cell. To date, nonetheless, details of these intricate interactions remain obscure. The current study is designed to illuminate both aforementioned favorable and unfavorable stem cell-mediated immune reactions. Findings of this study may shed some light on how stem cells may exert their therapeutic effect in type 1 diabetes through immune system-mediated mechanisms and illuminate the partially-obscure immune-caused rejection of these cells. METHODS AND ANALYSIS: For the purpose of this study, frozen whole blood samples obtained from patients with type 1 diabetes who received stem cells at the Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences in two different clinical trials will be thawed and analyzed. These clinical trials were carried out using two different sources of stem cells, namely allogenic fetal and autologous mesenchymal cells. The samples we aim to analyze were obtained from the patients before the procedure and regularly after it, one, three, six, 12, and 24 months later. For the purpose of this study, the following parameters will be measured: C-peptide levels, IDAA1c (a surrogate marker of beta cell function which is calculated as HbA1c (%) + [4 × insulin dose (units per kilogram per day)]), frequencies of islet-specific autoreactive CD8+ T cells (CTL), different lymphocyte subsets, thymic function indicators, T cell repertoire diversity (including Treg/Tconv ratios), plasma levels of several pro- and anti-inflammatory cytokines, diabetes autoantibodies, and HLA typing. ETHICS AND DISSEMINATION: The stem cell transplantation clinical trials which provided the primary source of our samples were carried out at the Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences between 2008 and 2012. These series of clinical trials have secured approval of the ethics committee of Tehran University of Medical Sciences (ethical code number: E-0089) and registered on the national clinical trial registry of Islamic Republic of Iran (IRCT) with the identifier codes: IRCT138810271414N8 (for autologous mesenchymal cells) and IRCT201103171414N23 (for allogenic fetal cells). Our findings are to be presented at international scientific events, published in peer-reviewed journals, and disseminated both electronically and in print. Besides, results of the current study will be used for design and implementation of future laboratory investigations and clinical trials at the Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences.

Diabetes management during Ramadan amid Covid-19 pandemic.

Management of fasting patients with diabetes during Ramadan has always posed a great challenge on clinicians. This year, Ramadan has coincided with the Covid-19 pandemic which per se can complicate diabetes care. Although patients with diabetes should be generally discouraged from fasting, those who insist to fact during the current Covid-19 pandemic should undergo strict risk assessment and receive thorough education. In patients with type 2 diabetes, administered antidiabetics and their dose should be modified to minimize the risk of hypoglycemia and dehydration. In type 1 diabetic patients, insulin dose and it timing should be precisely calculated based on regular and rigorous blood glucose monitoring. Nonetheless, it would be prudent to generally discourage patients with diabetes form fasting this Ramadan to avoid the risk of life-threatening complications such severe dehydration and ensuing kidney damage.

Safety and efficacy of hematopoietic and mesanchymal stem cell therapy for treatment of T1DM: a systematic review and meta-analysis protocol.

INTRODUCTION: Insulin standard treatment of T1DM cannot cure the patients as different chronic complications occurred subsequently. Investigations on a curative treatment in T1DM propose cell replacement or maintenance instead of exogenous insulin therapy, but different dimensions of this novel treatment are not clarified. METHODS AND ANALYSIS: We will include all clinical trials which have evaluated the efficacy MSC or HSC transplantation in T1DM treatment; electronically search bibliographic databases, country registration data banks, and gray literatures; and hand-search two key journals, two experts' article, and references of the included articles with no language restriction. Primary outcome is the extent of reduction in insulin requirement and secondary outcomes are safety of MSC and HSC therapy, effect of this therapy on diabetic parameters, effect of the rout of transplantation and origin of the MSC or HSC on efficacy of treatment, studies heterogeneity and potential reasons of it. Heterogeneity and its severity will be calculated with Q Cochrane test, P value, and I2 index. STATA software version 12 will be used for meta-analysis. PROSPERO Registration number: CRD42016047176. ETHICS AND DISSEMINATION: We will publish the systematic review in a peer review journal; as it presents an analysis of published literature, the study does not require ethical approval. STRENGTHS AND LIMITATIONS OF THIS STUDY: This systematic review and meta-analysis will investigate the efficacy of MSC and HSC transplantation in T1DM treatment with no language restriction. Also we will evaluate gray literatures after hand searching. This protocol is prepared according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Two reviewers will evaluate screened full texts, extract data, and asses risk of bias of eligible primary studies independently. As there is the possibility that we miss some unpublished primary studies due to negative results, we will use funnel plot to detect this and correct it with fill and trim method.

Transitional Meningioma After Fetal Liver-Derived Cell Suspension Allotransplant: A Case Report.

Diabetes mellitus is a disease with no definite cure. In recent years, stem cell transplant has led to treatment of various diseases including diabetes. We sought to report a type 1 diabetic patient with a brain mass, diagnosed as transitional meningioma, after a fetal hematopoietic stem cell transplant. A 57-year-old woman with type 1 diabetes who previously had undergone a fetal hematopoietic stem cell transplant, attended the clinic with a history of progressive bifrontal headaches accompanied by nausea, vomiting, and visual disturbances over the previous 8 months. Investigations revealed a 2-cm mass in the right temporal region. The patient underwent a craniotomy, and the lesion was removed and sent for pathological and genetic investigations. The results indicated transitional meningioma with the origin of transplanted fetal hematopoietic stem cells. To our knowledge, this is the first report of transitional meningioma as a result of stem cell transplant. Despite all unanswered questions about the safety of stem cell transplant, this novel therapy provides hope for patients with type 1 diabetes.

