type 2 diabetes prevalence: the ucsd filipino health study · filipino migration to the us...

Type 2 Diabetes prevalence:

the UCSD Filipino Health Study

AANHPI Diabetes Coalition

3th Diabetes Conference

May 2, 2014

San Francisco, CA

Maria Rosario (Happy) G. Araneta, PhD

Associate Professor

Department of Family and Preventive Medicine

???? 300,000 years ago – land bridges from Asia?

Polynesia?

Aetas (Negritos) ~ 25,000 years ago – from Asia via Africa?

~ 12,000 to 15,000 years ago, from Borneo

Indonesians 5,000 to 6,000 years ago; 1500 BC

Malays 800 and 500 BC; 200-300 BC

Indians (Hindus) 2nd to 15th century

Arabs 9th to 15th century

Chinese 900 - 1200

Spaniards 1521 - 1898

Mexicans 1565 - 1815

English 1762 - 1769

Americans 1898 - 1946; through 1992

Jocanda FL. Philippine Prehistory. An anthropologic overview of the beginnings of Filipino Society and Culture.

Univ of the Philippines, Diliman, Quezon City. 1975

Filipino migration to the US

1565-1898 Spain colonizes the Philippines

1587 Morro Bay, California

1763 Filipino settlement, Barataria Bay, Louisiana

1781 Antonio Poblador + 44 others establish the

City of Los Angeles

1898-1946 U.S. occupies the Philippines

1903 103 Filipinos to obtain an American education.

1906 - 35 125,000 Filipinos and Puerto Ricans

for Hawaiian sugar cane plantations, California

agriculture, Alaska fisheries

1945 - 65 US citizenship to Filipinos in US military

1965 - Occupational preferences; Nurses

1972 - Political asylum after Marcos declared martial law

Uninsured California residents,

<65 years of age, by ethnicity, 2011-2012

1416

17

32

18

37

0

5

10

15

20

25

30

35

40

Caucasian Asian/PI African-

American

Latino Native

American

Nat

Hawaiian/PI

%

California Health Interview Survey, 2012, http://www.chis.ucla.edu

Uninsured California residents, <65 years of age,

by Asian subgroup, 2011-2012

12.99.8 11.2

13.5

42.2

19.8

0

5

10

15

20

25

30

35

40

45

Chi

nese

Filip

ino

Sou

th A

sian

Japan

ese

Kor

ean

Vie

tnam

ese

%

Prevalence of type 2 diabetes among 2,123,548 adult members

of Northern California Kaiser Hospitals in 2010

Race/ethnicity Prevalence (%) Pacific Islander 18.3 Filipino 16.1 South Asian 15.9 Latino 14.0 African American 13.7 Native American 13.4 Southeast Asian 10.5 Japanese 10.3 Vietnamese 9.9 Korean 9.9 Chinese 8.2 White 7.3

Karter AJ et al; Diabetes Care 2013: 36;574-9

Prevalence of Gestational DM among 216,089 women at

Northern California Kaiser Hospitals

Asian Indians 11.1 %

Filipinas 9.6 %

Southeast Asians 8.8 %

Chinese 7.9 %

Pacific Islanders 7.2 %

Mexicans 7.1 %

Koreans 6.7 %

Japanese 5.5 %

Hispanics 5.4 %

Black 4.4 %

White 4.2 %

• Hedderson M; Paediatric and Perinatal Epidemiology 2010;24:441-448

Why study Filipinos?

• 1972, UCSD Rancho Bernardo Study

• One of 12 lipid research centers

• 99% Caucasian, not representative of California’s

ethnically diverse population

• 1995, UCSD faculty observed

• Dialysis patients at La Jolla Veteran’s Administration

hospital were THIN Filipino men

• Filipinos 2nd largest ethnic minority (6%) in San Diego

• No clinical studies of Filipinos in the US

• Ethnic differences in pathophysiology of diabetes?

Objectives of UCSD Filipino Women’s Health Study

1. To characterize:

cardiovascular disease hypertension

osteoporosis type 2 diabetes

metabolic syndrome obesity

among 40+ year old Filipinas in San Diego in 1995-1999.

