When Does Type 1 Diabetes Begin to Develop? Research Reveals How to Identify Those at Highest Risk
June 21, 2013
In a major step toward determining when type 1 diabetes begins to develop, researchers have created tools for accurately predicting who is at highest risk for this disease, opening possibilities for earlier intervention and potentially greater preservation of beta cell function, according to scientists at a joint American Diabetes Association/Juvenile Diabetes Research Foundation (JDRF) symposium today at the American Diabetes Association's 73rd Scientific Sessions®.
The symposium also highlighted ongoing research to identify the triggers for type 1 diabetes, which, like type 2 diabetes, has been increasing globally in recent decades. But unlike type 2, which is associated with the global rise in obesity and an aging population, the causes for the increase in type 1 remain unclear. In addition, finding out just how much type 1 is increasing overall has not been easy for researchers, who have run into hurdles collecting data, particularly in low-income countries. The symposium also drew attention to the difficulty people in low-income countries often have accessing insulin and other diabetes supplies.
When Does Prediction Become Diagnosis?
Though researchers are still searching for answers for how to prevent type 1 diabetes, great strides have been made recently in predicting who is most likely to develop the disease, allowing researchers to identify type 1 at the earliest stages of development and potentially intervene to preserve beta cell function at a much earlier stage and ultimately prevent onset of symptomatic diabetes.
Analyzing the database from the Diabetes Prevention Trial of Type 1 Diabetes (DPT1), Jay Sosenko, MD, Professor of Medicine and Epidemiology at the University of Miami, identified the variables that were most predictive of who would develop symptomatic type 1 diabetes and used them to create a "risk score." These variables included BMI, age, fasting C-peptide levels, a measure of overall C-peptide production and a measure of overall glucose. The C-peptide and glucose measurements were obtained from oral glucose tolerance tests. Sosenko then applied the "DPT1 Risk Score" (DPTRS) to data from another study, known as the TrialNet Natural History Study (also known as the Pathway to Prevention Study). This is a large multicenter study which is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and which also receives support from the American Diabetes Association and JDRF. The main objective of TrialNet is to delay or prevent the onset of type 1 diabetes in individuals at high risk (relatives of type 1 diabetes patients who have pancreatic autoantibodies) for the disease. The findings showed that the DPTRS was highly predictive of who would ultimately be diagnosed with symptomatic type 1 diabetes in TrialNet.
"The DPTRS can identify even those who have normal glucose tolerance but who are nonetheless at risk, in part because it takes age into account," Dr. Sosenko said. "If you look at normal glucose values in children compared to adults, they tend to be lower. Dysglycemia, which is currently used to identify high risk individuals, is based upon the glucose thresholds of adults and these thresholds might not be appropriate for children. In other words, an 8-year-old with a normal two-hour glucose level for an adult (for example, 135 mg/dl) could possibly be at higher risk than an adult with a higher level (for example, 150 mg/dl). If age isn't also considered, a child at high risk could be missed."
Dr. Sosenko said he found that once the DPTRS passed a certain threshold, individuals were highly likely to develop symptomatic type 1 diabetes. "So, a very high DPTRS value could possibly mean that someone has diabetes. The data suggest that the DPTRS, or a modification of it, could potentially provide an additional means for diagnosing type 1 diabetes."
A second study, The Environmental Determinants of Diabetes in the Young (TEDDY), is looking at population-based predictions of type 1 diabetes and potential triggers for the disease. "Most new cases of type 1 are not in first degree relatives of those who have already been diagnosed, but rather sporadic cases from the population at large," said lead researcher William Hagopian, MD, PhD, Scientific Director of Pacific Northwest Diabetes Research Institute in Seattle, and Clinical Associate Professor of Medicine at the University of Washington in Seattle.
The TEDDY study screened children at birth to identify those with the highest genetic risk of developing type 1 and is following those children for development of islet antibodies and diabetes. The study has enrolled 1,300 participants at each of six medical centers in Sweden, Finland, Germany, Georgia/Florida, Colorado and Washington, for a total of 8,600 participants. The researchers estimate that 400 of them will ultimately develop type 1 diabetes. So far, 150 participants have been diagnosed with type 1 diabetes.
