Evidence for the Association Between Adverse Childhood Family Environment, Child Abuse, and Caregiver Warmth and Cardiovascular Health Across the Lifespan: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: This study aimed to quantify the association between childhood family environment and longitudinal cardiovascular health (CVH) in adult CARDIA (Coronary Artery Risk Development in Young Adults) Study participants. We further investigated whether the association differs by adult income. METHODS: We applied the CVH framework from the American Heart Association including metrics for smoking, cholesterol, blood pressure, glucose, body mass index, physical activity, and diet. CVH scores (range, 0-14) were calculated at years 0, 7, and 20 of the study. Risky Family environment (range, 7-28) was assessed at year 15 retrospectively, for childhood experiences of abuse, caregiver warmth, and family or household challenges. Complete case ordinal logistic regression and mixed models associated risky family (exposure) with CVH (outcome), adjusting for age, sex, race, and alcohol use. RESULTS: The sample (n=2074) had a mean age of 25.3 (±3.5) years and 56% females at baseline. The median risky family was 10 with ideal CVH (≥12) met by 288 individuals at baseline (28.4%) and 165 (16.3%) at year 20. Longitudinally, for every 1-unit greater risky family, the odds of attaining high CVH (≥10) decreased by 3.6% (OR, 0.9645 [95% CI, 0.94-0.98]). Each unit greater child abuse and caregiver warmth score corresponded to 12.8% lower and 11.7% higher odds of ideal CVH (≥10), respectively (OR, 0.872 [95% CI, 0.77-0.99]; OR, 1.1165 [95% CI, 1.01-1.24]), across all 20 years of follow-up. Stratified analyses by income in adulthood demonstrated associations between risky family environment and CVH remained significant for those of the highest adult income (>$74k), but not the lowest (<$35k). CONCLUSIONS: Although risky family environmental factors in childhood increase the odds of poor longitudinal adult CVH, caregiver warmth may increase the odds of CVH, and socioeconomic attainment in adulthood may contextualize the level of risk. Toward a paradigm of primordial prevention of cardiovascular disease, childhood exposures and economic opportunity may play a crucial role in CVH across the life course.

The association of aldosterone and endothelin-1 with incident diabetes among African Americans: The Jackson Heart Study.

Introduction: African Americans (AAs) have the highest prevalence of hypertension among United States racial/ethnic groups. Regulators of blood pressure, such as aldosterone and endothelin-1, impact glucose regulation. The relationship between these factors and incident diabetes is not well elucidated among AAs. Methods: Among 3914 AA participants without prevalent diabetes in the Jackson Heart Study, linear regression models were used to examine cross-sectional associations of exposures (aldosterone, endothelin-1, and a combined aldosterone-endothelin-1 score [2-8]) with glycemic measures (fasting plasma glucose [FPG], HbA1c, homeostatic model assessments of beta cell function [HOMA-ß] and insulin resistance [HOMA-IR]). Longitudinal associations of exposures with incident diabetes were examined using Cox proportional hazard models. Models were adjusted for age, sex, education, occupation, systolic blood pressure, smoking, physical activity, dietary intake, alcohol use and adiponectin. Results: Aldosterone and the combined aldosterone-endothelin score were positively associated with FPG, HOMA-IR, and HOMA-ß (all p < 0.05). Endothelin-1 was negatively associated with FPG but positively associated with HOMA-ß (both p < 0.05). Only the aldosterone-endothelin score was positively associated with HbA1c (p < 0.01). A 1-SD higher serum aldosterone and endothelin-1 was associated with a 22 % and 14 % higher risk of incident diabetes, respectively, while a 1-point higher aldosterone-endothelin score was associated with a 13 % higher risk of incident diabetes after adjustment for diabetes risk factors (all p < 0.01). Conclusions: Aldosterone and endothelin-1, factors integral in blood pressure regulation, may play a significant role in the development of diabetes among AAs.

Childhood environment early life stress, caregiver warmth, and associations with the cortisol diurnal curve in adulthood: The coronary artery risk development in young adults (CARDIA) study.

