Current Research
Diabetes Action is committed to funding promising and innovative research to prevent, treat, and cure type 1 and type 2 diabetes and their complications. The following studies are currently being funded by Diabetes Action.
Type 1 diabetes research
A Non-Invasive Patient-Reported Symptom Screening Tool (EPI/PEI-SS) to Identify Exocrine Pancreatic Insufficiency (EPI) in Type 1 Diabetes
Researcher:
Brittany S. Bruggeman, MD
Assistant Professor of Pediatric Endocrinology
University of Florida
Gainesville, FL
Purpose:
Type 1 diabetes (T1D) may be accompanied by a lesser-known condition called exocrine pancreatic insufficiency (EPI), where the pancreas fails to produce enough digestive enzymes. Up to 30% of people with T1D might have EPI, but this condition is very underdiagnosed. A non-invasive screening survey called the Exocrine Pancreatic Insufficiency Symptom Score (EPI/PEI-SS) was created with input from people living with EPI and T1D. This tool evaluates 15 symptoms to distinguish EPI from other gastrointestinal conditions like celiac disease or food intolerances, showing promising results in preliminary studies including in people with diabetes. Dr. Bruggeman’s lab will run a larger study in adults with Type 1 diabetes who will take the EPI/PEI-SS and provide a stool sample for a fecal elastase test. By comparing these results, they can evaluate the effectiveness of the EPI/PEI-SS in screening for EPI, with the goal of improving detection and treatment of EPI in people with T1D.
Nanogels for localized immunomodulation of cellular allografts for type 1 diabetes
Researcher:
Maria M Coronel, PhD
Assistant Professor
University of Michigan
Ann Arbor, MI
Purpose:
Type 1 diabetes is caused by the immune system attacking insulin-producing cells in the pancreas, leading to insulin deficiency. Treatment with insulin injections can be emotionally taxing and only partly prevents complications. Islet transplantation, the infusion of insulin-producing cells into the liver, can achieve durable near-normal glycemic control and insulin independence posttransplant. However, the widespread use of this treatment has been held back by several challenges, with the need for systemic immunosuppression being the most significant hurdle. Dr. Coronel’s lab seeks to address this challenge by developing nano-sized degradable materials to deliver checkpoint inhibitors. These inhibitors aim to induce regulatory T cell phenotypes that establish an immune-privileged site, thus preventing rejection without the need for immunosuppressive drugs. By achieving successful transplant engraftment through a drug-free regimen, this approach could mitigate a significant obstacle in islet transplantation and extend the therapeutic potential of this treatment to all individuals with Type 1 diabetes
A PROGRAM FOR THE CURE OF TYPE 1 DIABETES USING A GENERIC DRUG: PHASE II
Researcher:
Denise L. Faustman, MD, PhD., Associate Professor
Harvard Medical School and Director Immunobiology Laboratory
Massachusetts General Hospital
Charlestown, MA
Purpose:
Dr. Faustman’s research centers on the benefits of BCG vaccine even for those with established type 1 diabetes. These discoveries now allow people beyond new onset diabetes to benefit from this innovative therapy. The BCG vaccine is a 125-year-old generic drug originally identified for prevention of tuberculosis, but now clinical trials show the benefits extend to those with type 1 diabetes, autoimmune multiple sclerosis, and in the broad prevention of infections. In 2018 the Faustman research group identified that repeat BCG vaccines could lower blood sugars from 10-18% by correcting an underlying defect in metabolism of white blood cells. This benefit was seen even in those who have had type 1 diabetes for decades. With BCG treatment, the blood sugars stably dropped by allowing the diabetic white blood cells to now use sugar as an energy source and yielded safe and fine regulatory blood sugar control. In 2022, a Phase II double blinded clinical trial began with subjects from 11-18 years of age who had diabetes for more than two years. Dr. Faustman’s group, through clinical trial, is also showing the susceptibility of type 1 diabetes to infections which also improved with this established and safe vaccine.
Investigating the Role of the Sympathetic Nervous System in Glucose Toxicity-induced Insulin Resistance in Type 1 Diabetes
Researcher:
Kenichi Sakamoto MD, PhD
Assistant Professor
Rutgers, The State University of New Jersey
Piscataway, NJ
Purpose:
While insulin has transformed Type 1 Diabetes (TlD) management, many patients struggle with glucose toxicity induced insulin resistance, leading to complications like nephropathy and neuropathy. Despite its clinical significance, the exact mechanisms by which glucose toxicity leads to insulin resistance remain poorly understood. Dr. Sakamoto’s lab hypothesizes that heightened sympathetic nervous system (SNS) activity is a key driver and aims to investigate 1) if glucose toxicity increases SNS activity and 2) whether increases in SNS activity is sufficient to induce insulin resistance and 3) to explore if reducing SNS overactivity prevents glucose toxicity-induced insulin resistance in TlD. By elucidating these mechanisms, they aim to pave the way for the development of novel therapeutic interventions aimed at improving blood glucose management and mitigating the complications associated with TlD.
type 2 diabetes research
Role of gut lymphatics in dyslipidemia and cardiometabolic abnormalities
Researcher:
Vincenza Cifarelli, PhD
Assistant Professor of Pharmacology and Physiology
Saint Louis University School of Medicine
St. Louis, MO
Purpose:
A healthy response to a meal is characterized by low levels of fat in the blood due to fat retention in the intestine; instead during diabetes, there are high blood fat levels, but the mechanisms are unknown. Dr. Cifarelli’s lab is studying the lymphatic vessels important to carry fat in our body. Dysfunctions of the lymphatic vessels result in high levels of fat in the blood and in tissues which is a risk factor for the development of heart diseases. This study will provide novel mechanistic insights on the complex interaction between insulin signaling and lymphatic function and help identify mechanism-based treatments to reverse dyslipidemia and systemic metabolic abnormalities.
