RACE/ETHNIC DISPARITIES IN THE INCIDENCE OF DIABETES COMPLICATIONS 

Release Date:  December 15, 1999 (see replacement PA-02-165)

PA NUMBER:  PAS-00-028

National Institute of Diabetes and Digestive and Kidney Diseases

THIS PA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  IT INCLUDES 
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED 
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS PA.

PURPOSE

This Program Announcement (PA) solicits research to investigate (1) 
differences among contemporary populations in the United States, categorized 
by race-ethnicity and other factors, in risk factors for complications of 
diabetes and in rates of these complications; and (2) the extent to which 
factors, including inherent metabolic and genetic variations, medical care, 
socioeconomic status, and behavioral factors account for these differences.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2000," a PHS-
led national activity for setting priority areas.  This PA, Race/Ethnic 
Disparities in Diabetes Complications, is related to the priority area of 
diabetes and chronic disabling conditions.   Potential applicants may obtain 
a copy of "Healthy People 2000" at http://odphp.osophs.dhhs.gov/pubs/hp2000
 
ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and nonprofit 
organizations, public and private, such as universities, colleges, hospitals, 
laboratories, units of State and local governments, and eligible agencies of 
the Federal Government.  Racial/ethnic minority individuals, women, and 
persons with disabilities are encouraged to apply as principal investigators.

MECHANISM OF SUPPORT

This PA will use the National Institutes of Health (NIH) research project 
grant (R01) and Exploratory/Development Research Grant (R21) award 
mechanisms.  Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant.  The total project 
period for an R01 application submitted in response to this PA may not exceed 
5 years.

The R21 awards are to demonstrate feasibility and to obtain preliminary data 
testing innovative ideas that represent clear departure from ongoing research 
interests.  These grants are intended to 1) provide initial support for new 
investigators; 2) allow exploration of possible innovative new directions for 
established investigators; and 3) stimulate investigators from other areas to 
lend their expertise to research within the scope of this solicitation.  
Applicants for the R21 must limit their requests to $100,000 direct costs per 
year and are limited to two years.  These R21 grants will not be renewable; 
continuation of projects developed under this program will be through the
regular research grant (R01) program.

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH.  
Complete and detailed instructions and information on Modular Grants can be 
found at http://grants.nih.gov/grants/funding/modular/modular.htm

FUNDS AVAILABLE

$2 million per year will be set aside by NIDDK for three years to fund 
applications relevant to this PA.  Funding is dependent on the receipt of a 
sufficient number of applications of high scientific merit and on the 
availability of funds for this purpose.  This PA will remain active for three 
years, through the October/November 2003 receipt date, after which 
applications submitted within the scientific scope of this PA will compete 
without benefit of a set aside of funds.

RESEARCH OBJECTIVES

Background

Extant information on the incidence of complications of diabetes in the 
United States is often based on community populations or large clinic 
populations in which the onset of diabetes occurred several decades ago.  
These studies generally found a striking and large excess of microvascular 
disease in minority racial and ethnic groups, including Native Americans, 
African Americans, Hispanic Americans, and Asian and Pacific Islanders.  
Whether these disparities in diabetes complications continue to occur in 
contemporary diabetic patients is not known.  For example, new advances in 
treating diabetes and blood pressure may lessen the race-ethnic differentials 
in glycemic control and blood pressure control.  This might, in turn, lead to 
decreases in the risk for diabetes-related microvascular complications in 
minorities, relative to risk in the majority Caucasian population.

Despite improvements in health care, some of the racial differences in 
diabetic complications may be explained by differences in availability and 
quality of health services.  There may be differences by race/ethnicity and 
socioeconomic status in self-care practices, health care provider practices, 
and/or access to quality health care and prevention services that directly 
impinge on the frequency and magnitude of risk factors for diabetes 
complications and the intensity of medical care for early stages of 
complications to prevent progression to end-stage disease.

