The association between reproductive history and abdominal adipose tissue among postmenopausal women: results from the Women's Health Initiative.

STUDY QUESTION: What is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women? SUMMARY ANSWER: Higher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity. WHAT IS KNOWN ALREADY: Postmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI. STUDY DESIGN, SIZE, DURATION: This study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Women who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies. LIMITATIONS, REASONS FOR CAUTION: The WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention. STUDY FUNDING/COMPETING INTEREST(S): HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Longitudinal patterns of abdominal visceral and subcutaneous adipose tissue, total body composition, and anthropometric measures in postmenopausal women: Results from the Women's Health Initiative.

BACKGROUND: Abdominal adiposity, including visceral and subcutaneous abdominal adipose tissue (VAT and SAT), is recognized as a strong risk factor for cardiometabolic disease, cancer, and mortality. OBJECTIVE: The primary aim of this analysis is to describe longitudinal patterns of change in abdominal adipose tissue in postmenopausal women, overall and stratified by age, race/ethnicity, and years since menopause. METHODS: The data are from six years of follow up on 10,184 postmenopausal women (7828 non-Hispanic White women, 1423 non-Hispanic Black women, and 703 Hispanic women) who participated in the Women's Health Initiative (WHI). The WHI is a large prospective cohort study of postmenopausal women across the United States. All participants in this analysis had DXA scans in the 1990s as part of the WHI protocol. Hologic APEX software was used to re-analyze archived DXA scans and obtain measures of abdominal adipose tissue. Analyses examined differences in abdominal adipose tissue, overall adiposity, and anthropometric variables. RESULTS: There were important differences in VAT and SAT by age and race/ethnicity. In women <60 years, VAT increased over the follow-up period, while in women ≥70 years, VAT decreased. Non-Hispanic Black women had the highest levels of SAT. Hispanic women had the highest VAT levels. Women more than ten years since menopause had less SAT and more VAT than women less than ten years since menopause, resulting in a higher VAT/SAT ratio. There was a moderate to strong correlation between measures of abdominal adipose tissue and anthropometric measurements of body size. Still, there were substantial differences in the quantity of VAT and SAT within BMI and waist circumference categories. CONCLUSIONS: These results demonstrate differences in VAT and SAT according to age, race/ethnicity, time since menopause, and compared to standard measures of body composition in a large and diverse cohort of postmenopausal women.

Frequency of Consuming Breakfast Meals and After-Dinner Snacks Is not Associated with Postmenopausal Breast Cancer Risk: Women's Health Initiative Observational Study.

BACKGROUND: There has been little investigation into how the timing of meals and eating occasions associates with postmenopausal breast cancer risk. OBJECTIVE: We examined the association between the frequency of consuming breakfast meals and after-dinner snacks with the risk for postmenopausal breast cancer. METHODS: A prospective analysis of 74,825 postmenopausal women aged 49 to 81 y from the Women's Health Initiative Observational Study cohort. Breakfast and after-dinner snack intake were assessed at year 1 examination. Risk for invasive and in situ breast cancer diagnosed before 28 February 2020 was modeled with multivariable Cox proportional hazards regression models according to breakfast and after-dinner snack consumption frequencies. The models were adjusted for age, self-identified race/ethnicity, education, income, physical activity, smoking, alcohol intake, diet quality score (Healthy Eating Index 2015), energy intake, diabetic status, hormone therapy, and BMI. RESULTS: During the follow-up period, 5313 participants were diagnosed with invasive breast cancer and 1197 participants with in situ breast cancer. Compared with participants who did not eat breakfast, those with daily breakfast consumption was not associated with invasive breast cancer (HR: 1.04; 95% CI: 0.9, 1.19) nor in situ (HR: 1.25; 95% CI: 0.91, 1.74) breast cancer. There were monotonic higher point estimates of in situ breast cancer for each higher category of breakfast intake from 0 to 7 times per week (P-trend = 0.04, Wald test). Compared with consumption of daily after-dinner snacks, avoidance of after-dinner snacks was not associated with invasive breast cancer (HR: 0.97; 95% CI: 0.87, 1.08) nor in situ (HR: 1.12; 95% CI: 0.89, 1.42) breast cancer. CONCLUSIONS: There was no association between intake frequency of breakfast meals or after-dinner snack habits and with risk of breast cancer in postmenopausal women.