Effectiveness of short message service-based intervention (SMS) on self-care in type 2 diabetes: A feasibility study.

AIM: The objective of the current study is to assess the effectiveness of Mobile Short Message Service (SMS) intervention on education of basic self-care skills in patients with type 2 diabetes. Moreover, we aimed to determine whether delivering individually-tailored educational messages can be more effective than general educational messages. METHODS: A total of 150 patients with diabetes type 2 were randomized into three groups: tailored SMS group, non-tailored SMS group, and the control group. Biochemical parameters including HbA1c, FBS, lipid profile were evaluated for the three groups at baseline and after 12 weeks. Moreover, self-care Inventory (SCI), Diabetes Management Self-Efficacy Scale (DMSES) and Diabetes Self-Care Barriers assessment scale for Older Adults (DSCB-OA) were completed. In the tailored SMS group, each person received 75% of their messages based on the top two barriers to adherence that they had experienced and reported in their scale. In the non-tailored SMS group, random messages were sent to every patient. RESULTS: After 12 weeks, although HgA1c levels did not significantly change, significant decline was observed in FBS and mean BMI in both intervention groups. Mean SCI-R scores significantly increased and mean DSCB and DMSES scores significantly decreased in both tailored and non-tailored SMS groups. In the control group, mean SCI-R scores decreased and mean DSCB and DMSES scores significantly increased (P<0.001). CONCLUSION: Sending short text messages as a method of education in conjunction with conventional diabetes treatment can improve glycemic control and positively influence other aspects of diabetes self-care. According to our findings, sending SMS regularly in particular times appears to be as effective as sending individually tailored messages.

Comparison of a Bioimplant Dressing With a Wet Dressing for the Treatment of Diabetic Foot Ulcers: A Randomized, Controlled Clinical Trial.

BACKGROUND: The authors aimed to evaluate the efficacy of a bioimplant dressing in comparison with a wet dressing in patients with diabetic foot ulcers (DFUs). MATERIALS AND METHODS: Fifty-seven patients with diabetes who had an ulcer of Wagner Grades 2-4 were included in this controlled clinical trial. The study was conducted in the outpatient diabetic foot clinic of Dr. Shariati Hospital, affiliated with the Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran, from November 2010 to March 2012. Fifty-seven cases of DFUs were equally and randomly divided into control and test groups. The bioimplant group received an amniotic membrane dressing while the control group was treated with a wet dressing. Both groups were evaluated once a week for 6 weeks for the degree of epithelialization and granulation tissue of the wound. RESULTS: The complete healing rate (ie, wound closure) in the whole study population was 28.1% (control group, 16.7%; bioimplant group, 40.7%, P = 0.04). In 21 patients (77.77%) of the bioimplant group, granulation tissue was extended within the third visit. Amputation and hospitalization rates were higher in the control group compared to the bioimplant group; however, the difference was not statistically significant (relative risk [RR]: 1.11, 95% CI 0.91-1.34, P = 0.258; RR: 1.27, 95% CI 0.97-1.66, P = 0.076, respectively). CONCLUSION: The bioimplant dressing was significantly superior to the wet dressing in prompting the complete healing of DFUs. Ease of use, absence of adverse effects, and a facilitated wound healing process are among properties of amniotic membrane that make it an appropriate dressing in the management of DFUs. Additional research will shed more light on the promising advantages of this material in healing DFUs.

Comparative Analytical Performance of Various HbA1c Assays in Iran.

INTRODUCTION: Hemoglobin A1c (HbA1c) measurement devices are widely used to evaluate glycemic control in diabetic patients. The aim of this study was to investigate the comparability of various HbA1c instruments used in Iran. METHODS: In the present study, 154 fresh whole blood samples from diabetic patients, with different HbA1c levels (4.0%-10%) and no types of hemoglobinopathy were analyzed by six HbA1c assays including one high performance liquid chromatography (HPLC) method (D10 HbA1c), two immunoassay methods (COBAS INTEGRA 400 and Pars Azmoon kit), one Boronate affinity method (Nycocard Reader II), and two ion exchange methods (Biosystems and DS5). The two National Glycohemoglobin Standardization Programs (NGSP) certified system, D10 and COBAS INTEGRA 400 which are certified as secondary reference measurement procedures, were considered as reference methods. The CLSI document (EP9-A2) - Method comparison and Bias estimation using patient samples, approved guideline - was used to compare the performance of different HbA1c instruments. RESULTS: The mean of HbA1c in all four types of assays was less than the reference methods (P-value < 0.01).The mean of absolute difference between the reference methods was the least (0.11%). Among the other four tests, Biosystems had the smallest mean of difference (-0.21%), while Pars Azmoon had the highest (-1.18%). Pars Azmoon showed the greatest difference (95% confidence interval) when compared to D10 [-15.5%(-5.7%to -25.3%)] and COBAS INTEGRA [-17% (-9.16% to -24.84%)]. The highest regression slope (B) was found in DS5 method (0.96) in regression model with both reference methods. CONCLUSION: It can be concluded that although HbA1c standardization programs have resulted in great improvements in the comparability of HbA1c assays, unacceptable errors still exist and further national and international projects are required for standardization of HbA1c measurement. In this situation, it is recommended to use the same laboratory for HbA1c measurement to monitor diabetic patients.