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1.  Association of Electrocardiographically Determined Left Ventricular Mass With Incident Diabetes, 1985–1986 to 2010–2011 
Diabetes Care  2013;36(3):645-647.
Electrocardiographic indices reflecting left ventricular hypertrophy are associated with incident diabetes in clinical populations at risk for coronary heart disease. We tested whether electrocardiographically determined left ventricular mass was positively associated with incident diabetes in a population sample.
Coronary Artery Risk Development in Young Adults (CARDIA) study participants (n = 4,739) were followed from 1985–1986 to 2010–2011 for incident diabetes. Validated sex- and race-specific formulas were applied to standard electrocardiograms to determine left ventricular mass.
Over 25 years, 444 participants developed diabetes (9.4%). After adjustment for demographic, behavioral, and clinical covariates, participants in the highest quartile of left ventricular mass index (LVMI) were twice as likely to develop diabetes than participants in the lower three quartiles (hazard ratio 2.61 [95% CI 2.16–3.17]). Neither Cornell voltage nor Cornell voltage product was associated with incident diabetes in fully adjusted models.
Electrocardiographically determined LVMI may be a useful noninvasive marker for identifying adults at risk for diabetes.
PMCID: PMC3579342  PMID: 23160723
2.  Null Association between Abdominal Muscle and Calcified Atherosclerosis in Community-Living Persons Without Clinical Cardiovascular Disease: the Multi-Ethnic Study of Atherosclerosis 
Metabolism: clinical and experimental  2013;62(11):10.1016/j.metabol.2013.06.001.
Detrimental effects of lean muscle loss have been hypothesized to explain J-shaped relationships of body mass index (BMI) with cardiovascular disease (CVD), yet associations of muscle mass with CVD are largely unknown. We hypothesized that low abdominal lean muscle area would be associated with greater calcified atherosclerosis, independent of other CVD risk factors.
We investigated 1020 participants from the Multi-Ethnic Study of Atherosclerosis who were free of clinical CVD. Computed tomography (CT) scans at the 4th and 5th lumbar disk space were used to estimate abdominal lean muscle area. Chest and abdominal CT scans were used to assess coronary artery calcification(CAC), thoracic aortic calcification (TAC), and abdominal aortic calcification (AAC).
The mean age was 64±10 years, 48% were female, and mean BMI was 28±5 kg/m2. In models adjusted for demographics, physical activity, caloric intake, and traditional CVD risk factors, there was no inverse association of abdominal muscle mass with CAC(Prevalence Ratio [PR] 1.02 [95% CI 0.95,1.10]), TAC (PR 1.13 [95%CI 0.92, 1.39]) or AAC (PR 0.99 [95%CI 0.94, 1.04]) prevalence. Similarly, there was no significant inverse relationship between abdominal lean muscle area and CAC, TAC, and AAC severity.
In community-living individuals without clinical CVD, greater abdominal lean muscle area is not associated with less calcified atherosclerosis.
PMCID: PMC3740763  PMID: 23916063
Cardiovascular Disease; atherosclerosis; lean muscle
3.  Quantifying the contributions of behavioral and biological risk factors to socioeconomic disparities in coronary heart disease incidence: The MORGEN study 
European journal of epidemiology  2013;28(10):10.1007/s10654-013-9847-2.
Quantifying the impact of different modifiable behavioral and biological risk factors on socioeconomic disparities in coronary heart disease (CHD) may help inform targeted, population-specific strategies to reduce the unequal distribution of the disease. Previous studies have used analytic approaches that limit our ability to disentangle the relative contributions of these risk factors to CHD disparities. The goal of this study was to assess mediation of the effect of low education on incident CHD by multiple risk factors simultaneously. Analyses are based on 15,067 participants of the Dutch Monitoring Project on Risk Factors for Chronic Diseases aged 20–65 years examined 1994–1997 and followed for events until January 1, 2008. Path analysis was used to quantify and test mediation of the low education-CHD association by behavioral (current cigarette smoking, heavy alcohol use, poor diet, and physical inactivity) and biological (obesity, hypertension, diabetes, and hypercholesterolemia) risk factors. Behavioral and biological risk factors accounted for 56.6% (95% CI: 42.6%–70.8%) of the low education-incident CHD association. Smoking was the strongest mediator, accounting for 27.3% (95% CI: 17.7%–37.4%) of the association, followed by obesity (10.2%; 95% CI: 4.5%–16.1%), physical inactivity (6.3%; 95% CI: 2.7%–10.0%), and hypertension (5.3%; 95% CI: 2.8%–8.0%). In summary, in a Dutch cohort, the majority of the relationship between low education and incident CHD was mediated by traditional behavioral and biological risk factors. Addressing barriers to smoking cessation, blood pressure and weight management, and physical activity may be the most effective approaches to eliminating socioeconomic inequalities in CHD.
PMCID: PMC3844527  PMID: 24037117
socioeconomic status; coronary heart disease; health behaviors; risk factors
4.  Status of Cardiovascular Health in US Adults: Prevalence Estimates from the National Health and Nutrition Examination Surveys (NHANES) 2003-2008 
Circulation  2011;125(1):45-56.
The American Heart Association's 2020 Strategic Impact Goals define a new concept, “cardiovascular (CV) health”; however, current prevalence estimates of the status of CV health in U.S. adults according to age, sex and race/ethnicity have not been published.
