type ii diabetes the roles of race, culture, genetics, environment, and behavior ajay dharia, ms iv...

Type II DiabetesThe 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

Race /Ethnicity

Race /Ethnicity

GeneticsGenetics

Health CareHealth Care

EnvironmentEnvironment

LifestyleLifestyle

CultureCulture

DiabetesRisk

PrevalenceOutcomes

DiabetesRisk

PrevalenceOutcomes

Influences on Diabetes Risk, Prevalence, and Outcomes

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

w

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?

Race /Ethnicity

Race /Ethnicity

GeneticsGenetics



LifestyleLifestyle

CultureCulture

DiabetesRisk

PrevalenceOutcomes

DiabetesRisk

PrevalenceOutcomes


0

20

40

60

80

100

*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.

Comparison of diabetes prevalence*:United States, by specified race, 1999

Black/African American,not-Hispanic

American Indian/Alaska Native**

Hispanic***

White, not-Hispanic

Asian/Pacific Islander**

Rate

per

10

0,0

00

popula

tion

Race/Ethnicity and DM Variation Among

Asian and Pacific Islander Populations

2.6 4.3 6.49.6 10.5

15.1

0

10

20

30

40

50

60

China India Philippines Thailand South Korea Tonga

Asia Pacific Cohort Studies Collaboration. Asia Pac J Clin Nutr. 2007.

Race/Ethnicity and DM Variation Among

Latino and American Indian Populations

7.6 7.611.8

14.9

25.7

51.4

0

10

20

30

40

50

60

Argentina Brazil Cuba Mexican(Mexico

City)

MexicanAmerican

(US)

Pima (US)

Barcelo, Pan Am J Public Health, 2001.

Disparities in Diabetes Death Rates

16.6

22.3

32.1

39.2

48.0

24.5

0

5

10

15

20

25

30

35

40

45

50

All Races Asian/PacificIslander

White Hispanic AmericanIndian/Alaska

Native

AfricanAmerican

Ag

e-A

dju

ste

d D

ea

th R

ate

pe

r 1

00

,00

0 P

ers

on

s

* Age-adjusted, per 100,000 U.S. population, 2004

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

87838180

6563

83

-10

10

30

50

70

90

Total AmericanIndian or

Alaska Native

Hispanic orLatino

Black, NH NativeHawaiian andOther Pacific

Islander

Asian White, NH

Age

-adj

uste

d P

erce

nt

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

Karter, JAMA, 2002.

• 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

Diabetes Disparities Among Adults with Insurance

Race/EthnicityGenetics, 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…

Race /Ethnicity

Race /Ethnicity

GeneticsGenetics



LifestyleLifestyle

CultureCulture

DiabetesRisk

PrevalenceOutcomes

DiabetesRisk

PrevalenceOutcomes


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

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

Malecki, Diabetes Research and Clinical Practice, 2008.

Many candidates but little certainty

Currently no commercially-available tests to help risk for developing T2DM

Cornelis, M. C. et. al. Ann Intern Med 2009;150:541-550

Association of reported loci and risk for type 2 diabetes in pooled analysis of men and women


Genetic risk score and risk for type 2 diabetes


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

Race /Ethnicity

Race /Ethnicity

GeneticsGenetics



LifestyleLifestyle

CultureCulture

DiabetesRisk

PrevalenceOutcomes

DiabetesRisk

PrevalenceOutcomes


Cultural Factors in DM

• Attribution

• Interactions with providers

• Attitudes toward prevention and treatment– “Fatalismo”

Race /Ethnicity

Race /Ethnicity

GeneticsGenetics



LifestyleLifestyle

CultureCulture

DiabetesRisk

PrevalenceOutcomes

DiabetesRisk

PrevalenceOutcomes


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

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.

South LA has the highest concentration of fast food restaurants in the city

Getty Images – Los Angeles July 24th 2008

Auchincloss, Epidemiology. 2008. California Center for Public Health Advocacy, April 2008, http://www.publichealthadvocacy.org/designedfordisease.html, last accessed March 22, 2009

http://www.publichealthadvocacy.org/designedfordisease.html

Does Environment affect Diabetes Outcomes?

• 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.

Diabetes patients with increased neighborhood problems have more cardiovascular risk

In neighborhoods with more perceived problems

•Crime•Trash

•Lighting•Traffic

Higher rates of smoking

Worse blood pressure control

association

Race /Ethnicity

Race /Ethnicity

GeneticsGenetics



LifestyleLifestyle

CultureCulture

DiabetesRisk

PrevalenceOutcomes

DiabetesRisk

PrevalenceOutcomes


Prevention of DMLifestyle Modification

Nurses Health study• Up to 85% of T2DM could be prevented by behavior

modification (e.g., healthy diet, exercise, BMI <25 kg/m2)

Placebo Metformin Lifestyle Modification (Diet / Exercise)

Incidence of T2DM (% per year)

11.0% 6.8% 4.8%

Reduction in incidence compared to placebo

---- 31% 58%

Diabetes Prevention Program (DPP)

Hu, NEJM, 2001; DPP,

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

Lifestyle modification / behavior change can overwhelm genetic risk

Florez. NEJM, 2006.

With lifestyle modification (diet/exercise):• TT variant no longer associated with increased risk of DM

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?

Adjusted for: 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

47% of increased risk is explained by modifiable factors

In a study comparing African American to white women:

Brancati, JAMA, 2000.

15.1

10.5 9.66.4

4.32.6

0

15

30

45

Tonga SouthKorea

Thailand Philippines India China

Variation in DM Prevalence Among Asian and PI Populations

Prevalence (%)

Asia Pacific Cohort Studies Collaboration. Asia Pac J Clin Nutr. 2007.

Race/Ethnicity and DM

11.8

7.6 7.6

14.9

25.7

51.4

0

15

30

45

60

Cuban Argentina Brazil Mexican(Mexico City)

US- Mexican US- Pima Indian

Barcelo, Pan Am J Public Health, 2001.

Variation in DM Prevalence in Latino and Native American Populations

Prevalence(%)


Overview

• Introduction– Defining and Diagnosing Diabetes– Determining Risk

Race / Ethnicity

Environment

GeneticsDiabetes:• Risk• Prevalence• Outcomes

Behavior


Harris, Diabetes Care, 1998.

African Americans and Latinos have increased prevalence of DM

type ii diabetes the roles of race, culture, genetics, environment, and behavior ajay dharia, ms iv...

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