April 3, 2000

TO: Anthony S. Fauci, M.D.
Co-Chair, Trans-NIH Working Group on Health Disparities

Yvonne T. Maddox, Ph.D.
Co-Chair, Trans-NIH Working Group on Health Disparities

FROM: Director, NIDDK

SUBJECT: NIDDK's Draft Strategic Plan on Minority Health Disparities

Attached please find the current working draft of the Strategic Plan on Minority Health Disparities developed by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). We have prepared this draft in the context of the format and fiscal planning guidance provided by the Trans-NIH Working Group on Health Disparities.

In generating this draft Plan, we have sought proposed initiatives from NIDDK scientific staff and have shared those concepts with our National Advisory Council and with a representative group of individuals from organizations having particular expertise and interests with respect to minority health issues.

I particularly wish to acknowledge the efforts and contributions of Dr. Lawrence Agodoa to this planning process. Dr. Agodoa provided scientific leadership and direction across the NIDDK in his capacity as Managing Editor for the NIDDK draft Plan. Dr. Agodoa is the End Stage Renal Disease Program Director of the NIDDK Division of Kidney, Urologic and Hematologic Diseases, as well as the Minority Health Program Director for that Division.

We recognize the need to gain broader public input to our planning process as we continue to revise our draft Plan. Therefore, we expect to post the attached draft on the NIDDK web site as soon as possible and to actively seek additional comments and suggestions.

Allen M. Spiegel, M.D.

NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
STRATEGIC PLAN ON MINORITY HEALTH DISPARITIES

Introduction and Background

This document is a working draft of a Health Disparities Strategic Plan developed by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) for major disease programs within its research mission.

Part of NIH-Wide Process: The NIDDK Plan is just one part of a much larger NIH-wide planning process that is being undertaken under the auspices of a Trans-NIH Working Group on Health Disparities. The NIH-wide Working Group will use the NIDDK Plan, together with those developed by the other NIH institutes and centers, to help formulate an overall "NIH Strategic Plan to Reduce Racial and Ethnic Health Disparities." It is expected that the NIH-wide Plan will be completed by the end of May 2000. This process will be an important source of input to the NIH budget formulation process for FY 2002.

General NIH Guidance and Format for Developing Plan: The NIDDK has developed its draft Plan in accordance with Guidance provided by the Trans-NIH Working Group on Minority Health Disparities.

• Scientific Scope: Based on the format provided, the NIDDK has focused on identifying goals and proposed initiatives in areas of research focus within its mission. The NIDDK shares many of these research focus areas with other institutes, which are likewise developing initiatives. Thus, for trans-NIH research areas such as hepatitis, diabetes, and AIDS, it is important to recognize that the NIDDK Plan will contribute to the NIH-wide Plan, but it is not intended to be a comprehensive, stand-alone document.



• Trans-NIH Collaborations: It is expected that initiatives in cross-cutting scientific areas would provide opportunities for collaborative efforts involving multiple Institutes. In some cases, the NIDDK has referred to ongoing or potential collaborations with other NIH components, but only by way of illustrative example, not in an exhaustive manner.



• Highlights of Ongoing Programs: In accordance with the guidance, the draft NIDDK Plan contains only the briefest highlights of its current efforts with respect to health disparities. These highlights do not fully convey the vigorous, ongoing programs of research on type 2 diabetes, hepatitis C, obesity, end stage renal disease, and other diseases that place a disproportionately heavy burden on minority groups. These are all high-priority research areas, which are central to the NIDDK mission.



• Fiscal Context of Ongoing Programs: Using the general definition of health disparities research provided by the Trans-NIH Working Group, the NIDDK expended nearly $90 million in the last fiscal year (Fiscal Year 1999) on programs that are directly targeted to minority populations. Not included in this funding level is a wide range of clinical research that, although not targeted specifically to minorities, is highly relevant to understanding the underlying aspects of disease processes, such as insulin resistance in type 2 diabetes, that affect both minority and non-minority populations. Likewise excluded from the $90 million funding level are extensive NIDDK basic research efforts on genetic, metabolic and other processes that underlie many of the diseases that disproportionately affect minorities. Although this fundamental research cannot be attributed to any specific disease question, it provides a critical knowledge base upon which future clinical progress will be built. Such basic research is applicable to a wide range of diseases and will thus help pave the way to the development of important new treatment and prevention strategies.



• Three NIH Fiscal Planning Levels for FY 2002: The guidance calls for the use of three fiscal planning levels in the development of proposed initiatives targeting health disparities in FY 2002. These planning levels are amounts equal to increases of 5%, 10% and 15% over the total proposed President's Budget request for each Institute for FY 2001. Within the fiscal planning levels, the NIDDK could implement some proposed initiatives at the 5% level, but implementation could be accelerated and broader in scope at the 10% or 15% level. For other proposed initiatives, implementation would not be possible at all unless a 10% or 15% funding increase were provided. The funding estimates for each initiative represent the total amount of funds proposed to be expended for implementing that initiative in FY 2002 at the applicable fiscal planning levels.

Public Input: Within the time frame specified by the Trans-NIH Working Group, the NIDDK has sought public input from a representative group of individuals from the research and lay communities who have particular knowledge of minority health issues. The NIDDK is appreciative of the comments it has received thus far, but recognizes that this draft Plan needs to be shared more broadly. Thus, the NIDDK will continue to seek additional public input in the months ahead by posting it on the Institute's web site at:

www.niddk.nih.gov

The draft NIDDK Plan, and the more comprehensive NIH-wide plan that will be developed shortly, are both works in progress, which will be revised as this planning process continues. The NIDDK encourages a broad public input to help ensure that the Institute is including key areas of public interest and concern, and that it is framing and presenting its Plan in a way that will be most useful and well-received.

1. STATEMENT OF MISSION

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports research on many chronic and costly diseases affecting the public health. Several diseases studied by the NIDDK are among the leading causes of disability and death in the Nation; all affect seriously the quality of life of those suffering from them.


The strategic vision that guides the NIDDK is improved health and quality of life for all Americans, through basic, clinical, and behavioral research to address the diseases and disorders within the Institute's statutory research mandate. Many diseases and disorders that disproportionately impact the health of minority populations in the United States receive high priority in NIDDK research areas. These include diabetes, obesity, nutrition-related disorders, hepatitis C, gallbladder disease, H. pylori  infection, sickle cell disease, kidney diseases, and complications from infection with the human immunodeficiency virus. The NIDDK gives increased priority to support research and to encourage specific efforts in these areas of health disparity in order to advance the foundation of knowledge in the biomedical sciences.


A focus on basic research has traditionally guided the Institute's programs. It is grounded in the belief that a fundamental understanding of biologic systems will ultimately explain the abnormalities underlying each disease and thus is imperative for the development of the most effective strategies for prevention and therapy. In addition to basic research, however, the Institute has a strong commitment to apply advances in the understanding of disease processes to appropriate clinical studies and ultimately to efforts to transmit knowledge and effective technologies to practicing physicians, as well as those affected, and their families.


The NIDDK's Division of Diabetes, Endocrinology, and Metabolic Diseases is responsible for extramural research and research training related to diabetes mellitus; endocrinology, including osteoporosis; and metabolic diseases, including cystic fibrosis, an area for which the Institute has lead responsibility within the NIH. The Division of Digestive Diseases and Nutrition has responsibility for managing research programs related to liver and biliary diseases, pancreatic diseases, gastrointestinal diseases, including neuro-endocrinology, motility, immunology, and digestion in the gastrointestinal tract, nutrient metabolism, obesity, eating disorders, and energy regulation. The Division of Kidney, Urologic, and Hematologic Diseases supports research on the physiology, pathophysiology, and diseases of the kidney, genitourinary tract, and the blood-forming organs to improve or develop preventive, diagnostic, and treatment methods. The Division of Intramural Research conducts research and training within the Institute's laboratories and clinical facilities in Bethesda, Maryland, and Phoenix, Arizona.


Shared interests in the biochemical and genetic processes underlying disease provide a linkage mechanism for the programs and divisions of the Institute, and serve to foster integration of fundamental knowledge with clinical research. The same is true for the close communication between NIDDK and other NIH programs' vital areas of investigation.


2. Area of Focus #1 -- Diabetes Mellitus -- Type 2

• Diabetes mellitus is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both.
• Type 1 diabetes accounts for about five to ten percent of all cases of diabetes in the US and type 2 diabetes for 90 to 95 percent. Gestational diabetes, a transient elevation of blood glucose during pregnancy, occurs in about 3 to 5 percent of pregnancies. About one to two percent of the diabetes syndrome is comprised of other types of diabetes, which have a variety of causes, such as genetic defects in insulin action, diseases of the pancreas, or drug-induced diabetes.
• Diabetes affects about 16 million people in the US, with one-third of these being unaware that they have the disease. Minority populations do not appear to have a higher prevalence of type 1 diabetes. However, they are more frequently affected by type 2 diabetes. These groups comprise 25 percent of all adult patients with diabetes in the US and represent the majority of children and adolescents with type 2 diabetes.
• African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans and Pacific Islanders are at particularly high risk for development of type 2 diabetes. On average, African-American adults are 1.7 times as likely and Mexican-Americans and Puerto Ricans are twice as likely to have the disease as non-Hispanic whites of similar age. Cuban-Americans do not seem to have an elevated risk of diabetes. Diabetes prevalence rates among American Indians are two to five times those of Whites. Some Asian American and Pacific Islander groups, such as Japanese Americans, Samoans, and Native Hawaiians, also have elevated rates of diabetes.
• All patients with diabetes are at high risk for microvascular complications affecting the eyes, nerves, and kidneys; for lower extremity amputations; and for coronary heart disease. Diabetes patients from racial and ethnic minorities are more likely to develop the microvascular complications of diabetes and to have lower extremity amputations, compared with non-Hispanic white patients with diabetes.
• The rates of coronary heart disease in minority populations may not be greater than in non-Hispanic whites with diabetes; however, the frequency of cardiovascular complications in all patients with diabetes is two to five times that of people who do not have diabetes.
• Much of the racial and ethnic disparity in diabetes microvascular complications may be due to higher levels of risk factors for these conditions in minority patients with diabetes, such as hyperglycemia and hypertension. However, there also seems to be a genetic component that influences the development of certain of the microvascular complications of diabetes. In addition, there may be other physiologic, metabolic, behavioral, and health care differences that account for part of the disparity in the frequency of diabetes complications.
• Diabetes in pregnancy is associated with an increased risk of congenital malformations and complications during delivery and in the perinatal period.
• Due to the intrauterine environment, offspring of diabetic pregnancies have greatly increased risks of obesity and type 2 diabetes during childhood and adolescence. Women from minority groups, especially American Indian women, are much more likely to have type 2 diabetes during their child-bearing years.
• In American Indian populations, maternal diabetes during pregnancy increases the risk of type 2 diabetes in childhood ten fold and is the most important risk factor for development of type 2 diabetes in childhood.
• The mechanisms of how maternal diabetes increase the risk of diabetes and obesity in children, and knowledge of how to modify these risks is largely unknown.
• Type 2 diabetes, once considered a disease of adults only, has been increasing in children and adolescents. Childhood diabetes clinics have reported that as many as one-third of their new-onset diabetes patients have type 2 diabetes. More than three-quarters of these children are minorities.
• Rates of type 2 diabetes in adolescent Pima Indians have doubled in the past 30 years. Thirty years ago, type 2 diabetes was not found in Pima children in age group five to nine. Now more than one percent of children this age have type 2 diabetes.
• Type 2 diabetes in childhood and adolescence leads to the development of serious kidney, eye, and heart disease in young adulthood in many of these children. Currently, there are no approved medications for treatment of childhood obesity or type 2 diabetes in childhood. Low calorie diets, behavior modification, and exercise are the mainstays of treatment, but have had limited success in the past.