Association between urinary phthalate biomarker concentrations and adiposity among postmenopausal women.

BACKGROUND: Obesity is a leading risk factor for chronic diseases, potentially related to excess abdominal adiposity. Phthalates are environmental chemicals that have been suggested to act as obesogens, driving obesity risk. For the associations between phthalates and adiposity, prior studies have focused primarily on body mass index. We hypothesize that more refined measures of adiposity and fat distribution may provide greater insights into these associations given the role of central adiposity in chronic disease risk. OBJECTIVES: To evaluate associations between urinary phthalate biomarkers and both visceral and subcutaneous adipose tissue (VAT and SAT) among postmenopausal women enrolled in the Women's Health Initiative (WHI). METHODS: We included 1125 WHI participants with available, coincident measurements of urinary phthalate biomarkers (baseline, year 3) and VAT and SAT (baseline, year 3, year 6). VAT and SAT measurements were estimated from DXA scans. Multilevel mixed-effects models estimated the prospective associations between urinary phthalate biomarkers at baseline and VAT and SAT three years later. RESULTS: In multivariable adjusted models, we observed positive associations between some phthalate biomarkers, including the sum of di-isobutyl phthalate (ΣDiBP) biomarkers, MCNP, and ΣDEHP, with VAT three years later. For example, we observed positive associations between concentrations of ΣDiBP and VAT (Q4 vs Q1 ß = 7.15, 95% CI -1.76-16.06; Q3 vs Q1 ß = 10.94, 95% CI 3.55-18.33). Associations were generally attenuated but remained significant after additional adjustment for SAT. MBzP was positively associated with SAT. Other phthalate biomarkers investigated (MEP, MCOP, MCPP, ΣDBP) were not significantly associated with VAT or SAT. DISCUSSION: Based on robust measures of adiposity, this study provides supportive evidence that higher urinary concentrations of select phthalate compounds were associated with higher VAT levels over time in postmenopausal women. Efforts to replicate these findings are needed.

MRI Based Validation of Abdominal Adipose Tissue Measurements From DXA in Postmenopausal Women.

INTRODUCTION: Visceral adipose tissue (VAT) is a hypothesized driver of chronic disease. Dual-energy X-ray absorptiometry (DXA) potentially offers a lower cost and more available alternative compared to gold-standard magnetic resonance imaging (MRI) for quantification of abdominal fat sub-compartments, VAT and subcutaneous adipose tissue (SAT). We sought to validate VAT and SAT area (cm2) from historical DXA scans against MRI. METHODOLOGY: Participants (n = 69) from the Women's Health Initiative (WHI) completed a 3 T MRI scan and a whole body DXA scan (Hologic QDR2000 or QDR4500; 2004-2005). A subset of 43 participants were scanned on both DXA devices. DXA-derived VAT and SAT at the 4th lumbar vertebrae (5 cm wide) were analyzed using APEX software (v4.0, Hologic, Inc., Marlborough, MA). MRI VAT and SAT areas for the corresponding DXA region of interest were quantified using sliceOmatic software (v5.0, Tomovision, Magog, Canada). Pearson correlations between MRI and DXA-derived VAT and SAT were computed, and a Bland-Altman analysis was performed. RESULTS: Participants were primarily non-Hispanic white (86%) with a mean age of 70.51 ± 5.79 years and a mean BMI of 27.33 ± 5.40 kg/m2. Correlations between MRI and DXA measured VAT and SAT were 0.90 and 0.92, respectively (p ≤ 0.001). Bland-Altman plots showed that DXA-VAT slightly overestimated VAT on the QDR4500 (-3.31 cm2); this bias was greater in the smaller subset measured on the older DXA model (QDR2000; -30.71 cm2). The overestimation of DXA-SAT was large (-85.16 to -118.66 cm2), but differences were relatively uniform for the QDR4500. CONCLUSIONS: New software applied to historic Hologic DXA scans provide estimates of VAT and SAT that are well-correlated with criterion MRI among postmenopausal women.

