Characterize clinical features of diabetes. mellitus in Pima Indians. Identify risk factors for diabetes mellitus. Determine its pathogenesis …
Lessons from conducting research in an American Indian community: The Pima Indians of Arizona
Peter H Bennett, MB, FRCP
Scientist Emeritus National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA
Pittsburgh, December 13th, 2007
Phoenix
Salt River
N
10 miles Gila River Indian Reservation Gila River Sacaton
What did we learn in 1963?
RA and AS common in this population
We provided care and treatment for the affected
Community willing to take part in research Diabetes appeared to be a very common problem Further assessment of diabetes and its complications is needed
1965 Diabetes survey
75g OGTT Anthropometry Height and weight Medical history medical record review Physical examination- BP, ophthalmoscopy, joints etc and in those age30: Retinal photos, ECG, Plasma glucose, serum creatinine, cholesterol Urine glucose protein and if ve, protein/creatinine ratio
What did we learn in 1965?
The Pima have the worlds highest reported prevalence of diabetes Diabetes has a major impact on the community Plasma glucose levels show a bimodal distribution Current criteria for diagnosis seem inappropriate Retinopathy and nephropathy are
frequent complications Pregnancy in the diabetic is associated with considerable excess perinatal mortality Further assessment of determinants of diabetes and its complications is indicated A longitudinal study could elucidate risk factors for diabetes and its complications Very little known about the development and course of the disease
Addressing a problem that community perceived as important Discussed ideas for longitudinal study with community leaders
Ask for their suggestions Become aware of local cultural sensitivities
Obtain appropriate community approval and endorsement beyond the IRB
Eg Tribal council
Initial Goals of Longitudinal Study
Characterize clinical features of diabetes mellitus in Pima Indians Identify risk factors for diabetes mellitus Determine its pathogenesis Distribution and determinants of its complications
Establishing the Longitudinal Population-based Study
Detailed census of community including identification of parents, siblings and children Examine all aged 5 years and over Repeat examination at two-yearly intervals 75g OGTT Anthropometry-Height and weight Medical history medical record review Physical examination- BP, ophthalmoscopy,
etc and in those age15: Retinal photos, ECG, Plasma glucose, serum creatinine, cholesterol Urine glucose protein and if ve, protein/creatinine ratio Initiate Pregnancy study -Third trimester GTT and examination of newborn-birth weight and congenital anomalies
Risk Factors for Diabetes
Diabetes in Pima by Parental Diabetes
60
Prevalence
40 20 0
None
Father
Mother
Both
Diabetes in Parents
Incidence of Diabetes by BMI in Pima Indians
Cases/1000 person-yr
80 60 40 20 0 20 -25 -30 -35
Obese
-40
40
Body Mass Index kg/m2
Knowler, Am J Epidem, 1981
Five-year Incidence of Type 2 Diabetes in Pimas aged 25-44yrs by BMI
40
Incidence
30 20 10 0
Type 2 DM in Parents Neither One affected Both affected
20-25
20-25
25-30
30-35
35
BMI kg/meters squared
Adapted -Knowler AJEpid 1981;113:144-56
Type 2 DM and Current Leisure Activity
in Pima Indians, aged 37-46 years
25 MEN WOMEN
Prevalence
20 15 10 5 0 Low Medium High Low Medium High
Physical Activity
Pathogenesis
Five-year Incidence of Type 2 Diabetes in Pima Indians with Normal Glucose Tolerance by fasting insulin levels
Cumulative Incidence
12 10 8 6 4 2 0 55 55-90 91-145 145 Fasting Insulin uU/ml
Diabetes
Incidence cases/1000 p-yr by Insulin Sensitivity and Secretion
100 Incidence 75 50 25 0
Low Mid on ti High re High Mid Low
ec S
Sensitivity
Complications
Incidence of Proteinuria by Duration of Diabetes
Cases/1,000 Person-Years
200 150 100 50 0
2h glucose mg/dl 450 250-449 250
200 150 100 50 0
Systolic BP mm Hg 160 140-159 140
0
5
10
15
0
5
10
15
Duration of Diabetes years
Kidney Int 35:681-687, 1989
Incidence of End-Stage Renal Disease in Diabetic Patients, 1984-93
Cases per 100,000/year
1500
Relative Incidence Whites 10 Blacks 21x Pima 92 x
1000
500
0
Age-sex-adjusted
Whites
Blacks
Pima Indians
Pregnancy study
Perinatal mortality Congenital defects Long-term effects of diabetic pregnancy on offspring Type 2 diabetes in childhood and adolescence
Prevalence of Diabetes in Children if Mother had Diabetes while Pregnant
70
Prevalence
60 50 40 30 20 10 0 10-14
Mothers Diabetes Prediabetic Diabetic
15-19
20-24
25-29
Age years
Diabetes Prevalence in Pima Indian 1965-1969 Children 1998-2002
6 with Diabetes
4
2
0 5-9 10-14 15-19 Age years 5-9 10-14 15-19
Risk Factors
