TYPE 2 DIABETES IN THE PEDIATRIC POPULATION

Release Date:  December 1, 1999

RFA:  DK-00-008

National Institute of Diabetes and Digestive and Kidney Diseases
National Institute of Child Health and Human Development

Letter of Intent Receipt Date: March 24, 2000
Application Receipt Date: April 25, 2000

THIS RFA 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 
RFA.

PURPOSE

The National Institute of Diabetes and Digestive and Kidney Diseases 
(NIDDK) and the National Institute of Child Health and Human 
Development (NICHD) invite  investigator-initiated research grant 
applications to study the epidemiology, natural history, 
pathophysiology, prevention and treatment of type 2 diabetes in 
children in the U.S. Type 2 diabetes has traditionally been viewed 
as a disease of adults.  Recently, however, it has become apparent 
that an increasing number of cases of type 2 diabetes are being 
reported in children.  This rise in type 2 diabetes in the pediatric 
population is presumed to be a consequence of widespread obesity and 
decreased physical activity among children. However, much of the 
available data concerning type 2 diabetes in children is anecdotal.  
This RFA is intended to stimulate epidemiologic, metabolic and 
clinical research into this important public health problem.  The 
intent of this RFA is to intensify investigator-initiated research, 
to attract new investigators to the field and to encourage 
interdisciplinary approaches to research in this area.

HEALTHY PEOPLE 2000

The Department of Health and Human Services (DHHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Healthy People 2000," a DHHS-led national activity for setting 
priority areas. This RFA, Type 2 Diabetes in the Pediatric 
Population, 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 RFA will use the National Institutes of Health (NIH) research 
project grant (R01) and Exploratory/Development Research Grant (R21) 
award mechanisms.  Except as otherwise stated in this announcement, 
awards will be administered under NIH grants policy as stated in the 
NIH Grants Policy Statement.

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.

Applicants from institutions which have a General clinical Research 
Center (GCRC) funded by the NIH National Center for Research 
Resources may wish to identify the GCRC as a resource for conducting 
the proposed research.  In such a case, a letter of agreement from 
either the GCRC program director or principal investigator should be 
included with the application.  

This RFA is a one-time solicitation.  Future unsolicited competing 
continuation applications will compete with all investigator-
initiated applications and be reviewed according to the customary 
peer review procedures.  Responsibility for the planning, direction, 
and execution of the proposed project will be solely that of the 
applicant.  The anticipated award date is September 30, 2000.

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 Grant applications can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm

Modular Grant applications will request direct costs in $25,000 
modules.  The total direct costs must be requested in accordance 
with the program guidelines and the modifications made to the 
standard NIH 398 application instructions. 

FUNDS AVAILABLE

For FY 2000, the NIDDK intends to commit approximately $2 million, 
and the NICHD plans to commit $500,000 to fund 10-12 new and/or 
competing continuation grants in response to this RFA.  An applicant 
may request a project period of up to 5 years for an R01.  

Because the nature and scope of the research proposed may vary, it 
is anticipated that the size of awards will also vary.  Prospective 
applicants anticipating the submission of applications with direct 
cost budgets larger than $500,000 per year are encouraged to 
consult, at an early opportunity, with the appropriate program 
official listed under INQUIRIES.  

Although the financial plans of the NIDDK and NICHD provide support 
for this program, awards pursuant to this RFA are contingent upon 
the availability of funds and the receipt of a sufficient number of 
applications of outstanding scientific and technical merit.

RESEARCH OBJECTIVES

Background

Type 2 diabetes is characterized by insulin resistance and impaired 
insulin secretion, although its precise etiology and pathogenesis 
are only incompletely understood.  The public health impact of type 
2 diabetes is enormous. 

Clearly associated with aging and obesity, type 2 diabetes has 
traditionally been considered a disease of adults.  Children 
presenting with diabetes are usually assumed to have type 1 
diabetes, an autoimmune disease. In recent years, however, it has 
become apparent that an increasing number of children who present 
with hyperglycemia actually have type 2 diabetes.  Although many of 
the reports of type 2 diabetes in children are of an anecdotal 
nature, several published series have recently demonstrated a 
dramatic rise in the disorder in children.  In general, population-
based screening data are not available.  However, data culled from 
diabetes clinics in several locations suggest that the percentage of 
children diagnosed with diabetes who are classified as having type 2 
diabetes has risen from less than 5% (prior to 1994) to 20-30% 
(after 1994).  The number of children being diagnosed with type 1 
diabetes during this period has not changed substantially. 