Methods and Results
We included 14,515 adults (≥20 years) from the 2003-2008 National Health and Nutrition Examination Surveys. Participants were stratified by young (20-39 years), middle (40-64 years), and older ages (65+ years). CV health behaviors (diet, physical activity, body mass index, smoking) and CV health factors (blood pressure, total cholesterol, fasting blood glucose, smoking) were defined as poor, intermediate, or ideal. Less than 1% of adults exhibited ideal CV health for all 7 metrics. For CV health behaviors, non-smoking was most prevalent (range:60.2-90.4%) while ideal Healthy Diet Score was least prevalent (range:0.2-2.6%) across groups. Prevalence of ideal BMI (range:36.5-45.3%) and ideal physical activity levels (range:50.2-58.8%) were higher in young adults compared to middle or older ages. Ideal total cholesterol (range:23.7-36.2%), blood pressure (range:11.9-16.3%) and fasting blood glucose (range:31.2-42.9%) were lower in older adults compared with young and middle age adults.Prevalence of poor CV health factors was lowest in young age but higher at middle and older ages. Prevalence estimates by age and sex were consistent across race/ethnic groups.
These prevalence estimates of CV health represent a starting point from which effectiveness of efforts to promote CV health and prevent CV disease can be monitored and compared in U.S. adult populations.
PMCID: PMC4077723  PMID: 22095826
Cardiovascular Diseases; Diet; Epidemiology; Obesity; Risk Factors
5.  Racial and Ethnic Residential Segregation, the Neighborhood Socioeconomic Environment, and Obesity Among Blacks and Mexican Americans 
American Journal of Epidemiology  2013;177(4):299-309.
We used cross-sectional data on 2,660 black and 2,611 Mexican-American adult participants in the National Health and Nutrition Examination Survey (1999–2006) to investigate the association between metropolitan-level racial/ethnic residential segregation and obesity and to determine whether it was mediated by the neighborhood socioeconomic environment. Residential segregation was measured using the black and Hispanic isolation indices. Neighborhood poverty and negative income incongruity were assessed as mediators. Multilevel Poisson regression with robust variance estimates was used to estimate prevalence ratios. There was no relationship between segregation and obesity among men. Among black women, in age-, nativity-, and metropolitan demographic-adjusted models, high segregation was associated with a 1.29 (95% confidence interval (CI): 1.00, 1.65) times higher obesity prevalence than was low segregation; medium segregation was associated with a 1.35 (95% CI: 1.07, 1.70) times higher obesity prevalence. Mexican-American women living in high versus low segregation areas had a significantly lower obesity prevalence (prevalence ratio, 0.54; 95% CI: 0.33, 0.90), but there was no difference between those living in medium versus low segregation areas. These associations were not mediated by neighborhood poverty or negative income incongruity. These findings suggest variability in the interrelationships between residential segregation and obesity for black and Mexican-American women.
PMCID: PMC3566709  PMID: 23337312
health disparities; obesity; residential segregation; social environment
6.  Physical Activity, Change in Biomarkers of Myocardial Stress and Injury, and Subsequent Heart Failure Risk in Older Adults 
The aim of this study was to evaluate the association between physical activity and changes in levels of highly sensitive troponin T (cTnT) and N-terminal pro–B-type natriuretic peptide (NT-proBNP), and the subsequent risk of the development of heart failure (HF) in community-dwelling older adults.
Higher baseline levels of cTnT and NT-proBNP and increases over time correlate with the risk of HF in older adults. Factors modifying these levels have not been identified.
NT-proBNP and cTnT were measured at baseline and 2 to 3 years later in adults 65 years of age and older free of HF participating in the Cardiovascular Health Study. Self-reported physical activity and walking pace were combined into a composite score. An increase was prespecified for NT-proBNP as a >25% increment from baseline to ≥190 pg/ml and for cTnT as a >50% increment from baseline in participants with detectable levels (≥3 pg/ml).
A total of 2,933 participants free of HF had NT-proBNP and cTnT measured at both time points. The probability of an increase in biomarker concentrations between baseline and follow-up visits was inversely related to the physical activity score. Compared with participants with the lowest score, those with the highest score had an odds ratio of 0.50 (95% confidence interval: 0.33 to 0.77) for an increase in NT-proBNP and an odds ratio of 0.30 (95% confidence interval: 0.16 to 0.55) for an increase in cTnT, after adjusting for comorbidities and baseline levels. A higher activity score associated with a lower long-term incidence of HF. Moreover, at each level of activity, an increase in either biomarker still identified those at higher risk.
These findings suggest that moderate physical activity has protective effects on early heart failure phenotypes, preventing cardiac injury and neurohormonal activation.
PMCID: PMC3591516  PMID: 23158528
aging; exercise; heart failure; natriuretic peptides
7.  Correlates of heart rate recovery over 20 years in a population sample 
Medicine and science in sports and exercise  2012;44(2):10.1249/MSS.0b013e31822cb190.
Slow heart rate recovery (HRR) from a graded exercise treadmill test (GXT) is a marker of impaired parasympathetic reactivation that is associated with elevated mortality. Our objective was to test whether demographic, behavioral or coronary heart disease (CHD) risk factors during young adulthood were associated with the development of slow HRR.
Participants from the Coronary Artery Risk Development in Young Adults study underwent symptom-limited maximal GXT using a modified Balke protocol at baseline (1985–86) and 20-year follow-up (2005–06) examinations. HRR was calculated as the difference between peak heart rate (HR) and HR two-minutes following cessation of the GXT. Slow HRR was defined as 2-minute HRR < 22 beats·min−1.