BACKGROUND: Early life stress (ELS) is associated with increased morbidity and mortality across the lifecourse. Studies observing a relationship between ELS and stress physiology (cortisol), may help explain the connection to poor health outcomes, but have been limited by cortisol measures used. PURPOSE: We examined the association between ELS measured by a Risky Family (RF) environment questionnaire, and adult diurnal cortisol profile inclusive of multiple cortisol measures. METHODS: RF and cortisol were collected from Coronary Artery Risk Development in Young Adults Study participants at follow-up (Year 15). Complete case (n = 672) data were included in multi-variable regression analyses with log transformed cortisol measures (outcomes) including wake-up cortisol, cortisol awakening response [CAR], AUC and five other cortisol diurnal curve measures. RESULTS: Participants were age 39.9 + /- 3.7 years and 51.6% Black. For every 1 unit increase in RF, there was a 1.4% greater wake-up cortisol and flatter CAR after adjustment for age, sex, income, and smoking (B=0.014, p = 0.023; B=-0.014, p = 0.028, respectively). Each unit increase in caregiver warmth/affection was associated with a 6.9% higher (steeper) CAR (B=0.069, p = 0.03). Results remained significant after adjusting for other covariates except social support in adulthood. An interaction between child abuse and caregiver warmth was nearly significant (p = 0.068), such that for those with exposure to the greatest caregiver warmth and lowest child abuse, CAR was steepest CONCLUSIONS: We demonstrate that ELS is associated with altered cortisol regulation in adulthood. However, further research is needed to assess how healthy relationships throughout the life course may modulate cortisol regulation in adulthood.

The association of serum vitamin D with incident diabetes in an African American population.

BACKGROUND: Incident diabetes risk is inversely proportional to 25-hydroxyvitamin D [25(OH)D] levels among non-Hispanic white but is unclear among African American (AA) populations. Serum 25(OH)D2 may be an important component of total 25(OH)D among AA populations due to higher levels of melanin. OBJECTIVE: To assess the association of serum 25(OH)D with incident diabetes among AAs and stratify by detectable 25(OH)D2. DESIGN: Serum 25(OH)D2 and 25(OH)D3 were collected from 2000 to 2004 among AA participants in the Jackson Heart Study. A cosinor model was used to adjust for the seasonality of 25(OH)D3; 25(OH)D3 and 25(OH)D2 were combined to ascertain total 25(OH)D. Incident diabetes (fasting glucose ≥126 mg/dl, use of diabetes drugs, or HbA1c ≥6.5%) was assessed over 12 years among adults without diabetes at baseline. Participants with missing baseline covariates or diabetes follow-up were excluded. Hazard ratios (HR) were estimated using Cox modeling, adjusting for age, sex, education, occupation, smoking, physical activity, alcohol use, aldosterone, and body-mass index. RESULTS: Among 3311 adults (mean age 53.3 years, 63% female) 584 participants developed diabetes over a median of 7.7 years. After adjustment, 25(OH)D ≥20 compared to <12 ng/ml was associated with a HR 0.78 (95% CI: 0.61, 1.00). Among participants with detectable 25(OH)D2 and 25(OH)D3 (n = 1671), 25(OH)D ≥ 20 ng/ml compared to <12 ng/ml was associated with a 35% (HR 0.65, 95% CI: 0.46, 0.91) lower risk of diabetes. CONCLUSIONS: Higher levels of 25(OH)D may be protective against the development of diabetes among AA individuals, particularly among those with detectable 25(OH)D2 and 25(OH)D3.

Cardiovascular Impact of Race and Ethnicity in Patients With Diabetes and Obesity: JACC Focus Seminar 2/9.

Obesity and type 2 diabetes mellitus are highly prevalent and increasing in the United States among racial/ethnic minority groups. Type 2 diabetes mellitus, which is driven by many factors including elevated levels of adiposity, is an exemplar health disparities disease. Pervasive disparities exist at every level from risk factors through outcomes for U.S. racial/ethnic minority groups, including African American, Hispanic/LatinX American, and Asian American populations. Disparities in clinical care exist including hemoglobin A1c control, lower prescription rates of newer antihyperglycemic medications, along with greater rates of complications postbariatric surgery. Underpinning these disparities are the social determinants of health affecting provider-patient interactions, access to resources, and healthy built environments. We review the best practices to address cardiometabolic disparities in the current cardiovascular guidelines and describe recommendations for cross-cutting strategies to advance equity in obesity and type 2 diabetes across U.S. racial/ethnic groups.