Not surprisingly, the available published data reveal that one of 
the major risk factors for type 2 diabetes in children is obesity.  
Indeed, the increase in reports of type 2 diabetes among children 
parallels a similar rise in the adult population, as obesity has 
become a major public health concern.  In children, the rise in the 
incidence in type 2 diabetes appears to be concentrated largely in 
minority populations – African Americans, Hispanic Americans and 
Native Americans.  Indeed, type 2 diabetes (in all age groups) is 
one of the major chronic diseases where significant racial/ethnic 
health disparities exist.

Data from NHANES III suggests that up to 1/3 of adults who have type 
2 diabetes may go undiagnosed.  A similar situation may exist with 
children.  Indeed, the diagnosis of type 2 diabetes in children is 
often made because of routine laboratory screening being conducted 
as part of a school physical and not because the child presents to a 
health care provider with specific complaints.  Thus, many children 
who do not receive such screening may go undiagnosed until they 
become symptomatic, at which time they may have been hyperglycemic 
for many years and are at high risk for developing diabetic micro- 
and macrovascular complications.  In addition, the incidence of type 
2 diabetes in the pediatric population may be underestimated if all 
children with diabetes are assumed (but sometimes incorrectly) to 
have type 1 diabetes. Further confounding the situation are an 
increasing number of reports that many African American children 
with diabetes may present with ketoacidosis, traditionally 
considered the hallmark of type 1 diabetes, but subsequently can be 
managed without insulin.  Thus, the emerging epidemic of type 2 
diabetes in children also raises questions concerning the diagnostic 
criteria that have been used to distinguish type 1 and type 2 
diabetes.

The majority of children with type 2 diabetes are in the pre-
adolescent or adolescent age range.  The adolescent period presents 
special challenges to health care providers and families when 
attempting to promote behavior and life style changes.  Treatment 
options are further restricted by the lack of data on the use of 
pharmacologic agents for type 2 diabetes in the pediatric 
population.

Scope and Objectives

New hypothesis-driven studies are needed to describe the 
epidemiology, refine the diagnosis, define the metabolic 
abnormalities and formulate treatment options for type 2 diabetes in 
children.  Relevant topics listed below are examples and should not 
be construed as requiring or limiting. 

o Descriptive epidemiologic studies to define risk factors and 
metabolic or genetic markers for type 2 diabetes in children.  These 
studies should have as a long-term goal the establishment of case 
definition.

o Prospective screening studies in high-risk individuals to describe 
the incidence and prevalence of type 2 diabetes in specific sub-
populations.

o Studies to establish and validate practical screening programs for 
type 2 diabetes in children. 

o Metabolic studies to define early markers of insulin resistance 
and/or beta cell dysfunction in children.

o Studies to examine the relative roles of insulin resistance and 
beta cell dysfunction in children with type 2 diabetes.

o Studies to examine patterns of impaired glucose tolerance and 
determine the time course between the development of insulin 
resistance and clinical diabetes in children.

o Studies to determine whether weight loss and/or exercise in 
children reverses insulin resistance.

o Studies to define metabolic and/or genetic differences among 
various ethnic and/or racial groups which would predispose to the 
development of type 2 diabetes at a young age. 

o Studies to determine whether there are metabolic differences 
between children and adults with new-onset type 2 diabetes.

o Studies to determine whether there are identifiable metabolic 
and/or genetic differences between ketosis-prone and “typical” type 
2 diabetic children.

o Single or multi-center clinical studies to determine the risks and 
benefits of pharmacologic treatment of type 2 diabetes in children.

o Studies to describe the epidemiology of micro- and macrovascular 
complications in children with type 2 diabetes.

o Studies to develop appropriate screening strategies for the micro- 
and macrovascular complications of type 2 diabetes in children.

o Behavioral studies to define factors which impact on the 
pathogenesis of type 2 diabetes in children, and affect compliance 
with treatment and/or prevention programs.  Also of interest would 
be studies to test strategies to improve and/or maximize compliance.

o Studies to evaluate strategies for promoting weight loss, 
appropriate eating behavior, and increased exercise or physical 
activity in children and adolescents at risk for and/or with type 2 
diabetes.

