Trials of intensive glucose control have not improved cardiovascular disease (CVD) risk in populations with type 2 diabetes; however, in the general population, reports are inconsistent about the effects of maintaining lower glucose levels. Some speculate that low glycemic values are associated with increased glycemic variability, which is in turn associated with higher CVD risk. It has also been suggested that fasting glucose and hemoglobin A1c (HbA1c) in the lower ranges have a different relationship with CVD and mortality. In 4990 participants from the Multi-Ethnic Study of Atherosclerosis, we used logistic regression to investigate associations of low fasting glucose (<80 mg/dL) and HbA1c (<5.0%) from baseline and averaged across follow-up with incident CVD and mortality over 13 years. We used normal glycemic ranges (80 to <100 mg/dL and 5.0 to <5.7%) as references and analyzed glycemic levels with visit-matched covariates. We adjusted for potential confounding by age, sex, race/ethnicity, education, income, smoking status, body mass index, total cholesterol level, cholesterol medications, high-density lipoprotein cholesterol, and hypertension. Low baseline glucose and HbA1c were positively, but not significantly, associated with mortality, whereas low average fasting glucose and HbA1c were strongly and significantly associated with incident CVD [glucose OR, 2.04 (95% CI, 1.38-3.00); HbA1c OR, 2.01 (95% CI, 1.58-2.55)] and mortality [glucose OR, 1.93 (95% CI, 1.33-2.79); HbA1c OR, 2.51 (95% CI, 2.00-3.15)]. These results were not due to type 2 diabetes or medication use. Glucose variability did not explain CVD risk beyond average glucose levels. Chronic low fasting glucose and HbA1c may be better indicators of risk than a single low measurement.

The Centers for Population Health and Health Disparities program promotes multilevel and multifactorial health equity research and the building of research teams that are transdisciplinary. We summarized 5 areas of scientific training for empowering the next generation of health disparities investigators with research methods and skills that are needed to solve disparities and inequalities in cancer and cardiovascular disease. These areas include social epidemiology, multilevel modeling, health care systems or health care delivery, community-based participatory research, and implementation science. We reviewed the acquisition of the skill sets described in the training components; these skill sets will position trainees to become leaders capable of effecting significant change because they provide tools that can be used to address the complexities of issues that promote health disparities.

Background

Few studies have investigated the relationship of anthropometric measurements with computed tomography (CT) body fat composition, and even fewer determined if these relationships differ by sex and race.

Methods

CT scans from 1,851 participants in the population based Multi-Ethnic Study of Atherosclerosis were assessed for visceral and subcutaneous fat areas by semi-automated segmentation of body compartments. Regression models were used to investigate relationships for anthropometry with visceral and subcutaneous fat separately by sex and race/ethnicity.

Results

Participants were 50% female, 41% Caucasian, 13% Asian, 21% African American, and 25% Hispanic. For visceral fat, the positive relationship with weight (p = 0.028), waist circumference (p<0.001), waist to hip ratio (p<0.001), and waist to height ratio (p = 0.05) differed by sex, with a steeper slope for men. That is, across the range of these anthropometric measures the rise in visceral fat is faster for men than for women. Additionally, there were differences by race/ethnicity in the relationship with height (p<0.001), weight (p<0.001), waist circumference (p<0.001), hip circumference (p = 0.006), and waist to hip ratio (p = 0.001) with the Hispanic group having shallower slopes. For subcutaneous fat, interaction by sex was found for all anthropometric indices at p<0.05, but not for race/ethnicity.

Conclusion

The relationship between anthropometry and underlying adiposity differs by sex and race/ethnicity. When anthropometry is used as a proxy for visceral fat in research, sex-specific models should be used.

