Institute Activities and Advances
The NICHD research portfolio includes sizable efforts on diabetes within the context of preventing chronic disease and of understanding the early origins of health and disease. Projects on diabetes, its risk factors, and its associated conditions and outcomes are spread across multiple organizational units and include several large international clinical studies. Some of this research is described below.
The Pediatric Growth and Nutrition Branch (PGNB) supports research on multiple aspects of type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). Research priorities include developing methods for detecting potential diabetics in childhood and for developing successful techniques of immunomodulation to prevent or mitigate the body's immune attack on the pancreatic beta cell. Branch research has also pioneered immunogenetic methods that stratify levels of risk for T1DM. In addition to projects led by individual investigators, the PGNB also supports several large, long-term clinical studies and networks in the United States and abroad. Visit the Other Activities and Advances section for details on these projects.
Recent research findings from PGNB-supported researchers include the following:
Researchers Test a New Approach to Reduce Immune Reactions in T1DM
The most common form of T1DM is caused by an autoimmune reaction (the body attacks its own healthy cells) that destroys the insulin-producing beta (ß) cells of the pancreas. Because most newly diagnosed patients with diabetes still produce significant amounts of insulin, preserving remaining ß-cell function is desirable to reduce short- and long-term complications of the disease. Because T cells of the immune system play a central role in the T1DM autoimmune reaction, researchers investigated whether a drug that works to partially block T-cell function could benefit patients with early-stage T1DM. In a randomized clinical trial involving 112 patients, 77 were assigned to receive treatment with abatacept, a drug used to treat rheumatoid arthritis (also an autoimmune disease) by blocking the activity of T cells. The remaining patients received placebo treatments. The results showed that abatacept had an early beneficial effect in slowing the reduction in ß-cell function. However, over a 24-month period, the drop in ß-cell function in the abatacept group paralleled that in the placebo group. Moreover, patients receiving abatacept had similar insulin doses at the end of the study, although the abatacept patients did produce slightly more insulin from their own bodies. Although these results indicated that abatacept is not appropriate for clinical use at this time, scientists are planning further studies to see if abatacept might be useful as part of a combination therapy in early-stage T1DM. Visit http://www.ncbi.nlm.nih.gov/pubmed/21719096 for more information.
Stem Cell Treatment Controls Diabetes in Mice
Diabetes is a global epidemic that affects almost 3% of the world’s population and approximately 8% of the U.S. population. Many people with diabetes eventually develop heart, nerve, and kidney damage that can require long-term, expensive care. Stem cells offer a promising approach for producing the cell types needed to replace damaged cells in diabetes-related disorders. Diabetes is a disease long thought to be amenable to stem-cell therapy because T1DM, at least, is caused by the loss of the single type of cell that produces insulin and, therefore, might be cured by providing patients with insulin-producing cells produced in the laboratory.
The uterus contains numerous stem cells needed to make the new cells that replenish the uterine lining every month. Researchers took this rich source of stem cells and added various nutrients and growth factors that caused the cells to "differentiate" into insulin-producing cells. These cells were injected into a diabetic mouse model where they secreted insulin and stabilized blood glucose levels. In contrast, mice injected with control cells had high blood glucose levels, weight loss, and eye problems—conditions that develop in human diabetics if their blood glucose is not properly controlled. This impressive example of stem cell-based therapy suggests that individuals could successfully be treated for diabetes or other disorders using cells from the lining of the uterus. Such research is an excellent example of the potential of stem-cell therapy to effectively address major, chronic disorders. Visit http://www.ncbi.nlm.nih.gov/pubmed/21878900 for more information.
Glutamic Acid Decarboxylase (GAD) Not An Effective Therapy for Patients with Early-Stage T1DM
As noted above, the most common form of T1DM is caused by an autoimmune reaction that destroys the insulin-producing ß cells of the pancreas. Scientists are investigating whether the progression of T1DM can be slowed by preserving the body’s own secretion of insulin, especially if effective interventions can be provided in the early stages of the disease. In previous studies conducted in mice, GAD showed promise as a possible treatment for T1DM. Scientists attempted to translate this success in animal studies to treatment of T1DM in humans. In a randomized clinical trial, researchers gave two or three doses of three different formulations of GAD injections to 145 patients in the early stages of type 1 diabetes. They assessed the patients’ progress after 1 year. Unfortunately, the GAD-based treatment was not shown to slow the loss of insulin secretion in diabetes patients. For more information, visit http://www.ncbi.nlm.nih.gov/pubmed/21878900.
Researchers in the Division of Epidemiology Statistics and Prevention Research (DESPR) are leading multiple studies of diabetes management in adolescents. One of these studies is exploring the effectiveness of a family-focused management plan on diabetes outcomes. Visit the Division’s Prevention Research Branch to learn more about these studies. In addition, the Division’s Epidemiology Branch is examining the Epidemiology and Etiology of Gestational Diabetes to address critical data gaps and to improve detection and management of the condition.
The Institute’s Pregnancy and Perinatology Branch (PPB)
seeks to promote healthy pregnancy, labor, delivery, and infancy by supporting research on multiple topics within each of these critical development periods. PPB research addresses high-risk pregnancies that result from a variety of conditions, including gestational diabetes, as well as studies of safe delivery and neonatal health outcomes. Like the PGNB, the PPB also supports large-scale research studies and networks in addition to projects led by individual investigators.
Other Activities and Advances
The PGNB supports multiple ongoing research trials and networks that focus on understanding diabetes. Some of these projects include:
- DirecNet, the world’s first research network devoted to studying children with type 1 diabetes mellitus (T1DM)
- The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, examining the health effects of gestational diabetes in women and their offspring; Hyperglycemia and Adverse Pregnancy Outcomes Study PubMed Articles
- Trial to Reduce the Incidence of TIDM in the Genetically at Risk (TRIGR), the first large trials designed to ascertain if a simple nutritional intervention during infancy can delay or prevent the onset of Type 1 diabetes in children at high genetic risk of this condition
- TrialNet, a network of 14 diabetes centers dedicated to utilizing a four-prong paradigm to test the ability of biological agents to prevent type 1 diabetes in children who at risk, or to slow the course of the disease in newly diagnosed children
The PPB supports efforts to understand gestational diabetes, its symptoms, and its outcomes through the Maternal-Fetal Medicine Units (MFMU) Network. The MFMU Network studies various types of high-risk pregnancies and pregnancy outcomes, including gestational diabetes, preterm labor and birth, and preeclampsia.
The NICHD is also a sponsor of the Consensus Development Conference on Diagnosing GDM, which aims to better understand the benefits and risks of various GDM screening and diagnostic approaches by assessing the available scientific evidence.