Health Disparities in the U'S': Intersection with the Mission of NIDDK

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Health Disparities in the U.S.Intersection with
the Mission of NIDDK

• Griffin P. Rodgers, M.D.
• Deputy Director, NIDDK
• and
• Chief, Molecular Clinical Hematology Branch,
  NIDDK, National Institutes of Health

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Minority Health Disparities

• Racial and ethnic minorities in the U.S. have
  poorer overall health than the white,
  non-Hispanic population.
• Magnitude of disparities is increasing
• Diminished quality of life
• Premature death

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What Causes Disparities?

• Scientific factors
• Incomplete scientific and medical knowledge
• Ineffective translation of research into
  treatments
• Social and economic factors
• Diminished access to quality care
• Lower socioeconomic status
• Less healthy diets and lifestyles

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Addressing Minority Health Disparities Through
Research

• NIH is committed to reducing and ultimately
  eliminating disparities through
• Enhancing research
• Recruiting qualified, motivated scientists
• Bolstering public education and
• Enhancing strategic planning.

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National Institute of Diabetes and Digestive and
Kidney Diseases
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Organizational Structure of NIDDKs Three
Divisions
NIDDK
DDN
DEM
KUH
Division of Kidney, Urologic, and Hematologic Dise
ases
Division of Digestive Diseases and Nutrition
Division of Diabetes, Endocrinology, and
Metabolic Diseases
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Type 2 Diabetes as a Paradigm of NIDDKs
Integrated Research Programs
Type 2 Diabetes
Kidney Disease
Obesity
DDN
DEM
KUH
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Estimated Growth in Type 2 Diabetes and US
Population, 2000-2050
Bagust A, et al. Diabetes 50, Suppl 2 A205, 2001
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Diabetes in America

• Afflicts 16 million people
• 800,000 new cases a year one-third undiagnosed
• Sixth leading cause of death from disease
• Highest incidence in minorities
• Main cause of new blindness,
• kidney failure, and amputations
• Shortens lifespan by up to
• 15 years
• Costs more than 105 billion
• annually

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Burden of Diabetes in the U.S.

• Increases the risk of heart attack and stroke by
  2 - 4 fold
• The leading cause of new blindness, end stage
  renal disease, and amputations
• 193,140 deaths from diabetes a year (7th)
• Costs 98 billion or more per year

CDC National Diabetes Fact Sheet 1998
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Diabetes in the United States
Prevalence in Ethnic-Racial Groups
190
Percent of population with diabetes relative to
Caucasians
160
100
11.3
2.3
1.2
Total number of cases (millions)
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Type 2 Diabetes in Minorities

• Minorities comprise 25 of all adult patients
• Majority of children and adolescents with
  diabetes are minorities
• African Americans are 1.7 times more likely to
  have diabetes than non-Latino whites
• Obesity is major risk factor for diabetes

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Complications Disproportionately Affect Minorities

• Compared to white Americans, minorities are
• More likely to develop diabetic retinopathy, (50
  more in African Americans)
• More likely to develop diabetes-related end-stage
  renal disease, (4 fold more in African Americans,
  5X more in American Indians and Alaska Natives)
• 1.5 - 2.5 times more likely to have lower
  extremity amputations caused by diabetes in
  African Americans and Native Americans.

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Risk Factors for Type 2 Diabetes

• Age
• Obesity
• Body fat distribution
• Physical inactivity
• Family history of diabetes

• Race/ethnicity
• Previous gestational diabetes (GDM)
• Elevated fasting glucose levels
• Impaired glucose tolerance (IGT)

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Weight Gain Increases Diabetes Risk
Every 1 kilogram (2.2 pounds) of weight gain per
10 years is associated with a 4.5 increased risk
to develop diabetes
68 - 72 of diabetes risk in the U.S. is
attributable to or associated with excess weight
Ford et al. Amer J Epidemiol 146214,1997
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Obesity in America

• Half of Americans are overweight (BMI gt 25)
• 25 of Americans are obese (BMI gt 30)

• Obesity is a major risk
• factor for diabetes and
• other diseases
• 80 of people with
• type 2 diabetes are obese
• Genetics environment