Cumulative average dietary pattern scores in young adulthood and risk of incident type 2 diabetes: the CARDIA study.

AIMS/HYPOTHESIS: The evidence for the role of contemporary dietary patterns, trends and predominant aspects of energy intake in a typical American diet and in type 2 diabetes risk is limited. Therefore, we examined the association between dietary pattern scores created to reflect the 2015 Dietary Guidelines for Americans (DGA) Scientific Report, a Palaeolithic (Palaeo) diet, a diet high in 'empty calories', and the A Priori Diet Quality Score (APDQS) (cohort reference) and type 2 diabetes risk over time. METHODS: We carried out a prospective analysis of 4719 young adult black and white men and women from the Coronary Artery Risk Development in Young Adults (CARDIA) study with repeated dietary histories collected at study years 0, 7 and 20. Using multivariable Cox proportional hazards regression models, we examined the association between time-dependent cumulative average dietary pattern scores and incident type 2 diabetes. RESULTS: During the 30 year follow-up period, 680 (14.4%) incident cases of type 2 diabetes occurred. There was no association between the 2015 DGA, Palaeo or empty calorie scores and type 2 diabetes risk in the overall population. Participants in the fourth quartile of the APDQS, reflecting a more healthful dietary pattern, had a 45% lower risk of type 2 diabetes compared with those in the lowest quartile (HR 0.55 [95% CI 0.41, 0.74]). In stratified analyses there was an inverse association for the 2015 DGA in non-smokers per SD (HR 0.86 [95% CI 0.74, 0.99]) and an inverse association for the empty calorie score in white women (HR 0.76 [95% CI 0.60, 0.96]) as well as in a subgroup analysis of the Palaeo index of participants who maintained a high score over 20 years (per SD, HR 0.59 [95% CI 0.39, 0.88]). CONCLUSIONS/INTERPRETATION: Higher levels of the APDQS, which largely aligns with the 2015 DGA, were strongly inversely associated with 30 year type 2 diabetes risk in the CARDIA cohort; the results from the other patterns were nuanced and need to be considered in the context of the study and potential biases.

Comparative Effectiveness and Safety of Bariatric Procedures for Weight Loss: A PCORnet Cohort Study.

Background: There has been a dramatic shift in use of bariatric procedures, but little is known about their long-term comparative effectiveness. Objective: To compare weight loss and safety among bariatric procedures. Design: Retrospective observational cohort study, January 2005 to September 2015. (ClinicalTrials.gov: NCT02741674). Setting: 41 health systems in the National Patient-Centered Clinical Research Network. Participants: 65 093 patients aged 20 to 79 years with body mass index (BMI) of 35 kg/m2 or greater who had bariatric procedures. Intervention: 32 208 Roux-en-Y gastric bypass (RYGB), 29 693 sleeve gastrectomy (SG), and 3192 adjustable gastric banding (AGB) procedures. Measurements: Estimated percent total weight loss (TWL) at 1, 3, and 5 years; 30-day rates of major adverse events. Results: Total numbers of eligible patients with weight measures at 1, 3, and 5 years were 44 978 (84%), 20 783 (68%), and 7159 (69%), respectively. Thirty-day rates of major adverse events were 5.0% for RYGB, 2.6% for SG, and 2.9% for AGB. One-year mean TWLs were 31.2% (95% CI, 31.1% to 31.3%) for RYGB, 25.2% (CI, 25.1% to 25.4%) for SG, and 13.7% (CI, 13.3% to 14.0%) for AGB. At 1 year, RYGB patients lost 5.9 (CI, 5.8 to 6.1) percentage points more weight than SG patients and 17.7 (CI, 17.3 to 18.1) percentage points more than AGB patients, and SG patients lost 12.0 (CI, 11.6 to 12.5) percentage points more than AGB patients. Five-year mean TWLs were 25.5% (CI, 25.1% to 25.9%) for RYGB, 18.8% (CI, 18.0% to 19.6%) for SG, and 11.7% (CI, 10.2% to 13.1%) for AGB. Patients with diabetes, those with BMI less than 50 kg/m2, those aged 65 years or older, African American patients, and Hispanic patients lost less weight than patients without those characteristics. Limitation: Potential unobserved confounding due to nonrandomized design; electronic health record databases had missing outcome data. Conclusion: Adults lost more weight with RYGB than with SG or AGB at 1, 3, and 5 years; however, RYGB had the highest 30-day rate of major adverse events. Small subgroup differences in weight loss outcomes were observed. Primary Funding Source: Patient-Centered Outcomes Research Institute.

