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1.  Higher Protein Intake Is Associated with Diabetes Risk in South Asian Indians: The Metabolic Syndrome and Atherosclerosis in South Asians Living in America (MASALA) Study 
Despite a high prevalence of type 2 diabetes in South Asian Indians, the impact of diet in this high-risk ethnic group has not been fully explored. The association of macronutrient intake and diabetes in South Asian Indians was examined in this cross-sectional study.
A population-based cohort of 146 South Asian Indians aged 45–79 years without existing cardiovascular disease living in the San Francisco Bay Area was recruited between August 2006 and October 2007. Macronutrient intake was assessed with a food-frequency questionnaire developed and validated in South Asians. Diabetes was defined by use of a hypoglycemic medication, a fasting plasma glucose level ≥126 mg/dL, or a 2-hour post-challenge glucose level ≥200 mg/dL. The association between energy-adjusted macronutrient intake and diabetes was explored using multivariable logistic regression models.
Forty-one (28%) participants had type 2 diabetes; 20 were unaware of this diagnosis and were classified as having diabetes by laboratory testing. In a model fully adjusted for age, sex, waist circumference, and hypertension, there was a 70% increase in the odds of diabetes per standard deviation in gram of protein intake/day (standardized OR 1.70 [95% CI 1.08, 2.68], p = 0.02). There was a trend toward increased protein intake and diabetes in the subset of participants with previously unknown, laboratory-diagnosed diabetes. Results did not vary significantly by sex, body mass index, or dietary pattern.
Higher level of protein intake was associated with increased odds of diabetes in this cohort of South Asian Indians. Diet may be a modifiable lifestyle factor in this high-risk ethnic group.
PMCID: PMC4049291  PMID: 20679148
South Asians; nutrition; epidemiology
2.  Asian Indian Views on Diet and Health in the United States 
Family & community health  2013;36(4):311-323.
This study describes Asian Indian immigrant perspectives surrounding dietary beliefs and practices to identify intervention targets for diabetes and heart disease prevention. Participants were asked about conceptualizations of relationships between culture, food, and health during 4 focus groups (n = 38). Findings reveal influences of beliefs from respondents’ native India, preservation of cultural practices within the US social structure, conflicts with subsequent generations, and reinterpretation of health-related knowledge through a lens, hybridizing both “native” and “host” contexts. Galvanization of ethnically valued beliefs incorporating family and community structures is needed for multipronged approaches to reduce disproportionate burdens of disease among this understudied minority community.
PMCID: PMC3987985  PMID: 23986072
Asian Indian; chronic disease; cultural contexts; disparities; qualitative inquiry
3.  Endothelin-1 and Prevalent Coronary Heart Disease in Older Men and Women (The Rancho Bernardo Study) 
Endothelin-1 has been implicated in atherosclerotic and ischemic heart disease. No population-based studies have examined the association of endothelin-1 with coronary heart disease (CHD). We performed a cross-sectional analysis of 961 older women and men. CHD was defined as a history of myocardial infarction, coronary surgery, angina, or major Q-wave abnormality on electrocardiogram. We examined the association of endothelin-1 with CHD after adjusting for known risk factors and atherosclerosis measures. A total of 248 women and 156 men had CHD. Median endothelin-1 levels were similar by sex and higher among those with vs. those without CHD (3.3 vs. 3.1 pg/ml, p<0.001). After adjusting for age, smoking, low density lipoproteincholesterol, high density lipoprotein-cholesterol, hypertension, diabetes, alcohol use, exercise, aspirin, cholesterol-lowering medication and hormone therapy use, endothelin-1 had a stronger association with CHD in women (OR 3.02, 1.43-6.37) than in men (OR 1.82, 0.74-4.51). Age modified the effect of endothelin-1 with CHD in men (OR 0.47 for age <75 years vs. 3.84 in men ≥75 years, p-for-interaction=0.05). Further adjustment for ankle brachial index and carotid intima media thickness did not alter these results. In conclusion, higher endothelin-1 levels are independently associated with CHD in women of all ages, and among older men only.
PMCID: PMC3947589  PMID: 17293190
coronary disease; endothelin; risk factors; epidemiology
4.  Elevated Rates of Diabetes in Pacific Islanders and Asian Subgroups 
Diabetes Care  2013;36(3):574-579.
We estimated the prevalence and incidence of diabetes among specific subgroups of Asians and Pacific Islanders (APIs) in a multiethnic U.S. population with uniform access to care.
This prospective cohort analysis included 2,123,548 adult members of Kaiser Permanente Northern California, including 1,704,363 with known race/ethnicity (white, 56.9%; Latino, 14.9%; African American, 8.0%; Filipino, 4.9%; Chinese, 4.0%; multiracial, 2.8%; Japanese, 0.9%; Native American, 0.6%; Pacific Islander, 0.5%; South Asian, 0.4%; and Southeast Asian, Korean, and Vietnamese, 0.1% each). We calculated age-standardized (to the 2010 U.S. population) and sex-adjusted diabetes prevalence at baseline and incidence (during the 2010 calendar year). Poisson models were used to estimate relative risks.