The association of cortisol curve features with incident diabetes among whites and African Americans: The CARDIA study.

INTRODUCTION: A flatter diurnal cortisol curve has been associated with incident diabetes among older white adults. However, this relationship has not been examined among middle-aged individuals or African Americans [AA]. We analyzed the longitudinal association of baseline diurnal cortisol curve features with incident diabetes over a 10 year period in a cohort of AA and white participants who were, on average, 40 years old. METHODS: Salivary cortisol was collected immediately post-awakening, then subsequently 45 min, 2.5 h, 8 h, and 12 h later, as well as at bedtime. Cortisol curve features included wake-up cortisol; cortisol awakening response (CAR); early, late, and overall decline slopes; bedtime cortisol; and 16 -h area under the curve (AUC). Salivary cortisol (nmol/L) was log-transformed due to positively skewed distributions. Diabetes was defined as fasting plasma glucose ≥ 126 mg/dL or taking diabetes medication. Logistic regression models were used to investigate the association of log-transformed cortisol curve features with incident diabetes. The analysis was stratified by race and adjusted for age, sex, education, depressive symptoms, smoking status, beta-blocker and steroid medication use and BMI. RESULTS: Among 376 AA and 333 white participants (mean age 40 years), 67 incident diabetes cases occurred over 10 years. After full adjustment for additional covariates, a 1-unit log increase in CAR was associated with a 53 % lower odds of incident diabetes among whites (Odds Ratio [OR] 0.47, 95 % CI: 0.24, 0.90). A 1-SD increase in late decline slope was associated with a 416 % higher odds of incident diabetes among whites (OR 5.16, 95 % CI: 1.32, 20.20). There were no significant associations in AAs. CONCLUSION: A robust CAR and flatter late decline slope are associated with lower and higher odds of incident diabetes, respectively, among younger to middle-aged whites and may provide a future target for diabetes prevention in this population.

Discrimination Is Associated with Elevated Cardiovascular Disease Risk among African Immigrants in the African Immigrant Health Study.

Background: African Americans and other persons of African descent in the United States are disproportionately affected by cardiovascular diseases (CVD). Discrimination is associated with higher CVD risk among US adults; however, this relationship is unknown among African immigrants. Methods: The African Immigrant Health Study was a cross-sectional study of African immigrants in Baltimore-Washington, DC, with recruitment and data collection taking place between June 2017 and April 2019. The main outcome was elevated CVD risk, the presence of ≥3 CVD risk factors including hypertension, diabetes, high cholesterol, overweight/obesity, tobacco use, and poor diet. The secondary outcomes were these six individual CVD risk factors. The exposure was discrimination measured with the Everyday Discrimination Scale; summed scores ≥2 on each item indicated frequent experiences of discrimination. Resilience was assessed with the 10-item Connor-Davidson resilience scale. Logistic regression was used to examine the odds of elevated CVD risk, adjusting for relevant covariates. Results: We included 342 participants; 61% were females. The mean (±SD) age was 47(±11) years, 61% had at least a bachelor's degree, 18% had an income <$40,000, and 49% had lived in the US ≥15 years. Persons with frequent experiences of discrimination were 1.82 times (95%CI: 1.04-3.21) more likely to have elevated CVD risk than those with fewer experiences. Resilience did not moderate the relationship between CVD risk and discrimination. Conclusion: African immigrants with frequent experiences of discrimination were more likely to have elevated CVD risk. Targeted and culturally appropriate interventions are needed to reduce the high burden of CVD risk in this population. Health care providers should be aware of discrimination as a meaningful social determinant of CVD risk. At the societal level, policies and laws are needed to reduce the occurrence of discrimination among African immigrants and racial/ethnic minorities.

The Association of ARMC5 with the Renin-Angiotensin-Aldosterone System, Blood Pressure, and Glycemia in African Americans.

