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1.  Mediators of Atherosclerosis in South Asians Living in America (MASALA) study: Objectives, Methods, and Cohort Description 
Clinical cardiology  2013;36(12):713-720.
Background
South Asians (individuals from India, Pakistani, Bangladesh, Nepal, and Sri Lanka) have high rates of cardiovascular disease which cannot be explained by traditional risk factors. There are no prospective cohort studies investigating antecedents of cardiovascular disease in South Asians.
Methods
The Mediators of Atherosclerosis in South Asians Living in America (MASALA) study is investigating the prevalence, correlates and outcomes associated with subclinical cardiovascular disease (CVD) in a population-based sample of South Asian men and women between ages 40 – 79 years from two U.S. clinical field centers. This cohort is similar in methods and measures to the Multi-Ethnic Study of Atherosclerosis to allow for efficient cross-ethnic comparisons. Measurements obtained at the baseline examination include sociodemographic information, lifestyle and psychosocial factors, standard CVD risk factors, oral glucose tolerance testing, electrocardiogram, assessment of microalbuminuria, ankle and brachial blood pressures, carotid intima media wall thickness using ultrasonagraphy, coronary artery calcium measurement and abdominal visceral fat using computed tomography. Blood samples will be assayed for biochemical risk factors.
Results
Between October 2010 and March 2013 we enrolled 906 South Asians with mean age of 55±9 years, 46% women, 98% immigrants who have lived 27±11 years in the US.
Conclusions
The sociodemographic characteristics of this cohort are representative of US South Asians. Participants are being followed with annual telephone calls for identification of CVD events including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, congestive heart failure, therapeutic interventions for CVD, and mortality.
doi:10.1002/clc.22219
PMCID: PMC3947423  PMID: 24194499
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.
doi:10.1097/FCH.0b013e31829d2549
PMCID: PMC3987985  PMID: 23986072
Asian Indian; chronic disease; cultural contexts; disparities; qualitative inquiry
3.  Adipokines and Body Fat Composition in South Asians: Results of the Metabolic syndrome and Atherosclerosis in South Asians Living in America (MASALA) Study 
Objective
To investigate whether leptin and adiponectin are associated with body fat composition in a South Asian population independent of metabolic variables.
Design
Cross-sectional study
Subjects
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.
Measurements
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.
Results
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.
Conclusion
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.
doi:10.1038/ijo.2011.167
PMCID: PMC3224670  PMID: 21863003
South Asians; body composition; sex differences in adiposity; adiponectin and leptin; hepatic fat
4.  Association of Adiponectin and Mortality in Older Adults: Health ABC Study 
Diabetologia  2009;52(4):591-595.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1007/s00125-009-1261-7
PMCID: PMC2756826  PMID: 19159917
5.  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.
Objectives
We evaluated a community-based, translational lifestyle program to reduce diabetes risk in lower–socioeconomic status (SES) and ethnic minority adults.
Methods
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.
Results
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.
Conclusions
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.
doi:10.2105/AJPH.2011.300456
PMCID: PMC3395772  PMID: 22698027
6.  Heterogeneity of Diabetes Outcomes Among Asians and Pacific Islanders in the U.S. 
Diabetes Care  2011;34(4):930-937.
OBJECTIVE
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.
RESEARCH DESIGN AND METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
doi:10.2337/dc10-1964
PMCID: PMC3064053  PMID: 21350114
7.  Using appropriate body mass index cut points for overweight and obesity among Asian Americans 
Preventive medicine  2014;65:1-6.
Objective
Asian Americans have low prevalence of overweight/obesity based on standard BMI cut points yet have higher rates of diabetes. We examined the prevalence of overweight/obesity, using lower BMI cut points recommended by the World Health Organization (WHO) for Asians, and diabetes in Asian American subgroups in California.
Method
Secondary analysis of the 2009 adult California Health Interview Survey (n = 45,946) of non-Hispanic Whites (NHW), African Americans, Hispanics and Asians (Vietnamese, Chinese, Korean, Filipino, South Asian and Japanese). WHO Asian BMI cut points (overweight = 23–27.5 kg/m2; obese ≥ 27.5 kg/m2) were used for Asian subgroups. Standard BMI cut points (overweight = 25–29.9 kg/m2; obese ≥ 30 kg/m2) were applied for other groups.