There were 210,632 subjects with prevalent diabetes as of 1 January 2010 and 15,357 incident cases of diabetes identified during 2010. The crude diabetes prevalence was 9.9% and the incidence was 8.0 cases per 1,000 person-years and, after standardizing by age and sex to the 2010 U.S. Census, 8.9% and 7.7 cases per 1,000 person-years. There was considerable variation among the seven largest API subgroups. Pacific Islanders, South Asians, and Filipinos had the highest prevalence (18.3, 15.9, and 16.1%, respectively) and the highest incidence (19.9, 17.2, and 14.7 cases per 1,000 person-years, respectively) of diabetes among all racial/ethnic groups, including minorities traditionally considered high risk (e.g., African Americans, Latinos, and Native Americans).
High rates of diabetes among Pacific Islanders, South Asians, and Filipinos are obscured by much lower rates among the large population of Chinese and several smaller Asian subgroups.
PMCID: PMC3579366  PMID: 23069837
5.  Adipokines and Body Fat Composition in South Asians: Results of the Metabolic syndrome and Atherosclerosis in South Asians Living in America (MASALA) Study 
To investigate whether leptin and adiponectin are associated with body fat composition in a South Asian population independent of metabolic variables.
Cross-sectional study
150 South Asian men and women, between the ages of 45–79 years, in the San Francisco Bay Area without pre-existing clinical cardiovascular disease.
Blood samples were obtained to measure glucose metabolism variables, lipid profiles and adipokines. Total body fat was determined using dual-energy x-ray absorptiometry. Abdominal computed tomography was used to measure subcutaneous, visceral, and hepatic fat.
Average body mass index (BMI) was overweight at 26.1±4.6 kg/m2 and did not differ by sex. However, women had significantly more total body fat (p<0.001) and subcutaneous fat (p<0.001) than men, while men had significantly more visceral fat (p<0.001) and hepatic fat (p=0.04) than women. Women had significantly higher levels of adiponectin (p<0.01) and leptin (p<0.01). In sex-stratified analyses, leptin was strongly associated with all body composition measures in women (p<0.05) as well as in men (p<0.05 except for hepatic fat) while there was an insignificant trend towards an inverse association between adiponectin and body composition in both women and men which was significant in combined bivariate analyses. In multivariate analyses, leptin was strongly associated with all measures of adiposity, including BMI (p<0.001), total body fat (p<0.001), visceral fat (p<0.001), and hepatic fat (p=0.01). However, adiponectin’s inverse association with adiposity was significantly attenuated by high-density lipoprotein (HDL), triglycerides, and insulin resistance. The association between adipokines and diabetes was markedly attenuated after adjusting for body composition.
Despite only modestly elevated BMI, South Asians have elevated levels of total and regional adiposity. Leptin is strongly associated with adiposity while adiponectin’s association with adiposity is attenuated by metabolic variables in South Asians. Adipokines in association with adiposity play an important role in the development of diabetes.
PMCID: PMC3224670  PMID: 21863003
South Asians; body composition; sex differences in adiposity; adiponectin and leptin; hepatic fat
6.  Dietary patterns, insulin sensitivity and inflammation in older adults 
Several studies have linked dietary patterns to insulin sensitivity and systemic inflammation, which affect risk of multiple chronic diseases. The purpose of this study was to investigate the dietary patterns of a cohort of older adults, and examine relationships of dietary patterns with markers of insulin sensitivity and systemic inflammation.
The Health, Aging and Body Composition (Health ABC) Study is a prospective cohort study of 3075 older adults. In Health ABC, multiple indicators of glucose metabolism and systemic inflammation were assessed. Food intake was estimated with a modified Block food frequency questionnaire (FFQ). In this study, dietary patterns of 1751 participants with complete data were derived by cluster analysis.
Six clusters were identified, including a ‘Healthy foods’ cluster, characterized by higher intake of lowfat dairy products, fruit, whole grains, poultry, fish and vegetables. In the main analysis, the ‘Healthy foods’ cluster had significantly lower fasting insulin and HOMA-IR than the ‘Breakfast cereal’ and ‘High-fat dairy products’ clusters, and lower fasting glucose than the ‘High-fat dairy products’ cluster (P ≤ 0.05). No differences were found in 2-hour glucose. With respect to inflammation, the ‘Healthy foods’ cluster had lower IL-6 than the ‘Sweets and desserts’ and ‘High-fat dairy products’ clusters, and no differences were seen in CRP or TNF-α.
A dietary pattern high in lowfat dairy products, fruit, whole grains, poultry, fish and vegetables may be associated with greater insulin sensitivity and lower systemic inflammation in older adults.
PMCID: PMC3251708  PMID: 21915138
diet; dietary patterns; insulin sensitivity; inflammation; older adults
7.  Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels 
Human Molecular Genetics  2012;21(21):4774-4780.