In 2,730 participants who did not have slow HRR at baseline, mean HRR was 44 beats*min−1 (SD = 11) at baseline and declined to 40 beats·min−1 (SD=12) in 2005–06; slow HRR developed in 5% (n=135) of the sample by 2005–06. Female sex, black race, fewer years of education, obesity, cigarette smoking, higher depressive symptoms, higher fasting glucose, hypertension, metabolic syndrome and physical inactivity and low fitness were each associated with incident slow HRR. In a multivariable model higher BMI, larger waist, low education, fasting glucose and current smoking remained significantly associated with incident slow HRR. Increasing BMI (per SD higher) over follow-up and incident hypertension, diabetes and metabolic syndrome (in the subsets of participants who were free from those conditions at baseline), were each associated with a significantly elevated odds of incident slow HRR.
On average, HRR declines with aging; however, the odds of having slow HRR in early middle age is significantly associated with traditional CHD risk factors.
PMCID: PMC3838873  PMID: 21796053
Epidemiology; Cardiovascular Disease; Exercise; Autonomic Nervous System
8.  Depressive Symptom Clusters and 5-Year Incidence of Coronary Artery Calcification: The CARDIA Study 
Circulation  2012;126(4):410-417.
Because depression is a multidimensional construct and few studies have compared the relative importance of its facets in predicting cardiovascular risk, we evaluated the utility of depressive symptom clusters in predicting the 5-year incidence of coronary artery calcification (CAC).
Methods and Results
Participants were 2,171 middle-aged adults (58% female, 43% black) from the Coronary Artery Risk Development in Young Adults (CARDIA) Study who were free of cardiovascular disease. Depressive symptom clusters (z scores) were measured by questionnaires in 2000–2001, and CAC was measured by electron beam computed tomography in 2000–2001 and 2005–2006. There were 243 (11%) cases of incident CAC, defined as the absence of CAC at baseline and the presence of CAC at follow-up. Total depressive symptoms (OR = 1.16, 95% CI: 1.02–1.33, p = .03) and the depressed affect cluster (OR = 1.17, 95% CI: 1.03–1.33, p = .02) predicted incident CAC; however, the somatic, interpersonal distress, low positive affect, and pessimism clusters did not. The depressed affect-incident CAC relationship was independent of age, sex, race, education, and antidepressant use; was similar across gender and racial groups; and was partially accounted for by tobacco use and mean arterial pressure.
In contrast to recent results indicating that the somatic cluster is the most predictive of cardiovascular outcomes, we found that the prospective association between depressive symptoms and incident CAC was driven by the depressed affect cluster. Our findings raise the possibility that there may not be one facet of depression that is the most cardiotoxic across all contexts.
PMCID: PMC3422690  PMID: 22711275
atherosclerosis; cardiovascular disease risk factors; coronary artery calcification; depression; epidemiology
9.  Diurnal Salivary Cortisol and Urinary Catecholamines Are Associated With Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis 
Metabolism  2011;61(7):986-995.
To examine the cross-sectional association of diurnal salivary cortisol curve components and urinary catecholamines with diabetes status.
Up to 18 salivary cortisol samples over 3 days and overnight urinary catecholamines were collected from 1,002 participants in the Multi-Ethnic Study of Atherosclerosis. Diabetes was defined as a fasting blood glucose ≥126 mg/dL or medication use. Cortisol curve measures included awakening cortisol, cortisol awakening response (CAR), early decline, late decline, and cortisol area under the curve (AUC). Urinary catecholamines included epinephrine, norepinephrine, and dopamine.
Participants with diabetes had significantly lower CAR (β=−0.19; 95% CI: −0.34 to −0.04) than those without diabetes in multivariable models. While men with diabetes had a non-significant trend toward lower total AUC (β=−1.56; 95% CI: −3.93 to 0.80), women with diabetes had significantly higher total AUC (β=2.62; 95% CI: 0.72 to 4.51) (p=0.02 for interaction) compared to those without diabetes. Men but not women with diabetes had significantly lower urinary catecholamines, compared to those without diabetes (p<0.05).
Diabetes is associated with neuroendocrine dysregulation, which may differ by sex. Further studies are needed to determine the role of the neuroendocrine system in the pathophysiology of diabetes.
PMCID: PMC3319636  PMID: 22209664
diabetes; hypothalamic-pituitary-adrenal (HPA) axis; salivary cortisol; catecholamines; epidemiology
10.  Diurnal Salivary Cortisol is Associated With Body Mass Index and Waist Circumference: The Multi-Ethnic Study of Atherosclerosis 
Obesity (Silver Spring, Md.)  2013;21(1):E56-E63.
Neuroendocrine abnormalities, such as activation of the hypothalamic-pituitary-adrenal (HPA) axis, are associated with obesity; however, few large-scale population-based studies have examined HPA axis and markers of obesity. We examined the cross-sectional association of the cortisol awakening response (CAR) and diurnal salivary cortisol curve with obesity. The Multi-Ethnic Study of Atherosclerosis (MESA) Stress Study includes 1,002 White, Hispanic, and Black men and women (mean age 65±9.8 years) who collected up to 18 salivary cortisol samples over 3 days. Cortisol profiles were modeled using regression spline models that incorporated random parameters for subject-specific effects. Cortisol curve measures included awakening cortisol, CAR (awakening to 30 minutes post-awakening), early decline (30 minutes to 2 hours post-awakening), late decline (2 hours post-awakening to bedtime), and the corresponding areas under the curve (AUC). Body-mass-index (BMI) and waist circumference (WC) were used to estimate adiposity. For the entire cohort, both BMI and WC were negatively correlated with awakening cortisol (p<0.05), AUC during awakening rise and early decline and positively correlated to the early decline slope (p<0.05) after adjustments for age, race/ethnicity, gender, diabetes status, socioeconomic status, beta blockers, steroids, hormone replacement therapy and smoking status. No heterogeneities of effects were observed by gender, age, and race/ethnicity. Higher BMI and WC are associated with neuroendocrine dysregulation, which is present in a large population sample, and only partially explained by other covariates.
