May 2011 eUpdate
Breakthrough Genetic Discovery in Insulin Resistance and Type 2 Diabetes
Twenty-six million Americans now have type 2 diabetes and nearly 79 million more have pre-diabetes. Genetic defects play a role in causing type 2 diabetes, but for almost all patients these defects have been unknown.
Now, researcher Ira Goldfine, MD, of the UCSF Diabetes Center, and his colleagues, Clive Pullinger, PhD, and John Kane, MD, PhD, of the UCSF Cardiovascular Research Institute, participated in an international collaboration that discovered a flaw in a gene that causes type 2 diabetes. Their collaborators were Antonio Brunetti, MD, PhD, of the University of Catanzaro, Italy, a former UCSF post-doc with Dr. Goldfine, and Vincent Durlach, MD, of the University of Reims, France, a former visiting professor with Dr. Kane.
In 10% of diabetic patients, but in less than 0.5% of controls, the team discovered defects in the gene for the nuclear protein HMGA1 which regulates the insulin receptor. When this gene isn’t functioning, there is markedly reduced insulin receptor expression causing insulin resistance, and a very high risk for type 2 diabetes. In isolated cells from these patients, replacement of the defective HMGA1 gene with a normal one restored the cells to normal.
Recently these data were published in the prestigious Journal of the American Medical Association (JAMA). This research should lead to predictive markers for insulin resistance and type 2 diabetes, and could lead to the identification of new drugs and treatments to prevent these conditions. [JAMA] [UCSF News Center] [San Francisco Chronicle]
Pancreatic Development Expert Finds Link Between Inflammation and Pancreatic Cancer
Besides running the Diabetes Center as our Director, Matthias Hebrok, PhD, is one of the world's foremost experts on pancreatic development. Dr. Hebrok and his lab colleagues are studying how the insulin-producing pancreatic islets are formed during organogenesis and how their function is regulated in the mature pancreas. Ultimately, they hope to learn how changes in gene expression may allow islets to regenerate in individuals living with diabetes.
As is often the case in science, while studying one disease you often make a breakthrough discovery in another. Last month, Dr. Hebrok and his colleagues made headlines by linking the biological process of inflammation with the formation of pancreatic cancer. Recently published in the journal Cancer Cell, this study explains how two molecular signals produced in the pancreas during inflammation were key to the onset and development of pancreatic cancer. A protein called Stat3 helps to initiate the early stages of this cancer, while another protein called MMP7 appears to affect metastasis. By blocking these proteins in animal models, the number of potentially cancerous lesions were reduced and cancer metastasis diminished.
Pancreatic cancer is one of the deadliest forms of the disease, in large part because it is difficult to detect early. Dr. Hebrok's team also suspects that MMP7 may be a useful marker for staging the disease. [UCSF News Office]
New Type 1 Clinical Research Studies Launched
A number of new clinical studies using investigational drugs for type 1 diabetes have been launched by the UCSF Pediatric Diabetes Clinical Research Program under the leadership of Steve Gitelman, MD. Investigational drugs are those that are not approved for use in diabetes by the U.S. Food and Drug Administration (FDA).
One novel study involves the immune system’s T cells. There are different types of T cells, including T cells that unnaturally attack and destroy the insulin-producing beta cells in type 1 diabetes, and T cells called regulatory T cells that help call off the attack. Dr. Gitelman’s goal is to bolster the performance of the regulatory T cells, or “Tregs,” and therefore end the misdirected immune system attack on insulin-producing beta cells. This Treg study is open to adults ages 18 to 35 who are within two years of diagnosis.
A second study involving T cells aims to eliminate the T cells that attack insulin-producing beta cells, while increasing the number of Tregs, thereby resetting the balance of T cells. Dr. Gitelman and his colleagues are combining an antibody treatment anti-thymoctye globulin (brand name Thymoglobulin), which is FDA approved to prevent organ rejection in kidney transplant patients, with granulocyte colony-stimulating (brand name Neulasta), which is FDA approved to boost white blood cell counts in patients receiving chemotherapy. In mouse models of diabetes, this combination appears to be even more effective than Thymoglobulin alone. They hope the same will be true in people. This Thymoglobulin/Neulasta study is open to individuals ages 16 to 45 who are within two years of diagnosis.
For relatives of people with type 1 diabetes who are not yet diagnosed, but who are at risk for type 1 diabetes, there are now promising clinical trials available. Family members should take a simple blood test which screens for the presence of diabetes-related autoantibodies that may appear years before type 1 diabetes develops. This antibody screening is part of a national research program called Type 1 Diabetes TrialNet and is being conducted to help understand more about the development of this disease and to look at ways to delay or prevent it. For those found to be at intermediate risk of developing diabetes (25 percent chance of getting diabetes in the next five years), there is a trial introducing oral insulin . For those found to be at high risk (greater than 50 percent chance of diabetes in the next five years), there is a trial utilizing the anti-CD3 monoclonal antibody. [UCSF News Office]
For more information on these studies or other clinical research being conducted at UCSF, contact Kathleen Fraser: 415-353-9084.
UCSF Diabetes Center Resources
To make your lives with diabetes easier, we have created a number of resources for you and your family. Print a copy of this list and keep it for future reference!