2. To measure coronary artery calcium in women without known CVD (2001-02 and 2006-07)

3. To compare these outcomes to Caucasian and African-American women

UCSD Filipino Women’s Health Study, 1995-2007

Volunteer sample

• Recruited from churches,

grocery stores, festivals, social

and professional

organizations, local media

Criteria:

• self identified Filipina

• > 40 years of age

• Plan to live in San Diego for

next 5 years

UCSD Filipino Women’s Health Study

• Clinical evaluations at the Rancho Bernardo Clinic, using

same protocol and research staff

• 453 women

Age (years) 59 (40-86)

Philippine born 99%

Mean years since migration 17 (0.5 - 46)

Mean age at migration (yrs) 43 (15 - 68)

Methods -Structured Questionnaire

• Demographic characteristics

• Symptoms

• Medication use

• Medical history (self, family)

• Hospitalizations, surgeries, fractures

• Reproductive history, menopausal symptoms

• Diet (Willett food frequency)

• Alcohol, smoking, physical activity

• Visual care/history

• Beck interview, resilience

• Acculturation

Methods - Clinical Evaluation

• 75 gram OGTT after 8 hour fast

• Fasting glucose, insulin, proinsulin, c-peptide, HbA1c

• Fasting total, HDL, LDL cholesterol, triglycerides

• Blood Pressure (BP)

• Height, weight, waist and hip girth

• Bone mineral density and body fat DEXA

• Rose questionnaire, ECG, ankle-brachial index

• Creatinine, albumin

• Visual acuity, retinal photographs

• Adiponectin, leptin, ghrelin, IL-6, TNF-a, DNA samples

• Coronary artery calcium (2001-02 and 2006-07)

Characteristics of female cohort (n=453)

Age (years) 58.4

BMI (kg/m2) 25.3

College graduate 51.0%

Exercise >3x/wk 65.8%

Smoke (ever) 16.0%

Smoke currently 4.8%

Parent w/ type 2 diabetes 25.1%

Characteristics of female cohort

Fasting glucose (mg/dl) 107.10

2 hr glucose (mg/dl) 180.38

Triglycerides (mg/dl) 151.09

LDL cholesterol (mg/dl) 131.42

HDL cholesterol (mg/dl) 54.07

Systolic BP (mmHg) 133.52

Diastolic BP (mmHg) 79.04

8.7

14

36.4

8.8

0 5 10 15 20 25 30 35 40

T2DM

BMI>=30 kg/m2

%

Caucasian Filipina

Type 2 diabetes in 50-69 year old Filipina and

Caucasian women, San Diego

Araneta MRG, Diabetes Care, 2002;25:494-99

Age-adjusted BMI, fasting hyperglycemia and type 2 diabetes

among 40-79 year old Filipino women, in the Philippines, San

Diego, and Hawaii 1995-2001

0

5

10

15

20

25

30

35

Mean BMI BMI>30 FPG>126 T2DM*

Philippines San Diego Hawaii

p<0.001

NS

NS = not statistically significant; * 1999 WHO criteria

Araneta MRG, Diab Res Clin Pract 2006:71;306-12

NS

p<0.05

Demographic characteristics, by ethnicity,

among 55-80 year old women without known CVD

African-

Caucasian Filipina American

(n=196) (n=181) (n=193)

Age (yrs) 66.7* 64.4 66.7‡

College graduate (%) 36.8 52.5* 44.6

Smoker (ever, %) 50.0* 13.0 50.3‡

Alcohol (>3x week, %) 62.2*† 1.1 18.0‡

Exercise (> 3x week, %) 72.4 70.2 61.7†

Araneta MRG and Barrett-Connor E. Obesity 2007 (in press)

Araneta MRG and Barrett-Connor E. Obes Res 2005:13;1458-65

*p <0.05 Caucasian vs Filipino, † p<0.05 Caucasian vs African-American, ‡ p<0.05 African-American vs Filipino

Ethnic differences in obesity: Caucasian, Filipino and African-

American women, ages 55-80, San Diego, 2000-02

African-


(n=196) (n=181) (n=193)

Age (years) 66.7 64.4* 66.7

BMI (kg/m2) 26.0 25.5 29.7*

Waist girth (cm) 80.7 81.9 88.1*

Body fat (%, DXA) 27.3 28.2 39.6*

* p<0.05

Araneta MRG. Obes Res 2005:13;1458-65

CT-defined visceral adipose tissue:

African American vs Filipina women,

Weight: 160 lbs, Height: 5’7”

BMI=25 kg/m2,

VAT: 25.4cm3

Weight: 115 lbs, Height: 5’4”

BMI=20 kg/m2,

VAT: 84.0 cm3

African-American Filipina

Visceral adipose tissue by waist girth in women with

normal* BMI, by ethnicity

0

20

40

60

80

100

120

55 60 65 70 75 80 85 90

Waist (cm)