Goal 1 -- To prevent or delay the development of diabetes in Minority Populations (African Americans, American Indians/Alaskan Natives, Hispanic Americans, Asian Americans, and Pacific Islanders)
Current Activities:
NIDDK funds an extensive portfolio of basic, clinical, epidemiologic, and behavioral research on the etiology of diabetes. Advances in understanding the underlying causes of diabetes through such research are a critical first step in determining the factors that account for the higher rates of diabetes observed in racial/ethnic minority populations. The Institute has recently published a program announcement soliciting research to expand our understanding of the metabolic, genetic, epidemiologic, socio-cultural, and behavioral mechanisms that contribute to the racial and ethnic differences in the etiology of type 2 diabetes in the US. Determining the underlying genetic factors in diabetes is also an important step in understanding the higher rates of diabetes in minority populations. To enhance this area, NIDDK has established a consortium of investigators studying different populations who are cooperating to find the genes that cause diabetes. Type 2 diabetes in children is an emerging health problem that appears to disproportionately affect minority populations. NIDDK has recently published a Request for Application (RFA) soliciting applications for a research program on type 2 diabetes in children.

The Institute is conducting the Diabetes Prevention Program (DPP) clinical trial, which is a large multicenter study of diabetes prevention in 27 centers across the US. Recruitment is complete, and 45 percent of the study participants are from racial/ethnic minority populations. This study is collecting important data that will advance our understanding of the factors that lead to the development and prevention of diabetes. Similarly, NIDDK is conducting a prevention trial for type 1 diabetes (DPT-1). Although type 1 diabetes is not increased in racial/ethnic minority populations, it can be a devastating disease for patients. DPT-1 has been successful in screening minority populations and entering minority patients into the trial. This study may yield essential data on the factors leading to type 1 diabetes that may have important implications for all people at risk for the disease, including racial/ethnic minorities. The NIDDK Diabetes Research and Training Centers (DRTCs) are conducting research in behavioral science as well as demonstration and education projects that are advancing our knowledge of the behavioral and psychosocial factors underlying diabetes onset and control in racial/ethnic minorities.

Because of the extremely high incidence and prevalence of type 2 diabetes mellitus and obesity in the Pima Indians of Arizona, the NIDDK has conducted for many years an intramural program of research on diabetes and obesity in this American Indian population. In recent years, these clinical and epidemiological studies have been extended to include genetic studies. Also, there are current plans for increased emphasis on intervention trials, and studies of prevention and treatment of diabetes and its complications in this population. This Pima Indian population is currently participating in the DPP clinical trial, and is expected to participate in the ongoing SHOW trial (see the section on the SHOW trial below). Also listed below under diabetes initiatives are additional specific initiatives to be undertaken in the Pima Indians through the NIDDK Phoenix Epidemiology and Clinical Research Branch, Phoenix, Arizona.

Studies in the Pima Indian community are examining the underlying mechanisms that lead from maternal diabetes during pregnancy to obesity and type 2 diabetes in their offspring. These include examination of insulin resistance, insulin secretion, energy expenditure, physical activity, and eating behaviors in offspring of mothers who had diabetes during pregnancy.

Potential New Initiative 1:
Determine the underlying physiologic, metabolic, genetic, psychosocial, and behavioral factors that cause the racial and ethnic differences in the incidence of diabetes.
Expected Outcome:
This initiative will promote and further expand the program on the etiology of diabetes in minority populations and its program on type 2 diabetes in children. This will include expanding the program by extending the Program Announcements that were recently issued for two additional years to solicit further research grant applications, giving special consideration to grant applications in this area that would otherwise not receive funding, fully funding grants in this program area, and stimulating investigators to focus their research in these areas. Attracting new researchers to this area, including those from minority populations, is critical to the future success of this plan. Collaboration with the NIH Office of Research on Minority Health will be sought to enhance these research areas. The initiative will also help expand the research program on the genetics of diabetes in minority populations. A taskforce meeting is planned that will lead to a solicitation for new research applications. Genetic studies of susceptibility to type 2 diabetes and obesity in the Pima Indians will be continued and replicated in other populations.
Action Plan:
Mechanism of funding will include Research Project Grants (R01s) and Cooperative Agreements (U01s)
Funding Level:
The total estimated expenditure for expansion of programs to determine the etiology of type 2 diabetes in FY 2002 is $4.0 million each at 5%, 10%, or 15%. The total estimated funding of the taskforce on the genetics of diabetes in minority populations will be $25,000 at 5%, 10%, and 15%. The total estimated expenditure to expand genetic studies of type 1 diabetes in minority populations is $1.0 million at 5%, and $2.0 million each at 10% and 15%. The total funding of the type 2 diabetes linkage analysis consortium will be $500,000 at 5%, and $1.0 million each at 10% and 15%.

Potential New Initiative 2:
Develop and test interventions to reduce the frequency and adverse impact of risk factors for development of diabetes in minority populations.
Expected Outcome:
The Diabetes Mellitus Interagency Coordinating Committee (DMICC) will meet on May 11, 2000, with a committee of American Indian tribal leaders representing American Indian peoples to exchange ideas about the problem of type 2 diabetes in American Indian children. This meeting will foster cooperation between tribal Nations and investigators in the diabetes field, which will be important in devising effective, culturally sensitive approaches to prevention and management of diabetes. NIDDK plans to build on the program of research on the etiology of type 2 diabetes in children and to enhance collaboration with American Indian leaders on an initiative to develop interventions for the treatment and prevention of type 2 diabetes.

In November 1999, the NIDDK hosted a conference focusing on behavioral research in diabetes with a focus on the effective application of behavioral science to reduce the burdens associated with diabetes. Working groups comprised of experts in the fields of lifestyle modification, psychosocial therapies, health care delivery, communication of diabetes risk, and behavior, and the roles of psychology and education in prevention made recommendations for research priorities. Research opportunities identified at the workshop will be promoted through a solicitation in collaboration with the NIH Office of Behavioral and Social Sciences Research (OBSSR). This solicitation will foster research related to prevention and treatment of diabetes. Special consideration will be given to research projects that focus on health disparities, such as approaches to developing and promoting efforts to enhance exercise, healthy diet and early detection of diabetes in high-risk populations.

NIDDK will begin to develop an action plan for translating the results of the DPP, in the event that the trial demonstrates that lifestyle modification and/or drug treatment prevents or delays the onset of type 2 diabetes. To carry this forward, discussions have begun with the Centers for Disease Control and Prevention (CDC) and the National Diabetes Education Program (NDEP). Educational programs need to be developed, tested, and ready for implementation in the event that the study results are positive. These programs will be tailored to the special requirements of minority populations. Additional clinical trials of new pharmacological agents or different approaches to weight loss and physical activity in prevention of type 2 diabetes may be initiated in the Pima Indian population.
Action Plan:
Multiple mechanisms of funding will be utilized to implement this initiative.
Funding Level:
The total estimated expenditure for the program to prevent diabetes in American Indian children is $1.0 million at 5%, $2.0 million at 10%, and $3.0 million at 15%. The total estimated funding level for the program on behavioral and social science research related to diabetes prevention and treatment is $1.0 million at 5%, $2.0 million at 10%, and $3.0 million at 15%.

Potential New Initiative 3:
There is a need to understand the relationship of metabolic abnormalities in the mother and how maternal diabetes leads to adverse outcomes for her children and to determine if current management practices of diabetic pregnancy are effective in preventing adverse long-term consequences. A study should be conducted to examine the current delivery of care in diabetic pregnancies in the Pima Indian community, and how pre-natal factors (such as levels of glucose control in the mother, maternal insulin treatment and availability of dietetic, medical and nursing services) relate to pregnancy outcomes should be conducted.
Expected Outcome:
These initiatives will determine to what extent currently accepted practice is being delivered to women at risk, will identify those women who are having adverse outcomes, set new standards for clinical care based on health outcomes, and identify areas in which management might be improved. This information will in turn help reduce the burden of diabetes in childhood in American Indians and other minorities who have a high frequency of type 2 diabetes during the child bearing years.
Action Plan:
Funding will be sought to support a multi-center program examining the care of diabetic pregnancy in Pima Indian women through the NIDDK Phoenix Epidemiology and Clinical Research Branch in Phoenix, Arizona.
Funding Level:
The total estimated expenditure on research to study the relationship between maternal metabolic abnormalities and adverse outcomes in offspring, and evaluate current level of delivery of care in Pima Indians is $200,000 each at 5%, 10%, and 15%.

Goal 2 -- To prevent or delay the development of the complications of diabetes in minority populations
Current Activities:
NIDDK has an extensive research portfolio of basic, clinical, epidemiologic, and behavioral research related to the etiology of the complications of diabetes. Research is also supported on identifying the underlying genetic factors that place some individuals at higher risk for complications. Understanding the etiology of complications is a critical step in determining why minority populations are at higher risk for complications, and is the first step in developing tailored interventions for these specific populations. Program announcements and RFAs were recently published by NIDDK soliciting research on the factors leading to higher rates of complications in minority populations, the pathogenesis and treatment of complications of type 2 diabetes in children, the prevention and treatment of amputations in diabetic individuals with foot ulcers, the role of endothelial cell dysfunction in diabetic complications, and the role of growth factors in the development of diabetes complications. The Institute also supports an extensive research program in the pathogenesis of diabetic nephropathy (see section IV, End Stage Renal Disease). NIDDK, in collaboration with other NIH Institutes, has also recently published program announcements and RFAs soliciting research applications on the neurobiology of diabetic complications, cellular and molecular mechanisms of diabetic cardiomyopathy, enhancing adherence to diabetes self-management behaviors, and developing and testing interventions to improve adherence to pharmacological treatment regimens.

The Institute is supporting clinical trials in the prevention of diabetes complications. The Diabetes Prevention Program (DPP), discussed above, is investigating whether the onset of type 2 diabetes can be prevented or delayed. Delaying diabetes onset will reduce the lifetime exposure to high blood glucose levels due to diabetes and has the potential to reduce diabetes complications. This study, if positive, will have important implications for the prevention of diabetes complications in minority populations who comprise 45% of the study participants. The Study of Health Outcomes of Weight-Loss (SHOW) is a multicenter, randomized clinical trial to study whether interventions designed to produce sustained weight loss in obese individuals with type 2 diabetes mellitus improve health and prevent complications. Through the Veterans Health Administration, NIDDK is supporting a clinical trial of limb salvage in patients with diabetes who have advanced neuropathy. The Institute is cosponsoring, with the National Heart Lung and Blood Institute (NHLBI), the ACCORD study that is assessing whether the rate of major cardiovascular disease events can be reduced by intensive control of blood glucose, blood pressure, and blood lipids. NIDDK is collaborating with the Centers for Disease Control and Prevention on TRIAD (Translating Research Into Action for Diabetes), a study to examine the effectiveness and cost-benefit of improved quality of diabetes care, on quality of life, and health status for people with diabetes in managed care settings.

Potential New Initiative 1:
Investigate differences among contemporary populations in the United States, characterized by race/ethnicity and other factors, in the prevalence of risk factors for complications of diabetes and in rates of these complications.
Expected Outcome:
NIDDK recognizes a need to obtain data on the frequency and extent of health disparities in contemporary populations. In collaborating with the National Center for Health Statistics (NCHS) in implementing diabetes components into their national surveys, information will be obtained on the status of health care, glucose control, and complications in the U.S. population.
Action Plan:
Mechanism of funding will be by research project grants (R01)
Funding Level:
The total estimated expenditure for the collaboration with the NCHS on national surveys will be $250,000 at 5% and 10% each, and $500,000 at 15%. The total estimated expenditure to expand research on the complications of diabetes in minority populations will be $2.0 million each at 5%, 10%, and 15%.