CONTEXT: Armadillo repeat containing 5 (ARMC5) on chromosome 16 is an adrenal gland tumor suppressor gene associated with primary aldosteronism, especially among African Americans (AAs). We examined the association of ARMC5 variants with aldosterone, plasma renin activity (PRA), blood pressure, glucose, and glycosylated hemoglobin A1c (HbA1c) in community-dwelling AAs. METHODS: The Jackson Heart Study is a prospective cardiovascular cohort study in AAs with baseline data collection from 2000 to 2004. Kernel machine method was used to perform a single joint test to analyze for an overall association between the phenotypes of interest (aldosterone, PRA, systolic and diastolic blood pressure [SBP, DBP], glucose, and HbA1c) and the ARMC5 single nucleotide variants (SNVs) adjusted for age, sex, BMI, and medications; followed by Baysian Lasso methodology to identify sets of SNVs in terms of associated haplotypes with specific phenotypes. RESULTS: Among 3223 participants (62% female; mean age 55.6 (SD ± 12.8) years), the average SBP and DBP were 127 and 76 mmHg, respectively. The average fasting plasma glucose and HbA1c were 101 mg/dL and 6.0%, respectively. ARMC5 variants were associated with all 6 phenotypes. Haplotype TCGCC (ch16:31476015-31476093) was negatively associated, whereas haplotype CCCCTTGCG (ch16:31477195-31477460) was positively associated with SBP, DBP, and glucose. Haplotypes GGACG (ch16:31477790-31478013) and ACGCG (ch16:31477834-31478113) were negatively associated with aldosterone and positively associated with HbA1c and glucose, respectively. Haplotype GCGCGAGC (ch16:31471193-ch16:31473597(rs114871627) was positively associated with PRA and negatively associated with HbA1c. CONCLUSIONS: ARMC5 variants are associated with aldosterone, PRA, blood pressure, fasting glucose, and HbA1c in community-dwelling AAs, suggesting that germline mutations in ARMC5 may underlie cardiometabolic disease in AAs.

The association of morning serum cortisol with glucose metabolism and diabetes: The Jackson Heart Study.

BACKGROUND: Serum cortisol levels have been associated with type 2 diabetes (T2D). However, the role of cortisol in glycemia and T2D is not fully elucidated among African Americans (AAs). We hypothesized that among AAs morning serum cortisol would be positively associated with glycemic measures and prevalent T2D. METHODS: We examined the cross-sectional association of baseline morning serum cortisol with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), ß-cell function (HOMA-ß), and prevalent T2D in the Jackson Heart Study. Linear regression models were used to examine the association of log-transformed cortisol with glycemic traits, stratified by T2D status. Logistic regression was used to examine the association of log-transformed cortisol with prevalent T2D. Models were adjusted for age, sex, education, occupation, systolic blood pressure, waist circumference, physical activity, smoking, beta-blocker/hormone replacement medications and cortisol collection time. RESULTS: Among 4,206 AAs (mean age 55 ± 13 years, 64% female), 19% had prevalent T2D. A 100% increase in cortisol among participants without diabetes was associated with 2.7 mg/dL (95% CI: 2.0, 3.3) higher FPG and a 10.0% (95% CI: -14.0, -6.0) lower HOMA-ß with no significant association with HbA1c or HOMA-IR. In participants with diabetes, a 100% increase in cortisol was associated with a 23.6 mg/dL (95% CI: 13.6, 33.7) higher FPG and a 0.6% (95% CI: 0.3, 0.9) higher HbA1c. Among all participants, quartile 4 vs. 1 of cortisol was associated with a 1.26-fold (95% CI: 1.75, 2.91) higher odds of prevalent T2D. CONCLUSION: Higher morning serum cortisol was associated with higher FPG and lower ß-cell function among participants without T2D and higher FPG and HbA1c in participants with diabetes. Among all participants, higher cortisol was associated with higher odds of T2D. These findings support a role for morning serum cortisol in glucose metabolism among AAs.

Use of a pooled cohort to impute cardiovascular disease risk factors across the adult life course.

BACKGROUND: In designing prevention strategies, it may be useful to understand how early and midlife cardiovascular disease risk factor (CVDRF) exposures affect outcomes that primarily occur in mid to late life. Few single US cohorts have followed participants from early adulthood to late life. METHODS: We pooled four prospective cohorts that represent segments of the adult life course, and studied 15 001 White and Black adults aged 18 to 95 years at enrollment. We imputed early and midlife exposure to body mass index (BMI), glucose, lipids and blood pressure (BP). CVDRF trajectories were estimated using linear mixed models. Using the best linear unbiased predictions, we obtained person-specific estimates of CVDRF trajectories beginning at age 20 until each participant's end of follow-up. We then calculated for each CVDRF, summary measures of early and midlife exposure as time-weighted averages (TWAs). RESULTS: In the pooled cohort, 33.7% were Black and 54.8% were female. CVDRF summary measures worsened in midlife compared with early life and varied by sex and race. In particular, systolic and diastolic BP were consistently higher over the adult life course among men, and BMI was higher among Blacks, particularly Black women. Simulation studies suggested acceptable imputation accuracy, especially for the younger cohorts. Correlations of true and imputed CVDRF summary measures ranged from 0.53 to 0.99, and agreement ranged from 67% to 99%. CONCLUSIONS: These results suggest that imputed CVDRFs may be accurate enough to be useful in assessing the effects of early and midlife exposures on later life outcomes.