Results
Among Asian subgroups, overweight/obesity was highest among Filipinos (78.6%), which was higher than NHWs (p < 0.001) but similar to African Americans and Hispanics. Compared to NHW, diabetes prevalence was higher for Vietnamese, Koreans, Filipinos and South Asians with BMI = 23–24.9 kg/m2 and Koreans, Filipinos and Japanese with BMI = 27.5–29.9 kg/m2, the ranges WHO recommends as overweight or obese for Asians but not for other groups.
Conclusions
Filipinos should be a priority population for overweight/obesity screening. Filipinos, Vietnamese, Korean, South Asians and Japanese have higher diabetes prevalence at lower BMI cut points. WHO Asian BMI cut points may have clinical utility to identify at-risk Asian Americans.
doi:10.1016/j.ypmed.2014.04.010
PMCID: PMC4217157  PMID: 24736092
Obesity; Overweight; Type 2 diabetes mellitus; Asian Americans; Minority health
8.  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.
doi:10.1038/oby.2010.243
PMCID: PMC3196361  PMID: 20948516
Abdominal obesity; Adipokines; Adipose Tissue; Oxidative Stress; Weight Change
9.  Incidence of Type 2 Diabetes by Place of Birth in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Incidence of diabetes among US foreign-born individuals is not well studied. Data were from the Multi Ethnic Study of Atherosclerosis. Cox proportional hazards regression was used to examine diabetes risk by race/ethnicity, place of birth, and duration of residence among foreign-born. Foreign-born Latinos had a higher risk of incident diabetes compared to US-born Latinos (hazard ratio (HR) 1.79 [95 % confidence interval (CI) 1.00–3.21]). Latinos born in Mexico (HR, 2.26 [95 % CI, 1.18–4.33]) had higher risk of incident diabetes compared to US-born Latinos. Foreign-born living in the US ≥20 years had a higher adjusted risk of incident diabetes compared to those in the US for <20 years (HR, 1.60 [95 % CI, 1.05–2.55]). Incident diabetes may be higher among foreign-born compared to native born; incident diabetes may also be higher among those immigrants who have lived in the US for longer periods of time. Future studies should characterize individuals by race/ethnicity and place of birth to account for differences in biology and time spent in the US.
doi:10.1007/s10903-012-9683-6
PMCID: PMC4039384  PMID: 22833256
Immigrant; Foreign-born; Diabetes incidence; Latino; Chinese
10.  Type 2 Diabetes and 10-Year Risk of Dementia and Cognitive Impairment Among Older Mexican Americans 
Diabetes Care  2013;36(9):2600-2606.
OBJECTIVE
Type 2 diabetes has been linked with increased risk of dementia and cognitive impairment among older adults and with premature mortality in young and middle-aged adults. No studies have evaluated the association between diabetes and dementia among Mexican Americans, a population with a high burden of diabetes. We evaluated the association of diabetes with incidence of dementia and cognitive impairment without dementia (CIND) among older Mexican Americans while accounting for competing risk from death.
RESEARCH DESIGN AND METHODS
This study included 1,617 participants 60–98 years of age from the Sacramento Area Latino Study on Aging followed up to 10 years from 1998. We evaluated the association between diabetes and dementia/CIND with competing risk regression models.
RESULTS
Participants free of dementia/CIND at baseline (n = 1,617) were followed annually up to 10 years. There were 677 (41.9%) participants with diabetes, 159 (9.8%) incident dementia/CIND cases, and 361 (22.3%) deaths. Treated and untreated diabetes (hazard ratio 2.12 [95% CI 1.65–2.73] and 2.15 [1.58–2.95]) and dementia/CIND (2.48 [1.75–3.51]) were associated with an increased risk of death. In models adjusted for competing risk of death, those with treated and untreated diabetes had an increased risk of dementia/CIND (2.05 [1.41–2.97] and 1.55 [0.93–2.58]) compared with those without diabetes.