Resistin is a polypeptide hormone that was reported to be associated with insulin resistance, inflammation and risk of type 2 diabetes and cardiovascular disease. We conducted a genome-wide association (GWA) study on circulating resistin levels in individuals of European ancestry drawn from the two independent studies: the Nurses' Health Study (n = 1590) and the Health, Aging and Body Composition Study (n = 1658). Single-nucleotide polymorphisms (SNPs) identified in the GWA analysis were replicated in an independent cohort of Europeans: the Gargano Family Study (n = 659). We confirmed the association with a previously known locus, the RETN gene (19p13.2), and identified two novel loci near the TYW3/CRYZ gene (1p31) and the NDST4 gene (4q25), associated with resistin levels at a genome-wide significant level, best represented by SNP rs3931020 (P = 6.37 × 10–12) and SNP rs13144478 (P = 6.19 × 10−18), respectively. Gene expression quantitative trait loci analyses showed a significant cis association between the SNP rs3931020 and CRYZ gene expression levels (P = 3.68 × 10−7). We also found that both of these two SNPs were significantly associated with resistin gene (RETN) mRNA levels in white blood cells from 68 subjects with type 2 diabetes (both P = 0.02). In addition, the resistin-rising allele of the TYW3/CRYZ SNP rs3931020, but not the NDST4 SNP rs13144478, showed a consistent association with increased coronary heart disease risk [odds ratio = 1.18 (95% CI, 1.03–1.34); P = 0.01]. Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels. More studies are needed to verify the associations of the SNP rs13144478 with NDST4 gene expression and resistin-related disease.
PMCID: PMC3471394  PMID: 22843503
8.  Ratio of Trunk to Leg Volume as a New Body Shape Metric for Diabetes and Mortality 
PLoS ONE  2013;8(7):e68716.
Body shape is a known risk factor for diabetes and mortality, but the methods estimating body shape, BMI and waist circumference are crude. We determined whether a novel body shape measure, trunk to leg volume ratio, was independently associated with diabetes and mortality.
Data from the National Health and Nutritional Examination Survey 1999–2004, a study representative of the US population, were used to generate dual-energy X-ray absorptiometry-derived trunk to leg volume ratio and determine its associations to diabetes, metabolic covariates, and mortality by BMI category, gender, and race/ethnicity group.
The prevalence of pre-diabetes and diabetes increased with age, BMI, triglycerides, blood pressure, and decreased HDL level. After adjusting for covariates, the corresponding fourth to first quartile trunk to leg volume ratio odds ratios (OR) were 6.8 (95% confidence interval [CI], 4.9–9.6) for diabetes, 3.9 (95% CI, 3.0–5.2) for high triglycerides, 1.8 (95% CI, 1.6–2.1) for high blood pressure, 3.0 (95% CI, 2.4–3.8) for low HDL, 3.6 (95% CI, 2.8–4.7) for metabolic syndrome, and 1.76 (95% CI, 1.20–2.60) for mortality. Additionally, trunk to leg volume ratio was the strongest independent measure associated with diabetes (P<0.001), even after adjusting for BMI and waist circumference. Even among those with normal BMI, those in the highest quartile of trunk to leg volume ratio had a higher likelihood of death (5.5%) than those in the lowest quartile (0.2%). Overall, trunk to leg volume ratio is driven by competing mechanisms of changing adiposity and lean mass.
A high ratio of trunk to leg volume showed a strong association to diabetes and mortality that was independent of total and regional fat distributions. This novel body shape measure provides additional information regarding central adiposity and appendicular wasting to better stratify individuals at risk for diabetes and mortality, even among those with normal BMI.
PMCID: PMC3707853  PMID: 23874736
9.  Association of Adiponectin and Mortality in Older Adults: Health ABC Study 
Diabetologia  2009;52(4):591-595.
Despite the widely reported inverse associations with insulin resistance and adiposity, adiponectin has been associated with both increased and decreased risk of cardiovascular disease. We examined whether adiponectin is associated with total and cardiovascular mortality in a large population of older adults.
We analyzed data from 3,075 well-functioning adults ages 69–79 years. Total adiponectin concentrations were measured at baseline and body composition was measured with abdominal and thigh CT scans. Mortality data was obtained over 6.6±1.6 years. We used Cox proportional hazards models adjusting for covariates in stages to examine the association between adiponectin and total and cardiovascular mortality.
There were 679 deaths and 38% were from cardiovascular disease. Unadjusted levels of adiponectin were not associated with total or cardiovascular mortality. However, after adjusting for sex and race, adiponectin was associated with an increased risk of both total (HR 1.26, 95% CI 1.15–1.37, per SD) and cardiovascular mortality (HR 1.35, 95% CI 1.17–1.56, per SD). Further adjustment for study site, smoking, hypertension, diabetes, prevalent heart disease, HDL, LDL, cystatin C, fasting insulin, triglycerides, BMI, visceral fat, thigh intermuscular fat, and thigh muscle area did not attenuate this association. This association between adiponectin and increased mortality risk did not vary by sex, race, BMI, diabetes, smoking, or weight loss.
Higher levels of adiponectin were associated with increased risk of total and cardiovascular mortality in this study of well-functioning community-dwelling older persons. This paradoxical association needs further study of underlying factors that might explain these results including differential association for high molecular weight adiponectin.
PMCID: PMC2756826  PMID: 19159917
10.  Lipid Peroxidation and Depressed Mood in Community-Dwelling Older Men and Women 
PLoS ONE  2013;8(6):e65406.