Modifiable Lifestyle Risk Factors and Incident Diabetes in African Americans.

INTRODUCTION: The associations of modifiable lifestyle risk factors with incident diabetes are not well investigated in African Americans (AAs). This study investigated the association of modifiable lifestyle risk factors (exercise, diet, smoking, TV watching, and sleep-disordered breathing burden) with incident diabetes among AAs. METHODS: Modifiable lifestyle risk factors were characterized among 3,252 AAs in the Jackson Heart Study who were free of diabetes at baseline (2000-2004) using baseline questionnaires and combined into risk factor categories: poor (0-3 points), average (4-7 points), and optimal (8-11 points). Incidence rate ratios (IRR) for diabetes (fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes drugs, or glycosylated hemoglobin A1c ≥6.5%) were estimated using Poisson regression modeling adjusting for age, sex, education, occupation, systolic blood pressure, and BMI. Outcomes were collected 2005-2012 and data analyzed in 2016. RESULTS: Over 7.6 years, there were 560 incident diabetes cases (mean age=53.3 years, 64% female). An average or optimal compared to poor risk factor categorization was associated with a 21% (IRR=0.79, 95% CI=0.62, 0.99) and 31% (IRR=0.69, 95% CI=0.48, 1.01) lower risk of diabetes. Among participants with BMI <30, IRRs for average or optimal compared to poor categorization were 0.60 (95% CI=0.40, 0.91) and 0.53 (95% CI=0.29, 0.97) versus 0.90 (95% CI=0.67, 1.21) and 0.83 (95% CI=0.51, 1.34) among participants with BMI ≥30. CONCLUSIONS: A combination of modifiable lifestyle factors are associated with a lower risk of diabetes among AAs, particularly among those without obesity.

Aldosterone, Renin, Cardiovascular Events, and All-Cause Mortality Among African Americans: The Jackson Heart Study.

OBJECTIVES: This study examined the association of aldosterone and plasma renin activity (PRA) with incident cardiovascular disease (CVD), using a composite endpoint of coronary heart disease, stroke, and/or heart failure and mortality among African Americans in the Jackson Heart Study. BACKGROUND: There is a paucity of data for the association of aldosterone and PRA with incident CVD or all-cause mortality among community-dwelling African Americans. METHODS: A total of 4,985 African American adults, 21 to 94 years of age, were followed for 12 years. Aldosterone, PRA, and cardiovascular risk factors were collected at baseline (from 2000 to 2004). Incident events included coronary heart disease and stroke (assessed from 2000 to 2011) and heart failure (assessed from 2005 to 2011). Cox models were used to estimate hazard ratios (HRs) for incident CVD and mortality, adjusting for age, sex, education, occupation, current smoking, physical activity, dietary intake, and body mass index. RESULTS: Among 4,160 participants without prevalent CVD over a median follow-up of 7 years, there were 322 incident CVD cases. In adjusted analyses, each 1-U SD increase in log-aldosterone and log-PRA were associated with HR of 1.26 (95% confidence intervals [CI]: 1.14 to 1.40) and 1.16 (95% CI: 1.02 to 1.33) for incident CVD, respectively. Over a median of 8 years, 513 deaths occurred among 4,985 participants. In adjusted analyses, each 1-U SD increase in log-aldosterone and log-PRA were associated with HRs of 1.13 (95% CI: 1.04 to 1.23) and 1.12 (95% CI: 1.01 to 1.24) for mortality, respectively. CONCLUSIONS: Elevated aldosterone and PRA may play a significant role in the development of CVD and all-cause mortality among African Americans.

