Objective
At its core, AL-DIAR2 aims to build a national screening program for type 1 diabetes in Qatar. To achieve this goal, AL-DIAR2 will identify specific molecules in the blood that present before the physical symptoms of type 1 diabetes appear. These molecules are called autoantibodies, and they are present in 98% of type 1 diabetes patients at the time of diagnosis. The autoantibodies are responsible for attacking the insulin-producing cells within the pancreas, known as beta cells, causing sugar levels in the blood to rise and the appearance of many adverse health effects. The autoantibodies in T1D are called islet cell autoantibodies (ICAs), and AL-DIAR2 will screen for those autoantibodies using a simple blood test which can test for different autoantibodies at the same time. The appearance of the different autoantibodies in the blood varies depending on the individual's age and how long they’ve had diabetes. For example, the insulin autoantibody is usually one of the first autoantibodies to be detected in the blood, and the zinc transport protein 8 autoantibody decreases with age after the onset of type 1 diabetes Generally, type 1 diabetes autoantibodies levels peak at 1–2 years of age, so AL-DIAR2 focuses on all children aged 1.5 to 5.5 years.
Establishing the national screening program will have an immediate and long-term impact on type 1 diabetes in Qatar and worldwide. Throughout its operation, establishing the national-screening program will serve as the basis for pre-type 1 diabetes screening in the general children population in Qatar and act as a model approach to type 1 diabetes screening in the region. In the long run, however, AL-DIAR2 will also pave the road to determining the technical aspects of testing for pre-type 1 diabetes associated autoantibodies in the future screening efforts in Qatar and the region. These will include the determination of the best targetable age for population-wide screening of pre-type 1 diabetes, the optimal laboratory conditions for sensitive detection of the markers, and the determination of factors that cause autoantibody variation in pre-T1D individuals.
Beyond detecting type 1 diabetes early in its tracks, AL-DIAR2 will also become a resource for the fight against type 1 diabetes at the national, regional, and international levels. This is especially important as we do not know why the body initiates the autoimmune attack against the insulin-producing cells in the pancreas. Specifically, by determining the individuals most likely to develop type 1 diabetes, AL-DIAR2 will become the focal point in guiding future clinical trials in Qatar. These clinical trials usually include potential drugs and therapeutics that may completely change how we approach type 1 diabetes treatment, either by restoring the cells in the pancreas or preventing the progression of type 1 diabetes.
Background Rationale
Type-1 diabetes is a serious disease that can affect anyone at any age. In type 1 diabetes, the body mistakenly attacks the pancreas, which makes insulin, the hormone responsible for controlling blood sugar levels. Although type 1 diabetes is increasing worldwide, there is mainly an unexplained increase in type 1 diabetes in minority populations. Case in point, compared to many European countries, the incidence of type 1 diabetes in Qatar is increasing at an alarming rate. The rate of type 1 diabetes in Qatar has more than doubled between 2010 and 2020, making Qatar the 4th highest in terms of type 1 diabetes incidence worldwide. Furthermore, even after a diagnosis, type 1 diabetes -diabetics in Qatar still show low adherence to the physician's recommendations, and many suffer from poor glycemic control. The high rates of type 1 diabetes and accompanying poor management choices in the course of type 1 diabetes in Qatar highlight the need for urgent and committed efforts to treat, prevent, and cure the disease through new therapies, screening, and intervention programs. Early detection of type 1 diabetes provides patients most likely to develop the disease a window of opportunity to reduce the burden of the illness through making healthier lifestyle choices.
Screening the population for markers of pre- type 1 diabetes onset aiming to tackle the increasing disease rates, owing to advances in immunology, biotechnology, and genetics. Typically, type 1 diabetes diagnosis occurs after the onset of physical symptoms. Those symptoms, which appear due to high blood sugar levels, include frequent hunger and urination, weight loss, and lethargy (a general feeling of tiredness or sleepiness). When those symptoms appear, the blood sugar level has been dangerously high for several weeks, and it is often too late to reverse the disease. However, we can now screen anyone for the earliest signs of type 1 diabetes and predict the onset of type 1 diabetes before it occurs. The key to this early prediction of type 1 diabetes onset is to screen for autoantibodies – proteins made by the body to attack itself mistakenly. We now know that in type 1 diabetes, the body makes autoantibodies that attack the cells in the pancreas, which eventually cause high blood glucose sugar levels and the subsequent appearance of symptoms associated with type 1 diabetes. When we screen for autoantibodies, we use a simple blood test that screens for a panel of a few autoantibodies known to appear before the onset of type 1 diabetes. Screening for autoantibodies has the potential to save many lives, as it could reduce the possibility of emergency hospitalization due to severe complications of type 1 diabetes, such as diabetic ketoacidosis, which can lead to brain injuries, comas, and death.
Developing an autoantibody screening program in Qatar has many benefits: (1) The screening program will allow the general Qatari population to benefit directly from the capacity to detect type 1 diabetes before it occurs, reducing the harmful impact of debilitating consequences of type 1 diabetes -onset; (2) the population-wide screen will allow scientists to determine the best candidates for clinical trials aiming to test treatments that may reverse the progression of type 1 diabetes; (3) Qatar has many other ongoing programs that aim to decode individuals' genetic information in the general population. Identifying individuals with pre (T1D) status may allow us to better comprehend type 1 diabetes by studying the factors that cause the disease to advance in those individuals, ultimately allowing us to design more promising prevention and clinical trials in the future.