It has been hypothesized that cellular damage caused by oxidative stress is associated with late-life depression but epidemiological evidence is limited. In the present study we evaluated the association between urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), a biomarker of lipid peroxidation, and depressed mood in a large sample of community-dwelling older adults. Participants were selected from the Health, Aging and Body Composition study, a community-based longitudinal study of older persons (aged 70–79 years). The present analyses was based on a subsample of 1027 men and 948 women free of mobility disability. Urinary concentration of 8-iso-PGF2α was measured by radioimmunoassay methods and adjusted for urinary creatinine. Depressed mood was defined as a score greater than 5 on the 15-item Geriatric Depression Scale and/or use of antidepressant medications. Depressed mood was present in 3.0% of men and 5.5% of women. Depressed men presented higher urinary concentrations of 8-iso-PGF2α than non-depressed men even after adjustment for multiple sociodemographic, lifestyle and health factors (p = 0.03, Cohen’s d = 0.30). This association was not present in women (depressed status-by-sex interaction p = 0.04). Our study showed that oxidative damage may be linked to depression in older men from a large sample of the general population. Further studies are needed to explore whether the modulation of oxidative stress may break down the link between late-life depression and its deleterious health consequences.
PMCID: PMC3679197  PMID: 23776478
11.  Thyroid Function and Prevalent and Incident Metabolic Syndrome in Older Adults: The Health, Aging, and Body Composition Study 
Clinical Endocrinology  2012;76(6):911-918.
Both subclinical hypothyroidism and the metabolic syndrome have been associated with increased risk of coronary heart disease events. It is unknown if the prevalence and incidence of metabolic syndrome is higher as TSH levels increase, or in individuals with subclinical hypothyroidism. We sought to determine the association between thyroid function and the prevalence and incidence of the metabolic syndrome in a cohort of older adults.
Data was analyzed from the Health, Aging, and Body Composition Study, a prospective cohort of 3,075 community-dwelling US adults.
2,119 participants with measured TSH and data on metabolic syndrome components were included in the analysis.
TSH was measured by immunoassay. Metabolic syndrome was defined per revised ATP III criteria.
At baseline, 684 participants met criteria for metabolic syndrome. At 6yr follow-up, incident metabolic syndrome developed in 239 individuals. In fully adjusted models, each unit increase in TSH was associated with a 3% increase in the odds of prevalent metabolic syndrome (OR 1.03, 95% CI 1.01–1.06, p=0.02), and the association was stronger for TSH within the normal range (OR 1.16, 95% CI 1.03–1.30, p=0.02). Subclinical hypothyroidism with a TSH>10mIU/L was significantly associated with increased odds of prevalent metabolic syndrome (OR 2.3, 95% CI 1.0–5.0, p=0.04); the odds of incident MetS was similar (OR 2.2), but the confidence interval was wide (0.6–7.5).
Higher TSH levels and subclinical hypothyroidism with a TSH>10 mIU/L are associated with increased odds of prevalent but not incident metabolic syndrome.
PMCID: PMC3334430  PMID: 22187968
Thyroid Function; Metabolic Syndrome; Subclinical Hypothyroidism
12.  Oxidative Damage, Platelet Activation, and Inflammation to Predict Mobility Disability and Mortality in Older Persons: Results From the Health Aging and Body Composition Study 
Inflammation, oxidative damage, and platelet activation are hypothesized biological mechanisms driving the disablement process. The aim of the present study is to assess whether biomarkers representing these mechanisms predicted major adverse health-related events in older persons.
Data are from 2,234 community-dwelling nondisabled older persons enrolled in the Health Aging and Body Composition study. Biomarkers of lipid peroxidation (ie, urinary levels of 8-iso-prostaglandin F2α), platelet activation (ie, urinary levels of 11-dehydro-thromboxane B2), and inflammation (serum concentrations of interleukin-6) were considered as independent variables of interest and tested in Cox proportional hazard models as predictors of (severe) mobility disability and overall mortality.
The sample’s (women 48.0%, whites 64.3%) mean age was 74.6 (SD 2.9) years. During the follow-up (median 11.4 years), 792 (35.5%), 269 (12.0%), and 942 (42.2%) events of mobility disability, severe mobility disability, and mortality occurred, respectively. Only interleukin-6 showed significant independent associations with the onset of all the study outcomes. Higher levels of urinary 8-iso-prostaglandin F2α and 11-dehydro-thromboxane B2 independently predicted increased risk of death (hazard ratio 1.10, 95% confidence interval 1.03–1.19 and hazard ratio 1.14, 95% confidence interval 1.06–1.23, respectively). No significant interactions of gender, race, cardiovascular disease, diabetes, and antiplatelet drugs were detected on the studied relationships.
The inflammatory marker interleukin-6 is confirmed to be a robust predictor for the onset of negative health-related events. Participants with higher urinary levels of 8-iso-prostaglandin F2α and 11-dehydro-thromboxane B2 presented a higher mortality risk.
PMCID: PMC3348494  PMID: 22389462
Oxidative damage; Platelet activation; Inflammation; Disability; Mortality
13.  Glycemic Associations With Endothelial Function and Biomarkers Among 5 Ethnic Groups: The Multi‐Ethnic Study of Atherosclerosis and the Mediators of Atherosclerosis in South Asians Living in America Studies 
The association of prediabetic states with endothelial dysfunction measured by flow‐mediated dilation (FMD) or endothelial biomarker levels remains controversial. We examined data from 5 ethnic groups to determine the association between glucose categories and FMD or endothelial biomarkers. We determined whether these associations vary by ethnic group or body mass index.