PMCID: PMC3602310  PMID: 23404865
adiposity; hypothalamic-pituitary-adrenal (HPA) axis; salivary cortisol; diurnal cortisol; cortisol awakening response; epidemiology; obesity; body mass index; waist circumference; epidemiology
11.  Fasting and Post-Glucose Load Measures of Insulin Resistance and Risk of Ischemic Stroke in Older Adults 
Background and purpose
Few studies have assessed post-glucose load measures of insulin resistance and ischemic stroke risk, and data are sparse for older adults. We investigated whether fasting and post-glucose load measures of insulin resistance were related to incident ischemic stroke in non-diabetic older adults.
Participants were men and women in the Cardiovascular Health Study, aged 65+ and without prevalent diabetes or stroke at baseline, followed for 17 years for incident ischemic stroke. The Gutt insulin sensitivity index was calculated from baseline body weight and fasting and 2-hour post-load insulin and glucose; a lower Gutt index indicates higher insulin resistance.
Analyses included 3,442 participants (42% men) with a mean age of 73. Incidence of ischemic stroke was 9.8 strokes per 1,000 person years. The relative risk (RR) for lowest quartile vs. highest quartile of Gutt index was 1.64 (95% confidence interval: 1.24, 2.16), adjusted for demographics and prevalent cardiovascular and kidney disease. Similarly, the adjusted RR for highest quartile vs. lowest quartile of 2-hour glucose was 1.84 (95% CI: 1.39, 2.42). In contrast, the adjusted RR for highest quartile vs. lowest quartile of fasting insulin was 1.10 (95% CI: 0.84, 1.46).
In non-diabetic older adults, insulin resistance measured by Gutt index or 2-hour glucose, but not fasting insulin, was associated with risk of incident ischemic stroke.
PMCID: PMC3226936  PMID: 21998054
Non-diabetic older adults; Cohort study; Gutt insulin sensitivity index
12.  Association of Weight Status with Mortality in Adults with Incident Diabetes 
Type 2 diabetes in normal weight (body mass index [BMI] <25kg/m2) adults is an intriguing representation of the metabolically obese normal weight phenotype with unknown mortality consequences.
To minimize the influence of diabetes duration and voluntary weight loss on mortality, we tested the association of weight status with mortality in adults with new onset diabetes.
Pooled analysis of five longitudinal cohort studies: Atherosclerosis Risk in Communities Study, 1990–2006; Cardiovascular Health Study, 1992–2008; Coronary Artery Risk Development in Young Adults, 1987–2011; Framingham Offspring Study, 1979–2007; Multi-Ethnic Study of Atherosclerosis, 2002–2011. Participants contributed 27,125 person-years of follow-up.
2,625 participants with incident diabetes
Men and women (age>40 years) who developed incident diabetes based on fasting glucose ≥ 126 mg/dL or newly-initiated diabetes medication and who had concurrent measurements of body mass index (BMI). Participants were classified as normal weight if their BMI was 18.5 to 24.99kg/m2 or overweight/obese if BMI≥25 kg/m2.
Main Outcome Measures
Total, cardiovascular, and non-cardiovascular mortality
The proportion of adults who were normal weight at the time of incident diabetes ranged from 9–21% (overall=12%). Over follow-up, 449 participants died, 178 from cardiovascular causes and 253 from non-cardiovascular causes (18 were not classified). The rate of total, cardiovascular and non-cardiovascular mortality was higher in normal weight participants (248.8, 99.8, and 198.1 per 10,000 person-years, respectively) than overweight/obese participants (152.1, 67.8, and 87.9 per 10,000 person-years, respectively). Following adjustment for demographic characteristics and blood pressure, lipids, waist circumference and smoking status, hazard ratios comparing normal weight participants to overweight/obese participants for total, cardiovascular, and non-cardiovascular mortality were 2.08 (95% confidence interval [CI]: 1.52, 2.85), 1.52 (95% CI: 0.89, 2.58) and 2.32 (95% CI: 1.55, 3.48), respectively.
Adults who are normal weight at the time of incident diabetes have higher mortality than adults who are overweight or obese.
PMCID: PMC3467944  PMID: 22871870
type 2 diabetes; obesity; cardiovascular disease; longitudinal studies
13.  Lower Extremity Fat Mass Is Associated With Insulin Resistance in Overweight and Obese Individuals: The CARDIA Study 
Obesity (Silver Spring, Md.)  2011;19(11):2248-2253.
