Ohio State basic scientist researches role of key proteins in pancreatic cancer
Why do high numbers of patients with acute pancreatitis go on to develop diabetes mellitus?
Researchers at The Ohio State University Wexner Medical Center will seek to answer this critical question as they join other top research centers across the country in a landmark study about the pathogenesis and progression of diabetes mellitus after acute pancreatitis.
“This will be the first time that 10 different clinical centers throughout the country with expertise in pancreatitis and diabetes will jointly enroll patients with pancreatitis and follow them for a long period of time—at least five years,” says Georgios Papachristou, MD, PhD. “Our goal is to understand which patients will develop diabetes after acute pancreatitis and why.”
Dr. Papachristou, a pancreatologist at the Ohio State Wexner Medical Center, is the principal investigator of the study, “Epidemiology and Pathophysiology of Acute Pancreatitis-Related Diabetes Mellitus.”
Finding answers—and eventually new treatments—is imperative, due to the high rate at which patients with acute pancreatitis develop diabetes.
“Studies estimate that 25% of patients will develop diabetes within three years after a single episode of acute pancreatitis, and 40% of patients will develop diabetes within five years after pancreatitis,” says David Bradley, MD. “The results of this study will impact many lives.”
Dr. Bradley is a co-investigator in the consortium and diabetologist at the Ohio State Wexner Medical Center.
The Ohio State Wexner Medical Center was selected as one of 10 sites nationally to participate in the consortium. The U01 grant funding award was announced in October 2020 by the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Getting to the root of two key health burdens – and learning the connection
Both pancreatitis and diabetes are huge public health issues that impact major patient populations. The consortium researchers here at the Ohio State Wexner Medical Center and around the country aim to unlock the mystery surrounding their epidemiology.
Acute pancreatitis, a devastating, inflammatory disease of the pancreas, accounts for more than 300,000 hospitalizations in the United States each year, with costs exceeding $2 billion annually.
“Patients become very sick with abdominal pain, nausea and vomiting. Some die during their hospitalization. We do not have disease-specific treatments. Treatment of pancreatitis is still a black box for us as scientists,” Dr. Papachristou explains. “It’s extremely important for us to observe patients with acute pancreatitis for a long time and gain a better understanding of the mechanisms of the disease.”
Meanwhile, diabetes affects approximately 30 million people, nearly 10% of the population in the United States. Estimated health costs exceed $245 billion annually as many patients suffer serious complications.
“Diabetes is a costly disease for both patients and health care systems,” Dr. Bradley says. “We see comorbidities such as cardiovascular and microvascular complications, including vision loss, end-stage renal disease and neuropathy leading to amputation.”
To learn more about pancreatitis, diabetes and their connection, researchers will examine many questions, including:
- What is the unique pathology of acute pancreatitis?
- What is the unique pathology of diabetes?
- Is there an autoimmune process that happens in patients with acute pancreatitis that leads to a high insulin dependence in these same patients who go on to develop type 1 diabetes?
- What role do obesity and high triglycerides play in the development of diabetes and insulin resistance after pancreatitis?
“As researchers, we will be looking at all the factors. I am particularly interested in the connection with obesity and insulin resistance,” Dr. Bradley says. “What’s unknown is why obese patients have a higher rate of getting diabetes after acute pancreatitis than normal patients do. There’s some factor with obesity and insulin resistance that propagates the diabetes.”
In addition to gaining clinical information, researchers will develop an extensive biorepository.
“Upon enrollment, we’ll collect samples to include blood, body fluids, saliva and urine. We’ll use these samples in our scientific investigations to develop novel diagnostic and prognostic markers for diabetes after pancreatitis,” Dr. Papachristou explains.
Creating a study to help develop new treatment strategies
Researchers are now developing the study protocol. They plan to enroll patients with a well-documented episode of acute pancreatitis in the hospital setting. Enrollment of patients should start by the end of 2021.
“We strongly believe our consortium research will reveal important details about the development of diabetes after pancreatitis,” Dr. Papachristou says, “and will also allow us to better help people with diabetes, regardless of its etiology.”
“Our paramount goal is to find new treatments and management strategies to help patients and to prevent devastating complications,” Dr. Bradley says.
Georgios Papachristou, MD, PhD, is a professor and the vice chair of translational research in the Department of Medicine at The Ohio State University College of Medicine.
David Bradley, MD, is assistant professor in the Division of Diabetes, Endocrinology and Metabolism at The Ohio State University College of Medicine.
Their research team from The Ohio State University Wexner Medical Center also includes Darwin Conwell, MD, a gastroenterologist and director of the Division of Gastroenterology, Hepatology and Nutrition; Philip Hart, MD, a gastroenterologist who specializes in treating patients with pancreatic disorders; and Kathleen Dungan, MD, who specializes in diabetes and endocrinology.
