Top Research Highlights

Scientist at work in the lab

Every day, JDRF leverages the expertise and innovation of distinguished researchers from across the globe to support research for life-changing treatments and ultimately a cure for type 1 diabetes (T1D). Our aim is to progressively reduce the burden of the disease on people’s lives until we can achieve a world without T1D. Please enjoy reading about some of the ways that we are working tirelessly to make that happen.

Leading the Way for Biomarkers Discovery

Type 1 diabetes (T1D) can progress at a different rate in each person who develops it. Measurements to reliably identify disease stage or predict disease progression would greatly help researchers design faster, smaller, and more cost-effective clinical trials and could possibly lead to individually tailored therapies. Biomarkers—molecular “signatures” in the body that could be used to make diagnoses—indicate disease status and stage, or predict and/or monitor response to a therapy, are one such avenue of exploration. Biomarkers could be found in blood, urine, or other body fluids or tissues. Ideally, biomarkers for T1D could be used to precisely assess and track the underlying disease process—from identifying people at risk for the disease, to analyzing the rate and manner of disease progression, to evaluating the effectiveness of treatments.

The lack of reliable biomarkers that can be used to stage the disease, understand its core mechanisms, and design appropriate therapies led JDRF to convene its first biomarkers conference in December 2011, when it brought together leading investigators from academia, industry, and government to exchange ideas and move the research forward. The outcome of the meeting was recently published in Clinical and Experimental Immunology. “There is a major need for the development of biomarkers that focus on the mechanistic elements of islet-specific immunity and beta cell loss, to characterize each stage of the disease, and also to monitor specific therapeutic interventions associated with these stages,” says Simi T. Ahmed, Ph.D., JDRF scientific program manager of immune therapies and lead author of the paper.

The workshop focused on three categories of biomarkers that could transform translational research in T1D. Biomarkers of disease progression, which could identify individuals in imminent danger of losing glucose-sensitive insulin secretion from pancreatic beta cells, could allow for an early intervention strategy for people who are not yet diagnosed with T1D; patient-stratification biomarkers could allow for better and more effective design of clinical trials; and surrogate biomarkers for response to therapy could correlate with a clinical endpoint and might lead to faster trials and personalization of treatment options.

The group also addressed challenges to developing biomarker tools for T1D research. Access to large patient cohorts or stored samples from cohorts are needed, as are standardized protocols for the handling, processing, and interrogation of blood volumes that are practical yet allow for measurement of rare lymphocyte (white blood cell) populations that are at the center of the disease. Technology in this field also needs refinement, and there should be exploration into new technologies that may be utilized in conjunction with existing tests to better accelerate T1D biomarker discoveries.

Recognizing the critical gaps in biomarker tools for T1D research, JDRF released a request for applications after the workshop and subsequently funded a number of applications ranging from discovery efforts to test optimization and clinical validation. If successful, these could be applied to disease staging, patient stratification for therapy, and/or clinical response to therapy. In addition, JDRF plans to bring together its funded biomarker investigators to establish a working group to foster collaboration and data sharing among its members, as it expands its strategic T1D biomarker efforts. “Ultimately, JDRF hopes to expand the number of scientists or groups participating in this project and include other promising biomarker efforts or technologies from academia, industry, or other sectors of the scientific community toward achieving clinically useful biomarkers in T1D,” Dr. Ahmed says.

Key point: Biomarkers—molecular “signatures” in the body that could be used to make diagnoses, indicate disease status and stage, or predict and/or monitor response to a therapy—may help researchers design faster, smaller, and more cost-effective clinical trials and could possibly lead to individually tailored therapies. JDRF convened its first biomarkers conference in December 2011, when it brought together leading investigators from academia, industry, and government to exchange ideas and move this research forward. The outcome of the meeting was recently published in Clinical and Experimental Immunology.

Dietary Fat Impacts Insulin Requirements

Dietary fat is essential for human health—it is a key source of metabolic energy, and its components are important building blocks of the cells in the body. But for people with T1D, meals high in dietary fat can affect blood-glucose levels and insulin requirements, according to a recent study by JDRF-funded researchers at Joslin Diabetes Center in Boston.

Previous research has shown that dietary fat and free fatty acids impair insulin sensitivity and increase glucose production, but many of those studies focused on the role of fat in the development of type 2 diabetes. This trial focused on people with T1D, and its findings were recently published in Diabetes Care.