VA

T (

cm

3)

Filipino African-American

Caucasian Linear (Filipino)

Linear (African-American) Linear (Caucasian)

*Normal BMI: Filipino: <23 kg/m2; African-American, Caucasian: <25 kg/m2

Araneta and Barrett-Connor. Obes Res 2005:13;1458-65

Ethnic differences in visceral adipose tissue (VAT) in

women without known CVD, San Diego, CA

African-

Caucasian Filipina American (n=196) (n=181) (n=193)

Age (years) 66.7 64.4* 66.7

BMI (kg/m2) 26.0 25.5 29.7*

Waist girth (cm) 80.7 81.9 88.1*

Body fat (%, DXA) 27.3 28.2 39.6*

VAT (cm3) 62.3 69.1* 57.5

Subcutaneous fat (cm3) 158.5 155.4 229.2*

Type 2 diabetes† (%) 5.8% 32.1%* 12.1% * p<0.05, †1999 WHO criteria

Araneta MRG et al. Obes Res 2005:13;1458-65

0 10 20 30 40 50

>=74.9

46.1-74.8

<=46

VA

T (

cm

3)

Type 2 Diabetes (%)

Caucasian .

Type 2 diabetes, by tertile of CT-defined visceral fat, San

Diego, 1995-2002


0 10 20 30 40 50

>=74.9

46.1-74.8

<=46

VA

T (

cm

3)

Type 2 Diabetes (%)

Caucasian Filipina

Type 2 diabetes, by tertile of CT-defined visceral fat, San

Diego, 1995-2002


0 10 20 30 40 50

>=74.9

46.1-74.8

<=46

VA

T (

cm

3)

Type 2 Diabetes (%)

Caucasian Filipina African-American

Type 2 diabetes, among 50-69 year old Filipino, Caucasian,

and African-American women, by tertile of CT-defined

visceral fat, San Diego, 1995-2002


VAT among women with normal weight: Filipinas: BMI<23 kg/m2;

Caucasians & African-Americans: BMI<25 kg/m2

African-


VAT (cm3) 43.8 53.8*† 37.9

Type 2 diabetes (%) 2.1 21.6*† 7.5

*p <0.05 Caucasian vs Filipino, † p<0.05 Filipino vs African-American,

Araneta MRG and Barrett-Connor E. Obesity 2007 (in press)

Araneta MRG et al. Obes Res 2005:13;1458-65

Adipose Tissue Is an Endocrine Organ: Its Function in Health and Disease

Reprinted in adapted form from Trayhurn P, Wood IS. Br J Nutr. 2004;92:347–355, with permission of Cambridge University Press. | Eckel RH, et al. Lancet. 2005;365:1415–1428. | Lyon CJ, et al. Endocrinology. 2003;144:2195–2200.

CRP = C-reactive protein; IL-6 = interleukin-6; TNFα = tumor necrosis factor-alpha

Inflammation Atherogenic Dyslipidemia

Type 2 Diabetes

Thrombosis

Atherosclerosis

Hypertension Lipoprotein lipase

Angiotensinogen IL-6

CRP

Plasminogen

activator inhibitor-1

(PA-1)

Insulin

Lactate

Resistin

Leptin

Adiponectin

TNF

Adipsin

(Complement D)

Free Fatty Acids

Adiponectin

• Secreted by adipose tissue

• 244-amino acid protein hormone discovered in 1995

• adiponectin risk of diabetes and CVD

insulin sensitivity, suppress inflammation, anti-atherogenic

• adiponectin obesity, insulin resistance, type 2 diabetes,

myocardial infarction

(Matsuzawa, 2005)

Adiponectin concentration in normoglycemic women,

ages 40-86

0

2

4

6

8

10

12

14

16

18

BMI Waist WHR Insulin HOMA-IR HOMA+

Aid

po

necti

n (

ug

/ml

)

Causasian African-American Filipino

*†‡ *† *† *† *†

*p <0.05 Filipino vs Caucasian, † p<0.05 African-American vs Caucasian, ‡ p<0.05 African-American vs Filipino

Araneta et al. Obesity 2007;15:2454-62

*†‡

WHR

*

†

*† *† *† *†

Age-adjusted adiponectin concentration, by VAT tertiles and

ethnicity, 55 to 80 year old women without known CVD

Araneta MRG, Wassel C, Laughlin G, et al. American Diabetes Assn 71st Scientific Sessions