Potential New Initiative 2:
Investigate the extent to which variations in glycemic control and other aspects of health care, metabolic and genetic factors, socioeconomic status, and behavioral and other factors contribute to the higher risk for development and progression of complications in minority patients with diabetes.
Expected Outcome:
This initiative, if successful, will expand research on the factors leading to higher rates of complications in minority populations.
Action Plan:
This initiative will be accomplished by extending the Program Announcements that were recently issued for two additional years to solicit further research grant applications, giving special consideration to research grants in this area, and fully funding these applications where appropriate. Collaboration with the NIH Office of Research on Minority Health will be sought to enhance these research areas.
Funding Level:
The total estimated expenditure to implement the initiatives of research on complications of diabetes in minority populations will be $2.0 million each at 5%, 10%, and 15%. The total funding for the intramural research on complications of diabetes in minority populations will be $400,000 each at 5%, 10%, and 15%.

Potential New Initiative 3:
Develop and test appropriate and efficacious strategies for treatment and management of diabetes and its complications that are tailored to the needs of minority populations.
Expected Outcome:
Research will be targeted to develop effective interventions for patients at risk for diabetes and with established diabetes with the goal of reducing complications. Development and translation of effective interventions targeted at high risk populations prior to onset of diabetes will reduce the risk of developing diabetes and thus prevent complications. Another initiative will lead to expansion of the research program on prevention of amputations in patients with diabetes. Depression is three to four times more prevalent in patients with diabetes than in the general population and may have a devastating impact on management of diabetes and increase risk for developing the complications of diabetes. Little is known about the biological, psychosocial and developmental processes contributing to depression in diabetes in minority populations. A task force meeting on depression in diabetes, a factor that may contribute to increased diabetes complications and risk for onset of diabetes, is being planned for July, 2000, with the National Institute of Mental Health (NIMH). This meeting will be followed by a solicitation to increase research efforts in this important area.
Action Plan:
Provide additional funding for grants in this area. Special consideration will be given to applications in this area, and successful applications will be fully funded where appropriate.
Funding Level:
The total estimated expenditure to expand research on complications of type 2 diabetes in minority populations is $1.0 million at 5%, $2.0 million at 10%, and $3.0 million at 15%. To expand research in the area of depression and psychosocial issues in the diabetic patient population, it is estimated that the total expenditure will be $500,000 at 5%, $750,000 at 10%, and $1.0 million at 15%.

PUBLIC INFORMATION AND OUTREACH
Goal 1 -- To expand diabetes education and outreach to populations disproportionately affected by diabetes, that is, African Americans, Hispanic Americans, American Indians/Alaskan Natives, and Asian Americans and Pacific Islanders.
Current Activities:
The National Diabetes Education Program (NDEP) is a joint partnership of the NIDDK, the Centers for Disease Control and Prevention, and over 150 public and private sector partners. The purpose of the program is to improve the treatment and outcomes for people with diabetes, to promote early diagnosis, and, ultimately, to prevent the onset of diabetes.

The participation of representatives of African American, Hispanic/Latino, American Indian/Alaskan Native, and Asian/Pacific Islander communities is a key feature of the NDEP Partnership. With NIDDK support, the Special Populations Workgroup designed and implemented campaigns through the mass media in communities throughout the U.S. The campaign, "Control Your Diabetes. For Life." was officially launched at a news conference in June 1998. Over the next year, the TV public service announcement (PSA), "The Many Faces of Diabetes," received millions of dollars of free airtime.

The NDEP African American Workgroup introduced a media campaign at the Congressional Black Caucus annual meeting in September 1998. Concepts center around the idea of family and a reunion theme with a "control your diabetes for life" message. The entire campaign was released in summer 1999. The radio announcement, "Give It Up" challenges families to support people with diabetes in their efforts to eat fewer high fat foods. Through July 1999, the radio public service announcement aired 36,090 times on 597 stations in 395 cities in 49 states. An accompanying print advertisement reached more than 2.5 million people. The TV PSA, "Family Reunion," aired over 8,000 times in the six-month period June 1999 to January 2000.

"Rayos y Truenos" (Thunder and Lightning) was first developed by the NDEP Hispanic and Latino Workgroup and launched in June 1998. The 1998 campaign featured the comfort of home and family during a stormy night. The new 1999 television, radio and print campaign materials feature a rainstorm and a car stuck in snow to bring home the message "There are many things in life that can't be controlled. Fortunately, diabetes isn't one of them." Through November 1998, the TV PSA reached more than 6.6 million people, the radio advertisement more than 8 million, and the printed advertisement more than 6 million.

The American Indian campaign is developed and distributed by the NDEP American Indian Workgroup. Featuring television, print, and recorded radio PSAs, the campaign, "Future Generations," emphasizes controlling diabetes as an example for the children who carry on the traditions of the culture.

The Asian American and Pacific Islander Workgroup chose to focus on a campaign featuring a series of print PSAs and a live radio script. The diversity of cultures and languages in this population group is illustrated by the need of the work group to translate materials into eight different languages.

More than four million Medicare beneficiaries suffer from diabetes. Under the NDEP and in collaboration with the Health Care Financing Administration an initial public awareness campaign aimed at older African Americans was implemented when Medicare benefits were expanded to cover the costs of diabetes equipment and supplies. In April 1999, the campaign began promoting TV, radio and print PSAs in English and Spanish and a community development kit.

The National Diabetes Information Clearinghouse (NDIC) is an NIDDK program designed to disseminate information about diabetes and its complications to health professionals, patients and the public. The NDIC works with the NDEP to design and distribute informational materials to minority audiences, especially African American and Hispanic audiences. The NDIC developed a Spanish-language series of booklets on recommended practices for people with type 2 diabetes.

Potential New Initiative #1:
Develop additional media strategies to increase awareness of the seriousness of type 2 diabetes, and understanding of diabetes and its control, and promote a unified approach to diabetes care among minority populations with diabetes, health care providers, audiences at risk or undiagnosed, payers, health care purchasers, and policy makers.
Action Plan:
Expand the reach of the current NDEP "Control Your Diabetes. For Life" media campaign to minority audiences with culturally appropriate messages about diabetes and its control. Develop additional strategies and tools with NDEP partners representing Special Populations to promote NDEP messages, and develop additional evaluation mechanisms to assess effectiveness of the campaign and partner relationships.
Funding Level:
The estimated total expenditure is $750,000 each at 5%, 10%, and 15%.

Potential New Initiative #2:
Develop community interventions for African American, Hispanic/Latino American, American Indian, and Asian American and Pacific American Islanders through trusted and valued community channels and organizations that promote healthy lifestyle behaviors for diabetes care.
Action Plan:
Develop community intervention programs that are culturally and linguistically appropriate for minority audiences, provide technical assistance to tailor and implement programs for minority audiences, and develop evaluation mechanisms to assess effectiveness of programs.
Funding Level:
The total estimated level of funding is $1.5 million each at 5%, 10%, and 15%.

Potential New Initiative #3:
To promote health care policies that improve quality and access to diabetes care for minority audiences.
Action Plan:
Produce resources and training materials for health care providers that address cultural sensitivity issues for people with diabetes and their families, and produce educational materials and programs that support quality care for African Americans, Hispanic/Latino Americans, American Indians, and Asian Americans and Pacific Islanders with diabetes.
Funding Level:
The total estimated expenditure is $500,000 each at 5%, 10%, and 15%.

Potential New Initiative #4:
To communicate health messages to members of the Pima Indian community in Phoenix, Arizona.
Current Activities:
For many years, NIDDK has conducted research with the Gila River and Salt River Indian communities near Phoenix, Arizona. Tribal members suffer from a high incidence of type 2 diabetes and end-stage renal disease (ESRD). NIDDK distributes a culturally relevant booklet, which describes the Pima tribe's culture, history and health concerns.
Action Plan:
At the request of the Tribal Council, work with Council members to produce a culturally appropriate video about organ donation for people with ESRD at their local clinic. Develop continuing communications strategy to coordinate activities with NDEP.
Funding Level:
The total estimated expenditure is $200,000 each at 5%, 10%, and 15%.

3. Area of Focus # 2 -- Obesity

• Obesity and overweight represent the most common nutritional problem in the U.S, affecting more than one half of the adult population, an estimated 97 million Americans.
• Obesity is a major contributor to diabetes, hypertension, heart disease, stroke, osteoarthritis, and certain cancers.
• Obesity is more common among minority individuals in the US, with more than 65% of African American and Mexican American women overweight as defined by a body mass index (BMI) above 25.
• The prevalence of obesity (BMI above 30) in the US is increasing in all racial and ethnic groups, but affects minority populations disproportionately. More than 10% of non-Hispanic black women ages 40-60 are severely obese, with BMIs over 40.
• Rates of obesity in children and adolescents have increased by 80% from 1980 to 1994 in the US.
• Rates of obesity in American Indian children are more than twice as high as in the U.S. population as a whole.
• Obesity in childhood is associated with higher cholesterol levels, higher rates of hypertension, type 2 diabetes, and early coronary heart disease.
• Currently, there are no approved medications for treatment of childhood obesity. Low calorie diets, behavior modification, and exercise are the mainstays of treatment, but have had limited success in the past.
• Obesity is an important area of research supported by NIDDK, including basic research on appetite, satiety, energy expenditure, and genes that affect body weight, as well as clinical research on means of treating and preventing obesity.

Goal 1 -- To understand the biologic basis of the development of obesity
Current Activities:
A major part of the NIDDK portfolio in obesity relates to understanding the fundamental biologic basis for appetite, satiety and energy expenditure. Most promising has been the recent identification of obesity genes and the various hormones, receptors and intracellular signals that are important in appetite, satiety and energy expenditure. These basic research studies are important for all racial and ethnic groups that suffer from obesity. Some of these studies, however, focus in particular on certain minority populations, particularly those on the inheritance of obesity and search for genes conferring susceptibility to obesity. The NIDDK supports several large R01 grants in genetic and family studies of obesity in African Americans, Hispanics, and American Indians.

Potential New Initiative:
Expand the research portfolio on genetic studies of obesity in minority populations through special emphasis funding and in support of ancillary studies to clinical research protocols focusing on the genetics of obesity in minorities.
Expected Outcome:
Enhanced understanding of genes conferring susceptibility to obesity in minority populations.
Action Plan:
1) Request support for grants above the pay line in this area; 2) provide supplements to existing R01s; and 3) support a workshop to discuss development of a consortium to pool genetic research data on obesity.
Funding Level:
The total estimated expenditure on genetic studies in minority populations is $2.0 million at 5%, $3.0 million at 10%, and $3.5 million at 15%. The total expenditure on research in this area in the intramural program is estimated at $100,000 each at 5%, 10% and 15%. The total amount for supplements for ongoing studies in this area are estimated at $500,000 at 15%.

Goal 2 -- To develop the means of treating obesity and distribute sound, scientifically based information on therapy for obesity
Current Activities:
NIDDK supports several clinical trials on treatment of obesity, including studies of behavioral therapy and management of binge eating. Of major importance is the recently initiated multicenter clinical trial, "Study of Health Outcomes of Weight-loss" (SHOW). The trial is designed to determine if interventions to produce sustained weight loss lead to improved health in obese persons with diabetes. Participants from minority populations will be actively recruited to ensure that trial participants represent the U.S. population with diabetes and that the results of the trial are applicable to minority populations.

Potential New Initiative 1:
At the start of the SHOW trial, focus attention on recruitment and retention of minority individuals.
Expected Outcome:
Enhanced recruitment and retention of individuals from minority populations in SHOW.
Action Plan:
Supplements added to SHOW U01s to facilitate recruitment and retention efforts to insure adequate representation and retention.
Funding Level:
The total expenditure to supplement recruitment to the SHOW clinical trial is $800,000 at 5%, and $1.0 million each at 10% and 15%. The total funding for the intramural component will be $400,00 each at 5%, 10% and 15%.