The Association of Serum Carotenoids, Tocopherols, and Ascorbic Acid With Rapid Kidney Function Decline: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

OBJECTIVE: Nutritional intervention targeting dietary intake modification is a major component of treatment for chronic kidney disease; however, little is known about the relationship between dietary intake and kidney function decline in individuals with preserved kidney function. DESIGN AND METHODS: In this prospective cohort study we examined the association of biomarkers of dietary intake with kidney function decline over a 5-year interval in 2,152 men and women with cystatin-C-based estimated glomerular filtration rate > 60 mL/minute/1.73 m2 from the Coronary Artery Risk Development in Young Adults study. The biomarkers of interest included carotenoids, tocopherols, and ascorbic acid. Multivariable logistic regression was used to explore the relationship between serum concentrations of the sum of 4 carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin), lycopene, α-tocopherol, γ-tocopherol, and ascorbic acid and rapid kidney function decline, defined as .15% decline in cystatin-C-based estimated glomerular filtration rate over 5 years. RESULTS: During the 5-year follow-up, 290 participants (13.5%) experienced rapid kidney function decline. Relative to individuals in the lowest quartile of serum carotenoids, those in the highest quartile had significantly lower odds of rapid kidney function decline in the fully adjusted model (odds ratio, 0.51; 95% confidence interval [CI], 0.32-0.80; P trend, .02). No association of levels of serum tocopherols, ascorbic acid, or lycopene with kidney function decline was found. There was no evidence that results differed for individuals with hypertension or diabetes. CONCLUSIONS: These results demonstrate that higher serum carotenoid levels, reflective of a fruit- and vegetable-rich dietary pattern, inversely associate with rapid kidney function decline in early middle adulthood and provide insight into how diet might play a role in chronic kidney disease prevention.

Metabolic obesity phenotypes and risk of colorectal cancer in postmenopausal women.

Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR-a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross-classified by BMI (18.5-<25.0, 25.0-<30.0 and ≥30.0 kg/m2 ) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA-IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis.

Sedentary Behaviors and Cardiometabolic Risk: An Isotemporal Substitution Analysis.

Evidence suggests that time spent engaging in sedentary behaviors is associated with a greater risk of adverse cardiometabolic outcomes. We investigated the cross-sectional associations of 6 unique sedentary tasks (watching television, using the computer, completing paperwork, reading, talking on the telephone, and sitting in a car) with cardiometabolic risk factors, and also examined the effect of replacing one type of sedentary behavior with another on the level of cardiometabolic risk. Participants consisted of 3,211 individuals from the Coronary Artery Risk Development in Young Adults Study who visited the clinic between 2010 and 2011. Linear regression models examined the independent and joint associations of sedentary tasks with a composite cardiometabolic risk score, as well as with individual cardiometabolic risk factors (waist circumference, blood pressure, fasting glucose, insulin, triglycerides, and high density lipoprotein cholesterol) after adjusting for physical activity and other covariates. Replacing 2 hours of television viewing with 2 hours spent performing any other sedentary activity was associated with a lower cardiometabolic risk score of 0.06-0.09 standard deviations (all 95% confidence intervals: -0.13, -0.02). No other replacements of one type of sedentary task for another were significant. Study findings indicate that television viewing has a more adverse association with cardiometabolic risk factors than other sedentary behaviors.

Diet Quality Scores Inversely Associated with Postmenopausal Breast Cancer Risk Are Not Associated with Premenopausal Breast Cancer Risk in the California Teachers Study.