9 9

24

17

29

51

0

10

20

30

40

50

>=9.3 5.5-9.2 <5.4

Adiponectin (ug/ml)

Typ

e 2

dia

be

tes (

%)

Filipino African-American

Type 2 diabetes by adiponectin tertile,

Filipino and African-American women

Filipinas had higher diabetes prevalence, at every adiponectin tertile

20

35

44

0

10

20

30

40

50

>=14 7.2 - 13.9 <7.2

Adiponectin (ug/ml)

(%

)

Diabetes

Percent distribution of diabetic patients by adiponectin tertiles,

Philippine National Nutrition and Health Survey, 2003-2004

Almost half of diabetics in the Philippines had adiponectin levels <7.2 ug/ml

Paz-Pacheco E et al. Diab Vasc Dis Res 2009;6:231-7

Adiponectin polymorphism among

Filipinas in Cebu

• Genome wide association study to investigate the genetic loci

associated with plasma adiponectin

• 1776 unrelated Filipino women from the Cebu Longitudinal

Health and Nutrition Survey

• An uncommon haplotype of rs11924390 (KNG1) and rs864265

(ADIPOQ) was strongly associated with lower adiponectin levels

Wu et al. Hum Mol Genet. 2010;19:4955-64

Age-adjusted Tumor necrosis factor alpha (TNF-a) levels

among postmenopausal women without known CVD

0

0.2

0.4

0.6

0.8

1

1.2

1.4

BMI Waist VAT BMI

(nonDiabetic)

TN

F-a

(p

g/m

l )

Causasian Filipino African-American

*† *† *†

*p <0.05 Filipino vs Caucasian

* * *

Filipinos had significantly higher TNF-a levels compared to Whites

Araneta MRG, Wassel C, Laughlin G. American Diabetes Assn 67th Scientific Sessions 2011

Age-adjusted Interleukin-6 (IL-6) levels

among postmenopausal women without known CVD

0

0.5

1

1.5

2

BMI Waist VAT BMI

(nonDiabetic)

IL-6

(p

g/m

l )

Causasian Filipino African-American

*† *†

*p <0.05 Filipino vs Caucasian, † p<0.05 African-American vs Caucasian, ‡ p<0.05 AAvs Filipina

Filipinos had similar IL-6 levels as Whites, but lower than African-

Americans Araneta MRG, Wassel C, Laughlin G. American Diabetes Assn 67th Scientific Sessions 2011

† *† †‡ †‡

Type 2 diabetes at enrollment

13.4% Previously

diagnosed diabetes

13.4% were previously diagnosed by a physician

with type 2 diabetes

Type 2 diabetes by history and Fasting Plasma Glucose Test

13.4% Previously

diagnosed diabetes

• 5.7% were newly diagnosed with T2DM by FPG

5.7% Newly diagnosed

Fasting glucose >126 mg/dl

Type 2 diabetes by history and Oral Glucose Tolerance Test

13.4% Previously

diagnosed diabetes

• 32% had type 2 diabetes by history and OGTT

•Among Filipinas w/ diabetes, 59% were undiagnosed vs 27% in the US

•If screening is liming to fasting glucose measures, 70% of Filipinas with newly

diagnosed diabetes would be missed




Postchallenge glucose >200 mg/dl,

and normal FPG

Glucose abnormalities among Filipino-American women,

ages 40-86

35.8%

Normoglycemic

13.4% Previously diagnosed diabetes

32% had ‘pre-diabetes’ :

31% had impaired glucose tolerance, 1% impaired fasting glucose

Almost two-thirds (64%) of Filipinas had diabetes or pre-diabetes

30.7% IGT

2 hr glucose: 140-199 mg/dl

1% IFG 1% IFG:

fasting gluc >=100 mg/dl




PPG>=200mg/dl,

and normal FPG

Population Characteristics: Filipino, Japanese and

Hawaiian adults without prior T2DM diagnosis

Total Filipino

(SD)

Filipino

(HI)

Native

Hawaiian

Japanese

(HI)

A1C>

6.5%

8.9% 12.6% 8.8% 5.2% 4.2%

T2DM (by OGTT)

15.5% 22.0% 11.7% 10.0% 11.8%

Araneta MRG et al. Diabetes Care 2010;33:2626-28

15.5% had T2DM by OGTT, but only 8.9% had A1C>=6.5%

A1c >=6.5% vs OGTT

• Among 933 adults without a prior DM diagnosis

• 15.5% had diabetes by OGTT vs. 8.9% by A1C >=6.5%

• 58 (40%) of 145 diabetics would be diagnosed correctly by A1C

• But 87 (60%) of the 145 diabetics would be misclassified as ‘non-diabetic’

