ADA-funded researchers use the money from their awards to conduct critical diabetes research. In time, they publish their findings in order to inform fellow scientists of their results, which ensures that others will build upon their work. Ultimately, this cycle drives advances to prevent diabetes and to help people burdened by it. In 2018 alone, ADA-funded scientists published over 200 articles related to their awards!
ADA-funded researcher studying link between ageing and type 2 diabetes
One of the most important risk factors for developing type 2 diabetes is age. As a person gets older, their risk for developing type 2 diabetes increases. Scientists want to better understand the relationship between ageing and diabetes in order to determine out how to best prevent and treat type 2 diabetes. ADA-funded researcher Rafael Arrojo e Drigo, PhD, from the Salk Institute for Biological Studies, is one of those scientists working hard to solve this puzzle.
Recently, Dr. Arrojo e Drigo published results from his research in the journal Cell Metabolism. The goal of this specific study was to use high-powered microscopes and novel cellular imaging tools to determine the ‘age’ of different cells that reside in organs that control glucose levels, including the brain, liver and pancreas. He found that, in mice, the cells that make insulin in the pancreas – called beta-cells – were a mosaic of both old and young cells. Some beta-cells appeared to be as old as the animal itself, and some were determined to be much younger, indicating they recently underwent cell division.
Insufficient insulin production by beta-cells is known to be a cause of type 2 diabetes. One reason for this is thought to be fewer numbers of functional beta-cells. Dr. Arrojo e Drigo believes that people with or at risk for diabetes may have fewer ‘young’ beta-cells, which are likely to function better than old ones. Alternatively, if we can figure out how to induce the production of younger, high-functioning beta-cells in the pancreas, it could be a potential treatment for people with diabetes.
In the near future, Dr. Arrojo e Drigo’s wants to figure out how to apply this research to humans. “The next step is to look for molecular or morphological features that would allow us to distinguish a young cell from and old cell,” Dr. Arrojo e Drigo said.
The results from this research are expected to provide a unique insight into the life-cycle of beta-cells and pave the way to novel therapeutic avenues for type 2 diabetes.
Arrojo E Drigo, R., Lev-Ram, V., Tyagi, S., Ramachandra, R., Deerinck, T., Bushong, E., … Hetzer, M. W. (2019). Age Mosaicism across Multiple Scales in Adult Tissues. Cell Metabolism, 30(2), 343-351.e3. https://doi.org/10.1016/j.cmet.2019.05.010
Researcher identifies potential underlying cause of type 1 diabetes
Type 1 diabetes occurs when the immune system mistakenly recognizes insulin-producing beta-cells as foreign and attacks them. The result is insulin deficiency due to the destruction of the beta-cells. Thankfully, this previously life-threatening condition can be managed through glucose monitoring and insulin administration. Still, therapies designed to address the underlying immunological cause of type 1 diabetes remain unavailable.
Conventional approaches have focused on suppressing the immune system, which has serious side effects and has been mostly unsuccessful. The American Diabetes Association recently awarded a grant to Dr. Kenneth Brayman, who proposed to take a different approach. What if instead of suppressing the whole immune system, we boost regulatory aspects that already exist in the system, thereby reigning in inappropriate immune cell activation and preventing beta-cell destruction? His idea focused on a molecule called immunoglobulin M (IgM), which is responsible for limiting inflammation and regulating immune cell development.
In a paper published in the journal Diabetes, Dr. Brayman and a team of researchers reported exciting findings related to this approach. They found that supplementing IgM obtained from healthy mice into mice with type 1 diabetes selectively reduced the amount of autoreactive immune cells known to target beta-cells for destruction. Amazingly, this resulted in reversal of new-onset diabetes. Importantly, the authors of the study determined this therapy is translatable to humans. IgM isolated from healthy human donors also prevented the development of type 1 diabetes in a humanized mouse model of type 1 diabetes.