Background: Evidence for the association between diet and breast cancer risk is inconsistent Thus, research that compares indexes of overall diet quality may provide new insight. Objective: We examined the association between diet quality indexes and pre- and postmenopausal breast cancer risk in a large prospective cohort. Methods: This was a prospective analysis of 96,959 women, aged 22-104 y, in the California Teachers Study cohort (1995-2011). Diet quality was characterized by 4 different indexes. Specifically, we examined Alternate Mediterranean Diet (aMED), Alternative Healthy Eating Index-2010 (AHEI-2010), Dietary Approaches to Stop Hypertension (DASH), and Paleolithic index (PALEO) scores with the risk of developing breast cancer. We used multivariable Cox proportional hazards regression models to derive HRs and 95% CIs for breast cancer risk. Results: In the analysis of 42,517 women at risk of premenopausal breast cancer, there was no association between any of the indexes and incident breast cancer (346 cases). In the analysis of 54,442 women at risk of postmenopausal breast cancer at baseline, higher AHEI-2010, aMED, and DASH scores were inversely associated with incident breast cancer (3523 incident cases). Respectively, HRs (95% CIs) comparing quintile 5 to quintile 1 (reference) for AHEI-2010, aMED, and DASH indexes were 0.87 (0.78, 0.97; P-trend = 0.004), 0.91 (0.82, 1.02; P-trend = 0.03), and 0.89 (0.80, 1.00; P-trend = 0.03). The PALEO score was not associated with postmenopausal breast cancer (HR for quintile 5 compared with quintile 1: 1.05; 95% CI: 0.94, 1.17). Conclusions: Diet quality indexes that emphasize intake of whole grains, vegetables, fruits, legumes, and nuts and seeds and de-emphasize red and processed meats and sugar-sweetened beverages were modestly associated with a lower risk of incident postmenopausal breast cancer risk. However, they were not associated with premenopausal breast cancer, and the PALEO score was not associated with cancer risk regardless of menopausal status.

Twenty year fitness trends in young adults and incidence of prediabetes and diabetes: the CARDIA study.

AIMS/HYPOTHESIS: The prospective association between cardiorespiratory fitness (CRF) measured in young adulthood and middle age on development of prediabetes, defined as impaired fasting glucose and/or impaired glucose tolerance, or diabetes by middle age remains unknown. We hypothesised that higher fitness levels would be associated with reduced risk for developing incident prediabetes/diabetes by middle age. METHODS: Participants were from the Coronary Artery Risk Development in Young Adults (CARDIA) study who were free from prediabetes/diabetes at baseline (year 0 [Y0]: 1985-1986). CRF was quantified by treadmill duration (converted to metabolic equivalents [METs]) at Y0, Y7 and Y20 and prediabetes/diabetes status was assessed at Y0, Y7, Y10, Y15, Y20 and Y25. We use an extended Cox model with CRF as the primary time-varying exposure. BMI was included as a time-varying covariate. The outcome was development of either prediabetes or diabetes after Y0. Model 1 included age, race, sex, field centre, CRF and BMI. Model 2 additionally included baseline (Y0) smoking, energy intake, alcohol intake, education, systolic BP, BP medication use and lipid profile. RESULTS: Higher fitness was associated with lower risk for developing incident prediabetes/diabetes (difference of 1 MET: HR 0.99898 [95% CI 0.99861, 0.99940], p < 0.01), which persisted (difference of 1 MET: HR 0.99872 [95% CI 0.99840, 0.99904], p < 0.01] when adjusting for covariates. CONCLUSIONS/INTERPRETATION: Examining participants who had fitness measured from young adulthood to middle age, we found that fitness was associated with lower risk for developing prediabetes/diabetes, even when adjusting for BMI over this time period. These findings emphasise the importance of fitness in reducing the health burden of prediabetes and diabetes.

Oxidative stress, inflammation, endothelial dysfunction and incidence of type 2 diabetes.