for Diabetes in Children and Adolescents
Ten-year cumulative incidence of
diabe 
tes in Pima Indians aged 5-19years by Parental diabetes
Cumulative Incidence
15
Parental Diabetes Neither One diabetic parent Both parents diabetic
10
5
0 5-9 10-14 Age years
McCance DR et al, Diabetologia 37; 617-23, 1994
15-19
Prevalence of Diabetes by Exposure to Diabetes in Utero
25
Prevalence
20 15 10 5 0
No
Yes
5-9
10-14 Age years
15-19
Dabelea D et al, Diabetologia 41:904-910, 1998
Sib Pairs Discordant for Diabetes and Intrauterine Exposure to Diabetes
25
Number of sib pairs
20 15 10
OR30, p001
21
7
5 0 Born Before Born After Mothers Diagnosis
Percent of Offspring exposed to Diabetes in utero in three time intervals
8
Percent
6 4 2 0
1967-76 77-86 87-96 Time Period
Prevalence of Type 2 Diabetes in Pima Indians aged 20-39yrs by Birth Weight
Prevalence of diabetes
30
20
10
0
00 25
Age-Adjusted
00 0 -3
00 5 -3
00 0 -4
00 5 -4
00 45
Birth Weight g
Parental Risk of Diabetes according to birth weight of children
2
Hazard Rate Ratio
15 1 05 0 1
Father Mother
2
3
4
5
Childs Birth Weight Quintile
Lindsay, RS et al, Diabetes 49:445-449, 2000
Prevalence of Type 2 Diabetes and Infant Feeding
30
Prevalence
Breast Fed
2 months Never
25
20 15 10 5 0
Odds Ratio042 95 CI018-096
10-19
20-29 Age years
30-39
Adjusted for age, sex, birth date, obesity, birth weight parental diabetes and maternal diabetes in pregnancy
Prevalence of Diabetes in 5-19 year old Pima Children by Relative Weight
Prevalence
6 4 2 0 100 100-119 120-139 140-159 160
Relative Weight
Cumulative Incidence of Nephropathy by Age at Diagnosis and Attained Age
30
Incidence
Age at Diagnosis 15-24 25-34 35-44
20 10 0 20 30 40 50 Attained Age years
Death rates in Pima Indians with onset of diabetes 20years
Deaths/1000 pyrs
90 75 60 45 30 15 0 5-14 1524 2534 3544 4554 5564
Diabetes No diabetes
Age years
Consequences of youth-onset type 2 diabetes
Pregnancies are likely to be diabetic pregnancies Children will develop diabetes at an early age High likelihood of vascular complications by 30-40 years of age Likely to develop ESRD in the 40 year age range Premature mortality
Prevention
Diabetes Incidence Rates by Ethnicity DPP
L ife s tyle
Cases per 100 person-yr
12
M e tfo rm in
P la c e b o
8
4
0 C a u c a s ia n Afr ic a n n 1 7 6 8 Am e r ic a n n 6 4 5 His p a n ic n 5 0 8 Am e r ic a n In d ia n n 1 7 1 As ia n n 1 4 2
Ongoing Intervention studies
DPPOS Look AHEAD Early intervention in prevention of renal disease
Some Achievements from the Pima Indian Study
Identified phenotypic and etiologic differences in Type 1 IDDM and Type 2 diabetes mellitus Established criteria for definition and diagnosis of diabetes mellitus Now the International Criteria
Some Achievements from the Pima Indian Study
Established obesity as a major risk factor for type 2 diabetes Established importance of insulin resistance as a key feature of Type 2 diabetes Demonstrated that blood pressure predicts development and progression of diabetic retinopathy and nephropathy
Some Achievements from the Pima Indian Study
Demonstrated that intrauterine environment programs the development of obesity and diabetes in offspring Established nature of relationships of diabetes to low and high birth-weight Established that infant feeding practice is an important determinant of diabetes risk Established that type 2 diabetes can be prevented or delayed by lifestyle intervention or metformin Identified several genetic loci that confer genetic susceptibility to diabetes
Pima Indians of the Gila River Indian Community have contributed
enormously to knowledge and understanding of the causes of Type 2 diabetes and its complications, ways in which the disease is now treated, and possible ways by which it may be prevented
Guidelines for successful communitybased programs
Address a problem that community perceives as important Discuss ideas with community leaders
Ask for their suggestions Become aware of local cultural sensitivities
Obtain appropriate community approval and endorsement beyond the IRB
Eg Tribal council
Guidelines for successful community-based programs
Engage local community members in the work to the greatest extent possible Start slowly and simply to build confidence Explain the goals and procedures to participants in simple understandable languagebest done by a local community member Try to provide a service to the community that is not readily available Provide feedback to participants and the community–never enough
Guidelines for successful community-based programs
Be prepared for delays in approval process Can the work be done in conjunction with or as a component of other ongoing activities?
Thank
you
Source:readinghospital.org
