Type II Diabetes The Roles of Race, Culture, Genetics, Environment, and Behavior

1. Type II DiabetesThe Roles of Race, Culture, Genetics, Environment, and Behavior Ajay Dharia, MS IV Arleen Brown, MD, PhD

2. Overview • Type II diabetes mellitus (T2DM) • Definition / Diagnosis • Risk factors for T2DM • Race/ethnicity, culture, and other demographic characteristics • Behavior • Environment • Genetics

3. 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

4. Influences on Diabetes Risk, Prevalence, and Outcomes

5. 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.

6. 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

7. 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.

8. 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.

9. 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.

10. 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

11. 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

12. Influences on Diabetes Risk, Prevalence, and Outcomes

13. Comparison of diabetes prevalence*:United States, by specified race, 1999 Rate per 100,000 population American Indian/ Alaska Native** Asian/Pacific Islander** Hispanic*** White, not-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.

14. Race/Ethnicity and DMVariation Among Asian and Pacific Islander Populations Asia Pacific Cohort Studies Collaboration. Asia Pac J Clin Nutr. 2007.

15. Race/Ethnicity and DMVariation Among Latino and American Indian Populations Barcelo, Pan Am J Public Health, 2001.

16. Disparities in Diabetes Death Rates * Age-adjusted, per 100,000 U.S. population, 2004

17. 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.

18. Percent of Persons Under Age 65 yrs with Health Insurance, by Race/Ethnicity, 2000 Age-adjusted Percent

19. 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.

20. Risk of Diabetes Complications in the General Population

21. 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.

22. 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…

23. Influences on Diabetes Risk, Prevalence, and Outcomes

24. 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.

25. Genetic Polymorphism and DM Many candidates but little certainty Currently no commercially-available tests to help risk for developing T2DM Malecki, Diabetes Research and Clinical Practice, 2008.

26. 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

27. Genetic risk score and risk for type 2 diabetes Cornelis, M. C. et. al. Ann Intern Med 2009;150:541-550

28. 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

29. Influences on Diabetes Risk, Prevalence, and Outcomes

30. Cultural Factors in DM • Attribution • Interactions with providers • Attitudes toward prevention and treatment • “Fatalismo”

31. Influences on Diabetes Risk, Prevalence, and Outcomes

32. 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?

33. “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

34. Does Environment affect Diabetes Outcomes? Diabetes patients with increased neighborhood problems have more cardiovascular risk • 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 • In neighborhoods with more perceived problems • Crime • Trash • Lighting • Traffic Higher rates of smoking Worse blood pressure control association Gary, Diabetes Care, 2008.

35. Influences on Diabetes Risk, Prevalence, and Outcomes

36. 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) Diabetes Prevention Program (DPP) Hu, NEJM, 2001; DPP,

37. 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.

38. 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.

39. Conclusions • The risk and outcomes of a chronic disease like T2DM can be affected by • Race • Genetics • Environment – modifiable • Behaviors – modifiable

40. 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

41. Extra Slides

42. How much is race vs behavior? In a study comparing African American to white women: 47% of increased risk is explained by modifiable factors Brancati, JAMA, 2000.

43. Race/Ethnicity and DM Variation in DM Prevalence Among Asian and PI Populations Prevalence (%) Asia Pacific Cohort Studies Collaboration. Asia Pac J Clin Nutr. 2007.

44. Race/Ethnicity and DM Variation in DM Prevalence in Latino and Native American Populations Prevalence (%) Barcelo, Pan Am J Public Health, 2001.

45. Overview • Introduction • Defining and Diagnosing Diabetes • Determining Risk Race / Ethnicity • Diabetes: • Risk • Prevalence • Outcomes Genetics Environment Behavior

46. Race/Ethnicity and DM African Americans and Latinos have increased prevalence of DM Harris, Diabetes Care, 1998.