BACKGROUND: Oxidative stress, inflammation and endothelial dysfunction are interrelated factors in the etiology of cardiovascular disease, but their linkage to type 2 diabetes is less clear. We examined the association of these biomarkers with incident type 2 diabetes (T2D). METHODS: Analysis of 2339 participants in the community-based coronary artery risk development in young adults (CARDIA) study. Participants (age 40.1 ± 3.6 years, 44 % Black, 58 % women) were free of diabetes, and were followed 10 years. Cox regression was used to estimate hazard ratios (HRs) for incident T2D adjusting for the other biomarkers under study, demographic and lifestyle measures, dietary biomarkers, BMI (kg/m(2)) and metabolic syndrome components. RESULTS: F2-isoprostanes and oxidized LDL (oxidative stress) were positively associated with incident T2D, but the associations were attenuated by adjustment for BMI. C-reactive protein was positively associated with T2D even with full adjustment: HR (95 % CI) = 2.21 (1.26-3.88) for quartile 4 (Q4) v. quartile 1 (Q1). The HR (95 % CI) for T2D for biomarkers of endothelial dysfunction ICAM-1 and E-selectin for Q4 v. Q1 were 1.64 (0.96-2.81) and 1.68 (1.04-2.71) respectively, with full adjustment. Including these two markers in a common risk score incorporating BMI and clinical measures improved the prediction probability of T2D: relative risk for the average person classified up compared to the average person classified down: 1.09, (1.06-1.13), P < 0.0001. CONCLUSIONS: Biomarkers of inflammation and endothelial dysfunction were positively associated with incident T2D. ICAM-1 and E-selectin add to the prediction of T2D beyond a common risk score.

Beverage habits and mortality in Chinese adults.

BACKGROUND: There is limited research examining beverage habits, one of the most habitual dietary behaviors, with mortality risk. OBJECTIVE: This study examined the association between coffee, black and green tea, sugar-sweetened beverages (soft drinks and juice), and alcohol and all-cause and cause-specific mortality. METHODS: A prospective data analysis was conducted with the use of the Singapore Chinese Health Study, including 52,584 Chinese men and women (aged 45-74 y) free of diabetes, cardiovascular disease (CVD), and cancer at baseline (1993-1998) and followed through 2011 with 10,029 deaths. Beverages were examined with all-cause and cause-specific (cancer, CVD, and respiratory disease) mortality risk with the use of Cox proportional hazards regression. RESULTS: The associations between coffee, black tea, and alcohol intake and all-cause mortality were modified by smoking status. Among never-smokers there was an inverse dose-response association between higher amounts of coffee and black tea intake and all-cause, respiratory-related, and CVD mortality (black tea only). The fully adjusted HRs for all-cause mortality for coffee for <1/d, 1/d, and ≥2/d relative to no coffee intake were 0.89, 0.86, and 0.83, respectively (P-trend = 0.0003). For the same black tea categories the HRs were 0.95, 0.90, and 0.72, respectively (P-trend = 0.0005). Among ever-smokers there was no association between coffee or black tea and the outcomes. Relative to no alcohol, light to moderate intake was inversely associated with all-cause mortality (HR: 0.87; 95% CI: 0.79, 0.96) in never-smokers with a similar magnitude of association in ever-smokers. There was no association between heavy alcohol intake and all-cause mortality in never-smokers and a strong positive association in ever-smokers (HR: 1.56; 95% CI: 1.40, 1.74). Green tea and sugar-sweetened beverages were not associated with all-cause or cause-specific mortality. CONCLUSIONS: Higher coffee and black tea intake was inversely associated with mortality in never-smokers, light to moderate alcohol intake was inversely associated with mortality regardless of smoking status, heavy alcohol intake was positively associated with mortality in ever-smokers, and there was no association between sugar-sweetened beverages and green tea and mortality.

Western-style fast food intake and cardiometabolic risk in an Eastern country.