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 was 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.

LETTER OF INTENT 

Prospective applicants are asked to submit, by March 24, 2000, a 
letter of intent that includes a descriptive title of the proposed 
research; the name, address, and telephone number of the Principal 
Investigator; the identities of other key personnel and 
participating institutions; and the number and title of the RFA in 
response to which the application may be submitted.

Although a letter of intent is not required, is not binding, and 
does not enter into the review of a subsequent application, the 
information that it contains allows NIDDK staff to estimate the 
potential review workload and avoid conflict of interest in the 
review.

The letter of intent is to be sent to:

Chief, Review Branch 
Division of Extramural Activities, NIDDK
Natcher Building, Room 6AS-37F
45 Center Drive MSC 6600
Bethesda, MD 20892-6600 
Telephone:  (301) 594-8885
FAX:  (301) 480-3505

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be 
used in applying for these grants.  These forms are available at 
most institutional offices of sponsored research and 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.

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 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.)  
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 RFA label available in the PHS 398 (rev. 4/98) application form 
must be affixed to the bottom of the face page of the application.  
Failure to use this label could result in delayed processing of the 
application such that it may not reach the review committee in time 
for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must 
be marked.

The sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been 
modified to allow for this change.  Please note this is in pdf 
format.

Submit a signed, typewritten original of the application, including 
the Checklist, and three signed photocopies, 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)

At time of submission, two additional copies of the application must 
be sent to:

Chief, Review Branch
Division of Extramural Activities, NIDDK
Natcher Building, Room 6AS-37F
45 Center Drive MSC 6600
Bethesda, MD 20892-6600

Applications must be received by the application receipt date listed 
in the heading of the RFA.  If an application is received after that 
date, it will be returned to the applicant without review. 
Supplemental documents containing significant revision or additions 
will not be accepted, unless applicants are notified by the 
Scientific Review Administrator.  

The Center for Scientific Review (CSR) will not accept any 
application in response to this RFA 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 
previously reviewed, but such applications must include an 
introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the 
CSR and responsiveness by the NIDDK and NICHD.  Incomplete and/or 
non-responsive applications will be returned to the applicant 
without further consideration. 

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NIDDK in accordance with the review 
criteria stated below.  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 the applications under 
review, will be discussed, assigned a priority score, and receive a 
second level review by the Advisory Councils of NIDDK and/or NICHD.

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.

(1) 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?

(2) 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?

(3) 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? 

(4) 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)?

(5) 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.

Schedule
Letter of Intent Receipt Date: March 24, 2000
Application Receipt Date: April 25, 2000
Peer Review Date: June-July 2000
Council Review: September 2000
Earliest Anticipated Start Date: September 30, 2000.

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit as determined by peer review;

o Availability of funds;

o Programmatic priorities.

INQUIRIES

Inquiries concerning this RFA 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
Building 45, Room 5AN18A
45 Center Drive MSC 6600
Bethesda, MD 20892-6600
Telephone: (301) 594-0021
FAX: (301) 480-3503 
E-mail: LinderB@extra.niddk.nih.gov 

Gilman Grave, M.D.
Center for Research for Mothers and Children
NICHD
6100 Executive Blvd., Room 4B11
Bethesda, MD 20892-7510
Telephone: (301) 496-5593
FAX:  (301) 480-9791
E-mail: graveg@hd01.nichd.nih.gov

Direct inquiries regarding fiscal matters to:

Nancy Dixon
Division of Extramural Activities 
NIDDK
45 Center Drive MSC 6600
Bethesda, MD 20892-6600
Telephone:  (301) 594-8854 
FAX:  (301) 480-4237
E-mail:  dixonn@extra.niddk.nih.gov

E. Douglas Shawver
Grants Management Branch
NICHD
6100 Executive Blvd., Room 8A17
Bethesda, MD 20892-7510
Telephone:  (301) 496-1303
FAX:  (301) 402-0915
E-mail: shawverd@hd01.nichd.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic 
Assistance No. 93.847 and 93.865. Awards are 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 NIH 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 NIH mission to protect and advance the physical and mental 
health of the American people.


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