Potential New Initiative 2:
Add ancillary studies to the SHOW trial that focus upon differences in response rates to various interventions by ethnic group.
Expected Outcome:
Funding of new studies to investigate ethnic/racial differences in obesity pathophysiology, co-morbidities, and response to weight-loss interventions.
Action Plan:
RFA to be released July 2000.
Funding Level:
The total expenditure on ancillary studies to demonstrate racial/ethnic differences in response to the intervention will be $500,000 at 5%, and $1.0 million each at 10% and 15%.

Potential New Initiative 3:
Promote further pilot studies of treatment of obesity through the R03 planning grant mechanism.
Expected Outcome:
New full-scale clinical trials for the treatment of obesity.
Action Plan:
Ongoing PA-98-071: "Small Grants in Digestive and Nutritional Disorders."
Funding Level:
The total estimated expenditure on these small grants is $1.0 million each at 5%, 10% and 15%.

Goal 3 -- To develop the means of preventing obesity in minority populations, including children
Current Activities:
Existing Clinical Nutrition Research Units (CNRU) and Obesity-Nutrition Research Centers (ORC) funded by NIDDK support various activities aimed at understanding and treating the causes and negative health effects of obesity in minority populations. Examples of these activities include pilot and feasibility studies to evaluate metabolic rate differences between white and black women and differences in weight gain during pregnancy among Caucasian, African American, and Hispanic women; surveys of eating and exercise habits of women on the Lakota Indian reservation and of American Indian women in urban areas; and several activities in the Boston area to address the issue of obesity among African American women in the city.

A protocol for the use of the drug metformin in a sub-set of young children with obesity has been written. Children ages five and older are screened every two years for the development of diabetes. Efforts are underway to develop screening tests for diabetes that can be done in schools. Community prevention programs to encourage breastfeeding, which is likely to reduce obesity and thus type 2 diabetes, are underway. Programs to educate elementary school students with regard to nutrition, exercise and diabetes are ongoing.

Potential New Initiative 1:
Organization of community lifestyle programs to encourage exercise and change in diet. Protocols for obesity prevention with use of medication can be extended to evaluate their use as agents to prevent type 2 diabetes in children. Use of these agents will also be selectively evaluated in those children identified as particularly high risk for type 2 diabetes. Behavioral modification protocols to understand and encourage increase in exercise and decrease amount of calorie intake.
Expected Outcome:
If successful, these initiatives will reduce the increasing rate of obesity and type 2 diabetes among American Indian children through lifestyle and behavior changes, and with possible addition of certain medications.
Action Plan:
These programs will be developed with intramural funds in cooperation with the American Indian community.
Funding Level:
The total estimated expenditure on the community lifestyle programs is $1.0 million at 15%.

Potential New Initiative 2:
The NIDDK will convene a workshop in FY 2001 to strengthen research capabilities in obesity prevention and to focus on opportunities for full-scale obesity prevention studies. This workshop will build on the FY1999 trans-NIH RFA, "Innovative Approaches to Prevention of Obesity" (RFA-DK-99-010).
Expected Outcome:
Better methods of preventing the onset of obesity.
Action Plan:
Convene workshop.
Funding Level:
The cost for the workshop is estimated at $100,000 in FY 2001.

Potential New Initiative 3:
Use the recommendations of the workshop from initiative 2 to issue an RFA for full-scale clinical trials for prevention of obesity, emphasizing high-risk populations.
Expected Outcome:
Better methods of preventing the onset of obesity.
Action Plan:
Issue RFA for clinical trials.
Funding Level:
The total estimated expenditure on preventive intervention trials is $2.0 million at 10%, and $2.5 million at 15%.

Potential New Initiative 4:
The National Task Force on Prevention and Treatment of Obesity has identified modification of environmental factors affecting obesity as an under-funded area of research that holds great potential for preventing obesity.
Expected Outcome:
Better methods of preventing the onset of obesity.
Action Plan:
The NIDDK is exploring the possibility of a trans-NIH RFA in this area.
Funding Level:
The level of funding will be based on participation of other Institutes and Centers in this initiative.

Potential New Initiative 5:
Investigate the role of physical activity in health and obesity.
Expected Outcome:
Increased number and quality of investigator-initiated applications in the area of physical activity in preventing and treating obesity.
Action Plan:
The NIH Nutrition Coordinating Committee is developing a trans-NIH PA entitled "Role of Physical Activity in Health and Obesity."
Funding Level:
The estimated level of funding will depend on the number of meritorious applications received in response to the program announcement.

PUBLIC INFORMATION AND OUTREACH
Goal 1 -- To further encourage groups who are disproportionately impacted by obesity and overweight, particularly African-American women, to maintain a healthy weight by becoming more physically active and eating healthier foods
Current Activities:
Approximately 55 percent of the adult population, or 97 million people, are defined as either overweight or obese according to recent data from the first Federal guidelines to identify, evaluate, and treat overweight and obesity. Nearly 4.7 million American children are also classified as obese or overweight.

Overweight occurs disproportionately in people who are of African American, Mexican American, American Indian, and Native Hawaiian descent. Obesity is a known risk factor for diabetes, heart disease, high blood pressure, gallbladder disease, and some forms of cancer, and the prevalence of obesity is rising.

NIDDK's Weight-control Information Network (WIN) provides culturally appropriate, evidence-based information about obesity, weight control, physical activity, and childhood obesity to the general public, health care providers, the media, and the Congress.

WIN developed the Sisters Together: Move More, Eat Better Program for African-American women because data from the Third National Health and Nutrition Examination Survey (NHANES) indicate that they have the highest rates of obesity and overweight among all racial and ethnic groups in the US.

This three-year (1995-1998) pilot communication program for Boston-based African American women ages 18 to 35 used a variety tools such as walking groups, cooking demonstrations, and health and body image seminars to communicate and motivate these women to move more and eat better.

Potential New Initiative:
WIN will plan and implement a nation-wide, media-based Sisters Together: Move More, Eat Better Program for African American women via communications media aimed at this audience. WIN will establish a partnership that includes other agencies and organizations with similar objectives.
Action Plan:

• develop media outreach,
• create a Sisters Together Work Group,
• develop, print, and disseminate Sister Together materials for African American women and health care providers,
• plan kick-off events, and
• establish toll-free phone line for the Program to handle information requests. 

Funding Level:
The total estimated expenditure is $525,000 each at 5%, 10% and 15%.

• End-stage renal disease (ESRD) is a major public health problem in the U.S., and the incidence rate has steadily increased over the past decade, from 155 per million population in 1988 to 296 in 1997. Similarly, the point prevalence rate has increased from 557 per million population in 1988 to 1131 in 1997.
• There are striking racial and ethnic differences in the incidence and prevalence rates. Racial and ethnic minorities, specifically, African Americans, American Indians and Alaskan Natives, Pacific Islanders, and Hispanic Americans have disproportionately greater incidence and prevalence rates. For example, in 1997, the incidence rates were 218 per million population in Caucasians, 873 in African Americans, 344 in Asians and Pacific Islanders, and 586 in American Indians and Alaskan Natives. Eleven percent of all new ESRD patients were Hispanic Americans.
• The four major causes of ESRD include diabetes mellitus (primarily type 2), hypertension, glomerulonephritis, and cystic renal disease. There is significant variability in the cause of ESRD among the various racial and ethnic groups. For example, whereas diabetic nephropathy is the predominant cause of ESRD in American Indians/Alaskan Natives, Asians and Pacific Islanders, Hispanic Americans and Caucasians, hypertensive nephropathy is the most frequently reported cause of ESRD in African Americans. However, diabetes mellitus is also an important cause of ESRD among African Americans.
• When compared with Caucasians, African Americans show a disproportionate increase in the incidence rate of hypertensive ESRD in all age groups, beginning at age 15, with an overall ratio (African Americans to Caucasians) of 6 to 1. This ratio is nearly 20 to 1 in the 20 to 44 year age group. Other diseases causing ESRD in which African Americans and other racial and ethnic minorities show a disproportionate increase over Caucasians include systemic lupus erythematosus (SLE); focal and segmental glomerulosclerosis (FSGS), especially in children; and AIDS, which is especially an important cause of ESRD in African Americans and Hispanic Americans.
• The reasons for the racial and ethnic disparities in the incidence and prevalence rates of ESRD remain largely unknown. The Institute devotes considerable fiscal resources in understanding the basic mechanisms underlying the causes and progression of kidney disease to end stage. Specific programs have been initiated to address the racial and ethnic disparities in the specific areas identified. Following are goals that address specific areas of racial and ethnic disparity.

Goal 1 -- To identify risk factors associated with progression of kidney disease and development of cardiovascular disease in patients with renal disease.
Current Activities:
Current activities include support of the United States Renal Data System, which performs epidemiological investigation of determinants of morbidity and mortality in the end stage renal disease population. This program has been critical in establishing the increased burden of kidney disease in minority populations. A small portfolio of renal epidemiological investigation is also supported through R01 grants.

Potential Initiatives:
To establish a prospective cohort study of patients with chronic renal insufficiency with the following primary goals: (i) to establish the prognostic implications of proteinuria and elevated serum creatinine; (ii) to determine the risk factors for rapid progression of renal disease, and (iii) to determine the risk factors among patients with renal disease for cardiovascular disease. A number of secondary goals have been established for this study including: (i) to describe patterns of nutrition and the development of malnutrition; (ii) to assess the rates and causes of hospitalization, and prevalence and incidence rates of other important co-morbid events and diseases; (iii) to document the overall and cause-specific mortality rates; (iv) to estimate health services resource utilization; (v) to measure quality of life and psychosocial factors that may be associated with decline of renal function and the development of cardiovascular disease, productivity and health resource utilization; (vi) to establish a specimen bank for future evaluation of genetic and biochemical risk factors and to collect and evaluate information on family members that may be useful in studies of genetic factors associated with increased susceptibility to renal disease. The ultimate goal of this study is to identify risk factors amenable to intervention(s) that can be evaluated in randomized, controlled clinical trials. Recruitment will emphasize over-sampling of minority populations to insure representation proportionate to the heavy burden of ESRD on minorities. It is anticipated that 2,000 to 3,000 cohort study participants will need to be recruited. Approximately four to five recruiting sites (clinical centers), a single data-coordinating center with central laboratories, and an echocardiography and ultrasound reading center will be required.
Expected Outcome:
This prospective epidemiological study will serve as a national resource for investigators to access both patient clinical and demographic information as well as biological specimens that will be archived. This resource will permit interested investigators to test important hypotheses about susceptibility to and progression of chronic renal disease and occurrence of cardiovascular disease and other co-morbid conditions in minority populations.
Action Plan:
Solicitation will be by requests for applications (RFA), and funding provided through a Cooperative Agreement.
Funding Level:
The total estimated expenditure is $4.0 million at 5%, and $6.0 million each at 10% and 15%.

Goal 2 -- To understand the underlying causes of diabetic nephropathy, to prevent progression to ESRD, and to reduce the higher prevalence and incidence in African Americans, American Indians and Alaskan Natives, Pacific Islanders, and Hispanic Americans.
Current Activities:
The portfolio in this area of investigation includes basic science studies of the pathogenic and the pathophysiologic mechanisms of diabetic nephropathy, which may be different between the different racial and ethnic populations. There is also a portfolio of clinical investigations of diabetic nephropathy in Americans Indians. There are several clinical genetic projects attempting to map loci associated with renal disease in African American populations. In addition, the recently funded multicenter clinical consortium, the Family Investigation of Nephropathy and Diabetes (FIND), will investigate genetic loci associated with the presence and severity of diabetic nephropathy in Caucasian, African-American, Hispanic and Native American populations across the U.S.

A randomized, double-blinded, placebo-controlled clinical trial is underway in Pima Indians to determine whether blockade of the renin-angiotensin system can prevent or attenuate the development and progression of early diabetic kidney disease in type 2 diabetes. A clinical intervention is underway in Pima Indians to determine if angiotensin-converting enzyme inhibitors are effective in slowing the progression of advanced diabetic kidney disease. State-of-the-art measures of kidney structure and function are being made serially in Pima Indians to identify the factors responsible for the development and progression of diabetic kidney disease.