Methods and Results
We used data from 3516 participants from 5 race/ethnic groups with brachial FMD, endothelial biomarkers, and glucose category (normal, impaired fasting glucose [IFG], and diabetes) measures. There were significant ethnic differences in FMD, biomarker levels, and the prevalence of IFG and diabetes. However, all 5 ethnic groups showed similar patterns of higher FMD for the IFG group compared with the normal glucose and diabetes groups, which was most significant among whites and Asian Indians. Associations between glucose categories and endothelial biomarkers were more uniform, with the IFG and diabetes groups having higher biomarker levels than the normal glucose group. These associations did not change with further adjustment for fasting insulin levels. Whites with normal BMI had higher FMD values with higher glucose levels, but those with BMI in the overweight or obese categories had the inverse association (P for interaction=0.01).
The discordance of IFG being associated with higher FMD but more abnormal endothelial biomarker levels is a novel finding. This higher FMD for the IFG group was most notable in whites of normal BMI. The higher FMD among those with impaired fasting glucose may reflect differences in insulin signaling pathways between the endothelium and skeletal muscle.
PMCID: PMC3603246  PMID: 23525433
biomarkers; diabetes; endothelium; ethnicity; insulin resistance
14.  The Live Well, Be Well Study: A Community-Based, Translational Lifestyle Program to Lower Diabetes Risk Factors in Ethnic Minority and Lower–Socioeconomic Status Adults 
American Journal of Public Health  2012;102(8):1551-1558.
We evaluated a community-based, translational lifestyle program to reduce diabetes risk in lower–socioeconomic status (SES) and ethnic minority adults.
Through an academic–public health department partnership, community-dwelling adults at risk for diabetes were randomly assigned to individualized lifestyle counseling delivered primarily via telephone by health department counselors or a wait-list control group. Primary outcomes (6 and 12 months) were fasting glucose level, triglycerides, high- and low-density lipoprotein cholesterol, weight, waist circumference, and systolic blood pressure. Secondary outcomes included diet, physical activity, and health-related quality of life.
Of the 230 participants, study retention was 92%. The 6-month group differences for weight and triglycerides were significant. The intervention group lost 2 pounds more than did the control group (P = .03) and had decreased triglyceride levels (difference in change, 23 mg/dL; P = .02). At 6 months, the intervention group consumed 7.7 fewer grams per day of fat (P = .05) and more fruits and vegetables (P = .02) than did control participants.
Despite challenges designing effective translational interventions for lower-SES and minority communities, this program modestly improved some diabetes risk factors. Thus, individualized, telephone-based models may be a promising alternative to group-based interventions.
PMCID: PMC3395772  PMID: 22698027
15.  An Innovative Multiphased Strategy to Recruit Underserved Adults into a Randomized Trial of a Community-Based Diabetes Risk Reduction Program 
The Gerontologist  2011;51(Suppl 1):S82-S93.
Purpose: To conduct and evaluate a two-phased community-based approach to recruit lower socioeconomic status, minority, or Spanish-speaking adults at risk of developing diabetes to a randomized trial of a lifestyle intervention program delivered by a public health department. Design: Within geographic areas comprising our target population, 4 community organizations provided local space for conducting the study and program. Phase I—outreach in venues surrounding these organizations—included diabetes education, a short diabetes risk appraisal (DRA), and diabetes risk screening based on a fasting fingerstick glucose test. Phase II—trial recruitment—began concurrently for those found to be at risk of developing diabetes in Phase I by explaining the study, lifestyle program, and research process. Those interested and eligible enrolled in the 1-year study. Results: Over 2 years, approximately 5,110 individuals received diabetes education, 1,917 completed a DRA, and 1,164 were screened of which 641 (55%) had an elevated fingerstick result of ≥106 mg/dl. Of the study sampling frame—persons over age 25 at risk of developing diabetes (N = 544)—238 (43%) enrolled in the trial; of those who were study eligible (n = 427), 56% enrolled. In the final sample, mean age was 56 years (SD = 17), 78% were ethnic minorities, 32% were Spanish-speaking, and 15% had a high school education or less. Implications: Providing diabetes health education and screening prior to study recruitment may help overcome barriers to research participation in underserved communities, thus helping address difficulties recruiting minority and older populations into research, particularly research pertaining to chronic disease risk factors.
PMCID: PMC3092977  PMID: 21565823
Translational research; Recruitment; Health education; Minority populations; Academic–Community partnership
16.  Heterogeneity of Diabetes Outcomes Among Asians and Pacific Islanders in the U.S. 
Diabetes Care  2011;34(4):930-937.
Ethnic minorities with diabetes typically have lower rates of cardiovascular outcomes and higher rates of end-stage renal disease (ESRD) compared with whites. Diabetes outcomes among Asian and Pacific Islander subgroups have not been disaggregated.
We performed a prospective cohort study (1996–2006) of patients enrolled in the Kaiser Permanente Northern California Diabetes Registry. There were 64,211 diabetic patients, including whites (n = 40,286), blacks (n = 8,668), Latinos (n = 7,763), Filipinos (n = 3,572), Chinese (n = 1,823), Japanese (n = 951), Pacific Islanders (n = 593), and South Asians (n = 555), enrolled in the registry. We calculated incidence rates (means ± SD; 7.2 ± 3.3 years follow-up) and created Cox proportional hazards models adjusted for age, educational attainment, English proficiency, neighborhood deprivation, BMI, smoking, alcohol use, exercise, medication adherence, type and duration of diabetes, HbA1c, hypertension, estimated glomerular filtration rate, albuminuria, and LDL cholesterol. Incidence of myocardial infarction (MI), congestive heart failure, stroke, ESRD, and lower-extremity amputation (LEA) were age and sex adjusted.
