News

aNd

ResouRces

fRom the

NatioNal iNstitutes

of

health

Dateline
National Diabetes Information Clearinghouse

Diabetes

S p r i n g 2010

A Decade Later, Both Lifestyle Changes and Metformin Still Lower Type 2 Diabetes Risk
Study Reports on Persistence of Benefits Seen in the Diabetes Prevention Program
n 2002, the landmark randomized clinical trial, the Diabetes Prevention Program (DPP), reported outcomes 1 year early because of significant, positive study results. This study involved 3,234 adults at high risk for developing type 2 diabetes who were randomized to three treatment groups. The intensive lifestyle change group aimed at modest weight loss reduced the rate of developing type 2 diabetes over 3 years by 58 percent compared with the control group. Subsequently, DPP researchers provided support for lifestyle change to all participants in the DPP and followed participants to determine whether the benefit of intensive lifestyle intervention per sisted over time. Now, after following the partici pants for a total of 10 years after enrollment in the DPP, the Diabetes Prevention Program Outcomes Study (DPPOS) found that the early intensive lifestyle intervention reduced the rate of develop ing type 2 diabetes by 34 percent over 10 years. The results appeared online October 29, 2009, in The Lancet. In addition to the intensive lifestyle change group, DPP participants were also randomly assigned to receive treatment with the oral diabe tes drug metformin. This group had a 31 percent reduced rate of diabetes in the DPP. Contin ued medication was offered to this group in the DPPOS, and the researchers found an 18 percent reduced rate of developing diabetes after 10 years, compared with placebo.

Participants in the DPP who were randomly assigned to make lifestyle changes also had more favorable cardiovascular risk factors, includ ing lower blood pressure and triglyceride levels, despite taking fewer drugs to control their heart disease risk. Type 2 DiabeTes Risk,
continued on page 2

Inside This Issue

First Human Embryonic Stem Cell Lines Approved for Use under New NIH Guidelines ______ 3 Interagency Committee Explores Dissemination of Diabetes Prevention Programs _________________ 4 NIDDKs Tarbell Wins Prestigious PECASE _________ 8 NIDDK Director Rodgers Elected to Institute of Medicine ___________________________________ 10 NDEP News___________________________________ 11 Additional Resources___________________________ 12 Upcoming Meetings, Workshops, and Conferences ______________________________ 13

2 Diabetes Dateline

Type 2 DiabeTes Risk, from page 1

Millions of people
could delay diabetes for years and possibly prevent the disease altogether if they lost a modest amount of weight through diet and increased physical activity.
Griffin P. Rodgers, M.D., M.A.C.P.
Director, NIDDK

In 10 years, participants in the lifestyle change group delayed type 2 diabetes by about 4 years compared with placebo, and those in the metformin group delayed it by 2 years. The benefits of intensive lifestyle change were especially pronounced in the elderly. People age 60 and older lowered their rate of developing type 2 diabetes in the next 10 years by about half, said David M. Nathan, M.D., director of the Diabetes Center at Massachusetts General Hospital and DPP/ DPPOS chair.

Striking as the DPP findings were, the researchers did not know how long the benefit would endure, because DPP results were based on just 3 years of data. During a bridge period from January to July 2002, all participants were told the studys results and were offered the 16-session intensive lifestyle change program. The metformin group was also offered continued metformin therapy in the DPPOS. The majority of the DPP volunteers88 percentchose to participate in the DPPOS.

Intensive Lifestyle Changes

In the DPP trial, the intensive lifestyle change included lowering fat and calorie intake and increasing regular physical activity up to 150 minutes per week. Participants in this lifestyle intervention group received training in diet, exercise, and behavior modification. In the DPPs first year, this group lost 15 pounds on average, but those followed in the DPPOS regained all but about 5 pounds from their starting weight over 10 years. The metformin group lost about 5 pounds during the DPP study, and this loss in weight was maintained in those followed in the DPPOS. The placebo control group lost less than 2 pounds over the decade. About 5 to 6 percent of those in the lifestyle intervention group developed type 2 diabetes annually, an incidence rate that remained steady throughout the DPPOS. When the DPP ended in 2001, the metformin and placebo groups developed diabetes at the rate of 8 and 11 percent
Type 2 DiabeTes Risk,
continued on page 7