In addition to differences in blood glucose, lipid and blood pressure 
control, which may be modified by improved medical care, genetic 
susceptibility and other biological risk factors may contribute in unknown 
ways that lead to complications.  This is suggested by the clustering of 
complications (especially nephropathy) within families and by the excess risk 
of retinopathy in Hispanics versus non-Hispanics that remains when the degree 
of hyperglycemic exposure is taken into account.

Finally, lifestyle, psychosocial factors, stress, family structure, social 
support, diet and culture, and socioeconomic status vary among racial and 
ethnic minorities and may contribute to differential risk of developing 
diabetes complications and progression of complications.  Little is known 
about how these behavioral factors influence the risk of complications and 
the effectiveness of interventions designed to prevent or reduce diabetes 
complications in racial and ethnic minority groups.

Identification of these divergent etiologies and quantification of their 
correlation to risk have important implications for prevention and 
amelioration of microvascular complications.  Such information might improve 
the effectiveness of treatment to reduce the disparities in the incidence in 
diabetes complications among racial and ethnic groups.

In contrast to microvascular complications, racial and ethnic minorities with 
diabetes often have lower rates of macrovascular disease than Caucasian 
population groups.  Angina, myocardial infarction, and other forms of 
coronary heart disease appear to be less common in African Americans, Mexican 
Americans and Native Americans than in non-Hispanic whites.  The factors that 
account for the differing macrovascular disease rates are unknown.

Objectives and Scope

The overall objectives are to determine 1) whether minority race-ethnic 
populations continue to differ in their risk for microvascular and 
macrovascular complications, and, if so, 2) the reasons for these 
differences.  It is recognized that both biologic and non-biologic factors 
may be operating in these populations.
 
Approaches may include metabolic, genetic and/or epidemiologic studies in 
representative populations. Advantage might be taken of extant cohort studies 
that may have been established for investigation of diabetes or other 
diseases.  A collaboration among investigators of these established cohorts 
would be desirable, so that these studies might jointly develop protocols and 
evaluate findings.  Alternatively, investigators may propose to start a new 
cohort, appropriately powered, to capture the current risks and outcomes in 
the era of new medications for glycemic control, blood pressure control, and 
lipid control.  Such studies of current risks might appropriately be based in 
large HMOs with structure and data management practices conducive to 
efficient and cost-effective analyses.

Investigators are encouraged to incorporate appropriate surrogate markers for 
complications into study design to shorten the duration of studies.  Such 
surrogate markers might include early indicators of end-stage complications 
(background retinopathy, albuminuria, serum creatinine, basement membrane 
thickening, EKG, carotid ultrasound).

Appropriate topics for investigation would include but are not limited to:

o Epidemiologic studies to determine the rates of the  micro- and 
macrovascular diabetic complications in appropriate representative samples of 
contemporary populations.

o Studies to identify genes which might affect the development of micro- and 
macrovascular complications in different populations

o State-of-the-art, hypothesis-driven metabolic studies to determine whether 
there are differences in metabolism, insulin sensitivity, energy expenditure, 
beta cell function, and body composition that might influence glycemic 
control and risk of complications in different populations.

o Studies to investigate factors, such as medical care, behavior and 
lifestyle, and  socioeconomic status, that may contribute to risk for 
development and progression of complications.  Such studies could incorporate 
culturally-specific lifestyle factors into treatment and prevention 
strategies to reduce risk across racial and ethnic groups. 

Understanding the basis for differing susceptibilities could provide 
information that would lead to specific therapies likely to be useful in 
various subpopulations at high risk for the development of diabetes 
complications.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and 
their subpopulations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification is provided that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research.  This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).
 
All investigators proposing research involving human subjects should read the 
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical 
Research," which have been published in the Federal Register of March 28, 
1994 (FR 59 14508-14513) and in the NIH Guide For Grants and Contracts, Vol. 
23, No. 11, March 18, 1994, available on the web at 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS.