Pacific Islander women had the highest incidence of MI, whereas other ethnicities had significantly lower rates of MI than whites. Most nonwhite groups had higher rates of ESRD than whites. Asians had ~60% lower incidence of LEA compared with whites, African Americans, or Pacific Islanders. Incidence rates in Chinese, Japanese, and Filipinos were similar for most complications. For the three macrovascular complications, Pacific Islanders and South Asians had rates similar to whites.
Incidence of complications varied dramatically among the Asian subgroups and highlights the value of a more nuanced ethnic stratification for public health surveillance and etiologic research.
PMCID: PMC3064053  PMID: 21350114
17.  Association between oxidized LDL, obesity and type 2 diabetes in a population-based cohort, the Health Aging and Body Composition study 
Accumulating evidence suggests a cross-sectional association between oxidative stress and type 2 diabetes (T2D). Systemic oxidative stress, as measured by oxidized LDL (oxLDL), has been correlated with visceral fat. We examined the relationship between oxLDL, and T2D- and obesity-related traits in a bi-racial sample of 2,985 subjects at baseline and after 7 years of follow-up.
We examined six T2D-related traits (T2D status, HbA1c, fasting glucose, insulin, adiponectin and HOMA-IR) as well as six obesity-related traits (obesity status, BMI, leptin, % body fat, visceral and subcutaneous fat mass) using logistic and linear regression models.
In all subjects at baseline, oxLDL was positively associated with T2D (OR=1.3,95% CI:1.1–1.5), fasting glucose (β=0.03±0.006), HbA1c (β=0.02±0.004), fasting insulin (β=0.12±0.02), HOMA-IR (β=0.13±0.02) and negatively with adiponectin (β=−0.16±0.03), (all p<0.001). The strength and magnitude of these associations did not differ much between blacks and whites. In both blacks and whites, oxLDL was also associated with obesity (OR=1.3, 95% CI:1.1–1.4) and 3 of its related traits (β=0.60±0.14 for BMI, β=0.74±0.17 for % body fat, β=0.29±0.06 for visceral fat;
all p<0.001). Furthermore, of 4 traits measured after 7 years of follow-up (fasting glucose, HbA1c, BMI and % fat), their relationship with oxLDL were similar to baseline observations. No significant association was found between oxLDL and incident T2D. Interestingly, oxLDL was significantly associated with % change in T2D- and obesity-related traits in whites but not in blacks.
Our data suggest that systemic oxidative stress may be a novel risk factor for T2D and obesity.
PMCID: PMC3269343  PMID: 19780064
oxLDL; diabetes; oxidation; obesity
18.  Body fat distribution and inflammation among obese older adults with and without metabolic syndrome 
Obesity (Silver Spring, Md.)  2010;18(12):2354-2361.
The protective mechanisms by which some obese individuals escape the detrimental metabolic consequences of obesity are not understood. This study examined differences in body fat distribution and adipocytokines in obese older persons with and without metabolic syndrome. Additionally, we examined whether adipocytokines mediate the association between body fat distribution and metabolic syndrome. Data were from 729 obese men and women (BMI≥30kg/m2), aged 70-79 participating in the Health, Aging and Body Composition (Health ABC) study. Thirty-one percent of these obese men and women did not have metabolic syndrome. Obese persons with metabolic syndrome had significantly more abdominal visceral fat (men:p=0.04; women:p<0.01) and less thigh subcutaneous fat (men:p=0.09; women:p<0.01) than those without metabolic syndrome. Additionally, those with metabolic syndrome had significantly higher levels of IL-6, TNF-α and PAI-1 than individuals without metabolic syndrome. Per standard deviation (SD) higher in visceral fat, the likelihood of metabolic syndrome significantly increased in women (odds ratio (OR):2.16, 95% confidence interval (CI):1.59-2.94). In contrast, the likelihood of metabolic syndrome decreased in both men (OR:0.56, 95%CI:0.39-0.80) and women (OR:0.49, 95%CI:0.34-0.69) with each SD higher in thigh subcutaneous fat. These associations were partly mediated by adipocytokines; the association between thigh subcutaneous fat and metabolic syndrome was no longer significant in men. In summary, metabolically healthy obese older persons had a more favorable fat distribution, characterized by lower visceral fat and greater thigh subcutaneous fat and a more favorable inflammatory profile compared to their metabolically unhealthy obese counterparts.
PMCID: PMC3095947  PMID: 20395951
19.  F2-isoprostanes and Adiposity in Older Adults 
Obesity (Silver Spring, Md.)  2010;19(4):861-867.