Description of Project
The incidence rate of type 1 diabetes has raised dramatically in the recent years. Recent epidemiological data and that published by the International Diabetes Federation’s Diabetes Atlas (IDF) shows that Qatar has the globally 4th-highest incidence of type 1 diabetes, alongside Finland and Sweden. There is a lack of type 1 diabetes screening initiatives or studies both at general population and for those at high-risk that take advantage of complementary data such as age, genetic risk, and family history in association with islet autoantibody status to predict the disease future risk in children. Most screening for type 1 diabetes initiatives to recognize subjects at risk for developing type 1 diabetes have targeted relatives of individuals living with the disease to maximize participation and feasibility of programs. Though, latest data shows that more than 85% of those who progress to clinical type 1 diabetes do not have affected relatives with type 1 diabetes. Current successes in disease-modifying therapies to influence the sequence of early-stage of type 1 diabetes have provoked the deliberation of the necessity for and feasibility of population screening to characterize those at increased risk. Present population screening programs depend on on genetic or autoantibody screening, and these have produced momentous evidence about type 1 diabetes development and strategies for the best timing for screening in clinical practice. The primary objective of DIAR-2 study is to establish an islet autoantibody testing program for screening in Qatar using state-of-the-art developed detection assays. Furthermore, the study aim is to design a cross-sectional pilot screening program when genetics and autoimmunity screening is going simultaneously. The study is testing the feasibility of population screening for early-stage type 1 diabetes in Qatar. The screening will be performed in young children aged 1.5-5.5 years. With a combining the islet autoantibodies and genetics (MENA-GRS through Genome wide-array genotyping) testing, we intend to provide estimates of the prevalence of early-stage type 1 diabetes in early life in this part of the world. Furthermore, we will inform and follow up high-risk children for development of autoimmunity and early-stage type 1 diabetes and will design monitoring strategies and parent education and counselling plans. The study team is keen to expand the program to larger cohort and to include older age groups aiming to create a resource for recruitment into future prevention trials and natural history studies.
Anticipated Outcome
The AL-DIAR2-Program aims to assess early staging of type 1 diabetes among young children by establishing an islet autoantibody screening program in Qatar using state-of-the-art developed detection assays. Qatar is listed amongst the top 10 countries in the world with the highest prevalence (23%) of diabetes with recently reported prevalence of type 1 diabetes as 386.23 in children. Diabetes is the leading cause of cardiovascular and renal diseases that are both serious and costly. Improvement of the risk prediction is crucial to enable targeting individuals at high risk that could most benefit from an early prevention. However, this is most useful if prevention can be started early. Our proposed screening of autoantibodies in early life will lead to potential novel scientific discoveries that will help in early detection of at-risk type1 diabetic children minimizing their risk of future health complications. The early diagnosis of pre-type1 diabetic children will open the doors for precision clinical interventions to prevent and intercept the disease or its on-set at an appropriate stage. The study will also build the necessary infrastructure to conduct a future large-scale public healthcare research programme. This will thus pave the way to establish type 1 diabetes prevention trials at a population-wide scale. The parents of children with pre-type 1 diabetes will be counselled through routine education programs. This will help the families to alleviate the anxiety that may arise from the diagnosis and minimize their psychological distress.
Relevance to T1D
Diabetes is a disorder of increased glucose level in blood and/ or urine. Type 1 diabetes mostly occurs during early childhood and seriously affects the health and psychosocial life of patient and the family. According to International Diabetes Federation (IDF) Atlas 10th edition (2021), 73 million people are affected by diabetes in the Middle East and African region. Consistent high blood glucose level is associated with other health complications like heart disorders, kidney and eye disorders. The disease occurs progressively in three phases. In the first phase (early childhood), the patient is asymptomatic but disease-causing factors (auto-antibodies) start accumulating (prediabetes), which reaches to its maximum level in the 3rd phase and eventually the patient then exhibits the symptoms. The disease is caused due to an autoimmune response against the pancreas, the organ which synthesizes insulin. Better management of the disease is the sole way to spend a healthy life, which is only possible when early screening is performed to diagnose the pre-type1 diabetic individuals, so that the precautionary measures may be taken on time. If left undiagnosed and untreated in the early days, it may compromise the quality of life, result in visceral organ dysfunction and eventually death. Keeping in view the rising incidence of type 1 diabetes in Qatar and lack of screening programs for pre-school children, we will conduct a population level screening of autoantibodies in young children. This screening would assist in determining the ratio of pre-diabetes children, the spectrum of their auto-antibodies and pattern of their appearance in the different life stages. There are several benefits adhere to this population level screening program in children. Few of the most significant advantages include diminishing the risk of diabetic ketoacidosis, disease severity and diabetes associated life threatening complications. If the disease is managed on time, regularly monitored, and followed up, the person can then live normal and healthy life, save money to avoid extra expenditure on health, and can become strong emotionally. The screening program would explore the phenotypic spectrum of type 1 diabetes in pre-school children of Qatar, which would help in prognosis of disease in the future. It would help in determining the anticipated prevalence of type 1 diabetes in the country so that the health measures are undertaken to avoid the spread of disorder. Hence, conclusively, the success of population based early screening program would aid in prognosis, clinical counseling, risk prediction for other family members, cost effectiveness and preventing the fatal complications.