Type II Diabetes
The Roles of Race, Culture,
Genetics, Environment, and
Behavior
Ajay Dharia, MS IV
Arleen Brown, MD, PhD
Overview
• Type II diabetes mellitus (T2DM)
– Definition / Diagnosis
• Risk factors for T2DM
– Race/ethnicity, culture, and other demographic
characteristics
– Behavior
– Environment
– Genetics
Measurable Objectives*
•
•
•
•
List the diagnostic criteria for T2DM
Take a family history to understand a patient’s risk of
type 2 diabetes mellitus (T2DM)
Be able to explain how the following factors contribute
to diabetes risk, prevention, management, and
outcomes:
– Race/ethnicity
– Environment
– Behavior
– Genetic factors
Use T2DM as a template for other chronic conditions
* i.e., what you will be tested on
Influences on Diabetes Risk, Prevalence, and Outcomes
Race /
Ethnicity
Genetics
Culture
Diabetes
Risk
Prevalence
Outcomes
Health Care
Lifestyle
Environment
Case
• 45 year old Latino man with hypertension,
hyperlipidemia who presents to clinic with concerns
about developing diabetes.
• He is worried because there are several members of
his immediate family, including his mother, who
have diabetes. His mother has been struggling with
the complications of diabetes and was recently
started on dialysis for end-stage renal disease.
• The patient would like to know if he will also develop
diabetes.
• Additional clinical data: His waist circumference is
35” and his BMI is 27.
Introduction
• Diabetes is a group of metabolic diseases
characterized by hyperglycemia resulting from
insulin resistance and/or impaired insulin secretion
• Complications include neuropathy, nephropathy,
vascular disease, and retinopathy
• Classic Symptoms
– “Polys” – Polyuria, Polydipsia, Polyphagia
– Unexplained weight loss
How is Diabetes Mellitus Diagnosed?
• Fasting plasma glucose (FPG) >126 mg/dl (7.0 mmol/l)
– Fasting ==> No caloric intake for at least 8 hours.
• Random plasma glucose >200 mg/dl (11.1 mmol/l) with
classic symptoms of hyperglycemia
• 2-h plasma glucose >200mg/dl (11.1 mmol/l) during an
Oral glucose tolerance test (OGTT)
– World Health Organization (WHO) criteria
– Patients ingests 75g of glucose and blood glucose
retested at 2 hours
– Not recommended for routine clinical use, as it is
more difficult and less reliable
– Generally only used in pregnancy and selected
groups
ADA Guidelines, Diabetes Care Vol 32, Supplement 1, 2009.
Riccardi, Am J Epidemiol, 1985.
Risk Factors for T2DM
•
•
•
•
•
•
•
•
•
•
•
•
•
Age >45 years
BMI >25 kg/m2
First-degree relative with diabetes
Sedentary lifestyle
Race / Ethnicity
Impaired fasting glucose (fasting glucose 100-126 mg/dL)
Impaired glucose tolerance (2-h OGTT 140-200 mg/dL)
H/o gestational DM or delivery of a baby weighing >9 lbs
Hypertension (BP>140/90)
Dyslipidemia – HDL-c <35 mg/dL OR TG >250 mg/dL
Polycystic ovary syndrome
History of vascular disease
Genetic predisposition – but genetics “complex …and not
clearly defined”)
ADA Guidelines, Diabetes Care Vol 32, Supplement 1, 2009.
Importance of Family History
• If a single first degree relative has diabetes, the
prevalence of diabetes increases to about 15%,
i.e. an odds ratio of about 5
• Clinicians should ask about whether other family
members have:
–
–
–
–
–
–
Diabetes
Obesity
Hypertension
Chronic Kidney Disease (CKD)
Coronary Heart Disease
Stroke
Annis, Preventing Chronic Disease, 2005.
Risk Tree
45 y.o. Latino man
with a positive family
history and waist
circumference 35’’
What is his
predicted risk based
on this risk tree?
