Research Highlights from the Research Highlights from the National Institute of Diabetes and National Institute of Diabetes and

Digestive and Kidney DiseasesDigestive and Kidney Diseases

Griffin P. Rodgers, M.D., M.A.C.P.Griffin P. Rodgers, M.D., M.A.C.P.

Acting DirectorActing Director

National Institute of Diabetes and National Institute of Diabetes and Digestive and Kidney DiseasesDigestive and Kidney Diseases

Diabetes, Endocrinology, and Diabetes, Endocrinology, and Metabolic Diseases;Metabolic Diseases;Digestive Diseases and Nutrition; andDigestive Diseases and Nutrition; andKidney, Urologic, and Hematologic Kidney, Urologic, and Hematologic Diseases.Diseases.

The NIDDK conducts and supports The NIDDK conducts and supports basic and applied research and basic and applied research and provides leadership for a national provides leadership for a national program in:program in:

NIDDK’s Research and NIDDK’s Research and Dissemination SpectrumDissemination Spectrum

““Bench to Bedside and Beyond”Bench to Bedside and Beyond”

Organizational Structure of Organizational Structure of NIDDK’s Three Extramural NIDDK’s Three Extramural

Scientific DivisionsScientific Divisions

NIDDKNIDDK

KUHKUHDivision of Kidney,Division of Kidney,

Urologic, andUrologic, andHematologicHematologic

Diseases Diseases

DDNDDNDivision ofDivision of

Digestive DiseasesDigestive Diseasesandand

Nutrition Nutrition

DEDEMMDivision of Division of Diabetes, Diabetes,

Endocrinology, Endocrinology, and and

Metabolic Metabolic Diseases Diseases

A Paradigm of NIDDK’s Integrated A Paradigm of NIDDK’s Integrated Research ProgramsResearch Programs

ObesityObesity Type 2Type 2DiabetesDiabetes

KidneyKidneyDiseaseDisease

Overweight and ObesityOverweight and Obesity

BMI below 18.5 – UnderweightBMI below 18.5 – UnderweightBMI between 18.5 and 24.9 – Healthy weightBMI between 18.5 and 24.9 – Healthy weightBMI between 25 and 29.9 – OverweightBMI between 25 and 29.9 – OverweightBMI 30 and above – ObeseBMI 30 and above – Obese

BMI below 5th percentile – UnderweightBMI below 5th percentile – UnderweightBMI between 5th and less than 85th – Healthy BMI between 5th and less than 85th – Healthy weightweightBMI between 85th and less than 95th – At BMI between 85th and less than 95th – At Risk of OverweightRisk of OverweightBMI 95th percentile and above – OverweightBMI 95th percentile and above – Overweight

For AdultsFor Adults

For Children and AdolescentsFor Children and Adolescents

PhlebitisPhlebitisvenous venous stasisstasis

Coronary heart Coronary heart diseasedisease

Pulmonary diseasePulmonary diseaseabnormal functionabnormal functionobstructive sleep apneaobstructive sleep apneahypoventilation syndromehypoventilation syndrome

Gall bladder Gall bladder diseasedisease

GoutGout

DiabetesDiabetes

OsteoarthritisOsteoarthritis

Nonalcoholic fatty liver Nonalcoholic fatty liver diseasediseasesteatosissteatosissteatohepatitissteatohepatitiscirrhosiscirrhosis

HypertensionHypertensionDyslipidemiaDyslipidemia

CataractsCataracts

SkinSkin

PancreatitisPancreatitis

CancerCancerbreast, uterus, cervix, prostate, kidneybreast, uterus, cervix, prostate, kidneycolon, esophagus, pancreas, livercolon, esophagus, pancreas, liver

Gynecologic abnormalitiesGynecologic abnormalitiesabnormal mensesabnormal mensesinfertilityinfertilitypolycystic ovarian syndromepolycystic ovarian syndrome

StrokeStrokeHealth Complications of ObesityHealth Complications of Obesity

Idiopathic intracranial Idiopathic intracranial hypertensionhypertension

Obesity Trends Among U.S. Adults

No Data <10% 10-14% 15-19% 20-24% ≥25%

1991 2004

00

55

1010

1515

2020

00

55

1010

1515

2020

Perc

ent

Perc

ent

Perc

ent

Perc

ent6-11 years old6-11 years old

12-19 years old12-19 years old

Trends in U.S. Child and Trends in U.S. Child and Adolescent OverweightAdolescent Overweight