The Institute currently invests over $10 million yearly in this area of research.

Potential New Initiative 1:
Expand the FIND study to include more minority subjects, including useful comparisons of nephropathy susceptibility loci in the well-phenotyped subjects and their families from the African American Study of Kidney Disease and Hypertension (AASK) Trial.
Expected Outcome:
Identification of minority populations at risk of developing diabetic nephropathy, leading to more effective treatment and prevention of progression to ESRD.
Action Plan:
Supplement to R01 grants, and Cooperative Agreement.
Funding Level:
The total estimated expenditure on expansion of FIND program is $1.0 million at 5%, $2.0 million at 10% and by $2.5 million at 15%.

Potential New Initiative 2:

• Perform a community intervention to improve blood pressure and blood sugar control among diabetic American Indians.
• Investigate the role of adhesion molecules within the glomerular podocyte in the development and progression of diabetic kidney disease.

Goal 3 -- To prevent progression of hypertensive nephropathy to end-stage and eliminate the racial disparities.
Current Activities:
There is a portfolio of basic science grants investigating pathogenesis and the pathophysiology of hypertensive nephropathy in African Americans. In addition, there is a multicenter clinical trial, the African American Study of Kidney Disease and Hypertension (AASK) funded since 1994. The total Institute expenditure is approximately $9.0 million per year.

Potential New Initiatives:
Investigate the genesis and the factors that reduce progression of hypertensive nephropathy in African Americans through a cohort of approximately 800 African Americans with hypertensive kidney disease and their family members.
Expected Outcome:
This initiative, if successful, will improve identification of African Americans at risk of developing ESRD due to hypertensive nephropathy, and permit aggressive management to prevent hypertensive ESRD.
Action Plan:
Solicitation will include RFAs, and funding will be through Cooperative Agreement.
Funding Level:
The total estimated expenditure on the AASK follow-up study investigating genetic factors involved in progressive hypertensive kidney disease is $2.0 million each at 5% and 10%, and $2.5 million at 15%.

Goal 4 -- To treat and prevent the development of ESRD caused by systemic lupus erythematosus (SLE).
Current Activities:
The NIDDK supports a portfolio of investigator-initiated studies, which explore basic mechanisms in this disease. Currently supported research in the general area of glomerulonephritis and tubulointerstitial nephritis includes studies of the pathogenic mechanisms of immunologic injury and repair, nature of the nephritogenic antigens, role of chemokines, antibodies, interactions, genetic determinants that regulate susceptibility and severity, and mechanisms of fibrosis. In the specific area of lupus nephritis, ongoing studies address immunologic mechanisms, genetic determinants, autoimmune injury, cell-mediated renal injury, molecular and phenotypic relationships among T and B cells. The total Institute expenditure is approximately $7.0 million total, per year.

Potential New Initiatives:
Identify and characterize the genetic determinants of autoimmune-mediated renal diseases, the initiating antigens triggering the immune response leading to renal injury and disease, the mechanisms and biologic role of mediators on the specificity of the autoimmune response and its link to fibrinogenesis, mechanisms of repair and resolution, the genetic determinants, and the development of experimental models which better reflect the phenotypic features of human disease. Establish a collaborative network of investigators to study effective treatment options for lupus nephritis with a major focus on minority populations. The emphasis should be on promoting the development and testing of new therapies for immune-mediated renal diseases.
Expected Outcome:
This initiative is likely to greatly impact upon the understanding and management of immune-mediated renal diseases in general and, specifically, lupus nephritis, particularly as it impacts racial and ethnic minorities.
Action Plan:
Issuance of RFAs for the establishment of the collaborative network.
Funding Level:
The total estimated expenditure on research into the genetic and pathogenic mechanisms of lupus nephropathy is $500,000 at 15%. The total amount of funds required for the establishment of the collaborative network is estimated at $1.0 million at 15%.

Goal 5 -- To prevent progression of kidney disease due to focal and segmental glomerulosclerosis (FSGS) to ESRD, especially in children.
Current Activities:
The current activities listed under Goal 3 include, to a great extent, basic science research in the area of FSGS. No clinical studies are included in the current portfolio.

Potential Initiatives:
Although steroid therapy has been used in the treatment of children with FSGS, there has not been a predictable beneficial response. In some children the heavy proteinuria may improve, but at the cost of significant adverse effects from the steroids, and, furthermore, the disease may progress to end stage. Limited data suggest that immunosuppressive agents, such as cyclosporine, may be beneficial in arresting progression of the disease, and in reducing the proteinuria. A multicenter, prospective, randomized, double blind clinical trial in children will help determine the most efficient way to prevent progression of the disease. The estimated sample size of the study would be approximately 300 patients enrolled over a four year period and followed for 18 months.
Expected Outcome:
If successful, the results of the clinical trial will guide physicians and the health care team in providing the safest and most efficient medical care to children with FSGS.
Action Plan:
Solicitation will be by RFAs, and funding provided through a Cooperative Agreement.
Funding Level:
The total estimated expenditure on a clinical trial in African American children with FSGS is $500,000 at 15%.

Goal 6 -- To offer state-of-the-art treatment to improve survival of the transplanted kidney, and to increase the number of African Americans and American Indians with end stage kidney failure who receive kidney transplant.
Current Activities:
The newly established organ and tissue transplant center at the NIH clinical center is a collaboration between the National Naval Medical Center, the Walter Reed Army Medical Center, the Diabetes Research Institute of the University of Miami, the NIDDK, and the NIH Clinical Center. Since its inception just over nine months ago, this Transplant Program has evaluated over 250 patients, and performed three pancreas transplants and over 30 kidney transplants. One of the main goals of this organ transplantation program is to develop novel methods that will greatly reduce, and ideally eliminate, the need for long-term immunosuppressive drugs. Following promising preliminary results in experimental animals, the clinical investigators are pursuing studies of novel biologic agents that offer the prospect of modulating the immune system in such a manner that transplanted organs are indefinitely accepted by human recipients (a process termed immunological tolerance). Clinical studies applying immune modulation therapy have begun in patients receiving a kidney transplant for ESRD. Members of a multi-disciplinary team are undertaking studies of type 1 diabetes mellitus and its complications, particularly kidney failure. Since June 1999, 32 kidney transplants have been done in the program -- 17 in Caucasians, 14 in African Americans, and one in an Asian American.

Potential Initiative #1:
Initiate, in conjunction with the transplant group in Bethesda, Maryland, a kidney transplant program to increase transplant utilization in American Indians.
Expected Outcome:
For American Indians who develop end-stage kidney failure, greater access to kidney transplants will substantially reduce the cost of medical care incurred with either hemodialysis or peritoneal dialysis and improve their quality of life.
Action Plan:
Funding mechanisms will include the Intramural Transplantation Program funds.
Funding Level:
The total estimated expenditure to add a program to increase renal transplantation in American Indians is $900,000 each at 5%, 10%, and 15%.

Potential Initiative #2:
To increase the proportion of minority populations, particularly American Indians/Alaskan Natives, African Americans, Pacific Islanders, and Hispanic/Latino Americans that receive renal allografts, and to decrease the rates of graft loss in these populations.
Expected Outcome:
African Americans comprise 34% of those awaiting kidney transplant, but receive only 25% of the cadaveric kidneys. American Indians/Alaskan Natives, Pacific Islanders, and Hispanic/Latino Americans, likewise, are underrepresented in the patient population that receives renal allografts. Long-term renal allograft survival in these minority populations is also diminished, compared with Caucasians. This initiative, if successful, will increase the number of minorities who receive renal allografts, and improve both patient and graft survival.
Action Plan:
The National Institute of Allergy and Infectious Diseases (NIAID) has several initiatives addressing these disparities. The NIDDK will collaborate with co-funding of some of these initiatives.
Funding Level:
The estimated amount of funds to co-fund the initiatives with NIAID will be based on the total cost of the NIAID initiatives that both Institutes agree to fund together.

Goal 7 -- To increase organ and tissue donation from racial and ethnic minority communities and enhance the opportunities for organ (especially kidney) and tissue transplantation.
Current Activities:
The Institute, in collaboration with the NIH Office of Research on Minority Health, has funded and managed the newly established educational program, the Minority Organ and Tissue Transplantation Educational Program (MOTTEP) since 1995. The aim of this program is to establish educational programs in racial and ethnic minority communities in 15 cities across the US to help prevent the development of kidney failure, and to increase organ and tissue donation for transplantation. The total cost of the program has been approximately $1.2 million per year.

Potential Initiatives:
Expand the MOTTEP program into other minority communities, and establish a mechanism to assess the effectiveness of the program in these communities.
Expected Outcome:
If successful, racial and ethnic minority groups will be empowered in their welfare with respect to kidney health. They will also actively participate in organ and tissue donation for transplantation. There will be the opportunity to strengthen the aspects of the program that work, and eliminate the ineffective ones.
Action Plan:
Funding of individual investigator-initiated research project grants (R01) and educational grants (R25) in collaboration with the ORMH.
Funding Level:
The total estimated expenditure is $800,000 at 10%, and $1.0 million at 15%.

PUBLIC INFORMATION AND OUTREACH
Goal 1 -- Increase awareness in minority audiences about kidney diseases to prevent end-stage renal disease (ESRD) and to reduce its morbidity and mortality in African Americans, Hispanic/Latino Americans, Asians and Pacific Islanders, and American Indians/Alaskan Natives.
Current Activities:
African Americans, American Indians, and other minority populations are disproportionately affected by ESRD. In 1996 African Americans represented 29.8 percent of people treated for ESRD but only 12.6 percent of the U.S. population. Hardest hit are Blacks aged 20 to 44, who are 20 times more likely than their white counterparts to develop hypertension-related kidney failure. Native Americans account for 1.5 percent of ESRD patients and only 0.8 percent of the U.S. population. In addition, experts believe that Hispanics and Pacific Islanders are more vulnerable to kidney failure, but data are not yet available.

Under NIDDK's direction, the National Kidney and Urologic Diseases Information Clearinghouse produces and disseminates materials on kidney diseases and on treatments for ESRD. Existing publications include High Blood Pressure and Kidney Disease, which disproportionately affect African Americans. Publications under development include Childhood Nephrotic Syndrome; Care of Vascular Accesses; Proteinuria; and an easy-to-read Prevent Diabetes Problems: Keep Your Kidneys Healthy. In addition, NIDDK and the NIH Office of Research on Minority Health fund the National Minority Organ/Tissue Transplant Education Program, which supports grass roots efforts to encourage minorities to donate organs and to prevent the need for transplantation by increasing awareness about causes of ESRD.

Potential New Initiative:
Establish a National Kidney Diseases Education Program with special emphasis on reducing the impact of ESRD in African Americans, Hispanic/Latino Americans and American Indians.
Action Plan:
Work with major patient and professional groups and others to identify areas of consensus for both screening and disease interventions. With public and private partners, and representatives of minority organizations, plan and implement a National Kidney Diseases Education Program, targeting appropriate messages to specific audiences.
Funding Level:
The total estimated expenditure on the National Kidney Disease Education Program, with emphasis on African Americans and Hispanic/Latino Americans is $1.0 million at 5%, $1.5 million at 10% and $2.0 million at 15%.

5. Area of Focus # 4 -- Sickle Cell Disease

• Sickle cell disease is a generic term for a group of genetic disorders characterized by the predominance of hemoglobin S (Hb S).  In the United States, these disorders are most commonly observed in African Americans and Hispanics from the Caribbean, Central America, and parts of South America. It affects nearly one of every 600 African Americans.
• Tissue injury is usually produced by hypoxia secondary to the obstruction of blood vessels by an accumulation of sickled erythrocytes. Symptoms of the hypoxic injury may be either acute (e.g., painful events, acute chest syndrome) or insidious in onset (e.g., aseptic necrosis of the hips, sickle cell retinopathy). The effects of acute and chronic tissue injury may ultimately result in failure of organs like the kidney, particularly as the patient ages.
• Sickle cell anemia and its complications (painful hemolytic anemia crises, strokes, lung, heart and kidney) are a major cause of morbidity and premature mortality in African-Americans.
• While the molecular basis of sickle cell disorders has been well characterized, cure of this disease has not been realized to date.
• Drugs that increase production of red blood cells and normal hemoglobin have decreased the morbidity of sickle cell disease. Recent research suggests that drugs such as nitric oxide that increase oxygenation and blood flow through critical organs may decrease the complications of sickle cell disease.
• Preliminary studies indicate that stem cell transplantation (and possibly gene therapy) offers potential cures for sickle cell anemia.