Hemoglobin A1c and Mortality in Older Adults With and Without Diabetes: Results From the National Health and Nutrition Examination Surveys (1988-2011).

OBJECTIVE: Hemoglobin A1c (HbA1c) level has been associated with increased mortality in middle-aged populations. The optimal intensity of glucose control in older adults with diabetes remains uncertain. We sought to estimate the risk of mortality by HbA1c levels among older adults with and without diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from adults aged ≥65 years (n = 7,333) from the Third National Health and Nutrition Examination Survey (NHANES III) (1998-1994) and Continuous NHANES (1999-2004) and their linked mortality data (through December 2011). Cox proportional hazards models were used to examine the relationship of HbA1c with the risk of all-cause and cause-specific (cardiovascular disease [CVD], cancer, and non-CVD/noncancer) mortality, separately for adults with diabetes and without diabetes. RESULTS: Over a median follow-up of 8.9 years, 4,729 participants died (1,262 from CVD, 850 from cancer, and 2,617 from non-CVD/noncancer causes). Compared with those with diagnosed diabetes and an HbA1c <6.5%, the hazard ratio (HR) for all-cause mortality was significantly greater for adults with diabetes with an HbA1c >8.0%. HRs were 1.6 (95% CI 1.02, 2.6) and 1.8 (95% CI 1.3, 2.6) for HbA1c 8.0-8.9% and ≥9.0%, respectively (P for trend <0.001). Participants with undiagnosed diabetes and HbA1c >6.5% had a 1.3 (95% CI 1.03, 1.8) times greater risk of all-cause mortality compared with participants without diabetes and HbA1c 5.0-5.6%. CONCLUSIONS: An HbA1c >8.0% was associated with increased risk of all-cause and cause-specific mortality in older adults with diabetes. Our results support the idea that better glycemic control is important for reducing mortality; however, in light of the conflicting evidence base, there is also a need for individualized glycemic targets for older adults with diabetes depending on their demographics, duration of diabetes, and existing comorbidities.

Achieving Health Equity: Closing The Gaps In Health Care Disparities, Interventions, And Research.

In the United States, racial/ethnic minority, rural, and low-income populations continue to experience suboptimal access to and quality of health care despite decades of recognition of health disparities and policy mandates to eliminate them. Many health care interventions that were designed to achieve health equity fall short because of gaps in knowledge and translation. We discuss these gaps and highlight innovative interventions that help address them, focusing on cardiovascular disease and cancer. We also provide recommendations for advancing the field of health equity and informing the implementation and evaluation of policies that target health disparities through improved access to care and quality of care.

The association of ideal cardiovascular health with incident type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis.

AIMS/HYPOTHESIS: Levels of ideal cardiovascular health (ICH) and incident type 2 diabetes mellitus have not been examined in a multiethnic population. We assessed the total and race/ethnicity-specific incidence of diabetes based on American Heart Association (AHA) ICH components. METHODS: Incident diabetes was assessed among 5341 participants in the Multi-Ethnic Study of Atherosclerosis without prevalent diabetes between 2002 and 2012. ICH components (total cholesterol, BP, dietary intake, tobacco use, physical activity and BMI) were assessed at baseline and participants were categorised as having ideal, intermediate or poor cardiovascular health, as defined by the AHA 2020 impact goals. We developed a scoring system based on the number of ICH components (0-1 'poor', 2-3 'intermediate', and ≥4 'ideal'). HRs were calculated using Cox models. RESULTS: During a median follow-up of 11.1 years, we identified 587 cases of incident diabetes. After multivariable adjustment, participants with 2-3 and ≥4 ICH components vs 0-1 components had a 34% lower (HR 0.66; 95% CI 0.54, 0.80) and a 75% lower (HR 0.25; 95% CI 0.18, 0.35) diabetes incidence, respectively. There were significant differences by race/ethnicity: African-American and Hispanic-American participants with ≥4 ICH components had diabetes incidence rates per 1000 person-years of 5.6 (95% CI 3.1, 10.1) and 10.5 (95% CI 6.7, 16.4), respectively, compared with 2.2 (95% CI 1.3, 3.7) among non-Hispanic white Americans. CONCLUSIONS/INTERPRETATION: Meeting an increasing number of AHA 2020 impact goals for dietary intake, physical activity, smoking, BP, cholesterol and BMI was associated with a dose-dependent lower risk of diabetes with significant variation by race/ethnicity.