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them.  
This policy applies to all initial (Type 1) applications submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
“NIH Policy and Guidelines on the Inclusion of Children as Participants in 
Research Involving Human Subjects” that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators may also obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev. 
4/98) and will be accepted at the standard application deadlines as indicated 
in the application kit.  Application kits are available at most institutional 
offices of sponsored research, or may be obtained from the Division of 
Extramural Outreach and Information Resources, National Institutes of Health, 
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-
435-0714, email: GrantsInfo@nih.gov.

Applicants planning to submit an investigator-initiated new (type 1) 
competing continuation (type 2), competing supplement, or any amended/revised 
version of the preceding grant application types requesting $500,000 or more 
in direct costs for any year are advised that he or she must contact the 
NIDDK program staff before submitting the application, i.e., as plans for the 
study are being developed.  Furthermore, the application must obtain 
agreement from the staff that the NIDDK will accept the application for 
consideration for award.  Finally, the applicant must identify, in a cover 
letter sent with the application, the staff member and Institute or Center 
who agreed to accept assignment of the application.

This policy requires an applicant to obtain agreement for acceptance of both 
any such application and any such subsequent amendment.  Refer to the NIH 
Guide for Grants and Contracts, March 20, 1998 at 
http://grants.nih.gov/grants/guide/notice-files/not98-030.html. 

The modular grant concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach.  The 
just-in-time concept allows applicants to submit certain information only 
when there is a possibility for an award. It is anticipated that these 
changes will reduce the administrative burden for the applicants, reviewers, 
and Institute staff.  The research grant application form PHS 398 (rev. 4/98) 
is to be used in applying for these grants, with the modifications noted 
below.

BUDGET INSTRUCTIONS

Modular Grant applications for support under the R01 mechanism will request 
direct costs in $25,000 modules, up to a total direct cost request of 
$250,000 per year.  (Applications that request more than $250,000 direct 
costs in any year must follow the traditional PHS 398 application 
instructions.)  Applications for R21 grants will request up to 4 modules in 
direct costs.  The total direct costs must be requested in accordance with 
the program guidelines and the modifications made to the standard PHS 398 
application instructions described below:

PHS 398

o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $250,000) and Total Costs [Modular 
Total Direct plus Facilities and Administrative (F&A) costs] for the initial 
budget period.  Items 8a and 8b should be completed indicating the Direct and 
Total Costs for the entire proposed period of support.

o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD:  Do not complete Form Page 4 
of the PHS 398. It is not required and will not be accepted with the 
application.

o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT:  Do not complete the 
categorical budget table on Form Page 5 of the PHS 398.  It is not required 
and will not be accepted with the application.

o NARRATIVE BUDGET JUSTIFICATION:  Prepare a Modular Grant Budget Narrative 
page. (See  http://grants.nih.gov/grants/funding/modular/modular.htm
for sample pages.)  At the top of the page, enter the total direct costs 
requested for each year.  This is not a Form page.

o Under Personnel, list key project personnel, including their names, percent 
of effort, and roles on the project. No individual salary information should 
be provided. However, the applicant should use the NIH appropriation language 
salary cap and the NIH policy for graduate student compensation in developing 
the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (direct 
plus facilities and administrative) for each year, each rounded to the 
nearest $1,000.  List the individuals/organizations with whom consortium or 
contractual arrangements have been made, the percent effort of key personnel, 
and the role on the project.  Indicate whether the collaborating institution 
is foreign or domestic.  The total cost for a consortium/contractual 
arrangement is included in the overall requested modular direct cost amount.  
Include the Letter of Intent to establish a consortium. Provide an additional 
narrative budget justification for any variation in the number of modules 
requested.

o BIOGRAPHICAL SKETCH:  The Biographical Sketch provides information used by 
reviewers in the assessment of each individual's qualifications for a 
specific role in the proposed project, as well as to evaluate the overall 
qualifications of the research team. A biographical sketch is required for 
all key personnel, following the instructions below.  No more than three 
pages may be used for each person. A sample biographical sketch may be viewed 
at: http://grants.nih.gov/grants/funding/modular/modular.htm

- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations;

o CHECKLIST:  This page should be completed and submitted with the 
application. If the F&A rate agreement has been established, indicate the 
type of agreement and the date. All appropriate exclusions must be applied in 
the calculation of the F&A costs for the initial budget period and all future 
budget years.

o The applicant should provide the name and phone number of the individual to 
contact concerning fiscal and administrative issues if additional information 
is necessary following the initial review.  The program announcement title 
and number must be typed on line 2 of the face page of the application form 
and the YES box must be marked.

Submit the signed, original, single-sided application, including the 
Checklist, along with five signed photocopies and five collated sets of 
appendix materials in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040-MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express/courier service)

The Center for Scientific Review (CSR) will not accept any application in 
response to this PA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed.  This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must 
include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established Public Health 
Service referral guidelines.  Applications will be evaluated for scientific 
and technical merit by an appropriate scientific review group convened in 
accordance with the standard NIH peer review procedures.  As part of the 
initial merit review, all applications will receive a written critique and 
undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of applications under review, will 
be discussed, assigned a priority score, and receive a second-level review by 
the appropriate national advisory council or board.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewer will be asked to discuss the following aspects 
of the application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals.  Each 
of these criteria will be addressed and considered in assigning the overall 
score, weighting them as appropriate for each application.  Note that the 
application does not need to be strong in all categories to be judged likely 
to have major scientific impact and thus deserve a high priority score.  For 
example, an investigator may propose to carry out important work that by its 
nature is not innovative but is essential to move a field forward.

o Significance:  Does this study address an important problem?  If the aims 
of the application are achieved, how will scientific knowledge be advanced?  
What will be the effect of these studies on the concepts or methods that 
drive this field?

o Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

o Innovation:  Does the project employ novel concepts, approaches, or method?  
Are the aims original and innovative?  Does the project challenge existing 
paradigms or develop new methodologies or technologies? 

o Investigator:  Is the investigator appropriately trained and well suited to 
carry out this work?  Is the work proposed appropriate to the experience 
level of the principal investigator and other researchers (if any)?

o Environment:  Does the scientific environment in which the work will be 
done contribute to the probability of success?  Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements?  Is there evidence of institutional 
support?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  Adequacy of plans to include both genders, minorities and their subgroups, 
and children as appropriate for the scientific goals of the research.  Plans 
for the recruitment and retention of subjects will also be evaluated. 
o  The reasonableness of the proposed budget and duration to the proposed 
research.

o  The adequacy of the proposed protection of humans, animals, or the 
environment, to the extent that they may be adversely affected by the project 
proposed in the application.

o  Availability of special opportunities for furthering research programs 
through the use of unusual talent resources, populations, or environmental 
conditions in other countries which are not readily available in the United 
States or which provide augmentation of existing U.S. resources.

AWARD CRITERIA

Applications will compete for available funds with all other recommended 
applications assigned to the National Institute of Diabetes and Digestive and 
Kidney Diseases.  The following will be considered in making funding 
decisions:

o Quality of the proposed project as determined by peer review;
o Availability of funds;
o Program priority.

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or questions 
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Barbara Linder, M.D., Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
NIDDK
45 Center Drive MSC 6600
Bethesda, MD 20892-6600
Telephone:  (301) 594-0021
FAX:  (301) 480-3503
E-mail:  linderb@extra.niddk.nih.gov

Direct inquiries regarding fiscal and administrative matters to:

Florence Danshes
Division of Extramural Activities
NIDDK
45 Center Drive MSC 6600
Bethesda, MD 20892-6600
Telephone:  (301) 594-8861

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.847. Awards are made under authorization of the Public Health Service Act, 
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 
241 and 285) and administered under NIH grants policies and Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  This program is not 
subject to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking 
in certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care or early 
childhood development services are provided to children.   This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.

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