The scientists tweaked the original experiment by isolating IgM from mice prone to developing type 1 diabetes, but before it actually occurred. When mice with newly onset diabetes were supplemented with this IgM, their diabetes was not reversed. This finding suggests that in type 1 diabetes, IgM loses its capacity to serve as a regulator of immune cells, which may be contribute to the underlying cause of the disease.
Future studies will determine exactly how IgM changes its regulatory properties to enable diabetes development. Identification of the most biologically optimal IgM will facilitate transition to clinical applications of IgM as a potential therapeutic for people with type 1 diabetes. Wilson, C. S., Chhabra, P., Marshall, A. F., Morr, C. V., Stocks, B. T., Hoopes, E. M., Bonami, R.H., Poffenberger, G., Brayman, K.L., Moore, D. J. (2018). Healthy Donor Polyclonal IgM’s Diminish B Lymphocyte Autoreactivity, Enhance Treg Generation, and Reverse T1D in NOD Mice. Diabetes. https://doi.org/10.2337/db18-0456
ADA-funded researcher designs community program to help all people tackle diabetes
Diabetes self-management and support programs are important adjuncts to traditional physician directed treatment. These community-based programs aim to give people with diabetes the knowledge and skills necessary to effectively self-manage their condition. While several clinical trials have demonstrated the value of diabetes self-management programs in terms of improving glucose control and reducing health-care costs, whether this also occurs in implemented programs outside a controlled setting is unclear, particularly in socially and economically disadvantaged groups.
Lack of infrastructure and manpower are often cited as barriers to implementation of these programs in socioeconomically disadvantaged communities. ADA-funded researcher Dr. Briana Mezuk addressed this challenge in a study recently published in The Diabetes Educator. Dr. Mezuk partnered with the YMCA to evaluate the impact of the Diabetes Control Program in Richmond, Virginia. This community-academic partnership enabled both implementation and evaluation of the Diabetes Control Program in socially disadvantaged communities, who are at higher risk for developing diabetes and the complications that accompany it.
Dr. Mezuk had two primary research questions: (1) What is the geographic and demographic reach of the program? and (2) Is the program effective at improving diabetes management and health outcomes in participants? Over a 12-week study period, Dr. Mezuk found that there was broad geographic and demographic participation in the program. The program had participants from urban, suburban and rural areas, most of which came from lower-income zip codes. HbA1C, mental health and self-management behaviors all improved in people taking part in the Greater Richmond Diabetes Control Program. Results from this study demonstrate the value of diabetes self-management programs and their potential to broadly improve health outcomes in socioeconomically diverse communities. Potential exists for community-based programs to address the widespread issue of outcome disparities related to diabetes. Mezuk, B., Thornton, W., Sealy-Jefferson, S., Montgomery, J., Smith, J., Lexima, E., … Concha, J. B. (2018). Successfully Managing Diabetes in a Community Setting: Evidence from the YMCA of Greater Richmond Diabetes Control Program. The Diabetes Educator, 44(4), 383–394. https://doi.org/10.1177/0145721718784265
Using incentives to stimulate behavior changes in youth at risk for developing diabetes
Once referred to as ‘adult-onset diabetes’, incidence of type 2 diabetes is now rapidly increasing in America’s youth. Unfortunately, children often do not have the ability to understand how everyday choices impact their health. Could there be a way to change a child’s eating behaviors? Davene Wright, PhD, of Seattle Children’s Hospital was granted an Innovative Clinical or Translational Science award to determine whether using incentives, directed by parents, can improve behaviors related to diabetes risk. A study published this year in Preventive Medicine Reports outlined what incentives were most desirable and feasible to implement. A key finding was that incentives should be tied to behavior changes and not to changes in body-weight.