Aldosterone, Renin, and Diabetes Mellitus in African Americans: The Jackson Heart Study.

CONTEXT: Previous research has suggested that activation of the renin-angiotensin-aldosterone system may promote insulin resistance and ß-cell dysfunction, but the association with incident diabetes in African Americans is unknown. OBJECTIVE: We examined the association of aldosterone and renin with insulin resistance, ß-cell function, and incident diabetes in a large African American cohort. DESIGN: The Jackson Heart Study is a prospective study of the development and progression of cardiovascular disease in African Americans. SETTING: Participants were recruited from the tricounty area of metropolitan Jackson, Mississippi. PARTICIPANTS: A total of 5301 African American adults, aged 21­94 years, were assessed at baseline and through 12 years of follow-up. Data on aldosterone, renin, and risk factors were collected at baseline (2000­2004). Diabetes (fasting glucose ≥ 126 mg/dL, physician diagnosis, use of diabetes drugs, or glycated hemoglobin ≥ 6.5%) was assessed at baseline and through 12 years of follow-up. Participants were excluded for missing data on baseline covariates or diabetes follow-up. Cox regression was used to estimate hazard ratios (HR) for incident diabetes using sequential modeling adjusting for age, sex, education, occupation, systolic blood pressure, current smoking, physical activity, dietary intake, and body mass index. EXPOSURES: Aldosterone, renin, and diabetes risk factors were measured. OUTCOME: Outcomes included the homeostatic model assessment of insulin resistance (HOMA-IR) and incident diabetes. RESULTS: Among 3234 participants over a median of 8.0 years of follow-up, there were 554 cases of incident diabetes. Every 1% increase in log-transformed aldosterone was associated with a 0.18% higher log-transformed HOMA-IR in cross-sectional analyses of nondiabetic participants (P < .001). Log-transformed aldosterone and renin levels in the fifth vs first quintile were associated with a 78% (HR 1.78, 95% confidence interval 1.35­2.34) and 35% (HR 1.35, 95% confidence interval 1.06­1.72) increase in diabetes risk, respectively, in fully adjusted models. CONCLUSIONS: Activation of the renin-angiotensin-aldosterone system may play a significant role in the development of insulin resistance and diabetes in African Americans.

Cumulative social risk and type 2 diabetes in US adults: The National Health and Nutrition Examination Survey (NHANES) 1999-2006.

BACKGROUND: The cumulative effects of adverse social factors on the diabetes risk remains to be clarified. DESIGN: Cross-sectional analysis of the US National Health and Nutrition Examination Survey (NHANES) 1999-2006. METHODS: We included 10,276 adults aged ≥20 years. Diabetes mellitus was defined by physician diagnosis or fasting plasma glucose (≥126 mg/dl) or glycated hemoglobin (≥6.5%). Social risk factors (low family income, low education level, minority racial/ethnic group status, and single-living status) and health-related behaviors (physical activity and dietary intake) were self-reported. Social risk factors were combined in a cumulative social risk index (range 0 to ≥3) and logistic regression used to assess the association of cumulative social risk and diabetes, taking into account complex survey design and sampling weights. RESULTS: Of 10,276 participants, 1515 (weighted proportion - 10%) had diabetes, 3295 (32.3%) and 1830 (9.0%) were exposed to ≥1 adverse social risk factor and ≥3 social risk factors, respectively. Diabetes was associated with increasing cumulative social risk in a graded manner (p for trend <0.001). Compared with a cumulative social risk score of 0, the age- and sex-adjusted diabetes odds for a cumulative social risk score of ≥3 was 2.84 (95% confidence interval: 2.23-3.62), and 2.72 (95% confidence interval: 2.05-3.60) after further adjustment for family history of diabetes, body mass index, smoking, dietary intake and leisure time physical activity. Health behaviors and adiposity only partially influenced the cumulative social risk and diabetes relationship. CONCLUSIONS: Simultaneous exposure to several adverse social risk factors significantly influences the odds of diabetes. Better prevention and control of diabetes needs accounting for all aspects of social disadvantage.

Diabetes, race, and functional limitations in older U.S. men and women.