Lower extremity fat mass (LEFM) has been shown to be favorably associated with glucose metabolism. However, it is not clear whether this relationship is similar across varying levels of obesity. We hypothesized that lower amounts of LEFM is associated with higher insulin resistance (IR) and this association may vary according to weight status. Participants with available measures were examined from the Coronary Artery Risk Development in Young Adults study (CARDIA), a multi-center longitudinal study of the etiology of atherosclerosis in black and white men and women aged 38–50 years old in 2005–2006 (n = 1,579). The homeostasis model assessment of IR (HOMAIR) was calculated to estimate IR, regional adiposity was measured using dual energy X-ray absorptiometry (DXA), and weight status was defined according to BMI categories. Obese and overweight participants exhibited higher IR, total fat mass (FM), trunk FM (TFM), and LEFM compared to normal weight participants. After controlling for age, height, race, study center, education, smoking, and cardiorespiratory fitness (CRF), greater LEFM was significantly associated with higher IR only in normal weight men and women. Further adjustment for TFM revealed that lower LEFM was significantly associated with higher IR in overweight and obese men and women and the positive association in normal weight individuals was attenuated. These results suggest that excess adiposity in the lower extremities may attenuate the metabolic risk observed at a given level of abdominal adiposity in overweight and obese individuals. Weight status presents additional complexity since the metabolic influence of adipose tissue may not be homogenous across anatomic regions or level of obesity.
PMCID: PMC3203327  PMID: 21617639
14.  Longitudinal Examination of Age-Predicted Symptom-Limited Exercise Maximum Heart Rate 
To estimate the association of age with maximal heart rate (MHR).
Data were obtained in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants were black and white men and women aged 18-30 in 1985-86 (year 0). A symptom-limited maximal graded exercise test was completed at years 0, 7, and 20 by 4969, 2583, and 2870 participants, respectively. After exclusion 9622 eligible tests remained.
In all 9622 tests, estimated MHR (eMHR, beats/minute) had a quadratic relation to age in the age range 18 to 50 years, eMHR=179+0.29*age-0.011*age2. The age-MHR association was approximately linear in the restricted age ranges of consecutive tests. In 2215 people who completed both year 0 and 7 tests (age range 18 to 37), eMHR=189–0.35*age; and in 1574 people who completed both year 7 and 20 tests (age range 25 to 50), eMHR=199–0.63*age. In the lowest baseline BMI quartile, the rate of decline was 0.20 beats/minute/year between years 0-7 and 0.51 beats/minute/year between years 7-20; while in the highest baseline BMI quartile there was a linear rate of decline of approximately 0.7 beats/minute/year over the full age of 18 to 50 years.
Clinicians making exercise prescriptions should be aware that the loss of symptom-limited MHR is much slower at young adulthood and more pronounced in later adulthood. In particular, MHR loss is very slow in those with lowest BMI below age 40.
PMCID: PMC2891874  PMID: 20639723
prediction equations; graded exercise test; mixed models; epidemiologic study
15.  Parity and the Association With Diabetes in Older Women 
Diabetes Care  2010;33(8):1778-1782.
To examine the relationship of parity with diabetes and markers of glucose homeostasis in older women.
We used data from the female participants in the Cardiovascular Health Study, a longitudinal cohort of adults aged ≥65 years. These data included an assessment of parity (baseline) and fasting serum levels of glucose, insulin, and medication use (baseline and follow-up). We estimated both the cross-sectional relationship of parity with baseline diabetes and the relationship of parity with incident diabetes.
In unadjusted analyses, women with grand multiparity (≥5 live births) had a higher prevalence of diabetes at baseline compared with those with fewer births and with nulliparous women (25 vs. 12 vs. 15%; P < 0.001). In regression models controlling for age and race, grand multiparity was associated with increased prevalence of diabetes (prevalence ratio 1.57 [95% CI 1.20–2.06]); with addition of demographic and clinical factors to the model, the association was attenuated (1.33 [1.00–1.77]). In final models that included body anthropometrics, the association was no longer significant (1.21 [0.86–1.49]). In those without diabetes at baseline, parity was not associated with incident diabetes or with fasting glucose; however, there was a modest association of parity with fasting insulin and homeostasis assessment model of insulin resistance.
Grand multiparity is associated with diabetes in elderly women in cross-sectional analyses. This relationship seems to be confounded and/or mediated by variation in body weight and sociodemographic factors by parity status. In older nondiabetic women, higher parity does not pose an ongoing risk of developing diabetes.
PMCID: PMC2909061  PMID: 20424225
16.  The Metabolic Syndrome 
Archives of internal medicine  2003;163(4):427-436.
The metabolic syndrome is an important cluster of coronary heart disease risk factors with common insulin resistance. The extent to which the metabolic syndrome is associated with demographic and potentially modifiable lifestyle factors in the US population is unknown.
Metabolic syndrome–associated factors and prevalence, as defined by Adult Treatment Panel III criteria, were evaluated in a representative US sample of 3305 black, 3477 Mexican American, and 5581 white men and nonpregnant or lactating women aged 20 years and older who participated in the cross-sectional Third National Health and Nutrition Examination Survey.
The metabolic syndrome was present in 22.8% and 22.6% of US men and women, respectively (P=.86). The age-specific prevalence was highest in Mexican Americans and lowest in blacks of both sexes. Ethnic differences persisted even after adjusting for age, body mass index, and socioeconomic status. The metabolic syndrome was present in 4.6%, 22.4%, and 59.6% of normal-weight, overweight, and obese men, respectively, and a similar distribution was observed in women. Older age, postmenopausal status, Mexican American ethnicity, higher body mass index, current smoking, low household income, high carbohydrate intake, no alcohol consumption, and physical inactivity were associated with increased odds of the metabolic syndrome.
The metabolic syndrome is present in more than 20% of the US adult population; varies substantially by ethnicity even after adjusting for body mass index, age, socioeconomic status, and other predictor variables; and is associated with several potentially modifiable lifestyle factors. Identification and clinical management of this high-risk group is an important aspect of coronary heart disease prevention.