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Class III (Extreme) Obesity

• Affects 3.9 of US women 1.8 of men
• Disproportionately affects racial and ethnic
  minority populations
• 7.4 of African American women
• 4.5 of Mexican American women
• Population at great risk for comorbid conditions
• Rising health care and other economic costs

Flegal et al., 1998
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Greater Burden of Diabetes Complications in
Minorities

• Elevated risk of microvascular complications,
  which can result in blindness, end stage renal
  disease, and amputation. Why?
• Higher levels of hypertension and hyperglycemia
• Possible genetic components
• Physiologic and behavioral issues as well as
  differences in access to care

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Dialysis and Transplantation Treatments for
Kidney Failure

• 400,000 people were treated in 1998 6,000 were
  children and young adults
• 85,500 new cases in 1998
• 20 annual mortality
• Direct health costs 17 billion a year

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Incidence Rates of Diabetic ESRD by Race,
1998-2001, Adjusted for Gender and Age
ADR 2003
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Candidate Type 2 Diabetes Susceptibility Genes
Science 296 686-689, 2002.
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An Autosomal Genomic Scan for Loci Linked to Type
II Diabetes Mellitus and Body-Mass Index in Pima
Indians
Am. J. Hum. Genet., 631130-1138, 1998
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Animal Models

• Initiate major effort in defining environmental
  modifiers of disease

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Genetic Background Affects the Phenotype
of IR/IRS-1 Double Heterozygous Knockout Mice
C57Bl/6J
129/Sv
100

• Due to differences in Insulin action, not insulin
  secretion.
• Genome-wide scan has identified 4 loci on 3
  chromosomes which contribute to these phenotypic
  differences.

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DH
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Prevalence of Diabetes ()
40
20
DH
Wt
0
Wt
0 2 4 6
0 2 4 6
Age (months)
Age (months)
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Environmental Modifiers of Diabetes in NOD Mice
Geography
Diet
Virus Infection
100
80
Percent Mice with Diabetes
60
40
20
0
Japan
Control
Edmonton
Germ-Free
Bar Harbor
Protein-free
Yeast OG96
Control Diet
LCMV-Infected
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Nutrient Processing/ Uptake
SGLT-1 glucose
glucose
triglycerides

• Germ-free mice
• consume 30 more chow
• have half the body fat of conventionally
  raised mice

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B. thetaiotaomicron VPI-5482 Genome
6,260,372 bp
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Comparison of Proteomes
Nutrient Metabolism
Signal transduction
Mobile Elements
Capsular Polysaccharide Synthesis
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The Microflora as an Environmental Factor that
Influences Predisposition to Obesity
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Mapping a Path to Treatment of Obesity - NIDDK

• Improve flow of discovery from animal models to
  humans and from humans to animal models
• Accelerate discovery of new molecules and
  pathways
• Increase access to research data and tools to
  pave the way for assembly into integrative models

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Mapping a Path to Prevention of Obesity - NIDDK

• Understand the role of the environment in
  development of obesity
• Identify the biological and societal impediments
  to behavioral change
• Take lessons from successful models of behavioral
  change

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Stages in the Natural History of Diabetes
Prevention Is Possible
Normal
IGT
Disability Death
Diabetes
Complications
Primary Secondary
Tertiary prevention prevention
prevention
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Diabetes Research Goal Prevent or Delay
Development of Diabetes in Minority Populations

• Basic research on genetic environmental risk
  factors
• Type 2 diabetes in children
• DPP clinical trial aimed at primary prevention in
  high-risk populations

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Diabetes Prevention Program (DPP)

• Multi-center clinical trial evaluating lifestyle
  and drug intervention in preventing or delaying
  type 2 diabetes in persons with impaired glucose
  tolerance
• 3819 volunteers (at high risk of developing
  diabetes) recruited at 27 medical centers
• 20 of the volunteers are African American
  another 24 are Hispanic, Asian American, Pacific
  Islander, or American Indian
• Patients followed for 3-6 years

