Genetics and Epidemiology

More than a quarter of a million people have received care at Joslin Clinic since its founding in 1898, many of them living with diabetes for 25, 50 and even 75 years. Educated about their disease and empowered to self-manage it, Joslin patients willingly provided blood samples and detailed information about their family history, environmental exposures, symptoms and complications—encouraging relatives to do the same. As a result, they helped Joslin create an invaluable database of biological and psychosocial data about patients with diabetes.
 
Over the years this database evolved from the handwritten notes of Elliott P. Joslin, M.D., founder of Joslin Diabetes Center—who tracked his patients’ health in his famous “black books”—to a sophisticated computerized database that facilitates the collection and analysis of genetic, biological, clinical, behavioral and outcomes data.
 
Researchers in the Section on Genetics and Epidemiology have taken advantage of this unique database to narrow the search for the molecular-genetic causes of diabetes and to better understand how complications develop and progress over time.

Researchers in the section are narrowing the search for the genes that cause type 2 diabetes. In doing so, they have provided evidence that, from a genetic perspective, there may be several forms of the disease. Investigators analyzed genetic material from individuals in 126 large families in which type 2 diabetes was inherited through a single defective gene (diseases inherited this way are known as autosomal dominant diseases). From this analysis, investigators developed different profiles of type 2 diabetes: an early-onset form that appears to develop from a defective gene on chromosome 8, and an adult-onset form linked to mutations on chromosome 20. Investigators in the section are now close to identifying the precise genes on both chromosomes.
 
Other investigations are uncovering the mechanisms of susceptibility to particular complications. One team has found evidence that the same genes that predispose people to obesity and type 2 diabetes may also increase their susceptibility to heart disease later in life. The team is now working to identify the responsible genes and determine how they interact with each other and with environmental factors to cause diabetes and coronary artery disease.

Genetic susceptibility to kidney disease—which develops in 35 percent of people with type 1 diabetes and 10 to 20 percent of those with type 2 diabetes—is the focus of several investigations. To speed the identification of the responsible genes in both types of diabetes, researchers in the section are simultaneously conducting genome-wide scans to analyze large numbers of genes and using more traditional mapping and cloning techniques to focus on individual genes.
 
Recently launched studies focus on kidney disease in type 1 and type 2 diabetes. For example, section investigators have made significant contributions to the national GoKinD (Genetics of Kidneys in Diabetes) Study sponsored by the Juvenile Diabetes Research Foundation. Because of Joslin’s renowned access to patient data, investigators have contributed half of the 1,800 participants in this unique collection of cases with kidney disease and controls without kidney disease. This collection will be used for whole genome association study to speed up the identification of susceptibility genes for kidney complications in type 1 diabetes.

Other studies are under way to improve the long-term health outcomes of people with diabetes. After researchers in the section discovered that loss of renal function occurs about 10 years earlier than expected in diabetic kidney disease, they launched a major investigation to detect the onset of the disease as early as possible—improving the odds of treating and even preventing it. Current investigations focus on early determinants of kidney disease, such as microalbuminuria (slight amounts of protein in the urine) and its progression to proteinuria (high amounts of protein in the urine). Already, investigators have created a protein profile of early kidney disease, which can be detected with a urine sample.

Section researchers also conduct clinical studies to assess new technologies and therapies and to design and implement educational programs and behavioral interventions for preventing acute and chronic complications and improving health outcomes. For example, these studies demonstrated that adding a case manager or “Care Ambassador” —who stays in touch with a child with diabetes and the family between medical visits to help coordinate diabetes care and provide additional education—can improve control of blood glucose levels and prevent acute complications that lead to hospitalizations and emergency room visits. Consistent with Joslin’s approach of rapidly promoting the bench-to-bedside translation of research findings, all families of pediatric patients new to Joslin receive the support of a Care Ambassador during their first year of living with diabetes.  Other studies include investigating the use of wireless communication technologies between the patient and the Joslin team—with the goal of increasing adherence to diabetes management tasks.