PMCID: PMC3146257  PMID: 12588201
17.  Diabetes and Coronary Heart Disease as Risk Factors for Mortality in Older Adults 
The American journal of medicine  2010;123(6):556.e1-556.e9.
Type 2 diabetes has been described a coronary heart disease (CHD) “risk equivalent”. We tested whether cardiovascular and all-cause mortality rates were similar between participants with prevalent CHD versus diabetes in an older adult population in whom both glucose disorders and pre-existing atherosclerosis are common.
The Cardiovascular Health Study is a longitudinal study of men and women (n= 5784) aged ≥65 years at baseline who were followed from baseline (1989/92-93) through 2005 for mortality. Diabetes was defined by fasting plasma glucose ≥7.0 mmol/L or use of diabetes control medications. Prevalent CHD was determined by confirmed history of myocardial infarction (MI), angina, or coronary revascularization.
Following multivariable adjustment for other cardiovascular disease risk factors and subclinical atherosclerosis, CHD mortality risk was similar between participants with CHD alone vs. diabetes alone (hazard ratio [HR]=1.04, 95% CI, 0.83-1.30). The proportion of mortality attributable to prevalent diabetes (Population Attributable Risk Percent =8.4%) and prevalent CHD (6.7%) was similar in women, but the proportion of mortality attributable to CHD (16.5%) as compared with diabetes (6.4%) was markedly higher in men. Patterns were similar for cardiovascular disease mortality. By contrast, the adjusted relative hazard of total mortality was lower among participants with CHD alone (HR =0.85, 95% CI, 0.75-0.96) as compared with those who had diabetes alone.
Among older adults, diabetes alone confers a similar risk for cardiovascular mortality as established clinical CHD. The public health burden of both diabetes and CHD is substantial, particularly among women.
PMCID: PMC3145803  PMID: 20569763
type 2 diabetes; cardiovascular disease; longitudinal studies; older adults
18.  Serum Insulin, Obesity, and the Incidence of Type 2 Diabetes in Black and White Adults 
Diabetes care  2002;25(8):1358-1364.
In this study, we tested the hypothesis that fasting serum insulin is higher in nonobese black adults than in white adults and that high fasting insulin predicts type 2 diabetes equally well in both groups.
At the baseline examination (1987–1989) of the Atherosclerosis Risk in Communities Study, fasting insulin and BMI were measured in 13,416 black and white men and women without diabetes. Participants were examined at years 3, 6, and 9 for incident diabetes based on fasting glucose and American Diabetes Association criteria.
Fasting insulin was 19.7 pmol/l higher among nonobese (BMI <30 kg/m2) black women compared with white women (race and obesity interaction term, P < 0.01). There were no differences among men. Among nonobese women, the relative risk for developing diabetes was similar between racial groups: 1.4 (95% CI 1.2–1.5) and 1.3 (1.2–1.4) per 60 pmol/l increase in insulin (P < 0.01) for black and white women, respectively (interaction term, P = 0.6). Findings were similar among men. Adjusting for established risk factors did not attenuate this association.
Nonobese black women have higher fasting insulin levels than nonobese white women, and fasting insulin is an equally strong predictor of diabetes in both groups. These results suggest one mechanism to explain the excess incidence of diabetes in nonobese black women but do not explain the excess among black men. Future research should evaluate additional factors: genetic, environmental, or the combination of both, which might explain higher fasting insulin among black women when compared with white women.
PMCID: PMC3132185  PMID: 12145235
19.  Joint Associations of Physical Activity and Aerobic Fitness on the Development of Incident Hypertension: Coronary Artery Risk Development in Young Adults (CARDIA) 
Hypertension  2010;56(1):49-55.
Fitness and physical activity are each inversely associated with the development of hypertension. We tested whether fitness and physical activity were independently associated with the 20-year incidence of hypertension in 4618 men and women. Hypertension was determined in participants who had systolic blood pressure (SBP)≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg or who reported antihypertensive medication use. Fitness was estimated based on the duration of a symptom-limited graded exercise treadmill test and physical activity was self-reported. The incidence rate of hypertension was 13.8 per 1000 person-years (n=1022). Both baseline fitness (hazard ratio [HR]=0.63, 95% confidence interval [CI]: 0.56, 0.70 per standard deviation [SD; 2.9 minutes]) and physical activity (HR=0.86, 95% CI: 0.79, 0.84 per SD [297 exercise units]) were inversely associated with incident hypertension when included jointly in a model that also adjusted for age, sex, race, baseline smoking status, SBP, alcohol intake, HDL cholesterol, dietary fiber, dietary sodium, fasting glucose and BMI. The magnitude of association between physical activity and hypertension was strongest among participants in the high fitness (HR= 0.80, 95% CI: 0.68, 0.94) category, whereas the magnitude of association between fitness and hypertension was similar across tertiles of physical activity. The estimated proportion of hypertension cases that could be prevented if participants moved to a higher fitness category (i.e., preventive fraction) was 34% and varied by race and sex group. Fitness and physical activity are each associated with incident hypertension, and low fitness may account for a substantial proportion of hypertension incidence.
PMCID: PMC2909350  PMID: 20516395
epidemiology; exercise; ethnicity; risk factors; special populations
20.  Heterogeneity in the Relationship Between Ethnicity, BMI, and Fasting Insulin 
Diabetes care  2002;25(8):1351-1357.
To determine whether the association of BMI and fasting insulin is modified by ethnicity.