At-risk
In the United States, about 11 percent of adults24 million peoplehave diabetes, and up to 95 percent of these adults have type 2. An additional 57 million adults, based on a 2007 estimate, have glucose levels that are higher than normal but not yet in the diabetic range, a condition called pre-diabetes, which substantially raises the risk of a heart attack or stroke and of developing type 2 diabetes in the next 10 years. The spiraling epidemics of obesity and type 2 diabetes in the United States and worldwide show no signs of abating, said Griffin P. Rodgers, M.D., M.A.C.P., director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Millions of people could delay diabetes for years and possibly prevent the disease altogether if they lost a modest amount of weight through diet and increased physical activity.

Dateline
Diabetes Dateline, an email newsletter, is sent to subscribers by the National Diabetes Information Clearinghouse (NDIC). The newsletter features news about diabetes, special events, patient and professional meetings, and new publications available from the NDIC and other organizations. You can read or download a PDF version or subscribe to the newsletter at www.diabetes.niddk. nih.gov/about/newsletter.htm.

Diabetes

Executive Editor: Judith Fradkin, M.D. Dr. Fradkin is the director of the Division of Diabetes, Endocrinology, and Metabolic Diseases for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health in Bethesda, MD. Dr. Fradkin earned her M.D. from the University of California at San Francisco and completed an internship and residency at Harvards Beth Israel Hospital in Boston. Dr. Fradkin came to the NIDDK as a clinical associate in 1979 after an endocrinology fellowship at Yale University. She has overseen NIDDK-supported research in various roles, directing the Institutes research programs in diabetes, cystic fibrosis, endocrinology, and metabolic diseases. A practicing endocrinologist, Dr. Fradkin continues to treat patients at the National Naval Medical Center in Bethesda, where she worked as a staff endocrinologist in the early 1980s.

Research News

Spring 2010 3

First Human Embryonic Stem Cell Lines Approved for Use under New NIH Guidelines

I
am happy to say that we now have human embryonic stem cell lines eligible for use by our research community under our new stem cell policy. In accordance with the guidelines, these stem cell lines were derived from embryos that were donated under ethically sound informed consent processes.
Francis S. Collins, Ph.D., M.D.
NIH Director

n early December 2009, National Institutes of Health (NIH) Director Francis S. Collins, Ph.D., M.D., announced the approval of the first 13 human embryonic stem cell (hESC) lines for use in NIH-funded research under the NIH Guidelines for Human Stem Cell Research adopted in July 2009.
to the NIH by multiple institutions, and more than 200 lines were in the draft stage of the sub mission process. Information about these cell lines is available at the NIH Human Embryonic Stem Cell Registry website at http://grants.nih.gov/stem_cells/registry/ current.htm. Detailed information for approved cell lines can be accessed through a Details link in the far left column of the table of approved cell lines. Details for a selected cell line may include restrictions that apply to the specific line. These limitations are placed on the use of the hESCs by the provider of the line or by the NIH. For example, the provider may restrict the line to noncommercial use only. Limitations may also exist due to specific language in the informed consent. Accordingly, grantees must honor all restrictions when using the line. Submissions to the NIH receive either internal administrative review or consideration by the external Working Group for Human Embryonic Stem Cell Eligibility Review and the NIH Advi sory Committee to the Director (ACD). The Working Group provides findings to the ACD, which makes recommendations to the NIH director. The NIH director decides whether the hESCs may be used in NIH-funded research, and cell lines deemed eligible are then listed on the NIH Human Embryonic Stem Cell Registry.
embRyonic sTem cell,
continued on page 7

I am happy to say that we now have human embryonic stem cell lines eligible for use by our research community under our new stem cell policy, Dr. Collins said. In accordance with the guidelines, these stem cell lines were derived from embryos that were donated under ethically sound informed consent processes. More lines are under review now, and we anticipate continu ing to expand this list of responsibly derived lines eligible for NIH funding. Childrens Hospital Boston developed 11 of the first 13 approved lines and Rockefeller University in New York City developed two. Also, during December 2009, 27 lines developed by Harvard University were approved, bringing the total number of approved lines to 40. By the end of 2009, 90 additional cell lines had been submitted