At the same time, they are measuring environmental exposures for the children in the study so that they can ultimately make correlations between these exposures and who develops type 1 diabetes.
Not only will TEDDY help researchers to better understand what causes type 1 diabetes, it also provides clear direction into how to develop population-wide methods to predict type 1 diabetes in all children starting at birth. "This will help to decrease illness and medical cost at the time of onset, as well as help test new therapies to prevent the disease before clinical onset – an important step toward prevention and early intervention," Dr. Hagopian said.
Type 1 Diabetes in Low-Income Countries
Other speakers at the symposium focused on issues surrounding type 1 diabetes in low-income countries, where researchers struggle to gather the incidence data needed to track the disease. There is a lot of good quality data around the world for the incidence of type 1 diabetes collected within the framework of the World Health Organization's DIAMOND study, mapping the incidence of childhood-onset type 1 diabetes in most parts of the world, noted Jaakko Tuomilehto, Emeritus Professor of Public Health, University of Helsinki, Finland. "However," he said, "the information is very scarce for low and middle-income countries."
Access to and costs of necessary medicines and supplies remains a problem in many countries, with subsequent rationing and under-utilization. Researchers also discussed efforts to make insulin and diabetes-related medical supplies more accessible to people living in low-income countries, where the diagnosis of a single family member can be financially devastating. "In several countries in Latin America, sub-Saharan Africa and Asia, it can take 30-40 percent of the family’s income to provide the $250-$300 per year in insulin and other supplies," said John S. Yudkin, MD, Emeritus Professor of Medicine, University College London, who is Chairman of the International Insulin Foundation (IIF). He also noted that even in the U.S., families may end up in bankruptcy due to diabetes-related medical bills and the inability to afford treatment is a common cause of emergency department visits for ketoacidosis (a potentially life-threatening complication).
Dr. Yudkin said global efforts are underway through a collaboration of the IIF, the International Union Against TB and Lung Disease and the World Health Organization, with the Pan-American Health Organization, to create a non-communicable disease (NCD) drug facility to improve the availability and affordability of high quality essential drugs for NCDs, including insulin, for people in low-income countries.
"We have made tremendous progress in improving care for people with type 1 diabetes; however, much more needs to be done," said Jane Chiang, MD, Senior Vice President, Medical Affairs and Community Information, American Diabetes Association. "Type 1 diabetes has global impacts and affects countries where basic diabetes care is unavailable or severely limited. Data from large clinical trials, such as TEDDY, enables the American Diabetes Association to educate healthcare providers from these countries on identifying those at risk and providing Standards of Care for those with type 1 diabetes."
"The rising incidence and earlier age of onset of type 1 diabetes increases the urgency of developing approaches for its prevention," said Richard Insel, MD, JDRF's Chief Scientific Officer. "New approaches for detection of risk and staging of progression of type 1 diabetes have set the stage for improved design of prevention clinical trials. The joint ADA/JDRF symposium at the Scientific Sessions captures these exciting developments and recent progress that raises the possibility of intervening more knowledgeably and effectively in the at-risk setting to prevent type 1 diabetes."
The American Diabetes Association is leading the fight to Stop Diabetes and its deadly consequences and fighting for those affected by diabetes. The Association funds research to prevent, cure and manage diabetes; delivers services to hundreds of communities; provides objective and credible information; and gives voice to those denied their rights because of diabetes. Founded in 1940, our mission is to prevent and cure diabetes and to improve the lives of all people affected by diabetes. For more information please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit www.diabetes.org. Information from both these sources is available in English and Spanish.
JDRF is the leading global organization funding type 1 diabetes (T1D) research. JDRF's goal is to progressively remove the impact of T1D from people's lives until we achieve a world without T1D. JDRF collaborates with a wide spectrum of partners and is the only organization with the scientific resources, regulatory influence, and a working plan to better treat, prevent, and eventually cure T1D. As the largest charitable supporter of T1D research, JDRF is currently sponsoring $530 million in scientific research in 17 countries. In 2012 alone, JDRF provided more than $110 million to T1D research. More than 80 percent of JDRF's expenditures directly support research and research-related education. In 2012 Forbes magazine named JDRF one of its five All-Star charities, citing the organization’s efficiency and effectiveness. See www.jdrf.org for more information.