With this information in hand, Dr. Wright now wants to see if incentives do indeed change a child’s eating habits and risk for developing type 2 diabetes. She is also planning to test whether an incentive program can improve behavior related to diabetes management in youth with type 1 diabetes. Jacob-Files, E., Powell, J., & Wright, D. R. (2018). Exploring parent attitudes around using incentives to promote engagement in family-based weight management programs. Preventive Medicine Reports, 10, 278–284. https://doi.org/10.1016/j.pmedr.2018.04.007
Determining the genetic risk for gestational diabetes
Research has identified more than 100 genetic variants linked to risk for developing type 2 diabetes in humans. However, the extent to which these same genetic variants might affect a woman’s probability for getting gestational diabetes has not been investigated.
Pathway to Stop Diabetes® Accelerator awardee Marie-France Hivert, MD, of Harvard University set out to answer this critical question. Dr. Hivert found that indeed genetic determinants of type 2 diabetes outside of pregnancy are also strong risk factors for gestational diabetes. This study was published in the journal Diabetes.
The implications? Because of this finding, doctors in the clinic may soon be able to identify women at risk for getting gestational diabetes and take proactive steps to prevent it. Powe, C. E., Nodzenski, M., Talbot, O., Allard, C., Briggs, C., Leya, M. V., … Hivert, M.-F. (2018). Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus. Diabetes, 67(12), 2703–2709. https://doi.org/10.2337/db18-0203
Identification of a new player in chronic kidney disease
Diabetes is the most common cause of chronic kidney disease, the serious condition in which kidney function progressively deteriorates, ultimately resulting in failure. Current therapies are non-specific and only slow the progression of this debilitating disease. To address this critical gap, the ADA secured financial support from Boehringer Ingelheim to fund the Chronic Kidney Disease and Renal Insufficiency in the Setting of Diabetes Research Award.
Janos Peti-Peterdi, MD, PhD, of the University of Southern California received one of these awards to study a peculiar group of cells in the kidney called macula densa cells. Using novel microscopy and imaging techniques, Dr. Peti-Peterdi discovered that in diabetes, macula densa cells secrete factors which impair the function of the kidneys.
Dr. Peti-Peterdi hopes to target these cells with a drug to halt progression of chronic kidney disease. To this end, he has recently had a patent published on this topic. https://patents.justia.com/patent/20180133336
Understanding the relationship between fructose and type 2 diabetes
Soda consumption is associated with increased risk of developing type 2 diabetes, and it’s no secret that sugary beverages made with high-fructose corn syrup aren’t good for your health. But do we know precisely why?
Innovative Basic Science awardee Cholsoon Jang, PhD, of Princeton University wanted to answer this important question. In a study that received significant media attention, Dr. Jang determined that, in low amounts, fructose is metabolized in the intestines and never makes it into circulation. However, in high doses, like those found in soda, fructose overwhelms the normal intestinal disposal route and enters the bloodstream, ultimately causing toxicity in the liver and increasing risk for type 2 diabetes.
These findings suggest a mechanism by which soda consumption influences type 2 diabetes risk and supports nutritional guidance to reduce soda consumption in people with or at risk for type 2 diabetes. Jang, C., Hui, S., Lu, W., Cowan, A. J., Morscher, R. J., Lee, G., … Rabinowitz, J. D. (2018). The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids. Cell Metabolism, 27(2), 351-361.e3. https://doi.org/10.1016/j.cmet.2017.12.016
Communicating real time glucose levels to parents
For all parents, witnessing your child come of age can be both rewarding and distressing. Add in type 1 diabetes, including the necessity for a transition from parent-care to self-care, and this life stage becomes even more complicated, often accompanied by reduced adherence to treatment regimens and increased risk for poor health outcomes. Bree Holtz, PhD, of Michigan State University received an ADA Innovative Clinical or Translational Science award to address this issue. Dr. Holtz created an application called MyT1DHero which links real time patient health data to a parent or caregiver mobile device, thus facilitating a more stable transition period. Results from a study published recently by Dr. Holtz demonstrated that parents were pleased with the design and functionality of the app. Remarked one parent, “I really did like receiving the blood sugars, I always thought I was more aware of what was going on than I really was, so that was an eye opener.”