Goal 1 -- To improve understanding of sickle cell disease, its treatment, and prevention of its complications.
Current Activities:
There is a portfolio of current investigations aimed at the regulation of fetal globin gene transcription in a stage-specific manner, and the identification of molecules that may be used as drugs to enhance the levels of fetal hemoglobin in the circulating red blood cells of children and adults with hemoglobin disorders.

Studies in the NIDDK's intramural research program have shown that drugs that increase production of red blood cells and normal hemoglobin have improved the well-being of patients and decreased the morbidity of sickle cell disease. Other recent research findings indicate that drugs, such as nitric oxide, which increase oxygenation and blood flow through critical organs may decrease the complications of sickle cell disease. Preliminary studies have begun to examine whether stem cell transplantation (and possibly gene therapy) offers potential cures for sickle cell anemia.

Potential New Initiative 1:
Study of drugs that modulate production of normal adult hemoglobin, characterize the physiologic effects and clinical benefits of nitric oxide, and explore the use of allogeneic stem cell transplantation for correction of sickle cell anemia.
Action Plan:
Investigations will be carried out in the intramural program.
Funding Level:
The total estimated expenditure is $200,000 each at 5%, 10% and 15%.

Potential New Initiative 2:
Control of Fetal Globin Gene Expression and Development of Approaches for Therapeutic Induction of Fetal Globin Genes. The purpose of this initiative is to stimulate new avenues of research into the developmental processes involved in the differential expression of globin genes. The emphasis is on understanding the mechanisms of regulation of fetal hemoglobin synthesis and the development of new approaches of stimulation of fetal hemoglobin in patients with sickle cell anemia and other beta chain hemoglobinopathies by:

1. Identification and characterization of genetic, molecular, and cellular factors involved in the developmental regulation of the fetal and embryonic globin genes;
2. Investigation of the mechanisms involved in the activation and silencing of the fetal globin genes;
3. Studies of the linkage between erythroid cell differentiation and the developmental control of the globin genes;
4. Examination of the relationship between globin gene expression and the signal transduction mechanisms that are involved in erythroid cell maturation;
5. Determination of the mechanism of action of drugs, such as hydroxyurea and butyrate, that affect fetal hemoglobin (HbF) levels;
6. Discovery of new classes of compounds that can induce fetal hemoglobin in cultures of primary erythroid cells and in animal models;
7. Development of new model systems to study the regulation of fetal globin genes.

PUBLIC INFORMATION AND OUTREACH
Goal 1 -- Increase awareness about treatment of sickle cell disease in African Americans.
Current Activities:
The National Heart, Lung and Blood Institute (NHLBI) disseminates information about sickle cell disease. Existing publications include Facts About Sickle Cell Anemia, also translated into Spanish, and the fact sheets Hydroxyurea in Pediatric Patients with Sickle Cell Disease and The Multicenter Study of Hydroxyurea in Sickle Cell Anemia.

Potential New Initiatives:
None
Action Plan:
Work with NHLBI and public and private partners representing African Americans to identify additional information needs of patients, families and physicians, and distribute the available information to the communities.
Funding Level:
No additional funding needed for distribution of materials.

6. Area of Focus # 5 -- Hepatitis C Virus Infection and Liver Disease

• Liver disease ranks as the tenth most common cause of death in the U.S., and disproportionately affects minority populations.
• The leading causes of end-stage liver disease in the U.S. are alcoholic liver disease and hepatitis C.
• Hepatitis C affects 1.5% of the U.S. population and is two-to-three fold more common among African Americans and Hispanics than Caucasians.
• Therapy for hepatitis C is evolving, and current recommended regimens are effective in only 40% of patients. The response rate in African Americans is lower than in Caucasians.
• The only therapy for end-stage liver disease is liver transplantation. At present approximately 4,000 liver transplants are done yearly, but waiting lists are lengthening and a shortage of organs has caused an increase in deaths among patients while awaiting transplantation.
• Although end-stage liver disease is more common in minority individuals, those individuals are less likely to undergo liver transplantation. Furthermore, the survival rate after liver transplantation appears to be lower for African Americans than for Caucasians.

Another initiative, PA-98-086, "Liver and Biliary Diseases Among Women and Minorities," which was issued in collaboration with the NIH Offices of Research on Minority and Women's Health (ORMH and ORWH), NIDA, and NIAAA, solicits R03 and R01 grants for both clinical and basic research in these areas.

Potential Initiative:
To determine how hepatitis C (HCV) is transmitted and what factors contribute to its pathogenesis.
Expected Outcome:
Definition of the viral, host, and environmental factors contributing to the transmission and pathogenesis of HCV and the role of racial/ethnic and gender differences in the susceptibility to and outcomes of infection.
Action Plan:
PA entitled "Pathogenesis and Therapy of Hepatitis C in Special Populations" for R01s and R21s.
Funding Level:
The total estimated expenditure on research in the pathogenesis and transmission of HCV is $2.0 million at 10% and $3.0 million at 15%.

Goal 2 -- To improve the therapy for Hepatitis C, particularly for African-Americans
Current Activities:
The NIDDK convened a conference entitled "Hepatitis C in African Americans" held December 2, 1999, on the NIH campus. The workshop participants reviewed information on the prevalence, clinical course, complications, and therapy of hepatitis C among African-Americans and focused on comparisons of epidemiology and spread, serological and virological markers, disease severity and outcome, and treatment responses and complications between African-American and Caucasian populations. A central aim of that meeting was to plan future research directions. Also, the recently funded Hepatitis C Antiviral Long-term Therapy to prevent Cirrhosis (HALT-C) Trial is designed to determine the ability of long term treatment with interferon to prevent the development of cirrhosis and hepatocellular cancer. The trial will also provide information on the natural history of HCV. As the largest and longest study of HCV, this trial should provide answers concerning disease management and provide clinical criteria for grading, staging, and assessing the prognosis of people infected with HCV. This trial will include emphasis on recruitment of minority individuals.

Potential Initiative:
Initiate a large clinical trial of combination therapy for HCV that will enroll similar numbers of African American and Caucasian patients and provide intensive investigation of viral, cell biologic, and genomic resources for laboratory investigation of viral resistance and response in HCV infection.
Expected Outcome:
Characterization of the poor response rates of African Americans to current anti-HCV therapies. This characterization of resistance to interferon is key to developing effective therapy for all patients with this disease.
Action Plan:
RFA for U01s for clinical centers as well as a central data management, specimen bank center, and a specialized virology testing center, will be issued.
Funding Level:
The total estimated expenditure is $3.0 million at 5%, $6.0 million at 10%, and $7.5 million at 15%.

Goal 3 -- To improve the availability and efficacy of liver transplantation for all groups of Americans
Current Activities:
The NIDDK continues to fund a long-term study on outcomes of liver transplantation. With the advent of technical advances for living donor liver transplantation, this modality of transplant has increased significantly.

Potential New Initiative:
Foster discussion and collaborations on the technical, clinical, and research needs in the field.
Expected Outcome:
Stimulation and development of clinical investigation and research on optimizing donor and patient selection, surgical techniques, safety, and improvement in survival of liver transplantation.
Action Plan:
Organize and sponsor a clinical and research workshop on living donor liver transplantation in the Winter of 2000, to bring together clinicians and researchers to discuss the technical, clinical, and research advances in the field.
Funding Level:
The total estimated expenditure is $100,000 for the workshop in FY 2001, and $2.0 million each at 10% and 15% in FY 2002.

Goal 4 -- To prevent infection with Hepatitis C through vaccine development
Current Activities:
The group of intramural investigators at NIDDK has taken two complementary approaches to study the development of HCV vaccine. First, in collaboration with investigators in the Southwest Foundation for Biomedical Research, an NIH Regional Primate Center, the group is conducting studies on chimpanzees, the only nonhuman primate model for HCV infection. The investigators have developed methods of synthesizing and purifying large quantities of non-infectious hepatitis C virus-like particles (HCV-LP), and has demonstrated that HCV-LP are capable of eliciting a strong humoral immune response broadly directed against various regions of HCV structural proteins in mice and rabbits. In addition, the HCV-LP is capable of inducing a cytotoxic T cell response, which has been shown to be pivotal in controlling HCV infection. The other project involves detailed molecular, virologic and immunologic analyses of chimpanzees infected either acutely or chronically with HCV to dissect the viral factors and host immune responses (both cellular and humoral) in viral clearance and disease progression.

Potential New Initiative:
In the next five years, the plan is to expand along the same line of the research program in progress. The investigators will begin testing the immunogenicity and efficacy of the HCV-like particles and other modalities in the chimpanzee model.
Expected Outcome:
Given the higher prevalence of HCV infection (two-fold), increased incidence of liver cancer (three fold) and poorer response to treatment among African Americans (<50%), the impact of an effective HCV vaccine will be particularly relevant on the affected minority populations. These disparities could ultimately dissipate if the infection can be prevented.
Action Plan:
The proposed studies in chimpanzees will be conducted in collaboration with the Southwest Foundation for Biomedical Research. A contract has been developed with the support of NHLBI and NIDDK to perform these studies. In addition, the NIDDK investigators are also collaborating with academic investigators in extramural institutions on several NIAID-funded program projects and center grants on the immunology and vaccine development of hepatitis C.
Funding Level:
The total estimated expenditure on the collaboration with the NIAID and NHLBI in implementation of this initiative is $300,000 at each of 5%, 10% and 15%.

PUBLIC INFORMATION AND OUTREACH
Goal 1 -- Increase awareness of hepatitis C among African American and Hispanic/Latino American audiences
Current Activities:
NIDDK publishes a series of "easy-to-read" booklets on hepatitis through its National Digestive Diseases Information Clearinghouse (NDDIC). The series is available in the Spanish language. NIDDK also sponsored a conference entitled, "Hepatitis C in African Americans" at NIH in December 1999. The CDC publishes information for the lay public on all types of hepatitis.

Potential New Initiative:
Establish a coordinated information program about hepatitis C in African Americans and Hispanic/Latino Americans.
Action Plan:
Work with CDC and public and private partners representing African American and Hispanic/Latino Americans to identify additional needs of patients, families and physicians. Plan and develop messages and materials. Publicize clinical trial recruitment and the results of research. 
Funding Level:
The total estimated expenditure in the collaboration with the CDC and community organizations to improve delivery of messages to the African American and the Hispanic/Latino American communities is $300,000 each at 5%, 10% and 15%.

7. Area of Focus # 6 -- AIDS

• The human immunodeficiency virus (HIV) infection leading to the acquired immunodeficiency syndrome (AIDS) is a relatively recent epidemic and an important public health problem both in the US, and globally.
• The four distinct groups of individuals in whom the epidemic is rapidly spreading are male homosexuals, injecting drug users, infants of untreated or undetected HIV positive women, and heterosexual persons, principally in minority communities where HIV infection is facilitated by high rates of other sexually transmitted diseases.
• Over 600,000 persons have been diagnosed with AIDS in the US. A larger number are infected with HIV, many of whom are not yet diagnosed. In the US, African Americans and Hispanic or Latino Americans are disproportionately infected with HIV.
• Persons infected with the HIV may develop a multi-system dysfunction, and those with AIDS typically have severe abnormalities in many organ systems.
• Persons infected with HIV with or without AIDS may develop severe metabolic abnormalities, including severe wasting syndrome.
• Individuals co-infected with hepatitis C may follow a more virulent course to severe morbidity and/or death.
• Development of (HIV) nephropathy may occur early in the course of the disease, with/without AIDS, and may progress to end stage renal disease. Between 1993 and 1997, AIDS nephropathy was the reported cause of ESRD in 1.0 % of all incident ESRD patients, but was the fourth leading cause of ESRD in African Americans.