A major challenge in characterizing features of the daily cortisol curve is variability in features over time. Few studies have examined the stability of daily features of the cortisol curve over long periods or the predictors of long term changes. Repeated salivary cortisol measures on 580 adults from the MESA Stress study were used to examine the stability of various features of the daily cortisol curve (wakeup value, the cortisol awakening response (CAR), the early and late decline slope and the area under the curve (AUC)), over short periods (several days) and long periods (approximately 6-years) and to investigate the association of demographic factors with the changes. Intraclass correlation coefficients (ICCs) were used to estimate the short and long term stability. Piecewise linear mixed models were used to assess factors associated with changes in features over time. For most features, short term stability (ICCs: 0.17-0.74) was higher than long term stability (ICCs: 0.05-0.42), and long term stability was highest when several days were averaged for each time point. The decline over the day showed the highest long term stability: when several days for each wave were averaged the stability of the daily decline slope across 6 years was similar (or higher) than the stability across short periods. AUC had high stability over short periods (ICCs: 0.65-0.74) but much lower stability across long periods (ICC: 0.05). All features of daily cortisol curve investigated changed significantly over the approximately 6 year follow-up period. The wakeup cortisol became higher; the CAR became smaller; both the early and late decline became flatter; and the AUC became larger. Hispanics experienced significantly larger increases in the wakeup value; and African-Americans and Hispanics showed less flattening over time of the early decline slope than Non-Hispanic Whites. Our findings have implications for characterization of features in studies linking cortisol to health outcomes. The presence of variability over time suggests opportunities for future investigation of the predictors of changes over time as well as the links between these changes and health outcomes.

Context

Prior studies have shown a cross-sectional association between body mass index (BMI) and salivary diurnal cortisol profile features (cortisol features); however, to our knowledge prior population-based studies have not examined the longitudinal association of body-mass index (BMI) with cortisol features.

Objective

To examine the association of (1) prior annual BMI percent change over 7years with cortisol features, (2) baseline cortisol features with subsequent change in BMI over 6years and (3) the association of change in cortisol features with change in BMI over 6years.

Design

Longitudinal study.

Setting

Multi-Ethnic Study of Atherosclerosis (MESA) Stress I & II Studies (2004-2006 & 2010-2012).

Participants

1685 ethnically diverse men and women attended either MESA Stress exam (mean age 65±10years at MESA Stress I; mean age 69±9years at MESA Stress II).

Outcome measures

Log-transformed cortisol features including wake-up cortisol, cortisol awakening response, early decline slope (30min to 2h post-awakening), late decline slope (2h post-awakening to bedtime), bedtime, and total area under the curve (AUC) cortisol.

Results

Over 7years, following multivariable adjustment, (1) a 1% higher prior annual BMI % increase was associated with a 2.9% (95% CI: -5.0%, -0.8%) and 3.0% (95% CI: -4.7%, -1.4%) lower current wake-up and total AUC cortisol, respectively; (2) there was no significant association between baseline cortisol features and subsequent change in BMI and (3) among participants with BMI≥30kg/m², flattening of the late decline slope was associated with increases in BMI (every 1-unit increase late decline slope were associated with a 12.9% increase (95%CI: -1%, 26.8%) in BMI, respectively).

Conclusions

We found a significant association between prior annual BMI % change and cortisol features, but no significant association between baseline cortisol features and subsequent change in BMI. In participants with obesity increases in BMI were associated with less pronounced declined. Collectively, our results suggest that greater adiposity may lead to a blunted diurnal cortisol profile.

Latino immigrants have lower prevalence of depression, obesity and cardiovascular disease than US-born Latinos when they are recently arrived in the US, but this health advantage erodes with increasing duration of US residence. Cumulative exposure to psychosocial stress and its physiological sequelae may mediate the relationship between nativity and duration of US residence and poor health. We used data from Latino cohort study participants ages 45-84 to examine cross-sectional (n=558) and longitudinal (n=248) associations between nativity and duration of US residence and features of the diurnal cortisol curve including: wake-up cortisol, cortisol awakening response (CAR, wake-up to 30min post-awakening), early decline (30min to 2h post-awakening) and late decline (2h post-awakening to bed time), wake-to-bed slope, and area under the curve (AUC). In cross-sectional analyses, US-born Latinos had higher wake-up cortisol than immigrants with fewer than 30 years of US residence. In the full sample, over 5 years the CAR and early decline became flatter and AUC became larger. Over 5 years, US-born Latinos had greater increases in wake-up cortisol and less pronounced flattening of the early diurnal cortisol decline than immigrants with fewer than 30 years of US residence. Immigrants with 30 or more years of US residence also had less pronounced flattening of the early decline relative to more recent immigrants, and also had a less pronounced increase in AUC. In sum, we saw limited cross-sectional evidence that US-born Latinos have more dysregulated cortisol than recently-arrived Latino immigrants, but over time US-born Latinos had slower progression of cortisol dysregulation.