Now, Dr. Holtz wants to test whether using the app improves health outcomes in adolescents transitioning to self-care. A pilot study is currently underway.
Holtz, B. E., Murray, K. M., Hershey, D. D., Dunneback, J. K., Cotten, S. R., Holmstrom, A. J., … Wood, M. A. (2017). Developing a Patient-Centered mHealth App: A Tool for Adolescents With Type 1 Diabetes and Their Parents. JMIR MHealth and UHealth, 5(4), e53. https://doi.org/10.2196/mhealth.6654
Preventing heart disease while maintaining glucose control in type 2 diabetes
People with type 2 diabetes are at significantly increased risk for developing heart disease. While increasing insulin levels is important for managing diabetes, too much insulin may contribute to atherosclerosis by stimulating processes unrelated to glucose lowering.
Jenny Kanter, PhD, of the University of Washington wanted to resolve this insulin catch-22. In 2016, Dr. Kanter received an ADA Innovative Basic Science award supported by the Amaranth Diabetes Foundation. This year, Dr. Kanter published a fascinating study demonstrating that an insulin-like molecule can exhibit insulin’s glucose lowering effects without activating the processes that promote heart disease.
Further progression of this novel therapy could lead to a treatment for diabetes that also prevents heart disease.
Kanter, J. E., Kramer, F., Barnhart, S., Duggan, J. M., Shimizu-Albergine, M., Kothari, V., … Bornfeldt, K. E. (2018). A Novel Strategy to Prevent Advanced Atherosclerosis and Lower Blood Glucose in a Mouse Model of Metabolic Syndrome. Diabetes, 67(5), 946–959. https://doi.org/10.2337/db17-0744
Improving transplantation to eliminate the need for insulin injections
For people with type 1 diabetes, finger pricks and insulin injections are a part of everyday life. Can research change that? Qizhi Tang, PhD, of the University of California San Francisco received an ADA Innovative Basic Science award supported by the Foundation for Diabetes Research to investigate how to make beta cell replacement through transplantation a possibility for all people with type 1 diabetes. Dr. Tang and her team of researchers are working to figure out how to transform stem cells into insulin-producing cells and how to ensure they survive following transplantation. A recently published study in Stem Cell Reports highlights several simple ways to make sure these cells remain functional after transplantation.
The ability to convert stem cells into insulin-producing cells means the possibility of a limitless supply of cells to transplant. With this approach, it may become possible for all people with type 1 diabetes to replace their beta cells and eliminate the need to administer insulin.
Faleo, G., Russ, H. A., Wisel, S., Parent, A. V., Nguyen, V., Nair, G. G., … Tang, Q. (2017). Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant. Stem Cell Reports, 9(3), 807–819. https://doi.org/10.1016/j.stemcr.2017.07.012
A novel therapy for treating foot ulcers in diabetes
Diabetes is the leading cause of non-traumatic lower-limb amputations in the U.S. An impaired ability to sense and heal wounds is a major contributor to this diabetes complication. Mayland Chang, PhD, of the University of Notre Dame was granted a Pathway to Stop Diabetes® Visionary award to figure out a way to improve wound healing in people with diabetes. This year, Dr. Chang reported that she had identified a molecule that is higher in humans with diabetes and which prevents effective healing of foot ulcers. Inhibiting this molecule with a novel drug, ND-336, significantly improved the ability to timely and appropriately heal wounds in mice with diabetes. She even showed that her treatment was more effective than the only approved drug for dealing with foot ulcers related to diabetes.
Continued development of ND-336 holds promise to ultimately become the primary therapeutic option to treat wounds related to diabetes.
Nguyen, T. T., Ding, D., Wolter, W. R., Pérez, R. L., Champion, M. M., Mahasenan, K. V., … Chang, M. (2018). Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor That Accelerates Healing. Journal of Medicinal Chemistry, 61(19), 8825–8837. https://doi.org/10.1021/acs.jmedchem.8b01005