AIMS: The presence of diabetes is associated with increased odds of difficulties in functional tasks but it remains unclear if the burden is similar by race. METHODS: Our study included 122,004 non-Hispanic Black (NHB) and non-Hispanic White (NHW) adults ≥50 years from the U.S. National Health Interview Survey (2001-2012). Diabetes was defined as self-reported diagnosis or medication use. Functional limitations were defined as any self-reported difficulty in performing mobility tasks, general physical activities (GPA), or leisure and social activities (LSA). Logistic regression models were created to investigate the relationship of race with functional limitations accounting for key covariates, among men and women, by diabetes status. RESULTS: Among older U.S. adults, NHB versus NHW women without diabetes had a higher odds of limitations in mobility (OR=1.39, 1.30-1.49) and LSA (OR=1.13, 1.05-1.23) without diabetes but a similar odds of these limitations with diabetes by race, after adjusting for age, income, education, obesity, arthritis, heart disease, stroke, COPD, and cancer. Interestingly, NHB versus NHW women had significantly lower odds of GPA, irrespective of diabetes status. However, NHB versus NHW men with diabetes had a persistently higher odds for mobility and LSA limitations with diabetes as follows: mobility (OR=1.30, 1.12-1.51) and LSA limitations (OR=1.07, 1.06-1.34). The interaction of race and diabetes was significant among women for mobility limitations (p<0.01), but not men. CONCLUSIONS: The burden of functional limitations differs by race among both men and women with diabetes. Future studies should examine mechanisms underlying these differences to prevent progression to disability in older adults with diabetes.

Association of sex hormones with carotid artery distensibility in men and postmenopausal women: multi-ethnic study of atherosclerosis.

The decline in carotid distensibility with age is steeper in women than in men, however, the correlates of this sex difference are not known. We examined the association of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone-binding globulin, in 2783 postmenopausal women and 2987 men aged 45 to 84 years at the Multi-Ethnic Study of Atherosclerosis baseline examination. Carotid artery lumen diameters by ultrasound and brachial artery blood pressures were measured at systole and diastole. Regression models to determine the association of carotid distensibility coefficient and lumen diameter with sex-specific quartiles of sex hormones were adjusted for age, race, height, weight, diabetes mellitus, current smoking, antihypertensive medication use, total and high-density lipoprotein cholesterol levels, and hormone replacement therapy in women. A higher DC indicates a more distensible vessel. In women, higher dehydroepiandrosterone (P=0.008) and lower sex hormone-binding globulin (P=0.039) were associated with lower distensibility; higher dehydroepiandrosterone and lower estradiol were associated with smaller carotid diameters. In men, higher Bio-T (P=0.009) and lower estradiol (P=0.007) were associated with greater distensibility and also with smaller diameters (P=0.012 and 0.002, respectively). An androgenic internal milieu is associated with lesser carotid distensibility and diameter remodeling in women, but the opposite is true for men. Higher levels of estradiol are associated with smaller carotid diameters in both the sexes. Future longitudinal and experimental studies are needed to reveal the mechanism and clinical consequences of these associations.

Weight loss increases follicle stimulating hormone in overweight postmenopausal women [corrected].

OBJECTIVES: To examine the impact of a weight loss intervention upon follicle stimulating hormone (FSH) levels in postmenopause. METHODS: Participants were postmenopausal, overweight, glucose-intolerant women not using exogenous estrogen (n = 382) in the Diabetes Prevention Program. Women were randomized to intensive lifestyle change (ILS) with the goals of weight reduction of at least 7% of initial weight and 150 min per week of moderate-intensity exercise, metformin 850 mg twice a day, or placebo administered twice a day. RESULTS: Randomization to ILS led to small increases in FSH between baseline and 1-year follow-up vs. placebo (2.3 IU/l vs. -0.81 IU/l, P < 0.01). Increases in FSH were correlated with decreases in weight (r = -0.165, P < 0.01) and estradiol (E2) (r = -0.464, P < 0.0001) after adjustment for age, race/ethnicity, and randomization arm. Changes in FSH were still significantly associated with changes in weight even after adjustment for E2 levels. Metformin users had reductions in weight but non-significant changes in FSH and E2 levels vs. placebo. CONCLUSIONS: Weight loss leads to small increases in FSH among overweight, postmenopausal women, potentially through pathways mediated by endogenous estrogen as well as other pathways.