CONCLUSIONS
These findings provide evidence that the association between type 2 diabetes and dementia/CIND among Mexican Americans remains strong after accounting for competing risk of mortality. Treatments that modify risk of death among those with diabetes may change future dementia risk.
doi:10.2337/dc12-2158
PMCID: PMC3747945  PMID: 23514732
11.  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 
Objective
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.
Methods
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.
Results
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.
Conclusions
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
12.  Dietary patterns, insulin sensitivity and inflammation in older adults 
Background/Objectives
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.
Subjects/Methods
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.
Results
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.
Conclusions
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.
doi:10.1038/ejcn.2011.162
PMCID: PMC3251708  PMID: 21915138
diet; dietary patterns; insulin sensitivity; inflammation; older adults
13.  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.
doi:10.1016/j.amjcard.2006.09.096
PMCID: PMC3947589  PMID: 17293190
coronary disease; endothelin; risk factors; epidemiology
14.  Elevated Rates of Diabetes in Pacific Islanders and Asian Subgroups 
Diabetes Care  2013;36(3):574-579.
OBJECTIVE
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.
RESEARCH DESIGN AND METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
doi:10.2337/dc12-0722
PMCID: PMC3579366  PMID: 23069837
15.  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.
doi:10.1093/hmg/dds300
PMCID: PMC3471394  PMID: 22843503
16.  Description of an Academic-Community Partnership Lifestyle Program for Lower-Income, Minority Adults at Risk for Diabetes 
The Diabetes educator  2010;36(4):640-650.
Purpose
Translating strategies and approaches from the successful clinically-based Diabetes Prevention Program's lifestyle intervention to community settings is a key next step. This article describes a lifestyle program developed in partnership by researchers at a major university and public health professionals at a local health department.
Methods
The Live Well, Be Well (LWBW) program was designed to meet the needs of lower-income, minority, and low-literacy adults at risk for diabetes. It was adapted from interventions with demonstrated efficacy and delivered in Spanish and English by health department staff. The program consisted of a 6-month active phase and a 6-month maintenance phase and was primarily telephone-based, with one in-person planning session and several group workshops. In-person and group sessions were held in convenient community-based settings. Counselors provided education and skills training to modify diet and increase physical activity. Self-selected and attainable goal-setting and action plans were emphasized to enhance self-efficacy. LWBW is the intervention component of a randomized trial with primary outcomes of fasting glucose, weight, and other clinical measures.
Conclusions
The program provides a unique translational model for implementing diabetes risk reduction programs for underserved populations. Individually-tailored and non-prescriptive, it utilized existing health department infrastructure, focused on telephone counseling, used culturally-appropriate, low-literacy materials, and was delivered in local, community-based facilities.
doi:10.1177/0145721710374368
PMCID: PMC3771540  PMID: 20576836
Translational research; lifestyle intervention; minority populations; academic-community partnership
17.  Adipokines and the Risk of Fracture in Older Adults 
Adiponectin and leptin are adipokines that influence bone metabolism in vitro and in animal models. However, less is known about the longitudinal association of leptin and adiponectin with fracture. We tested the hypothesis that low leptin and high adiponectin levels are each individually associated with fracture risk in a prospective cohort study in Memphis and Pittsburgh, among 3,075 women and men, aged 70–79, from the Health Aging and Body Composition (Health ABC) study. There were 406 incident fractures (334 non-vertebral and 72 vertebral) over a mean of 6.5 ± 1.9 years. Cox regression was used to estimate the hazard ratios for fracture. Sex modified the association between adiponectin and fracture (p for interaction=0.025). Men with the highest adiponectin level (tertile 3) had a 94 % higher risk of fracture (HR=1.94; 95% CI 1.20, 3.16) compared to the lowest tertile (tertile 1), p for trend=0.007 after adjusting age, race, BMI, education, diabetes weight change, and hip BMD. Among women, after adjusting for age and race this association was no longer significant (p for trend=0.369). Leptin did not predict fracture risk in women (p for trend=0.544) or men (p for trend=0.118) in the multivariate models. Our results suggest that adiponectin, but not leptin, may be a novel risk factor for increased fracture risk independent of body composition and BMD and that these relationships may be influenced by sex. More research is needed to understand the physiological basis underlying these sex differences.
doi:10.1002/jbmr.361
PMCID: PMC3733555  PMID: 21312272
18.  Ratio of Trunk to Leg Volume as a New Body Shape Metric for Diabetes and Mortality 
PLoS ONE  2013;8(7):e68716.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1371/journal.pone.0068716
PMCID: PMC3707853  PMID: 23874736
19.  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.
doi:10.1371/journal.pone.0065406
PMCID: PMC3679197  PMID: 23776478
20.  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.