Terese Winslow

4 Diabetes Dateline

Research News

Interagency Committee Explores Dissemination of Diabetes Prevention Programs

T
Weve learned
through the Diabetes Prevention Program and other trials that intensive lifestyle management reduces the incidence of diabetes. The challenge now is to translate what weve learned into cost-effective health programs.
Judith Fradkin, M.D.
Director, Division of Diabetes, Endocrinology, and Metabolic Diseases

he Diabetes Mellitus Interagency Coordinating Committee (DMICC) met November 11, 2009, to discuss the dissemination and community-wide implementation of diabetes prevention pro grams aimed at the estimated 57 million U.S. residents with pre-diabetes, who are at risk of developing type 2 diabetes.
management reduces the incidence of type 2 diabetes, said Judith Fradkin, M.D., director of the Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and chair of the DMICC. The chal lenge now is to integrate what weve learned into cost-effective health programs. For more infor mation about the Diabetes Prevention Program (DPP) and its continuation study, the Diabetes Prevention Program Outcomes Study (DPPOS), see A Decade Later, Both Lifestyle Changes and Metformin Still Lower Type 2 Diabetes Risk in this issue.

Pre-diabetes is characterized by blood glucose, also called blood sugar, that is higher than normal but not high enough to be considered diabetes. This condition substantially raises a persons risk of developing type 2 diabetes. Congress formed the DMICC in 1974 to coordi nate the federal response to the diabetes epidemic and avoid unnecessary duplication of activities aimed at studying, preventing, diagnosing, and treating diabetes. The DMICC meetings bring together top experts in the Federal Government and leaders from the community, academia, and the private sector to discuss current and future activities and to identify opportunities for collaboration. Weve learned through the Diabetes Prevention Program and other trials that intensive lifestyle

Translating DPP
As compelling as the DPP data are, study results are not necessarily reproducible in the real world, said Ronald Ackerman, M.D., M.P.H. He and David Marrero, Ph.D., both professors at the Indiana University School of Medicine, summa rized the Diabetes Education and Prevention with a Lifestyle Intervention Offered at the YMCA (DEPLOY) Study, which aimed to determine if DPP methods could be applied in communitybased settings by non-research personnel. Funded by the NIDDK, DEPLOY compared the weight loss benefits of a brief one-time counseling session about steps to prevent diabetes with a 16-session, DPP-like intensive lifestyle management course taught by YMCA employees who were trained by DPP investigators. After
DiabeTes pRevenTion,
continued on page 5

In type 1 diabetes, the bodys immune system destroys cells of the pancreas that make insulin, a hormone that clears glucose from the blood stream. In type 2 diabetes, which is linked to obesity, the body becomes resistant to insulin and insulin production is not sufficient to main tain normal glucose levels. Both types of diabe tes cause chronically high blood glucose, which is detrimental to the cardiovascular system, potentially leading to blindness, stroke, and heart attack. The prevalence of type 2 diabetes has more than tripled during the last 30 years. Based on 2007 data, about 24 million U.S. residentsabout 8 percent of the population have diabetes, and 90 to 95 percent of these people have type 2.