1963

-1967

1963

-1967

1999

-2000

1999

-2000

2001

-2002

2001

-2002

2003

-2004

2003

-2004

1971

-1974

1971

-1974

1976

-1980

1976

-1980

1988

-1994

1988

-1994

Obesity: Gene/Environment Obesity: Gene/Environment InteractionsInteractions

Current environment

Past environment

Genetic susceptibility

Adip

ocity

phe

noty

pe(e

.g.,

body

mas

s ind

ex)

ObesityObesity Type 2Type 2DiabetesDiabetes

KidneyKidneyDiseaseDisease

A Paradigm of NIDDK’s A Paradigm of NIDDK’s Integrated Research ProgramsIntegrated Research Programs

Two Major Forms of DiabetesTwo Major Forms of Diabetes

Usually diagnosed in childhood, adolescence, or young Usually diagnosed in childhood, adolescence, or young adulthoodadulthoodBody’s immune defense system mistakenly destroys Body’s immune defense system mistakenly destroys insulin-producing cells in the pancreas (autoimmunity) insulin-producing cells in the pancreas (autoimmunity) Results in lack of insulin to control blood sugar levels; Results in lack of insulin to control blood sugar levels; insulin therapy lifesaving but not a cureinsulin therapy lifesaving but not a cure

Historically diagnosed in adults; now in children and Historically diagnosed in adults; now in children and adolescentsadolescentsBody has reduced sensitivity to insulinBody has reduced sensitivity to insulinTherapy increases insulin release/sensitivity; some insulin Therapy increases insulin release/sensitivity; some insulin administration may be requiredadministration may be requiredObesity is a serious risk factorObesity is a serious risk factorCan be prevented or delayed by diet and exercise as Can be prevented or delayed by diet and exercise as shown in NIH clinical trialsshown in NIH clinical trials

Type 1Type 1

Type 2Type 2

No Data <4% 4-4.9% 5-5.9% ≥6%

1994 2004

Estimates of Diagnosed Diabetes Among Adults in the U.S.

Diabetes: Burden of DiseaseDiabetes: Burden of Disease

20.8 million 20.8 million AmericansAmericans ((7 percent 7 percent of the of the U.S. population) have diabetesU.S. population) have diabetes90-9590-95 percent of cases are type 2 diabetes percent of cases are type 2 diabetesMinorities Minorities are disproportionately affected are disproportionately affected by type 2 diabetesby type 2 diabetes1 in 31 in 3 Americans born in 2000 is predicted Americans born in 2000 is predicted to develop diabetes during his or her to develop diabetes during his or her lifetime (for Hispanic females: lifetime (for Hispanic females: 1 in 21 in 2))

0

10

20

30

40

50

1960

1970

1970

1980

1980

1990

1990

2000

2000

2010

2010

2020

2020

2030

2030

2040

2040

2050

2050

Peop

le (

mill

ions

)Pe

ople

(m

illio

ns)

YearYear

Diagnosed Diabetes in the U.S. Diagnosed Diabetes in the U.S. Diagnosed (1960-2004) Diagnosed (1960-2004) and and

Projected Diagnosed (2005-2050)Projected Diagnosed (2005-2050) Cases Cases

Diagnosed casesDiagnosed casesProjected Projected

diagnosed casesdiagnosed cases

Results from the Diabetes Prevention Program Results from the Diabetes Prevention Program Substantial Reduction in DiabetesSubstantial Reduction in Diabetes

in All Race-Ethnic Groupsin All Race-Ethnic Groups

LifestyleLifestyle MetforminMetformin Placebo/Standard carePlacebo/Standard care

Case

s pe r

10 0

per

s on-

yea r

sCa

ses p

e r 1

00 p

erso

n -ye

a rs

00

33

66

99

1212

1515

All participantsAll participants CaucasianCaucasian AfricanAfricanAmericanAmerican

HispanicHispanic AmericanAmericanIndianIndian

AsianAsian

Complications Common to Both Complications Common to Both Type 1 and Type 2 DiabetesType 1 and Type 2 Diabetes

Blindness

Kidney Kidney DiseaseDisease

Stroke

Heart Disease

AtherosclerosisAtherosclerosis

Foot Ulcers and Amputations

Acute complicationsAcute complications

Chronic complicationsChronic complications

Dangerously high or low Dangerously high or low blood glucoseblood glucose

→ → ccoma, death oma, death

Affect all major organsAffect all major organsDevelop over time/ Develop over time/ exposure to high blood exposure to high blood glucoseglucoseTight control of blood Tight control of blood glucose can prevent or glucose can prevent or delaydelay

ObesityObesity Type 2Type 2DiabetesDiabetes

KidneyKidneyDiseaseDisease

A Paradigm of NIDDK’s A Paradigm of NIDDK’s Integrated Research ProgramsIntegrated Research Programs