Objective
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.
Design
Data was analyzed from the Health, Aging, and Body Composition Study, a prospective cohort of 3,075 community-dwelling US adults.
Participants
2,119 participants with measured TSH and data on metabolic syndrome components were included in the analysis.
Measurements
TSH was measured by immunoassay. Metabolic syndrome was defined per revised ATP III criteria.
Results
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).
Conclusions
Higher TSH levels and subclinical hypothyroidism with a TSH>10 mIU/L are associated with increased odds of prevalent but not incident metabolic syndrome.
doi:10.1111/j.1365-2265.2011.04328.x
PMCID: PMC3334430  PMID: 22187968
Thyroid Function; Metabolic Syndrome; Subclinical Hypothyroidism
21.  Oxidative Damage, Platelet Activation, and Inflammation to Predict Mobility Disability and Mortality in Older Persons: Results From the Health Aging and Body Composition Study 
Background.
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.
Methods.
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.
Results.
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.
Conclusions.
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.
doi:10.1093/gerona/glr246
PMCID: PMC3348494  PMID: 22389462
Oxidative damage; Platelet activation; Inflammation; Disability; Mortality
22.  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 
Background
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).
Conclusions
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.
doi:10.1161/JAHA.112.004283
PMCID: PMC3603246  PMID: 23525433
biomarkers; diabetes; endothelium; ethnicity; insulin resistance
23.  The Effects of Adiponectin and Leptin on Changes in Bone Mineral Density 
Introduction
Adiponectin and leptin are hormones secreted by adipose cells that may impact bone mineral density (BMD). Few studies have evaluated the longitudinal association of leptin and adiponectin levels with rates of BMD change.
Methods
Hip and whole body areal BMD (aBMD) were measured 5 times using dual energy x-ray absorptiometry (DXA) over 10 years. Trabecular lumbar spine volumetric BMD (vBMD) was measured using quantitative computed topography (QCT) at baseline and year 6 in the Pittsburgh cohort only. Random slope and intercept models were used to account for within person correlation as a result of repeated measures of hip and whole body aBMD. Linear regression was used to model changes in spine trabecular vBMD.
Results
Among women, the annualized rate of hip aBMD loss in the highest tertile of adiponectin was −0.67% (95% CI: −0.77, −0.58) compared to −0.43% (95% CI: −0.51, −0.35)] in the lowest tertile (p trend=0.019) after adjusting for age, race, BMI, diabetes, baseline hip aBMD, and weight change. In men, hip aBMD loss was greatest in the high adiponectin group (tertile 3), however this association was not significant, p trend=0.148. After adjusting for weight change in women, the association between higher leptin and lower hip aBMD loss was attenuated and no longer significant, p trend=0.134. Leptin and adiponectin levels were not associated with whole body aBMD or trabecular lumbar spine vBMD loss.
Conclusions
Adiponectin was associated with increased hip aBMD loss in women only; supporting evidence that adiponectin may have an important role in bone health.
doi:10.1007/s00198-011-1768-x
PMCID: PMC3536828  PMID: 21877199
leptin; adiponectin; bone loss; hip aBMD; whole body aBMD; trabecular lumbar spine vBMD
24.  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.
doi:10.1093/geront/gnr026
PMCID: PMC3092977  PMID: 21565823
Translational research; Recruitment; Health education; Minority populations; Academic–Community partnership
25.  Association between oxidized LDL, obesity and type 2 diabetes in a population-based cohort, the Health Aging and Body Composition study 
Aims/hypothesis
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.
Methods
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.
Results
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.
Conclusion/interpretation
Our data suggest that systemic oxidative stress may be a novel risk factor for T2D and obesity.
doi:10.1002/dmrr.1011
PMCID: PMC3269343  PMID: 19780064
oxLDL; diabetes; oxidation; obesity

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