Diabetes Education Online, www.deo.ucsf.edu - Our comprehensive, online diabetes self-management education program that mirrors our Diabetes Teaching Center curriculum taught to thousands of patients over 30 years.
Diabetes Teaching Center Classes and Workshops, www.deo.ucsf.edu/workshops - Educational classes for adults with diabetes and their loved ones are held each month. For a full listing, consult our website or call 415-353-2266.
Diabetes Teaching Center Education for Employers and Community Groups - As a public service to the community, we offer free, one hour diabetes group instruction focused on pre-diabetes, diabetes prevention and management. These sessions are led by Peggy Huang, RN, CDE, co-founder of the Teaching Center. Call 415-353-2266 to arrange a presentation.
Pediatric Diabetes Educational Handouts, www.diabetes.ucsf.edu/handouts - Free educational resources have been created by our pediatric endocrinologists, nurses, nurse educators and dietitians to help you and your family manage diabetes more effectively.
DIABETES CENTER NEWS
ATTENTION MEDICAL PROFESSIONALS: Upcoming Education Program Involving New Type 1 Research Study
You are invited to attend a presentation, "Rebalancing the Immune System in Type 1 Diabetes Without Drug Therapy: The Promise of Regulatory T Cells" on Wednesday, May 18th, 6 p.m. at the UCSF Medical Center, 513 Parnassus Ave, Room N-225, San Francisco. [Event Details]
Jeffrey Bluestone, PhD, UCSF Executive Vice Chancellor and Provost, and Stephen Gitelman, MD, Director of the UCSF Pediatric Diabetes Program, will be presenting their groundbreaking research involving regulatory T cells (Tregs) -- and will discuss their launch of the first Tregs human clinical trial, open to adults ages 18 to 35 who are within two years of diagnosis.
You'll also hear other clinical trial updates on preserving beta cells, and the benefits realized by all trial participants.
A complimentary dinner will be provided. RSVP to Kathleen Fraser: 415-353-9084.
UCSF: A Leader in Innovation and Discovery
Former Center Director, Jeffrey Bluestone, PhD, continues to stay busy in his current position as UCSF Executive Vice Chancellor and Provost. He is helping to tackle the university’s financial crisis while continuing to maintain his lab in the Diabetes Center.
Recently, Dr. Bluestone and his fellow leaders announced that UCSF serves as an economic engine for the Bay Area, driving $6.2 billion in industry output and creating more than 39,100 jobs regionwide. [Economic Impact Report]
IN THE NEWS
Pace Picks Up for Clinical Trials to Evaluate Stem Cell Therapies - UCSF News Office - Mentions Jeffrey Bluestone, PhD, Matthias Hebrok, PhD, and Michael German, MD
Stem Cell Advocates Cite Personal Connection in Advancing Field - UCSF News Office - Features Diabetes Center Leadership Council Member, Robert Klein
Is Sugar Toxic? - The New York Times Magazine - Features UCSF Pediatric Endocrinologist Robert Lustig, MD
The Diabetes Center at UCSF is among the premier institutions for clinical trials of emerging therapies in diabetes. Numerous clinical trials in type 1 and 2 diabetes are now underway.
Interested in participating? A sample of our trials currently enrolling patients:
Type 1 Diabetes: Treatment with Polyclonal Tregs Seeking volunteers newly diagnosed within 2 years, 18 to 35 years of age
Type 1 Diabetes: TrialNet Natural History Study [Antibody Screening] Seeking relatives of people with type 1 diabetes, 1 to 45 years of age
Type 1 Diabetes: An Oral Insulin Preventative Study Seeking relatives of people with type 1 diabetes, 3 to 45 years of age
Type 1 Diabetes: Treatment with Thymoglobulin + Neulasta Seeking volunteers newly diagnosed at least four months but not more than 2 years, 16 to 44 years of age
Type 1 Diabetes: Islet Transplantation Seeking volunteers 18 - 65 years of age
Type 1 Diabetes: Efficacy of Islet After Kidney Transplantation Seeking volunteers 18-65 years of age
Type 1 Diabetes: Peritransplant Deoxyspergualin in Islet Transplantation Seeking volunteers 18-65 years of age
Type 2 Diabetes: Diabetes Support Project (DSP) Seeking adults with type 2 diabetes, HbA1c of 7.5% or higher, can read and speak English, have a partner or spouse
Type 2 Diabetes: The Effects of Co-administration of Colesevelam HCI and Sitagliptin on Glucose Metabolism Seeking volunteers 18 - 80 years of age and not currently on any antidiabetic medications
Type 2 Diabetes: Paleolithic-Type Diets and Metabolic Control Seeking volunteers 18 years of age and older with type 2 diabetes
Bone Study for Postmenopausal Women With or Without Type 2 Diabetes Seeking volunteers between 50 and 75 years old
APS1 and Autoimmune Disease Seeking volunteers at least 6 weeks old who have either autoimmune disease, have evidence of autoimmunity, have a family member with autoimmunity, or do not have autoimmune disease (healthy volunteer control)
Diabetes Center at UCSF
If you wish to receive more information about the UCSF Diabetes Center’s clinical and research programs, or would like to financially support one or more of these efforts, please contact Suzanne Ritchie at 415-476-6334. You may also visit our donation website and designate your gift to “The Diabetes Center."