By reviewing continuous glucose monitoring and food-log data from adults with T1D, the researchers found that “several hours after eating high-fat meals, glucose levels went up,” says Howard Wolpert, M.D., senior physician in the Joslin Clinic Section on Adult Diabetes and director of Joslin’s Insulin Pump Program.

Participants in the study spent two days in the hospital eating carefully controlled meals and having their blood-glucose and insulin levels monitored. Breakfasts and lunches featured identical low-fat content, but the two dinners differed. Though they contained identical carbohydrate and protein content, one meal was low fat and the other high fat. For two 18-hour periods beginning before dinner, participants had their insulin automatically regulated by a closed-loop system and their blood-glucose and plasma insulin levels tested at frequent intervals.

The study found that the two breakfast meals required similar insulin doses but that more insulin was required after eating the high-fat dinner than the low-fat dinner. In fact, the average increase in insulin required was 42 percent. Even with the increased insulin, participants experienced greater hyperglycemia after the high-fat dinner with insulin levels elevated 5 to 10 hours after the meal.

The study has major implications for the management of T1D. “These findings highlight the limitations of basing mealtime insulin dosing for type 1 diabetes solely on carbohydrate intake,” says Dr. Wolpert. “We need to consider fat as well as carbohydrates in insulin dosing calculations as well as in nutritional recommendations.”

Key point: JDRF-funded researchers at Joslin Diabetes Center have found that dietary fat can affect insulin requirements in people with T1D. In a new study, meals high in fat boosted blood-glucose levels and the amount of insulin required to treat the resulting high. The findings suggest that the amount of fat in a meal should be considered, along with carbohydrates, to properly dose insulin.

Industry Partners Present at International Conference

Predicting changes in blood-glucose levels is a challenge for people with T1D?and crucial to their well-being. JDRF is leading the way to improving glucose sensing by partnering with industry leaders. At the Advanced Technologies and Treatments for Diabetes (ATTD) Conference recently held in Paris, outcomes from several projects sponsored by JDRF and funding partner The Leona M. and Harry B. Helmsley Charitable Trust, were unveiled by JDRF’s industry partners.

Results from a JDRF-funded feasibility study of a new system with the ability to constantly monitor a person’s blood-glucose levels and predict a rise or fall in blood glucose—and then correspondingly increase, decrease, suspend, or resume insulin delivery—were presented by Animas. This system, called a predictive hypoglycemia-hyperglycemia minimizer (HHM), includes a continuous subcutaneous insulin infusion pump, a continuous glucose monitor (CGM), and a control algorithm used to predict changes in blood-glucose levels. The study, which was the first conducted in humans to investigate the configuration of the predictive algorithm, tested the system’s ability to adjust insulin dosing to reduce instances of hypo- and hyperglycemia and provided insights into the sensitivity of the system. The results also indicated that the HHM reduced insulin delivery in advance of hypoglycemia and triggered timely warnings.

Becton Dickinson (BD) presented positive results from a pilot clinical trial that tested a novel type of CGM that uses optical sensing of a glucose-specific protein. An optical sensor uses a tiny optical fiber that is inserted under the skin. In BD’s new device, the sensor measures blood-glucose levels by detecting the change in intensity of the fluorescent dye in the sensor system worn by study participants. The study, which was co-funded by The Helmsley Charitable Trust, showed that this type of sensor was consistently accurate and has the potential to be used in overnight closed-loop and low-glucose suspension systems.

Also featured at ATTD was Medtronic’s first-of-its-kind glucose-sensor system that uses two different sensors to improve CGM accuracy and reliability. JDRF and The Helmsley Charitable Trust are funding Medtronic’s development of this novel approach, called orthogonal redundancy, which integrates two glucose-sensing technologies: optical and electrochemical. This system differs from those that run on simple redundancy (multiple sensors of the same type). In Medtronic’s new system, a unit houses miniature versions of both sensors in one insertion needle and a wireless interrogation device that connects to both sensors. The sensors respond to physiological changes and provide independent measurements that offer greater reliability than simple redundancy. Medtronic has tried the device in a preclinical study using rats and will further improve the sensor design and development of the algorithms so the system can be used in closed-loop applications.

Key point: Research into better glucose sensing is taking place through several industry partnerships. A few of those partners—Animas, BD, and Medtronic—reported positive results of their individual studies at the recent Advanced Technologies and Treatments for Diabetes (ATTD) Conference. Animas’ study was funded by JDRF, while both BD and Medtronic were funded by JDRF and The Leona M. and Harry B. Helmsley Charitable Trust.