Goal 1 -- To strengthen urological investigations of factors that influence sexual transmission of human immunodeficiency virus (HIV).
Current Activities:
The current research portfolio is focused on transmission of HIV in semen, sites of HIV replication in the male genitourinary tract, effect of protease inhibitors on HIV titer in male genitourinary (GU) tract compared with effect in serum, infectivity of HIV in semen compared with serum, relationships between semen white cells and HIV levels, effect of vasectomy on HIV titer, and relationships between STDS and HIV in semen. The level of funding in FY 1999 was approximately $750,000.

Potential New Initiatives:
A clinical study of the effect of protease inhibitors on viral replication in semen vs. serum and basic research studies focusing on localization of HIV replication in male GU tract, with and without vasectomy, will enhance our understanding of the urologic factors that influence HIV transmission.
Expected Outcome:
The data from these studies on the effectiveness of protease inhibitors in reducing HIV titers and HIV infectivity in semen, comparing serum response to semen response will ultimately help in targeting the appropriate site for eradication of the replicating HIV.
Action Plan:
The expected mechanisms for funding include investigator initiated research project grants (R01) and Cooperative Agreements (U01).
Funding Level:
The total estimated expenditure is $500,000 each at 5% and 10%, and $1.0 million at 15%.

Goal 2 -- To understand, prevent and treat the metabolic abnormalities and body composition changes associated with HIV and its therapy in minority populations.
Current Activities:
The advent of effective anti-retroviral therapies has resulted in a dramatic reduction in the mortality and morbidity associated with HIV infection. The incidence of wasting syndrome, once a major health concern amongst HIV-infected individuals, has been reduced dramatically. However, among certain segments of the population, the lack of appropriate health care and the concomitant prevalence of high-risk behaviors, such as intravenous drug abuse, have conspired to sustain both opportunistic infections and wasting. The NIDDK supports several studies on both the etiology and potential treatment for wasting syndrome associated with HIV including a trial of combination anabolic therapy. This trial includes a high percentage of minorities as subjects and has recently expanded to a fourth site with anticipation of even greater participation by minority individuals.

As the effectiveness of anti-HIV therapies has improved a new set of metabolic complications has emerged. These complications included peripheral weight loss with or without apparent increased abdominal fat, possible bone loss, atherogenic lipid profiles and diabetes. While a number of basic and clinical investigations into the pathophysiology of this constellation of abnormalities have been initiated with funding from NIDDK, the prevalence and association with particular therapeutic agents have not been established. The NIDDK in collaboration with NIAID, NHLBI, and the Office of AIDS Research, has funded a nationwide multicenter, cross-sectional study (FRAM) to determine the extent of this problem. As minority individuals from Hispanic and African-American backgrounds are already disproportionately affected by HIV, and are also at greater risk for diabetes and cardiovascular disease, the consequences of these metabolic complications may be particularly devastating in these populations. This study, which includes 16 sites across the country, will begin recruitment in April 2000, and has a target of 41% Caucasian and 59% minority representation, primarily African-American. This study has an ambitious schedule with plans to report results within two years of commencement of recruitment. The results should provide a strong scientific basis for development of potential therapies in addition to design of appropriate experiments to elucidate the pathobiology of these abnormalities.

Potential New Initiative:
As data emerges from the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study, investigations will be initiated to take advantage of these results particularly in respect to the potential disproportionate burden of these problems in minority populations. In addition, the NIDDK is participating in an RFA, entitled "Protease Inhibitor Related Atherosclerosis in HIV Infection," which will support collaborations between basic and clinical investigators. The NIDDK plans to give special consideration to those applicants who are focusing on minority populations.
Expected Outcome:
The FRAM study sponsored by NIDDK should provide insights into the cause and potential racial/ethnic disparity in extent of metabolic abnormalities associated with HIV. These results will provide the foundation for targeted studies on etiology and treatment in minority populations. Planning grants to develop recruitment strategies and increase the pool of qualified investigators working with ethnic/racial groups will enhance the likelihood of effective treatment for metabolic abnormalities in HIV within the populations most at risk.
Action Plan:
The expected mechanisms for funding include pilot and feasibility grants (R21), investigator initiated research project grants (R01), and Cooperative Agreements (U01).
Funding Level:
The total estimated expenditure is $500,000 at 5%, and $1.0 million each at 10% and 15%.

Goal 3 -- To understand and decrease the disproportionate burden of HIV nephropathy in African Americans and Hispanic Americans.
Current Activities:
This area of investigation includes extramural basic science grants, and intramural investigations in the pathogenesis and the pathophysiology of HIV nephropathy. Some of these studies are directed at elucidating the mechanisms of HIV nephropathy in different racial and ethnic populations. There are studies specifically examining the genetic and other determinants of differential susceptibility to the development of renal disease in HIV infected people and animal models. The Institute invests approximately $3 million yearly in this area of research.

Potential New Initiative:
Studies of the pathogenesis of HIV nephropathy and examination of the effects of highly active retroviral therapies on the progression of HIV nephropathy
Expected Outcome:
Effective antiretroviral therapy will prevent progression of HIV nephropathy to ESRD.
Action Plan:
R01s for the study of pathogenesis in humans. A Cooperative Agreement is expected to fund the treatment consortium.
Funding Level:
The total estimated expenditure is $1.0 million at 10% and $2.0 million at 15%.

8. Area of Focus # 7 -- Peptic Ulcer Disease and Helicobacter pylori

• In the U.S. population, H. pylori infection is much more common among Mexican Americans (62%) and non-Hispanic blacks (53%) than among non-Hispanic whites (26%). Non-Hispanic blacks are also more likely to be infected with virulent H. pylori strains.
• Up to 10% of the U.S. population is afflicted with peptic ulcer disease at some time during their lives. It is estimated that at least 50% of peptic ulcer disease in the U.S. is caused by H. pylori infection.
• H. pylori infection increases the risk of stomach cancer. In the U.S., the incidence of stomach cancer is about twice as high among non-Hispanic blacks as non-Hispanic whites. American Indians and Mexican Americans are also at increased risk.
• While the prevalence of H. pylori infection appears to be declining among non-Hispanic whites, no such decline has been found among minority groups.

Goal 1 -- To prevent the transmission of H. pylori
Current Activities:
NIDDK is currently supporting several studies of H. pylori infection in minority populations. In a study of Mexican American children, investigators are exploring factors that influence the acquisition and persistence of H. pylori in children from infancy until age three. In addition, an ongoing epidemiological study of infection in Alaska Natives is examining the natural history of H. pylori infection in this population. In partnership with the CDC, NIDDK is co-funding a study of the prevalence of H. pylori infection in the U.S.

Potential New Initiative 1:
Determine how H. pylori is transmitted and persists.
Expected Outcome:
Better understanding of the mode of infection by H. pylori and of the factors that contribute to persistence of infection, as well as insight into factors leading to re-infection in high risk populations
Action Plan:
PA/RFA to conduct epidemiological studies.
Funding Level:
The total estimated expenditure is $1.5 million at 10%, and $2.0 million at 15%.

Potential New Initiative 2:
Investigate the racial and ethnic differences in genetic and environmental factors that contribute to the higher prevalence of H. pylori infection in minority populations. Track the prevalence and incidence of H. pylori infection in minority populations and examine barriers to its prevention and elimination in these groups.
Expected Outcome:
Reduction in incidence and prevalence of H. pylori infection in minority populations.
Action Plan:
PA/RFA to conduct epidemiological and intervention studies.
Funding Level:
The total estimated expenditure is $1.0 million at 15%.

Goal 2 -- To reduce the complications of H. pylori infection in minority populations.
Current Activities:
None

Potential New Initiative 1:
Identify environmental, bacterial, and host genetic factors that increase the risk of H. pylori related ulcers. Determine effective strategies to reduce the incidence of such ulcers in minority populations.
Expected Outcome:
Reduction in the incidence of peptic ulcers.
Action Plan:
PA/RFA
Funding Level:
The total estimated expenditure on research on genetic and environmental factors is $1.0 million at 10%, and $1.5 million at 15%.

Potential New Initiative 2:
Identify environmental, bacterial, and host genetic factors that increase the risk of H. pylori related stomach cancer. Determine effective strategies to reduce the incidence of such cancers.
Expected Outcome:
Reduction in the incidence of stomach cancer.
Action Plan:
PA/RFA
Funding Level:
See initiative 1 above.

PUBLIC INFORMATION AND OUTREACH
Goal 1 -- To increase awareness of the causes and treatment of peptic ulcer disease in minority populations who are disproportionately affected.
Current Activities:
The Centers for Disease Control and Prevention has the lead role in information and education activities in peptic ulcer disease. The NIDDK's National Digestive Diseases Information Clearinghouse publishes a booklet about peptic ulcer disease in English and in Spanish.

Potential New Initiative:
Coordinate the dissemination of information about peptic ulcer disease with the CDC.
Action Plan:
Develop culturally appropriate materials for minority audiences.
Funding Level:
No additional funds are required to disseminate the information prepared by the CDC.

9. Area of Focus # 8 -- Diseases of the Prostate

• Benign prostatic hypertrophy (BPH) and chronic prostatitis are the two most common non-malignant diseases of the prostate. Their prevalence far exceeds that of prostate cancer. They affect adults of all ages, and account for the major health care costs in diagnosis and treatment of prostate diseases. They very commonly are present in patients with prostate cancer.
• They occur at an earlier age than prostate cancer; their causal relationship to the development of prostate cancer is not known.
• Although the available data show that prostate cancer has a higher prevalence in African-Americans, the racial disparities for these non-malignant diseases have never been accurately assessed. However, it is assumed that they follow a pattern similar to that of prostate cancer.
• In addition to racial disparities in disease prevalence, the disparities in types of therapy, effectiveness of therapy, and effectiveness of screening programs has never been studied or evaluated.

Goal 1 -- To improve the treatment of BPH and chronic prostatitis, and to reduce the racial disparity.
Current Activities:
The current NIDDK portfolio includes two clinical trials, the Medical Treatment of Prostatic Symptoms (MTOPS), which has minority enrollment of 18%, and Innovative therapeutic approaches in patients with chronic prostatitis, with minority enrollment in the cohort of about 3%. A prostate biopsy tissue bank has been established for the BPH study. Four George M. O'Brien research centers focus on basic research aspects of prostate disease including prostate cancer. Individual basic research grants are diverse and range from androgen and hormonal regulation of prostate growth, susceptibility alleles for BPH, molecular epidemiology of androgen gene expression in the prostate, growth factors, and neuro-endocrine factors in prostate growth regulation. Approximately $23 million was spent on research on prostate diseases in FY 1999.

Potential New Initiative:
Expand the current study cohort of patients with chronic prostatitis to include more racial/ethnic minorities. A clinical study identifying minority patients with prostate disease, with a component of therapeutic interventions, and a multicenter genetic epidemiology study focusing on risk factors for prostate disease in minorities.
Expected Outcome:
These studies will answer three basic questions that address the disparity in prostate diseases in minorities:

1. Is a minority male with either BPH or prostatitis more likely to develop concomitant prostate cancer than a white male?
2. Is the prostate disease of minority males at a more advanced stage when diagnosed than that of white males?
3. Are there differences in treatment and treatment outcomes for minority males, and are there specific risk factors for disease development and progression in minority males?