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The Diabetes Prevention Program
A Randomized Clinical Trial to Prevent Type 2
Diabetes in Persons at High Risk
Sponsored by the NIH, NIDDK, NIA, NICHD, IHS,
CDC, ADA and other agencies and corporations
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DPP Goals Primary
To prevent or slow the development of type 2
diabetes in persons with impaired glucose
tolerance (IGT)
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DPP Goals Secondary

• Reduce cardiovascular disease (CVD) events
• Reduce CVD risk factors
• Reduce atherosclerosis

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Study Interventions
Eligible participants Randomized Standard
lifestyle recommendations
Intensive Lifestyle Metformin
Placebo (n 1082)
(n 1073) (n 1079)
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Lifestyle Intervention
An intensive program with the following specific
goals

• 7 loss of body weight and maintenance of
  weight loss
• Dietary gat goal lt25 of calories from fat
• Calorie intake goal 1200-1800 kcal/day
• 150 minutes per week of physical activity

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Study Population
Caucasian1768 African-American
645 Hispanic-American 508 Asian-American
Pacific Islander142 American Indian 171
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Results Development of Diabetes
Placebo, Metformin and Life-style

• Placebo Metformin Life-styleDevelopment of
  diabetes 11.0 7.8 4.8(percent
  per year)
• Reduction of diabetes 31 58compared
  with placebo
• Number needed to treat 13.9 6.9 to
  prevent 1 case in 3 years

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Conclusions
Implications

• Diabetes can be prevented for at least 3 years
  in persons at high risk, such as those in the
  DPP
• Identification of similar at-risk populations
  in the US might require oral glucose tolerance
  testing

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Post-DPP Study
Questions

• What are the long-term effects of DPP
  interventions for the DPP cohort and across all
  sub-groups?
• How durable are the effects of DPP
  interventions on diabetes prevention?
• Does diabetes prevention translate into
  prevention or reduction of
  hard-endpoint clinical sequelae?

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• Look AHEAD Action for HEAlth in Diabetes
• Objective to examine in overweight persons with
  Type 2 Diabetes, the long-term effects of
  interventions designed to achieve and sustain
  weight loss.
• Study will follow up participants for 9 to 11.5
  years after entry.

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Clinical Sites
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Weight Control Information Network
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Post-doctoral Training
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Mentored Patient-oriented Research Career
Development Award (K23)

• Supports the career development of investigators
  who have made a commitment to patient-oriented
  research.
• Provides support for 3 to 5 years of mentored
  study and research for clinically trained
  professionals

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Loan Repayment Program
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Authorization

• Loan Repayment Program for Clinical Research
• Public Health Improvement Act of November 2000
• Loan Repayment Program for Pediatric Research
• Childrens Health Act of 2000

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Purpose

• Recruitment and retention of highly qualified
  health professionals as clinical investigators
  and pediatric researchers

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Features

• Participants can receive educational loan
  repayment of up to 35,000 annually, plus a
  Federal tax liability offset.
• Repayment level is dependent on the total
  educational loan debt and applies to each year of
  obligated service.
• The NIDDK intends to commit 2 million in Fiscal
  Year 2003.

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Clinical or Pediatric Research Loan Repayment
Program

• Qualifying educational debt equal to or in excess
  of 20 of annual compensation
• In exchange for a two-year commitment to
  research, NIH will repay up to 35,000 per year
  of qualified educational debt plus a Federal tax
  offset
• Open to all doctoral-level researchers with
  nonprofit or US government funding
• Must be a US citizen and devote at least 50
  effort over two years to clinical research
• Learn more at www.lrp.nih.gov

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Extramural Loan Repayment ProgramsApplications
Assigned to the NIDDK FY03
CLINICAL RESEARCH
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Commitment to Improving Minority Health and
Reducing Health Disparities

• NIH strategic planning process
• Each Institute develops a strategic plan.
• Plans of individual Institutes coordinated into
  trans-NIH strategies.
• NIDDKs plan may be found at www.niddk.nih.gov

Full NIDDK Strategic Plan on Minority Health
Disparities (Draft) is http//www.niddk.nih.gov/fe
deral/planning/strategicplan_minority.htm