Heikes, Diabetes Care. 2008
Risk for our patient
45 y.o. Latino man with a positive family history and
waist circumference 35’’
What is his predicted risk based on this risk tree?
w
Influences on Diabetes Risk, Prevalence, and Outcomes
Race /
Ethnicity
Genetics
Culture
Diabetes
Risk
Prevalence
Outcomes
Health Care
Lifestyle
Environment
Comparison of diabetes prevalence*:
United States, by specified race, 1999
Rate per 100,000 population
100
80
60
40
20
0
Asian/Pacific Islander**
White, not-Hispanic
Hispanic***
Black/African American,
not-Hispanic
*Diabetes that has been diagnosed by a physician.
**Includes persons of Hispanic and non-Hispanic origin.
***Persons of Hispanic origin may be any race.
Age-adjusted rates are adjusted to the year 2000 standard population.
Source: National Health Interview Survey (NHIS), Centers for Disease Control and Prevention, NCHS.
American Indian/
Alaska Native**
Race/Ethnicity and DM
Variation Among
Asian and Pacific Islander Populations
60
50
40
30
20
10
15.1
2.6
4.3
6.4
9.6
10.5
Thailand
South Korea
0
China
India
Philippines
Asia Pacific Cohort Studies Collaboration. Asia Pac J Clin Nutr. 2007.
Tonga
Race/Ethnicity and DM
Variation Among
Latino and American Indian Populations
60
51.4
50
40
25.7
30
20
10
7.6
7.6
Argentina
Brazil
11.8
14.9
0
Barcelo, Pan Am J Public Health, 2001.
Cuba
Mexican
(Mexico
City)
Mexican
American
(US)
Pima (US)
Age-Adjusted Death Rate per 100,000 Persons
Disparities in Diabetes Death Rates
48.0
50
45
39.2
40
35
32.1
30
25
24.5
20
22.3
16.6
15
10
5
0
All Races
Asian/Pacific
Islander
White
Hispanic
American
Indian/Alaska
Native
* Age-adjusted, per 100,000 U.S. population, 2004
African
American
Racial/Ethnic Disparities in DM
• In the U.S., higher relative risk of diabetes among
minority populations
• Up to 50% of increased relative risk among minorities
due to modifiable factors
– Physical activity
– Smoking
– Alcohol
– Dietary energy intake
– BMI
– Waist-to-hip ratio
• In addition to disparities in prevalence, there also are
disparities in access to care and quality of care between
whites and minorities.
Brancati, JAMA. 2000.
Percent of Persons Under Age 65 yrs
with Health Insurance, by
Race/Ethnicity, 2000
90
Age-adjusted Percent
83
80
81
Black, NH
Native
Hawaiian and
Other Pacific
Islander
70
63
83
87
65
50
30
10
Total
-10
American
Hispanic or
Indian or
Latino
Alaska Native
Asian
White, NH
Insurance Coverage Among Adults
with Diabetes
In patients with diabetes,
Mexican-Americans will be
more likely to have no
insurance coverage
Harris, Diabetes Care, 1999.
Risk of Diabetes Complications in
the General Population
Diabetes Disparities Among Adults with Insurance
• Insured patients (Kaiser)
• Similar / lower rates of most DM complications
for racial/ethnic minority patients compared to
whites suggests that improved access to care
and quality of care may reduce some
disparities
• Exception: End-Stage Renal Disease (ESRD)
• Unmeasured environmental / behavioral /
genetic factors
Karter, JAMA, 2002.
Race/Ethnicity
Genetics, Culture, Lifestyle, ….
• Race and ethnicity are complex constructs that include:
– Behavioral patterns
– Similar environments
– Shared genetic components
• Genetic variation is larger within a racial group than
between racial groups.
• We must be aware of our assumptions about racial
groups and continue to ask correct questions
• But there is a genetic component to T2DM…
Influences on Diabetes Risk, Prevalence, and Outcomes
Race /
Ethnicity
Genetics
Culture
Diabetes
Risk
Prevalence
Outcomes
Health Care
Lifestyle
Environment
Genetics and DM
• Both twin and population-based studies suggest
that T2DM has a strong genetic component
• Complex interactions between a multitude of
genes.