We examined whether a systemic marker of oxidative stress, F2-isoprostanes (F2-IP), was associated with total and regional adiposity, adipocytokines, and change in adiposity. Using data from 726 participants enrolled in the Health, Aging, and Body Composition study, F2-IP and adipocytokines were measured from baseline plasma samples. Total adiposity was measured by whole body DXA and regional adiposity by abdominal and thigh CT scans at baseline and 5-year follow-up. ANOVA models were estimated to examine associations between F2-IP tertiles and baseline adiposity and changes in body composition. Median F2-IP was 54.3 pg/ml; women had significantly higher levels than men (61.5 vs. 48.9 pg/ml, p<0.001). F2-IP was associated with higher levels of adiponectin, leptin, and TNF-α. Men in the highest F2-IP tertile had significantly higher total percent body fat than those in the lowest tertile. Positive associations were found between F2-IP and all measures of total and regional adiposity among women. In linear regression models, adipocytokines mediated associations among women. Over 5 years of follow up, women in the highest versus lowest F2-IP tertile exhibited significant loss of weight (lowest tertile: −1.1 kg, highest tertile: −2.7 kg, p<0.05). In conclusion, F2-isoprostanes were associated with measures of total and regional adiposity in women and with total body fat in men; associations for women were partially explained by adipocytokines. F2-isoprostanes predicted loss of total adiposity over time among women.
PMCID: PMC3196361  PMID: 20948516
Abdominal obesity; Adipokines; Adipose Tissue; Oxidative Stress; Weight Change
20.  The impact of US versus Indian BMD reference standards on the diagnosis of osteoporosis among South Asian Indians living in the United States 
The relationship between bone mineral density (BMD) and fracture risk is not well-established for non-white populations. There is no established BMD reference standard for South Asians. Dual energy x-ray absorptiometry (DXA) was used to measure BMD at total hip and lumbar spine in 150 US-based South Asian Indians. For each subject T-scores were calculated using BMD reference values based on US white, North Indian and South Indian populations, and the resulting WHO BMD category assignments were compared. Reference standards derived from Indian populations classified a larger proportion of US-based Indians as normal than did US white-based standards. The percentage of individuals reclassified when changing between reference standards varied by skeletal site and reference population origin, ranging from 13% (95% CI, 7–18%), when switching from US-white- to North Indian-based standard for total hip, to 40% (95% CI, 32–48%), when switching from US white to South Indian reference values for lumbar spine. These finding illustrate that choice of reference standard has a significant effect on the diagnosis of osteoporosis in South Asians, and underscore the importance of future research to quantify the relationship between BMD and fracture risk in this population.
PMCID: PMC2966549  PMID: 20663699
21.  Asian Americans and Obesity in California: A Protective Effect of Biculturalism 
Prior studies comparing US-born and foreign-born Asian Americans have shown that birth in the US conveys greater risk of obesity. Our study investigates whether retention of Asian culture might be protective for obesity despite acculturation to US lifestyle. We classified self-identified Asian American respondents of the California Health Interview Survey as traditional, bicultural, and acculturated using nativity and language proficiency in English and Asian language. We then examined the association of acculturation with overweight/obesity (BMI ≥ 25 kg/m2) in a multivariate regression model. Acculturated respondents had higher adjusted odds of being overweight/obese than bicultural respondents (2.13 [1.40–3.23] for men, 3.28 [2.14–5.04] for women), but bicultural respondents had similar odds of being overweight/obese as traditional respondents (.98 [.69–1.41] for men, .72 [.50–1.05] for women). Among the bicultural, second and first generation respondents were equally likely to be overweight/obese. Biculturalism in Asian Americans as measured by Asian language retention appears protective against obesity. Further research is needed to understand the mechanisms underlying this association.
PMCID: PMC3056137  PMID: 21153765
Asian Americans; Obesity; Acculturation; Epidemiology
22.  Association of glucose measures with total and coronary heart disease mortality: does the effect change with time? (The Rancho Bernardo Study) 
To compare the associations of three glucose measures with coronary heart disease (CHD) and total mortality and to examine how these associations changed over time.
Prospective study of 1,774 adults (median age 68 years, 56% female). Fasting plasma glucose (FPG), 2-hour post-challenge glucose (2hPG), and glycohemoglobin (GHb) were obtained in 1984–1987. Mortality data was obtained for all participants. Multivariable Cox models examined the association of baseline glucose measures with mortality during sequential periods of follow-up (0–6, 7–12, and 13–18 years), adjusting for age, sex, blood pressure, LDL-cholesterol, smoking, exercise, and aspirin use.
854 (48%) participants died during follow-up. In adjusted models, only GHb was associated with total mortality over the entire 18 years (p=0.007). In analyses of mortality in successive 6 year time intervals, the association of GHb and total mortality was only significant in years 0–6. For each 1% increase in GHb, the hazard ratio for death in years 0–6 was 1.14 (95% CI 1.01–1.30, p=0.04) and the hazard ratio for CHD death was 1.26 (95% CI 1.03–1.55, p=0.02). Stratification by sex and exclusion of participants with diabetes did not change our results.
Higher levels of GHb were associated with increased total and CHD mortality within the first six years independent of cardiac risk factors. Though further research is needed, this supports the hypothesis that early glycemic control may affect mortality outcomes.
PMCID: PMC2767115  PMID: 19671481
Diabetes mellitus; coronary disease; risk assessment; glucose; glucose tolerance test
23.  Prevalence and Risk Factors for Urinary Incontinence in Overweight and Obese Diabetic Women 
Diabetes Care  2009;32(8):1391-1397.
To determine the prevalence and risk factors for urinary incontinence among different racial/ethnic groups of overweight and obese women with type 2 diabetes.