PUBLIC INFORMATION AND OUTREACH
Goal 1 -- Increase awareness about prostate enlargement and chronic prostatitis in
African American and Hispanic/Latino American audiences.
Current Activities:
Under NIDDK's direction, the National Kidney and Urologic Diseases Information Clearinghouse produces and disseminates relevant materials, including Prostate Enlargement: Benign Prostatic Hyperplasia; Prostatitis: Disorders of the Prostate; and the executive summary of a scientific workshop on prostatitis. Under development is an easy-to-read booklet on prostate problems.

Potential New Initiative:
Establish a coordinated information program to reach African Americans and Hispanic/Latino American audiences.
Action Plan:
Work with public and private partners representing African Americans and Hispanic/Latino Americans to identify additional information needs of patients, families and physicians, and plan and develop culturally sensitive messages and materials.
Funding Level:
The total estimated expenditure is $300,000 each at 5%, 10% and 15%.

10. Area of Focus # 9 -- Gallbladder Disease

• Gallbladder disease (GBD), defined as the presence of gallstones or history of gallbladder surgery (cholecystectomies), affects 17% of women and 8% of men in the U.S.
• More than 700,000 cholecystectomies are performed yearly, making GBD among the most expensive of surgically treated diseases. The major indications for surgery are the development of acute attacks of pain (biliary colic) and obstruction of the bile ducts by gallstones.
• Established risk factors for GBD include obesity, rapid weight loss, prolonged fasting, sedentary activity, diabetes, smoking, hypertriglyceridemia, pregnancy, and use of estrogens.
• Gallstones are extremely common among American Indians, affecting over 50% of both men and women in some tribes. Gallstones are also particularly common among Mexican Americans.
• Gallstones are the only major identified risk factor for gallbladder cancer. Although this cancer is relatively uncommon in the U.S., it is a leading cause of cancer death among American Indians, particularly women.

Goal 1 -- To prevent the development of gallstones among American Indians and Mexican Americans.
Current Activities:
The NIDDK supports ongoing studies on the pathogenesis and prevention of gallstones. These include examining the role of defective muscle contraction in gallbladder stasis and its contribution to gallstone formation and growth and to the recurrence of gallstones; determining the mechanisms involved in chloride channel regulation in gallbladder epithelium in normal and disease states; developing mouse genetic models for gallstone susceptibility; examining the incidence of and the predictive factors for biliary sludge and gallstone formation during and after pregnancy; and defining the genetics of gallstone occurrence in a well characterized cohort of Mexican Americans families.

Potential New Initiative:
Determine the underlying genetic, physiological, and metabolic mechanisms that determine the racial/ethnic and gender differences in susceptibility to and outcomes of gallstones.
Expected Outcome:
Definition of the host and environmental factors that determine the high prevalence of gallstones in Mexican Americans and American Indians.
Action Plan:
RFA/PA for R01s and R21s
Funding Level:
The total estimated expenditure is $500,000 at 10%, and $1.0 million at 15%.

Goal 2 -- To reduce the incidence of complications of gallbladder disease in minority populations.
Current Activities:
None

Potential New Initiative 1:
Stimulate research aimed at identifying risk factors; surrogate and predictive markers; and prophylactic and therapeutic interventions to prevent the complications of gallstones such as bile duct obstruction, acute cholecystitis, and pancreatitis.
Expected Outcome:
Determine those factors that contribute to the complications of gallstones and develop the means to prevent or intervene.
Action Plan:
PA for R01s, R03s, R21s
Funding Level:
The total estimated expenditure is $1.0 million each at 10% and 15%.

Potential New Initiative 2:
Identify genetic and environmental risk factors for the high incidence of gallbladder cancer in Mexican Americans and American Indians, using new technologies (genomics, proteomics, microarrays).
Expected Outcome:
Better understanding of the basis for the increased risk of gallbladder cancer in minority populations.
Action Plan:
PA/RFA for R01s and R21s
Funding Level:
The total estimated expenditure is $500,000 at 10%, and $2.0 million at 15%.

PUBLIC INFORMATION AND OUTREACH
Goal 1 -- To increase awareness of gallstone disease prevention and treatment in Hispanic Americans.
Current Activities:
Obesity is a risk factor for gallstone disease, particularly for obese and overweight women. Recent investigations of ethnic trends of gallstone disease indicate that Mexican American women have a high prevalence of the disease. NIDDK has produced a fact sheet on the topic of gallstones, which is distributed through its National Digestive Diseases Information Clearinghouse.

Potential New Initiative:
To create culturally appropriate materials for Hispanic audiences related to obesity and gallstones, the Weight-control Information Network will develop materials in Spanish that address the issue of gallstones, obesity, dieting and physical activity.
Action Plan:
Create and promote availability of materials through culturally appropriate communication channels.
Funding Level:
The total estimated expenditure is $150,000 each at 5%, 10%, and 15%.

11. Area of Focus # 10 -- Urinary Tract Disease

• Urinary tract infections (UTIs) are a major public health problem in adult women of all ages.
• UTIs are particularly problematic in women with type 2 diabetes mellitus, and as a consequence of the greater prevalence of diabetes in minority women, the health burden consequent to UTI's is much greater in minority populations.
• In diabetic women, UTIs are more frequent and more difficult to eradicate. In addition, UTIs adversely impact glycemic control, and therefore may contribute to diabetic complications.
• Urinary incontinence is a major public health problem, and contributes to the large health care expenditure and concern in the U.S. Racial disparities in incidence, age of onset, access to care, and effective medical and surgical therapy, have never been carefully assessed. An NIDDK pilot study looking at the epidemiology and racial/ethnic differences of urinary incontinence in young to middle aged adult women in inner city Detroit, Chicago and Raleigh, North Carolina, showed a significant disparity in understanding of incontinence, treatment seeking, access to care, and provision of effective treatment.
• Incontinence is a major factor contributing to the difficulty in providing health care to the elderly. It is unclear whether or not there are racial/ethnic disparities in the incidence of incontinence in the elderly, but the burden of care falls more heavily on minority family members, since elderly minority individuals are cared for more frequently by families rather than in nursing homes.

Goal 1 -- To prevent the incidence of urinary tract infections, and reduce the racial disparity.
Current Activities:
The portfolio in this area includes a study focusing on risk factors for UTIs in post menopausal women, two program project grants and a series of individual research project grants which focus primarily on pathogenic mechanisms for UTIs, factors promoting infections, and immunization for UTIs. Total funding for FY 1999 was about $3.75 million.

Potential New Initiatives:
A multicenter clinical study focusing on the effectiveness of strategies to reduce recurrent urinary tract infections in women with type 2 diabetes. Studies would examine the effect of diabetes control, bladder function, home testing for infection, prophylactic antibiotics and, possibly, alternative medicine remedies such as cranberry juice. It will be critical that there be study sites in communities of racial/ethnic minorities, including American Indians, Hispanics and African Americans, so that effectiveness of treatments in these populations can be assessed. Coordination with the Indian Health Service, and the NIDDK Phoenix Epidemiology and Clinical Research Branch in Phoenix, Arizona, will allow recruitment of an appropriate American Indian population.
Expected Outcome:
If successful, the results of this study may establish methods to prevent urinary tract infection in diabetic minority women.
Action Plan:
The anticipated mechanism of funding is Cooperative agreement (U01). Some of the studies can be carried out in the Intramural program. Collaboration with the Indian Health Service is also expected.
Funding Level:
The total estimated expenditure on the clinical trial is $2.0 million at 5%, $3.0 million at 10%, and $4.0 million at 15%.

Goal 2 -- To reduce the prevalence of urinary incontinence in the general population, and address the racial disparity.
Current Activities:
In FY 1999 NIDDK funded two individual research grants focusing on stress incontinence and incontinence secondary to vaginal delivery. Another ongoing study focuses on hormonal risk factors for incontinence. Total amount of funding for FY 1999 was $1.0 million. In FY 2000 a major study of surgical outcomes for urinary incontinence will be initiated. At the present time, no mechanisms exist for selective minority recruitment in that study.

Potential New Initiatives:
Increase the scope and number of centers participating in the study of surgical outcomes for treatment of urinary incontinence to ensure adequate minority recruitment and enrollment, and develop a population based cohort study within the recruited population to answer the outstanding questions related to racial disparities.
Expected Outcome:
The expansion of the urinary incontinence treatment trial will allow us to answer many of the outstanding questions related to access to care, racial and ethnic differences in types of incontinence, age of onset, and the effective treatment in minority, community-dwelling women.
Action Plan:
The anticipated mechanism of funding is cooperative agreement (U01).
Funding Level:
No additional funds are required to expand the clinical trial.

PUBLIC INFORMATION AND OUTREACH
Goal 1 -- Increase awareness about urinary tract infections and urinary incontinence in African Americans and Hispanic/Latino American audiences
Current Activities:
Under NIDDK's direction, the National Kidney and Urologic Diseases Information Clearinghouse produces and disseminates relevant materials, including Urinary Tract Infections in Adults, Urinary Tract Infections in Children, and Bladder Control for Women. Under development is an easy-to-read booklet on urinary tract infections.

Potential New Initiative:
Coordinate an information program to reach minority populations disproportionately affected by urinary tract disease.
Action Plan:
Work with CDC and other public and private partners representing minority organizations to identify additional information needs of patients, families and physicians, and plan and develop culturally sensitive messages and materials.
Funding Level:
The total estimated expenditure is $100,000 each at 5%, 10%, and 15%.

12. INFRASTRUCTURE OR CROSS-CUTTING ISSUES

Goal 1 -- To enhance Minority Training and Career Development

Current Level of Activity:
See table.

Future Initiatives:

1. Continue with current level of activity in training and career development of minority investigators as shown on the attached table, and provide significant increases for certain programs, such as the Initiatives for Underrepresented Minorities in Biomedical Research.
2. Provide opportunities for short-term training of minority medical students on existing T32s at institutions holding DK-funded Center grants with the stipulation that Center facilities are at the disposal of the summer student and his/her mentor. Approximately ten awards yearly at $5,000 each, with a total of $50,000.
3. Provide financial assistance for minority medical students and Ph.D. students in biomedical related training programs. Estimate assistance to four students per year at $10,000 each, with a total of $40,000.
4. Pending legislative authorization by the US Congress, the NIDDK will provide loan repayment assistance for minority pre-doctoral and post-doctoral fellows. Estimate four awards at $35,000 each, with a total of $140,000 per year.
5. Issue an RFA/PAR for 'T31's to provide 1 year of research experience for minority medical students at institutions with DK-funded Centers between their second and third years. (Estimated total cost for five T31s, three slots each per year would be $300,000/year.)
6. Longitudinal program to enhance the pipeline -- from high school through professional school with emphasis on tracking. Total yearly support is approximately $1.8 million. NIDDK will work closely in collaboration with the ORMH and other interested Institutes and Centers in support of the program.
7. Pilot MD/Masters Program in Clinical Research at a historically black medical school. Estimated five awards per year at $50,000 each, with a total of $250,000.
8. Provide opportunities for up to five minority scientists to be mentored in the Intramural program.

Expected Outcome:
Increased numbers of minority scientists in both basic science and clinical research disciplines to address the health disparities and outcomes in minority populations.

NIDDK Minority Training and Career Development-FY 1999

Name of Program and Description	Division	# of NIDDK Awards	# of Participants	NIDDK Funding Level	ORMH Collab. Funding
Minority Access to Research Careers (MARC) T-34 and T-36 NIDDK co-funds with NIGMS. Funds pre-doctoral faculty fellowships, visiting scientists, conferences for minority investigators and minority health issues, and honors undergraduate training in biomedical research. Summer Internship Program in the NIDDK Division of Intramural Research (students-managed by NIDDK-EEO).	DK-wide	6	6	$28,537
Minority Biomedical Research Support Program (MBRS) NIDDK co-funds with NIGMS. Provides expanded opportunities for minorities to participate in biomedical research careers. Supports research projects of interest to the NIDDK at Minority and Equal Opportunity Institutions.	DK-wide	25	25	2,282,000