type 2 diabetes prevalence: the ucsd filipino health study · filipino migration to the us...
TRANSCRIPT
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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
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???? 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
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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
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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
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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
%
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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
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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
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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?
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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
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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
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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)
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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
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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)
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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%
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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
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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
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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
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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
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Ethnic differences in obesity: Caucasian, Filipino and African-
American women, ages 55-80, San Diego, 2000-02
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*
* p<0.05
Araneta MRG. Obes Res 2005:13;1458-65
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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
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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
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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
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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
Araneta MRG. Obes Res 2005:13;1458-65
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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
Araneta MRG. Obes Res 2005:13;1458-65
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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
Araneta MRG. Obes Res 2005:13;1458-65
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VAT among women with normal weight: Filipinas: BMI<23 kg/m2;
Caucasians & African-Americans: BMI<25 kg/m2
African-
Caucasian Filipina American
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
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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
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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)
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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
*
†
*† *† *† *†
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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
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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
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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
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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
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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
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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
† *† †‡ †‡
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Type 2 diabetes at enrollment
13.4% Previously
diagnosed diabetes
13.4% were previously diagnosed by a physician
with type 2 diabetes
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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
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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
5.7% Newly diagnosed
Fasting glucose >126 mg/dl
13.4% Newly diagnosed
Postchallenge glucose >200 mg/dl,
and normal FPG
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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
5.7% Newly diagnosed
Fasting glucose >126 mg/dl
13.4% Newly diagnosed
PPG>=200mg/dl,
and normal FPG
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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%
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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
Araneta MRG et al. Diabetes Care 2010;33:2626-28
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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
Araneta MRG et al. Diabetes Care 2010;33:2626-28
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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
Araneta MRG et al. Diabetes Care 2010;33:2626-28
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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%
Araneta MRG et al. Diabetes Care 2010;33:2626-28
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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
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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
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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.
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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
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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