End-stage Renal Disease in the U.S. End-stage Renal Disease in the U.S. Number of Patients per Million PopulationNumber of Patients per Million Population

19931993 20032003

End-stage Renal Disease in the U.S.End-stage Renal Disease in the U.S.All Values are for Calendar Year 2004All Values are for Calendar Year 2004

Prevalence: Prevalence: 472,099472,099 patients were patients were undergoing treatmentundergoing treatmentMortality: Mortality: 84,25284,252 deaths in patients deaths in patients undergoing treatment for ESRDundergoing treatment for ESRDPrimary cause:Primary cause:

Diabetes: Diabetes: 45,87145,871High blood pressure: High blood pressure: 28,13228,132

Primary treatment:Primary treatment:Dialysis: Dialysis: 335,963335,963 patients received dialysis patients received dialysisKidney Transplant: Kidney Transplant: 16,90516,905 performed performed

Minorities Minorities are disproportionately affectedare disproportionately affected

End-stage Renal Disease in the U.S. End-stage Renal Disease in the U.S. Adjusted Incident Rates & Annual Percent ChangeAdjusted Incident Rates & Annual Percent Change

Progress in Combating the Progress in Combating the U.S. ESRD EpidemicU.S. ESRD Epidemic

After 20 years of annual increases from 5 to 10 After 20 years of annual increases from 5 to 10 percent, rates for new cases of kidney failure percent, rates for new cases of kidney failure have stabilizedhave stabilizedBetter disease prevention methods appear to Better disease prevention methods appear to be responsiblebe responsible

Use of angiotensin-converting enzyme inhibitors Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and angiotensin receptor blockers Better glycemic controlBetter glycemic controlBetter blood pressure control Better blood pressure control

NIH research has established the value of these NIH research has established the value of these interventionsinterventions

But, progress has not yet been realized across all But, progress has not yet been realized across all U.S. populationsU.S. populations

Incident Diabetic End-stage Incident Diabetic End-stage Renal Disease in the U.S.Renal Disease in the U.S.

Age 20 to 29 YearsAge 20 to 29 Years

00

55

1010

1515

2020

2525

3030

3535

1980

1981

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

YearYear

Per m

illion

pop

ulat

ion

Per m

illion

pop

ulat

ion CaucasianCaucasian

African AmericanAfrican American

More Insights into Preventing More Insights into Preventing Complications of DiabetesComplications of Diabetes

Microvascular damage – retinopathy

Macrovascular damage – CVD

Preventing complications by preventing diabetes - DPP

Eye Disease: Intensive Diabetes Eye Disease: Intensive Diabetes Treatment Reduces RiskTreatment Reduces Risk

00

2525

5050

7575

100100

Study YearsStudy Years

00 11 22 33 44 55 66 77 88 99

Cum

ulat

ive

Per

cent

Cum

ulat

ive

Per

cent

ConventionalConventional

Cumulative Incidence Cumulative Incidence of of >> 3-Step Change 3-Step Change

p = 0.001p = 0.001

IntensiveIntensive

Cum

ulat

ive

Inci

denc

e of

Non

fata

lC

umul

ativ

e In

cide

nce

of N

onfa

tal

Myo

card

ial I

nfar

ctio

n, S

troke

, or

Myo

card

ial I

nfar

ctio

n, S

troke

, or

Dea

th fr

om C

ardi

ovas

cula

r Dis

ease

Dea

th fr

om C

ardi

ovas

cula

r Dis

ease

0.000.00

0.020.02

0.040.04

0.060.06

Years Since Entry into DCCT/EDIC StudyYears Since Entry into DCCT/EDIC Study

ConventionalConventional

IntensiveIntensive

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 210 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

Heart Disease: Heart Disease: Intensive Diabetes Intensive Diabetes Treatment Reduces RiskTreatment Reduces Risk

NIH and NIDDK Strategic NIH and NIDDK Strategic Research PlansResearch Plans

Strategic Plan for NIH Obesity ResearchStrategic Plan for NIH Obesity Research

Research Toward Preventing and Research Toward Preventing and Treating Obesity Through Behavioral Treating Obesity Through Behavioral and Environmental Approaches to and Environmental Approaches to Modify Lifestyle, with an Emphasis on Modify Lifestyle, with an Emphasis on Childhood ObesityChildhood Obesity

Research Toward Preventing and Research Toward Preventing and Treating Obesity Through Treating Obesity Through Pharmacologic, Surgical, or Other Pharmacologic, Surgical, or Other Medical ApproachesMedical Approaches

Research Toward Understanding the Research Toward Understanding the Relationship Between Obesity and Its Relationship Between Obesity and Its Associated Health ConditionsAssociated Health Conditions

Cross-cutting Topics – Technology, Cross-cutting Topics – Technology, Multidisciplinary/Interdisciplinary Multidisciplinary/Interdisciplinary Research Teams, Translational Research Teams, Translational Research, Training, Research, Training, Education/OutreachEducation/Outreach

Developed by the NIH Obesity Research Task Force with Developed by the NIH Obesity Research Task Force with critical input from external scientists and the publiccritical input from external scientists and the public

Although listed separately, the first two themes are interdependent. We seek to create an interdisciplinary approach in which lifestyle interventions are informed by an understanding of the basic biological and genetic factors and vice versa.

