University of Maryland researchers receive NIH grant to study personalized medicine for genetic diabetes

The National Institutes of Health (NIH) has awarded a four-year, $3.7 million grant to researchers at the University of Maryland School of Medicine to develop a personalized medicine program to help doctors diagnose and treat monogenic diabetes – a form of diabetes caused by a mutation in a single gene. The study will evaluate methods to implement this program in various health care settings, with an objective to develop a model that could also be applied to caring for patients with genetic variations of other common diseases.

Inherited forms of diabetes, resulting from defects in HNF1A, GCK, HNF4A and a host of other genes, account for at least 1 percent – or over 250,000 – of diabetes cases nationwide. The actual number may be much higher because of the current challenges in correctly diagnosing those affected.

The two primary forms of monogenic diabetes are maturity-onset diabetes of the young (MODY), a form of non-insulin-requiring diabetes found in young, sometimes lean, people, and neonatal diabetes mellitis (NDM), diagnosed in infants under 6 months old. The majority of these individuals are misdiagnosed with type 1 or type 2 diabetes and may not be receiving appropriate treatment for their genetically-based disease, according to Toni I. Pollin, M.S., Ph.D., a University of Maryland genetics researcher and lead investigator on the study.

"Most health care professionals – including endocrinologists and geneticists – know little about genetic types of diabetes. When they are familiar with them, the high cost and limited availability of genetic testing, which is not always covered by insurance, are major impediments to diagnosing the condition correctly," says Dr. Pollin, associate professor of medicine and epidemiology & public health and member of the Program in Personalized and Genomic Medicine at the University of Maryland School of Medicine "A recent study indicated that monogenic diabetes is only diagnosed correctly in about 6 percent of cases in the United States."

"This research will enhance our ability to identify and properly diagnose individuals and families with specific inherited forms of diabetes, tailor treatment to their diagnosis and identify other family members at risk for developing diabetes," Dr. Pollin says. "Correct and early diagnosis and treatment should improve blood sugar control and decrease life-threatening complications."

The most common forms of diabetes, type 1 and type 2, are polygenic – involving multiple genes. Environmental and lifestyle factors, such as diet and activity level in the case of type 2 diabetes, often also come into play.

It is important for doctors to identify the specific type of diabetes in order to determine the most effective treatment. For example, patients with type 1 diabetes – an autoimmune disorder that destroys insulin-producing beta cells in the pancreas – require treatment with insulin for survival. Those with type 2 diabetes, who don't produce enough insulin or use it properly, typically receive metformin as a first-line treatment. For patients with certain forms of genetic diabetes, oral medications called sulfonylureas enable the patient to release his/her own insulin and are more effective and far less invasive than insulin injections in controlling blood sugar levels.

Co-principal investigator Alan R. Shuldiner, M.D., the John L. Whitehurst Endowed Professor of Medicine, expects the research to lay important groundwork to help integrate genetic testing into clinical practice. "We believe this is the first effort to implement systematic screening for genetic forms of diabetes in all patients seen in diabetes and primary care clinics with follow-up genomic testing for those at risk," says Dr. Shuldiner, associate dean for personalized medicine and director of the Program in Personalized and Genomic Medicine. "We are reaching out to implement genomic medicine beyond academic hubs into diverse health care settings and in the community at large."

"By introducing genomic screening into community-based diabetes clinics, we will be able to identify patients with genetic types of diabetes who might otherwise be misdiagnosed and provide them with highly personalized care," says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and Dean of the University of Maryland School of Medicine. "Equally important, we will also reach out to family members who will likely benefit from early detection and treatment and in some cases may be able to intervene early enough to prevent them from developing the disease."

Dr. Reece adds, "We are confident that this genomic medicine demonstration project will serve as a model for identifying genetic types of many other common diseases."

This project will expand a pilot personalized medicine program at the University of Maryland Center for Diabetes and Endocrinology at UMMC Midtown Campus to include several other sites: University of Maryland Family Medicine; the Baltimore Veterans Administration Medical Center; Bay West Endocrinology Associates (located at Greater Baltimore Medical Center); and Geisinger Medical System in Danville, Pa. Diabetes educators and genetic counselors will also visit local primary care practices to increase community awareness and help customize the screening and testing strategy.

Patients potentially at risk for genetic diabetes will be identified through a simple screening questionnaire, routine lab tests and a comprehensive review of their medical and family history. Once the diagnosis is made using a customized cost-effective genetic sequencing test, patients will be offered treatment customized to their diagnosis. Family members also will be eligible for genetic counseling and testing.

Researchers will assess the clinical impact of the program by evaluating changes in blood-glucose control in patients diagnosed with monogenic diabetes and assessing patients' own experience of the impact on their lives. They will also engage healthcare payers and collect data to inform clinical practice recommendations and guide decisions regarding insurance coverage.

Provided by University of Maryland