Non-Hispanic black (black), non-Hispanic white (white), and Mexican-American men and women aged 20–80 years from the Third National Health and Nutrition Examination Survey (1988–1994) were included in this study. Linear regression models with an interaction term were used to test whether ethnicity modified the association between BMI and fasting insulin.
Fasting insulin was 19, 26, 20, and 19% higher in black women than white women with BMI levels of <22, 22–24, 25–27, and 28–30 kg/m2, respectively. These differences between black and white women converged at BMI levels >30 kg/m2. Mexican-American women had fasting insulin levels that were 17, 22, 20, and 16% higher than those of white women at BMI levels of 25–27, 28–30, 31–33, and >34 kg/m2, respectively, but were not different in individuals with BMI levels <25 kg/m2. Adjusting for established risk factors did not attenuate these associations in women. Differences in fasting insulin among men were not as apparent.
These findings suggest that the effect of obesity on insulin sensitivity is different for Americans in ethnic minorities. In black subjects, fasting insulin is higher at lean weight when compared with white and Mexican-American subjects. In Mexican-American subjects, fasting insulin is higher in overweight individuals when compared with white and black subjects. These findings are more pronounced in women than in men. This result reinforces the importance of designing prevention programs that are tailored to meet the needs of specific populations. Investigation of possible explanations for these differences seems warranted.
PMCID: PMC3121929  PMID: 12145234
21.  Comparative Validity of 3 Diabetes Mellitus Risk Prediction Scoring Models in a Multiethnic US Cohort 
American Journal of Epidemiology  2010;171(9):980-988.
Several models for estimating risk of incident diabetes in US adults are available. The authors aimed to determine the discriminative ability and calibration of published diabetes risk prediction models in a contemporary multiethnic cohort. Participants in the Multi-Ethnic Study of Atherosclerosis without diabetes at baseline (2000–2002; n = 5,329) were followed for a median of 4.75 years. The predicted risk of diabetes was calculated using published models from the Framingham Offspring Study, the Atherosclerosis Risk in Communities (ARIC) Study, and the San Antonio Heart Study. The mean age of participants was 61.6 years (standard deviation, 10.2); 29.3% were obese, 53.1% had hypertension, 34.9% had a family history of diabetes, 27.5% had high triglyceride levels, 33.8% had low high density lipoprotein cholesterol levels, and 15.3% had impaired fasting glucose. There were 446 incident cases of diabetes (fasting glucose level ≥126 mg/dL or initiation of antidiabetes medication use) diagnosed during follow-up. C statistics were 0.78, 0.84, and 0.83 for the Framingham, ARIC, and San Antonio risk prediction models, respectively. There were significant differences between observed and predicted diabetes risks (Hosmer-Lemeshow goodness-of-fit chi-squared test for each model: P < 0.001). The recalibrated and best-fit models achieved sufficient goodness of fit (each P > 0.10). The Framingham, ARIC, and San Antonio models maintained high discriminative ability but required recalibration in a modern, multiethnic US cohort.
PMCID: PMC2877477  PMID: 20375194
cohort studies; diabetes mellitus; models, statistical; risk; validation studies as topic
22.  Inflammation and the Incidence of Type 2 Diabetes 
Diabetes Care  2010;33(4):804-810.
Many studies have documented associations between inflammation and type 2 diabetes incidence. We assessed potential variability in this association in the major U.S. racial/ethnic groups.
Incident type 2 diabetes was assessed among men and women aged 45–84 years without prior clinical cardiovascular disease or diabetes in the prospective Multi-Ethnic Study of Atherosclerosis. Interleukin (IL)-6, fibrinogen, and C-reactive protein (CRP) were measured at baseline (2000–2002); fasting glucose and diabetes medication use was assessed at baseline and three subsequent in-person exams through 2007. Type 2 diabetes was defined as use of diabetes drugs or glucose ≥126 mg/dl. Covariates included baseline demographics, clinic, smoking, alcohol, exercise, hypertension medication, systolic blood pressure, insulin resistance, and BMI. Cox proportional hazards regression was used to calculate hazard ratios (HRs) by quartiles of CRP, IL-6, and fibrinogen.
Among 5,571 participants (mean age 61.6 years, 53% female, 42.1% white, 11.5% Chinese, 25.7% black, and 20.7% Hispanic), 410 developed incident diabetes during a median follow-up time of 4.7 years (incidence 16.8 per 1,000 person-years). CRP, IL-6, and fibrinogen levels were associated with incident diabetes in the entire sample. After adjustment, the associations were attenuated; however, quartile 4 (versus quartile 1) of IL-6 (HR 1.5 [95% CI 1.1–2.2]) and CRP (1.7 [1.3–2.4]) remained associated with incident diabetes. In stratified analyses, similar associations were observed among white, black, and Hispanic participants.
Higher levels of inflammation predict short-term incidence of type 2 diabetes in a multiethnic American sample.
PMCID: PMC2845031  PMID: 20097779
23.  Association Between Adiposity in Midlife and Older Age and Risk of Diabetes in Older Adults 
Adiposity is a well-recognized risk factor for type 2 diabetes among young and middle-aged adults, but the relationship between body composition and type 2 diabetes is not well described among older adults.
To examine the relationship between adiposity, changes in adiposity, and risk of incident type 2 diabetes in adults 65 years of age and older.
Design, Setting, and Participants
Prospective cohort study (1989-2007) of 4193 men and women 65 years of age and older in the Cardiovascular Health Study. Measures of adiposity were derived from anthropometry and bioelectrical impedance data at baseline and anthropometry repeated 3 years later.