Conquering Diabetes: A Scientific Conquering Diabetes: A Scientific Progress Report on Progress Report on The Diabetes Research The Diabetes Research

Working Group’sWorking Group’s Strategic Plan Strategic Plan

GeneticsGeneticsAutoimmunity and the Autoimmunity and the Beta CellBeta CellCell Signaling and Cell Cell Signaling and Cell RegulationRegulationObesityObesityClinical Research and Clinical Research and Clinical Trials of Critical Clinical Trials of Critical ImportanceImportance

Highlights of Program Efforts, Highlights of Program Efforts, Research Advances and Research Advances and Opportunities related to:Opportunities related to:

Progress and Priorities: Progress and Priorities: Renal Disease Research PlanRenal Disease Research Plan

Important scientific Important scientific resources needed to resources needed to reach research goals reach research goals include:include:Conducting More Conducting More Epidemiological StudiesEpidemiological StudiesCreating Centers and Creating Centers and CooperativesCooperativesCreating New Ways to Study Creating New Ways to Study Renal InjuryRenal InjuryFocusing More on Genetic Focusing More on Genetic SusceptibilitySusceptibilityDeveloping a Renal Genomics Developing a Renal Genomics ProjectProjectIncreasing Research on Increasing Research on TreatmentsTreatments

Examples of NIH and NIDDK Examples of NIH and NIDDK Education and Outreach ProgramsEducation and Outreach Programs

The The Weight-control Information NetworkWeight-control Information Network (WIN) is an information service of the NIDDK. (WIN) is an information service of the NIDDK. WIN was established in 1994 to provide the WIN was established in 1994 to provide the general public, health professionals, the general public, health professionals, the media, and Congress with up-to-date, media, and Congress with up-to-date, science-based information on obesity, weight science-based information on obesity, weight control, physical activity, and related control, physical activity, and related nutritional issues. nutritional issues.

WIN produces, collects, and disseminates WIN produces, collects, and disseminates materials on obesity, weight control, and materials on obesity, weight control, and nutrition.nutrition.

Weight-control Weight-control Information NetworkInformation Network

National Diabetes National Diabetes Education ProgramEducation Program

The The National Diabetes Education National Diabetes Education ProgramProgram (NDEP) is a federally (NDEP) is a federally funded program sponsored by the funded program sponsored by the National Institutes of Health and National Institutes of Health and the Centers for Disease Control and the Centers for Disease Control and Prevention and includes over 200 Prevention and includes over 200 partners at the federal, state, and partners at the federal, state, and local levels, working together to local levels, working together to reduce the morbidity and mortality reduce the morbidity and mortality associated with diabetes.associated with diabetes.

Components of the National Components of the National Diabetes Education ProgramDiabetes Education ProgramControl Your Diabetes. For Life.Control Your Diabetes. For Life. - To promote the - To promote the importance and benefits of diabetes controlimportance and benefits of diabetes controlBe Smart About Your Heart. Control the ABCs of Be Smart About Your Heart. Control the ABCs of DiabetesDiabetes - Encourages control of blood sugar, - Encourages control of blood sugar, blood pressure, and cholesterolblood pressure, and cholesterolSmall Steps. Big Rewards. Prevent type 2 Small Steps. Big Rewards. Prevent type 2 DiabetesDiabetes - Translate and promote the Diabetes - Translate and promote the Diabetes Prevention Program (DPP) clinical trial findingsPrevention Program (DPP) clinical trial findings

National Kidney DiseaseNational Kidney DiseaseEducation ProgramEducation Program

NKDEP

The The National Kidney Disease National Kidney Disease Education ProgramEducation Program (NKDEP) is an (NKDEP) is an initiative of the National Institutes of initiative of the National Institutes of Health, designed to reduce the Health, designed to reduce the morbidity and mortality caused by morbidity and mortality caused by kidney disease and its complications.kidney disease and its complications.

Aerial View of NIH campus in Aerial View of NIH campus in Bethesda, MDBethesda, MD