Research News
DiabeTes pRevenTion, from page 4

Spring 2010 5

6 months in the study, participants who attended the lifestyle management course decreased their body weight an average of 6 percent, compared with an average of 2 percent among those who received only brief counseling. Those who attended the lifestyle management course also saw reductions in total cholesterol. On average, participants in the intensive lifestyle management group had kept the weight off when measured again at 12 months from the studys start. Build ing on DEPLOYs initial success in Indiana, the program is expanding to five new states. Various other DMICC member organizations are actively translating DPP knowledge into community health programs. Several states receive funds from the Centers for Disease Control and Preventions (CDCs) Diabetes Prevention and Control Programs (DPCPs) to implement DPP-like pilot programs. The primary goal of the DPCPs, which are active in all 50 states and several U.S. territories, is to improve access to affordable high-quality
The Diabetes Mellitus Interagency Coordinating Committee (DMICC) comprises several key Government organizations. Members of the DMICC within the U.S. Depart ment of Health and Human Services (HHS) include the
Centers for Disease Control and Prevention National Institutes of Health Agency for Healthcare Research and Quality Centers for Medicare and Medicaid Services Office of Disease Prevention and Health Promotion Office of Minority Health Food and Drug Administration Health Resources and Services Administra tion Indian Health Service

diabetes care and services with the priority of reaching high-risk and disproportionately affected populations. The Indian Health Service (IHS), through the Special Diabetes Program for Indians Diabe tes Prevention Demonstration Project, is also implementing DPP-like programs. Funded by Congress, this program uses the DPP Lifestyle Change Program Manual of Operations adapted for American Indian and Alaska Native (AI/AN) communities and supports AI/AN communities in custom-tailoring programs to suit their unique needs. Involvement of tribal leaders has been essential to gaining community support, said Kelly Acton, M.D., M.P.H., director, Division of Diabetes Treatment and Prevention at the IHS. While focusing on lessons learned from the DPP, each tribe participated in the process of building their program creatively. Acton said programs and many participants are meeting DPP goals.

Cost-effectiveness
DPP-like pilot programs are demonstrating their ability to turn back the clock on diabetes, but for health care insurers such as Medicare and private insurance companies to begin paying for them, DPP-like programs must also be cost-effective. Analyses of the cost-effectiveness of the DPP interventions have found that its lifestyle inter vention resulted in greater health benefits at lower cost than metformin treatment. Some private insurers are already putting DPP results to good use. In early 2009, UnitedHealth Group, one of the United States largest health and well-being com panies, serving more than 70 million Americans and one in five Medicare beneficiaries, launched the Diabetes Health Plan pilot. Offered by employers as stand-alone plans or as an add-on feature to UnitedHealthcare benefit designs, the Diabetes Health Plan encourages participants to take an active role in their health. In exchange for adhering to the Plans evidence-based preven tive care guidelines, which include requirements for periodic health screenings and, if necessary,
DiabeTes pRevenTion,
continued on page 6

Non-HHS members include the

Department of Defense Department of Agriculture Veterans Health Administration

6 Diabetes Dateline

Research News
DiabeTes pRevenTion, from page 5

Ph.D., R.N., director of the CDCs Division of Diabetes Translation, include the following: Training. The CDC will develop a trained work force of lifestyle interventionists through collaboration with Emory Universitys Diabetes Training and Technical Assistance Center. Recognition. The CDC will develop a Diabetes Prevention Program Recognition System to assure quality and fidelity of the lifestyle program and provide a registry to track and report data, performance, and outcomes of the national diabetes prevention program. Model sites. The YMCA is currently working with model sites that can deliver the translated DPP lifestyle program with funding provided by the CDC as well as other model sites supported by UnitedHealth Group. The CDC will provide funding for an additional five to seven model sites in 2010. Health marketing. The CDC is working with health marketing consultants to develop effective tools and programs to inform popu lations at highest risk for diabetes about the dangers of pre-diabetes and raise awareness among both health care providers and highrisk populations to increase effective referral of people at high-risk to lifestyle intervention programs. Going forward, the DMICC seeks to broaden its membership to increase opportunities for collaboration and bring new perspectives and expertise to DMICC member activities. To learn more about the DMICC, read Diabetes Mellitus Interagency Coordinating Committee: Coordinating the Federal Investment in Diabetes Programs to Improve the Health of Americans, available at the DMICC website, www.diabetescommittee.gov. The National Diabetes Information Clearing house has information about diabetes, including a fact sheet about the DPP. For more information or to obtain copies, visit www.diabetes.niddk.nih.gov.