Free fatty acid carrier proteins in insulin resistance
Researcher:
Gregory C. Henderson
Assistant Professor
Purdue University
West Lafayette, IN
Purpose:
A specific type of fat, free fatty acids (FFA), is elevated in blood of people that are prone to developing type 2 diabetes. One reason for this relationship would be that FFA uptake into the liver can lead to fatty liver disease, and liver fat accumulation impairs the body’s response to insulin. It is important to develop a deeper understanding of the transport of FFA through the blood in order to generate knowledge that could help in developing new therapies for type 2 diabetes. The albumin protein is a main carrier of FFA, but it is not the only carrier. Dr. Henderson’s lab will test how albumin impacts the uptake of FFA into the liver and other organs, and we will identify other proteins that are also involved in the transfer of FFA through the bloodstream. Ultimately a deeper understanding of FFA transport could inform therapeutic development for diabetes.
Asprosin-Ptprd receptor signaling: Effects on pancreatic beta cell function and therapeutic strategies for diabetes treatment
Researcher:
Ila Mishra, PhD
Assistant Professor
University of Kentucky
Lexington, KY
Purpose:
A recently discovered hormone, asprosin, plays a significant role in the development of type 2 diabetes by raising blood sugar levels, increasing hunger, and interfering with how the body produces and uses insulin. This study investigates a specific receptor called Ptprd and a molecule that can block its effects, to see how they influence asprosin's impact on the function of pancreatic beta cells. Both humans and mice with diabetes often have higher levels of asprosin; lowering these levels either genetically or with medication can help protect against diabetes. One promising approach involves use of antibody to block asprosin, which has shown to reduce appetite and blood sugar levels in diabetic mice. However, Dr. Mishra’s lab still needs to find out if this antibody can also improve pancreatic function and insulin sensitivity. This research is an important step towards understanding of pancreatic function of asprosin and creation of new treatments for diabetes.
Investigation of dietary polyphenols vs. their microbial metabolites on intestinal inflammation and gut hormone secretion in ileal organoids
Researcher:
Diana E. Roopchand, PhD
Associate Professor
Rutgers University, The State University of New Jersey
New Brunswick, NJ
Purpose:
Dietary polyphenols found in plant foods (i.e., fruits, berries, vegetables, teas, spices, etc.) are linked to protection from type-2 diabetes and other cardiometabolic disease. Most dietary polyphenols are not absorbed therefore mechanisms underlying their health benefits are not well understood. Since dietary polyphenols reach high levels in the intestinal lumen, Dr. Roopchand’s lab hypothesizes that they mediate their metabolic health benefits by modulating the intestinal epithelium and gut microbiota, which also metabolizes parent polyphenol compounds into more bioavailable microbial metabolites. They hypothesize that polyphenols and their microbial metabolites have differential abilities to directly modulate the intestinal epithelium leading to protection from metabolic disease. This project will use murine gut organoids to model the intestinal epithelium and compare the ability of parent polyphenols vs. their microbial metabolites to 1) reduce the expression of host inflammatory mediators after challenge with bacterial components; and 2) promote secretion of gut hormones that regulate glucose metabolism.
The acute effects of BCAAs on glycemic control, insulin sensitivity, and their underlying mechanisms
Researcher:
Andrew C. Shin, PhD
Assistant Professor
Texas Tech University
Lubbock, TX
Purpose:
Branched-chain amino acids (BCAAs) are essential amino acids we need to obtain through diet. Studies show that circulating BCAAs are elevated in individuals with obesity/type 2 diabetes, and that dietary BCAAs can lead to insulin resistance and abnormally high blood glucose. These findings suggest that BCAAs may be causal in development of insulin resistance and diabetes, but the mechanism by which this occurs is not clear since almost all studies are based on a chronic supplementation design. Understanding the short-term consequences of BCAAs will allow Dr. Shin’s lab to gain better insight into pathophysiology following a prolonged exposure to high BCAAs. This project will study the acute effects of BCAAs on glucose homeostasis, insulin sensitivity, and their potential underlying mechanisms.
Elucidating the mechanisms involved in diabetes induction in patients receiving radiation therapy
Researcher:
Sarah Shuck, PhD
Assistant Professor
Beckman Research Institute of the City of Hope
Duarte, CA
Purpose:
An emerging population battling diabetes are patients receiving cancer treatment. Often, these patients are unprepared to manage an additional diagnosis and significant challenges arise when managing this aspect of their disease. How cancer treatments such as chemotherapy and radiation therapy lead to type 2 diabetes is not known. Defining these mechanisms will allow development of both preventative and therapeutic treatments. Dr. Shuck’s lab is exploring how the use of drugs that are approved for diabetes may prevent the development of diabetes in cancer patients. Their data suggests that pre-treatment with these drugs before cancer treatment can prevent damage to tissue that leads to diabetes. They are now defining the specific changes that are occurring, which will allow them to develop tailored drug treatments for these patients.