Sensitivity: 40%; Specificity: 96.8%; area under ROC curve: 0.68

T2DM*

No diabetes Total

A1C>=6.5% 58 25 83 (8.9%)

A1C<6.5% 87 763 850

Total 145 (15.5%) 788 933


A1C >6.5% vs diabetes by FPG>=126 mg/dl

• Among 933 adults without a prior DM diagnosis

42 (69%) of 61 with diabetes (by FPG) will be correctly classified as diabetic by A1C

But 31% (n=19) will be misclassifed as ‘non-diabetic’

Sensitivity: 69%; Specificity: 95%; area under ROC curve: 0.82

A1C (%) FPG>=126

mg/dl

FPG <126

mg/dl

Total

>=6.5% 42 41 83

<6.5% 19 831 850

Total 61 872 933


A1C >6.5% vs PPG>200 mg/dl but normal FPG

• Among 872 adults with normal FPG without a prior DM diagnosis

Only 16 (19%) of the 84 with diabetes (by PPG) will be correctly classified as diabetic by A1C >=6.5%

but 81% (n=68) will be misclassified as ‘nondiabetic’

Sensitivity: 19.1%; Specificity: 92%; area under ROC curve: 0.56

A1C (%) PPG>=200

mg/dl

PPG <200

mg/dl

Total

>=6.5% 16 25 41

<6.5% 68 763 831

Total 84 788 872


A1C cutpoint >=5.8%

• Using an A1C cutpoint >=5.8% improves the sensitivity

to diagnose diabetes by OGTT:

• Sensitivity: 75.9% Specificity: 80.0%

• Area under ROC curve: 0.78

• And retinopathy:

• Sensitivity: 64.3%


Body size* and fat distribution*, by parity, Filipino women, San Diego, CA,

Live Births

1-2 3-5 6-12 (n=40) (n=76) (n=36)

BMI (m/kg) 24.5 25.7 25.8

Waist (cm) 78.3 82.9* 83.0†

VAT (cm3) 59.4 72.1* 73.2 †

Adiponectin (ug/ml) 7.5 5.7* 6.0

Type 2 Diabetes (%) 25.0 30.3 50.0 †

*3-5 live births vs 1-2 live births; ‡ † 6-12 live births vs 1-2 live births

• BMI did not differ by parity, whereas VAT increased with higher parity category.

Araneta MRG and Barrett-Connor E. American Diabetes Assn. 68th Scientific Sessions, June 2008 Araneta et al, Diabetes Care 2010:33;358-389

Covariates associated with type 2 diabetes:

Covariate Odds ratio (95% CI)

Family Hx T2DM 4.4 1.95 - 4.73

Multiparity (>=6 births) 3.4 1.10 – 10.2

Adiponectin 0.42 0.20 - 0.89

Hypertension 3.0 1.26 - 7.07

adjusting for age, VAT, education, estrogen use.

Araneta et al, Diabetes Care 2010:33;358-389

Conclusions

• Two thirds of women in the UCSD Filipino Health Study

had diabetes or prediabetes

• Risk factors for type 2 diabetes among Filipino include:

low adiponectin concentration, family history, hypertension

and multiparity.

• 70% of newly diagnosed diabetics had isolated post-

challenge hyperglycemia

• Screening by HbA1c alone fails to identify 60% of

Filipinas, Japanese and Native Hawaiians with newly

diagnosed T2DM.

Acknowledgements

Elizabeth Barrett-Connor MD Noralinda Kamantigue, RN Deborah Wingard PhD Nancy Thielen RN Mary Lou Carrion-Peterson RN Luzana Sechler Maggie Wong Gabriela Centeňo-Reno Patricia Miller Mark Stephens

National Institutes of Health / NIDDK R01 31801, R03 60575 American Heart Association 0070088Y

Amgen, Procter & Gamble

74th Scientific Sessions of the

American Diabetes Association

San Francisco, CA June 13-17, 2014

Saturday, June 14, 8:00 am

Optimum BMI Cut points to Screen Asian-Americans for

Type 2 Diabetes – The UCSD Filipino Health Study

and the North Kohala Study

Sunday, June 15, 12 – 2 pm poster session

Optimum BMI Cut points to Screen Asian-Americans for Type

2 Diabetes

type 2 diabetes prevalence: the ucsd filipino health study · filipino migration to the us...

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