• Genes seem to be strongly influenced by
environmental and behavioral factors.
• Are there specific genes that have been
identified?
Hawkes, Diabetic Medicine, 1997.
Genetic Polymorphism and DM
Many candidates but little certainty
Genes
Mechanism
Transcription factor 7-like 2 gene
(TCF7L2)
B-cell dysfunction (not insulin
resistance)
PPAR-gamma
Insulin resistance
KCNJ11
B-cell dysfunction
CDKAL1
B-cell dysfunction
CDKN2A/B
B-cell dysfunction
FTO
Obesity
HHEX/IDE
B-cell dysfunction
IGF2BP2
B-cell dysfunction or insulin resistance
SLC30A8
B-cell dysfunction
TCF2
B-cell dysfunction
WFS1
B-cell dysfunction
Currently no commercially-available tests to help risk for developing T2DM
Malecki, Diabetes Research and Clinical Practice, 2008.
Association of reported loci and risk for type 2 diabetes
in pooled analysis of men and women
Cornelis, M. C. et. al. Ann Intern Med 2009;150:541-550
Genetic risk score and risk for type 2 diabetes
Cornelis, M. C. et. al. Ann Intern Med 2009;150:541-550
Receiver-operating characteristic curves for T2DM
Conventional risk factors: age, sex,
body mass index, family history of
diabetes, smoking, alcohol intake, and
physical activity
GRS = genetic risk score.
AUC = area under the curve
Cornelis, M. C. et. al. Ann Intern Med 2009;150:541-550
Influences on Diabetes Risk, Prevalence, and Outcomes
Race /
Ethnicity
Genetics
Culture
Diabetes
Risk
Prevalence
Outcomes
Health Care
Lifestyle
Environment
Cultural Factors in DM
• Attribution
• Interactions with providers
• Attitudes toward prevention and treatment
– “Fatalismo”
Influences on Diabetes Risk, Prevalence, and Outcomes
Race /
Ethnicity
Genetics
Culture
Diabetes
Risk
Prevalence
Outcomes
Health Care
Lifestyle
Environment
Environment and DM
• Residing in certain communities may put individuals at risk for
diabetes.
• African Americans, Latinos, and poorer persons are often
segregated into neighborhoods that:
– have fewer resources (such as clinics, pharmacies, parks,
and supermarkets)
– fewer safe places to exercise
– fewer places to obtain nutritious foods
– poorer quality foods in the available supermarkets
– are more stressful (due to noise, crime, more difficulty
obtaining needed services) – stress has been associated
with poorer glucose metabolism and higher levels of stress
hormones that contribute to obesity
• Do people living in these communities have a difference
prevalence of DM?
“Obesogenic” and “Diabetogenic”
Environments
South LA has the highest
concentration of fast food
restaurants in the city
Getty Images – Los Angeles July 24th 2008
A high the ratio of fast-food and convenient stores to grocery
and produce stores is associated with higher prevalence of
both diabetes and obesity, even after controlling for
race/ethnicity, income, age, gender, and physical activity.
Auchincloss, Epidemiology. 2008.
California Center for Public Health Advocacy, April 2008, http://www.publichealthadvocacy.org/designedfordisease.html, last
accessed March 22, 2009
Does Environment affect Diabetes
Outcomes?
Diabetes patients with increased neighborhood
problems have more cardiovascular risk
In neighborhoods with
more perceived problems
•Crime
•Trash
•Lighting
•Traffic
association
Higher rates of
smoking
Worse blood
pressure control
• Effect was seen even after adjusting for age, sex,
race/ethnicity, education, co-morbidities, and income
• Smoking and elevated blood pressure are strongly
associated with worse outcomes in DM
Gary, Diabetes Care, 2008.