Cross-sectional analysis of baseline data from the Action for Health in Diabetes (Look AHEAD) study, a randomized clinical trial with 2,994 overweight/obese women with type 2 diabetes.
Weekly incontinence (27%) was reported more often than other diabetes-associated complications, including retinopathy (7.5%), microalbuminuria (2.2%), and neuropathy (1.5%). The prevalence of weekly incontinence was highest among non-Hispanic whites (32%) and lowest among African Americans (18%), and Asians (12%) (P < 0.001). Asian and African American women had lower odds of weekly incontinence compared with non-Hispanic whites (75 and 55% lower, respectively; P < 0.001). Women with a BMI of ≥35 kg/m2 had a higher odds of overall and stress incontinence (55–85% higher; P < 0.03) compared with that for nonobese women. Risk factors for overall incontinence, as well as for stress and urgency incontinence, included prior hysterectomy (40–80% increased risk; P < 0.01) and urinary tract infection in the prior year (55–90% increased risk; P < 0.001).
Among overweight and obese women with type 2 diabetes, urinary incontinence is highly prevalent and far exceeds the prevalence of other diabetes complications. Racial/ethnic differences in incontinence prevalence are similar to those in women without diabetes, affecting non-Hispanic whites more than Asians and African Americans. Increasing obesity (BMI ≥35 kg/m2) was the strongest modifiable risk factor for overall incontinence and stress incontinence in this diverse cohort.
PMCID: PMC2713631  PMID: 19487639
24.  Adiponectin and inducible ischemia in patients with stable coronary heart disease: data from the Heart and Soul study 
Atherosclerosis  2008;205(1):233-238.
Elevated concentrations of adiponectin are associated with a favorable metabolic profile but also with adverse cardiovascular outcomes. This apparent discrepancy has raised questions about whether adiponectin is associated with an increased or decreased risk of coronary heart disease (CHD). We sought to determine whether higher adiponectin levels are associated with exercise-induced ischemia in patients with stable CHD.
Methods and results
We measured total serum adiponectin concentrations and evaluated exercise-induced ischemia by stress echocardiography in a cross-sectional study of 899 outpatients with documented stable CHD. Of these, 217 (24%) had inducible ischemia. Although adiponectin levels correlated negatively with diabetes prevalence, body mass index, serum insulin, fasting glucose, low-density lipoprotein cholesterol, and triglycerides and positively with high-density lipoprotein cholesterol (all P< 0.005), elevated adiponectin concentrations were also associated with a greater risk of inducible ischemia. Each standard deviation (0.08 μg/mL) increase in log adiponectin was associated with a 35% greater odds of inducible ischemia (unadjusted odds ratio 1.35; 95% confidence interval 1.15–1.57; P=0.0002). Although attenuated, this association remained present after multivariable adjustment for traditional cardiovascular risk factors and other measures of cardiac function (adjusted odds ratio 1.21; 95% confidence interval 1.02–1.43; P=0.03).
Elevated concentrations of adiponectin are independently associated with inducible ischemia in patients with stable CHD. These findings raise the possibility that the presence of chronic inducible ischemia may alter the cardio-protective effects afforded by adiponectin secretion in the healthy population.
PMCID: PMC2779844  PMID: 19111833
Adiponectin; Coronary heart disease (CHD); Ischemia; Adipokine; Reverse epidemiology
25.  Plasma Oxidized Low-density Lipoprotein Levels and Arterial Stiffness in Older Adults: the Health ABC Study 
Hypertension  2009;53(5):846-852.
Arterial stiffness is a prominent feature of vascular aging and is strongly related to cardiovascular disease (CVD). Oxidized low-density lipoprotein (ox-LDL), a key player in the pathogenesis of atherosclerosis, may also play a role in arterial stiffening, but this relationship has not been well studied. Thus, we examined the cross-sectional association between ox-LDL and aortic pulse wave velocity (aPWV), a marker of arterial stiffness, in community-dwelling older adults. Plasma ox-LDL levels and aPWV were measured in 2,295 participants (mean age, 74 yrs; 52% female; 40% black) from the Health, Aging and Body Composition study. Mean aPWV significantly increased across tertiles of ox-LDL (tertile 1, 869 ± 376 cm/s; tertile 2, 901 ± 394 cm/s; tertile 3, 938 ± 415 cm/s; p=0.002). In multivariate analyses, ox-LDL remained associated with aPWV after adjustment for demographics and traditional CVD risk factors (p=0.008). After further adjustment for hemoglobin A1c, abdominal visceral fat, anti-hypertensive and antilipemic medications, and CRP the association with ox-LDL was attenuated, but remained significant (p=0.01). Results were similar when ox-LDL was expressed in absolute (mg/dL) or relative amounts (percent of LDL). Moreover, individuals in the highest ox-LDL tertile were 30-55% more likely to have high arterial stiffness, defined as aPWV > 75th percentile (p≤0.02). In conclusion, we found that among elderly persons, elevated plasma ox-LDL levels are associated with higher arterial stiffness, independent of CVD risk factors. These data suggest that ox-LDL may be related to the pathogenesis of arterial stiffness.
PMCID: PMC2692957  PMID: 19332658
aging; epidemiology; aortic stiffness; pulse wave velocity; oxidative stress

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