Background

The cross-sectional area of total muscle mass has been reported to decrease by about 40% for those 20-60 years of age. Depressive symptoms may discourage motivation to engage in physical activity such as strength training shown to negate muscle loss. Inflammation related to depressive symptoms may also contribute to muscle atrophy. Physiological differences by sex and race/ethnicity may also modify the association between depression and muscle mass. Evidence on the relationship between depression (or depressive symptoms) and adiposity has been mounting; however, little is known about the depressive symptoms-muscle mass association. We sought to determine the association between elevated depressive symptoms (EDS) and lean muscle mass and whether this varies by sex and race/ethnicity.

Methods

Evaluating 1605 adults (45-84 years of age) from the Multi-ethnic Study of Atherosclerosis Abdominal Body Composition, Inflammation and Cardiovascular Disease Study, we examined the cross-sectional association between EDS (Center for Epidemiologic Studies for Depression Scale score≥16 and/or antidepressant use) and computed tomography-measured abdominal lean muscle mass using linear regression. Muscles were evaluated as a whole and by functionality (locomotion vs. stabilization/posture). Covariates included height, body mass index, sociodemographics, comorbidities, inflammatory markers and health behaviors (pack-years of smoking, alcohol locomotion compared to men, total intentional exercise, daily caloric intake). Sex and race/ethnicity were assessed as potential modifiers. Statistical significance was at a p<0.05 for main effects and <0.20 for interaction.

Results

Men with elevated depressive symptoms had 5.9 cm2 lower lean muscle mass for locomotion compared to men without EDS, fully-adjusted (CI=-10.5, -1.4, p=0.011). This was statistically significantly different from the null finding among women (interaction p=0.05). Chinese participants with EDS had 10.2 cm2 lower abdominal lean muscle mass for locomotion compared to those without EDS (fully-adjusted, CI=-18.3, -2.1, p=0.014), which was significantly different from the null relationship among White participants (interaction p=0.04). No association was observed between elevated depressive symptoms and muscle for stabilization/posture evaluating the whole population or stratified by sex or race/ethnicity.

Conclusions

In the presence of elevated depressive symptoms, men and Chinese participants may have lower muscle mass, particularly for locomotion.

Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is to review the current literature and key clinical trials pertaining to blood pressure and blood glucose control, cholesterol management, aspirin therapy, and lifestyle modification. We present a synthesis of the recent literature, new guidelines, and clinical targets, including screening for kidney and subclinical cardiovascular disease for the contemporary management of patients with type 2 diabetes mellitus.

Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (P _interaction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.

Sex hormone binding globulin (SHBG) levels are reported to be inversely associated with diabetes risk. It is unknown whether diabetes prevention interventions increase SHBG and whether resultant changes in SHBG affect diabetes risk. The purpose of this analysis was to determine whether intensive lifestyle intervention (ILS) or metformin changed circulating SHBG and if resultant changes influenced diabetes risk in the Diabetes Prevention Program (DPP). This is a secondary analysis from the DPP (1996-2001), a randomized trial of ILS or metformin versus placebo on diabetes risk over a mean follow-up of 3.2 years. The DPP was conducted across 27 academic study centers in the USA. Men, premenopausal and postmenopausal women without hormone use in the DPP were evaluated. The DPP included overweight/obese persons with elevated fasting glucose and impaired glucose tolerance. Main outcomes measures were changes in SHBG levels at 1 year and risk of diabetes over 3 years. ILS resulted in significantly higher increases (postmenopausal women: p<0.01) or smaller decrements (men: p<0.05; premenopausal women: p<0.01) in SHBG compared with placebo or metformin. Changes in SHBG were primarily attributable to changes in adiposity. There were no consistent associations of change in SHBG with the risk of diabetes by treatment arm or participant group. Lifestyle intervention may be associated with favorable changes in circulating SHBG, which is largely due to changes in adiposity. Changes in circulating SHBG do not independently predict reductions in diabetes incidence.