Influences on Diabetes Risk, Prevalence, and Outcomes
Race /
Ethnicity
Genetics
Culture
Diabetes
Risk
Prevalence
Outcomes
Health Care
Lifestyle
Environment
Prevention of DM
Lifestyle Modification
Nurses Health study
• Up to 85% of T2DM could be prevented by behavior
modification (e.g., healthy diet, exercise, BMI <25 kg/m2)
Diabetes Prevention Program (DPP)
Incidence of T2DM
(% per year)
Reduction in incidence
compared to placebo
Hu, NEJM, 2001; DPP,
Placebo
Metformin
Lifestyle Modification
(Diet / Exercise)
11.0%
6.8%
4.8%
----
31%
58%
Interplay between Risk Factors
• Higher BMI associated with higher incidence of T2DM
• At low BMI, exercise doesn’t alter T2DM risk
• At higher BMI, exercise is protective against diabetes and is dose-dependent
Helmrich, NEJM, 1991.
Lifestyle Modification and Genetics
Polymorphism rs7903146
• CC and CT genotype similar
• TT variant was associated with increased
risk of DM
With lifestyle modification
(diet/exercise):
• TT variant no longer associated
with increased risk of DM
Lifestyle modification / behavior
change can overwhelm genetic risk
Florez. NEJM, 2006.
Conclusions
• The risk and outcomes of a chronic disease like
T2DM can be affected by
• Race
• Genetics
• Environment – modifiable
• Behaviors – modifiable
Main Learning Points
•
•
•
•
•
•
Type II DM is a common chronic disease with high individual
and societal costs
Behavioral, cultural, genetic, and environmental factors all
contribute to diabetes risk and diabetes disparities
Family history can be a valuable tool:
– Provides insight into behavioral, cultural, genetic, and
environmental factors that determine diabetes
– Can be used to promote prevention and management
With advances in genomic technology, large number of
specific genetic polymorphisms are being associated with
T2DM, but genetics of diabetes are complex and each
polymorphism carries only a modest increase in relative risk.
The environment may affect diabetes risk directly or through
behaviors
Lifestyle modification can prevent diabetes or delay its
incidence in those with biologic risk
Extra Slides
How much is race vs behavior?
In a study comparing African American to white women:
Relative Risk
(95% CI)
Excess in Risk due to
contributing factors
Age and Family History (Base model)
2.63 (2.26-3.06)
Baseline
Base model + EDUCATION
2.41 (2.06-2.82)
13.5
Base model + BEHAVIORS (physical
activity, smoking, alcohol, and dietary
energy intake)
2.21 (1.86-2.63)
25.8
Base model + BODY CHARACTERISTICS
(body mass index and waist-to-hip ratio)
1.98 (1.69-2.31)
39.9
Base model + BEHAVIORS + BODY
CHARACTERISTICS
1.85 (1.55-2.21)
47.8
Adjusted for:
47% of increased risk is explained by modifiable factors
Brancati, JAMA, 2000.
Race/Ethnicity and DM
Variation in DM Prevalence Among Asian and
PI Populations
Prevalence
(%)
45
30
15.1
15
10.5
9.6
6.4
4.3
2.6
0
Tonga
South
Korea
Thailand
Philippines
Asia Pacific Cohort Studies Collaboration. Asia Pac J Clin Nutr. 2007.
India
China
Race/Ethnicity and DM
Prevalence
(%)
Variation in DM Prevalence in
Latino and Native American Populations
60
51.4
45
30
25.7
14.9
15
11.8
7.6
7.6
Argentina
Brazil
0
Cuban
Barcelo, Pan Am J Public Health, 2001.
Mexican
(Mexico City)
US- Mexican
US- Pima Indian
Overview
• Introduction
– Defining and Diagnosing Diabetes
– Determining Risk
Race / Ethnicity
Diabetes:
• Risk
• Prevalence
• Outcomes
Genetics
Environment
Behavior
Race/Ethnicity and DM
African Americans and Latinos have increased prevalence of DM
Harris, Diabetes Care, 1998.