Main Outcome Measure
Incident diabetes was ascertained based on use of antidiabetic medication or a fasting glucose level of 126 mg/dL or greater.
Over median follow-up of 12.4 years (range, 0.9-17.8 years), 339 cases of incident diabetes were ascertained (7.1/1000 person-years). The adjusted hazard ratio (HR) (95% confidence interval [CI]) of type 2 diabetes for participants in the highest quintile of baseline measures compared with those in the lowest was 4.3 (95% CI, 2.9-6.5) for body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), 3.0 (95% CI, 2.0-4.3) for BMI at 50 years of age, 4.2 (95% CI, 2.8-6.4) for weight, 4.0 (95% CI, 2.6-6.0) for fat mass, 4.2 (95% CI, 2.8-6.2) for waist circumference, 2.4 (95% CI, 1.6-3.5) for waist-hip ratio, and 3.8 (95% CI, 2.6-5.5) for waist-height ratio. However, when stratified by age, participants 75 years of age and older had HRs approximately half as large as those 65 to 74 years of age. Compared with weight-stable participants (±2 kg), those who gained the most weight from 50 years of age to baseline (≥9 kg), and from baseline to the third follow-up visit (≥6 kg), had HRs for type 2 diabetes of 2.8 (95% CI, 1.9-4.3) and 2.0 (95% CI, 1.1-3.7), respectively. Participants with a greater than 10-cm increase in waist size from baseline to the third follow-up visit had an HR of type 2 diabetes of 1.7 (95% CI, 1.1-2.8) compared with those who gained or lost 2 cm or less.
Among older adults, overall and central adiposity, and weight gain during middle age and after the age of 65 years are associated with risk of diabetes.
PMCID: PMC3047456  PMID: 20571017
24.  Autonomic function and change in insulin for exercising post-menopausal women 
Maturitas  2010;65(3):284-291.
Obesity, physical inactivity and altered estrogen metabolism play an integrated role contributing to the disease risk profiles of postmenopausal women. These same risk factors also affect modulation of the autonomic nervous system (ANS).
We examined 332 postmenopausal, overweight, previously sedentary women (Mean ± SD; Age, 57.6 ± 6.3 y; Wt, 84.3 ± 11.9 kg; BMI, 31.7 ± 3.7 kg/m2) participating in a 6-month, moderate intensity, aerobic exercise training intervention to determine the relationship between heart rate variability (HRV) derived autonomic function and fasting insulin. We analyzed quartiles of change in time and frequency domain indices of ANS activity and changes in insulin for between and within group differences using ANCOVA and Tukey post-hoc tests adjusted for age, ethnicity, randomization group, change in fitness, and change in weight.
We observed at baseline that insulin was positively correlated with body anthropometry (body weight, r2 = 0.34; BMI, r2 = 0.39; waist circumference, r2 = 0.29; all, P < 0.001), and inversely associated with rMSSD (r2= −0.12) and SDNN (r2 = −0.18; all, P < 0.01). After the intervention, changes in rMSSD (r2 = −0.21, P<0.002) and SDNN r2 −0.19, P<0.0001) were inversely correlated to insulin change. Further ANCOVA analysis revealed that rMSSD and SDNN were both significant (P<0.0001); however, only rMSSD exhibited a step-wise pattern of improvement when quartiles of rMSSD were compared to corresponding insulin reductions: Q1 (referent group, 8.41 ± 3.2 uIU/ml), Q2, (−3.30 ± −3.2 uIU/ml), Q3 (−5.66 ± −3.2 uIU/ml; P < 0.02), and Q4 (−9.60 ± −3.2 uIU/ml; P<0.006).
Our study shows that changes in autonomic function are associated with changes in insulin and that exercise training may influence this relationship in postmenopausal women.
PMCID: PMC2852034  PMID: 20022188
heart rate variability; autonomic balance; exercise training
25.  Neighborhood Resources for Physical Activity and Healthy Foods and Incidence of Type 2 Diabetes Mellitus 
Archives of internal medicine  2009;169(18):1698-1704.
Despite increasing interest in the extent to which features of residential environments contribute to incidence of type 2 diabetes mellitus, no multisite prospective studies have investigated this question. We hypothesized that neighborhood resources supporting physical activity and healthy diets are associated with a lower incidence of type 2 diabetes.
Person-level data came from 3 sites of the Multi-Ethnic Study of Atherosclerosis, a population-based, prospective study of adults aged 45 to 84 years at baseline. Neighborhood data were derived from a population-based residential survey. Type 2 diabetes was defined as a fasting glucose level of 126 mg/dL or higher (≥7 mmol/L) or taking insulin or oral hypoglycemic agents. We estimated the hazard ratio of type 2 diabetes incidence associated with neighborhood (US Census tract) resources.
Among 2285 participants, 233 new type 2 diabetes cases occurred during a median of 5 follow-up years. Better neighborhood resources, determined by a combined score for physical activity and healthy foods, were associated with a 38% lower incidence of type 2 diabetes (hazard ratio corresponding to a difference between the 90th and 10th percentiles for resource distribution, 0.62; 95% confidence interval, 0.43–0.88 adjusted for age, sex, family history of diabetes, race/ethnicity, income, assets, educational level, alcohol use, and smoking status). The association remained statistically significant after further adjustment for individual dietary factors, physical activity level, and body mass index.
Better neighborhood resources were associated with lower incidence of type 2 diabetes, which suggests that improving environmental features may be a viable population-level strategy for addressing this disease.
PMCID: PMC2828356  PMID: 19822827

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