participation in weight-loss programs, partici pants receive free or discounted physician visits, medication, and supplies. Because only 15 percent of Americans with prediabetes know they have it, UnitedHealthcare analyzes claims data and biometric informationwithin the bounds of privacy regulationsto identify candidates who would benefit from the plan. With over 40 percent of UnitedHealth Groups commercial expenditures being spent on people living with diabetes, said Deneen Vojta, M.D., senior vice president of UnitedHealth Groups Center for Health Reform and Moderniza tion, UnitedHealth Group is very interested in collaborating with CDC and other DMICC members on ways to prevent diabetes with evidence-based interventions such as the DPP. But despite such potential savings, obstacles to broad implementation of DPP-like programs persist. Medicare does not have the authority to cover diet and exercise programs like DEPLOY that are intended to prevent diabetes in people with pre-diabetes. Doing so would require statutory changes, according to Marc Hartstein, deputy director of the Hospital and Ambulatory Policy Group at the Centers for Medicare and Med icaid Services, which runs Medicare. Hartstein noted that Congress recently established new benefits for pulmonary and intensive cardiac rehabilitation that include diet and exercise, but the statute requires these programs to be under the direct supervision of a physicianmeaning the physician does not have to be present when the services are provided but must be immedi ately available to assist the patient if there is a problem. Medicare does not pay for any DPPlike programs that would not be supervised by a physician.

Key Levers
The four key levers the CDC is actively putting in motion, as summarized by Ann Albright,

Research News
Type 2 DiabeTes Risk, from page 2

Spring 2010 7

a year, respectively. However, 10 years after ran domization of the DPP participants, the yearly diabetes incidence rates for those in the DPPOS metformin and original DPP control groups also fell to about 5 to 6 percent. Researchers are looking at a number of explana tions for the convergence of diabetes incidence rates for the three DPP groups. One possibility is that lifestyle change adopted by the metformin and placebo groups after the DPP ended lowered their rate of type 2 diabetes over time.

The DPP and the DPPOS have been funded by the NIDDK and other National Institutes of Health Institutes and Centers, with additional funding from the Indian Health Service, the Centers for Disease Control and Prevention, the American Diabetes Association, and the private sector. The NIDDK offers free easy-to-read booklets and fact sheets about diabetes, including a fact sheet about the DPP. For more information or to obtain copies, visit www.diabetes.niddk.nih.gov.

embRyonic sTem cell, from page 3

Research using hESCs is already yielding information about the complex events that occur during human development. Researchers hope that eventually cells differentiated from hESCs may be used to treat a myriad of diseases, condi tions, and disabilities and to test the safety of new drugs in the laboratory. On March 9, 2009, President Obama issued Executive Order 13505: Removing Barriers to Responsible Scientific Research Involving Human Stem Cells. The Executive Order states that the secretary of Health and Human Services, through the director of the NIH, may support and conduct responsible, scientifically worthy human stem cell research, including hESC research, to the extent permitted by law. The NIH Guidelines for Human Stem Cell Research were published on July 7, 2009, and are available at http://stemcells.nih.gov/ policy/2009guidelines.htm. The guidelines implement the Executive Order, as it pertains to extramural NIH-funded stem cell research; establish policy and procedures under which the NIH will fund such research; and help ensure that NIH-funded research in this area is ethically responsible, scientifically worthy, and conducted in accordance with applicable laws.

More than 30 NIH grants funded in the 2009 fiscal yeartotaling more than $20 million proposed to use hESCs, but these grants were restricted until approved lines became available on the NIH registry. Now, with NIH approval, the principal investigators of these grants may obtain registry-listed hESCs from the owners of the lines and proceed with their research. This group of grants includes research using hESCs for the therapeutic regeneration of diseased or damaged heart muscle cells, developing systems for the production of neural stem cells and differ ent types of neurons from hESCs in culture, and developing a cell culture system for the largescale production and self-renewal of hESCs. In addition, a number of Challenge Grant applications, which could be funded through the American Recovery and Reinvestment Act in the 2010 fiscal year, proposed to use hESCs. Researchers examining other topics that could benefit from the use of hESCs are encouraged to apply for funding to use these approved lines. For additional information about stem cells and NIH research, visit http://stemcells.nih.gov.