BACKGROUND: Western-style fast food contributes to a dietary pattern portending poor cardiometabolic health in the United States. With globalization, this way of eating is becoming more common in developing and recently developed populations. METHODS AND RESULTS: We examined the association of Western-style fast food intake with risk of incident type 2 diabetes mellitus and coronary heart disease mortality in Chinese Singaporeans. This analysis included men and women 45 to 74 years of age who enrolled in the Singapore Chinese Health Study from 1993 to 1998. For CHD mortality, 52 584 participants were included and 1397 deaths were identified through December 31, 2009, via registry linkage. For type 2 diabetes mellitus, 43 176 participants were included and 2252 cases were identified during the follow-up interview (1999-2004) and validated. Hazard ratios for incident type 2 diabetes mellitus and coronary heart disease mortality were estimated with thorough adjustment for demographic, lifestyle, and dietary factors. Chinese Singaporeans with relatively frequent intake of Western-style fast food items (≥2 times per week) had an increased risk of developing type 2 diabetes mellitus (hazard ratio, 1.27; 95% confidence interval, 1.03-1.54) and dying of coronary heart disease (hazard ratio, 1.56; 95% confidence interval, 1.18-2.06) relative to their peers with little or no reported intake. These associations were not materially altered by adjustments for overall dietary pattern, energy intake, and body mass index. CONCLUSIONS: Western-style fast food intake is associated with increased risk of developing type 2 diabetes mellitus and of coronary heart disease mortality in an Eastern population. These findings suggest the need for further attention to global dietary acculturation in the context of ongoing epidemiological and nutrition transitions.

Artificially sweetened beverages--do they influence cardiometabolic risk?

The sweeteners in artificially sweetened beverages (ASB) are potent stimulators of sweetness on the palate, yet contain no energy. This "mismatch" between sweetness and energy in ASB has raised concern about metabolism and health. This article provides a review of the recent literature on the effect of ASB on cardiometabolic risk factors and disease. Physiologic mechanisms are discussed, as well as epidemiologic studies. Prospective studies of ASB intake and the risk of obesity, diabetes, and cardiovascular disease have revealed inconsistent results. Higher-quality studies suggest either no effect of ASB or perhaps a protective effect through replacement of calorically dense alternatives. Although some studies have reported that ASB may increase risk, these observations appear to be an artifact of reverse causality. The limited experimental evidence does not support an effect of ASB on obesity or chronic disease. Indeed, experimental studies in humans suggest ASB may be effective for weight loss when replacing sugar-sweetened beverages.

Wrist breadth and homeostasis model assessment of insulin resistance in youth: the Fels Longitudinal Study.

OBJECTIVES: There is biological crosstalk between insulin signaling and bone remodeling pathways, and wrist circumference and bone area were recently found to associate with insulin resistance independent of body mass index (BMI) in overweight/obese children. We aimed to expand on this work by using more specific measures of adiposity for adjustment and examining children with broader range of BMI. METHODS: We used serial data (1,051 total measures) on 313 non-Hispanic white youth (ages 8-18 y) from the Fels Longitudinal Study with homeostasis model assessment of insulin resistance (HOMA-IR) as the outcome. Internal standard deviation score (SDS) for wrist breadth was evaluated as a predictor of HOMA-IR (log-transformed) before and after adjusting for internal-sample SDSs for BMI, waist circumference (WC), and total body fat (TBF) from dual energy X-ray absorptiometry, in addition to age, sex, Tanner stage, and birth year, using generalized estimating equations. RESULTS: Before additional adiposity adjustment, we found a significant positive association between wrist breadth SDS and log-transformed HOMA-IR (ß = 0.13; 95%CI: 0.09-0.17), which remained significant after adjusting for TBF SDS (ß = 0.09; 95%CI: 0.05-0.13; P < 0.001), BMI SDS (ß = 0.06; 95%CI: 0.02-0.10; P = 0.007), and WC SDS (ß = 0.06; 95%CI: 0.02-0.09; P = 0.005). CONCLUSIONS: Further work is needed to determine whether simple frame size measures such as wrist breadth may be useful markers of metabolic risk.

A hypothetical intervention of the timing of dietary intake on weight and body composition after initial weight loss.

OBJECTIVE: This study estimated the effect of hypothetical interventions of higher and lower frequency of breakfast and post-dinner snack consumption (breakfast consumption 0-4 vs. 5-7 times/week and post-dinner snack consumption 0-2 vs. 3-7 times/week) on changes in body weight and composition over 18 months after a successful 6-month standard behavioral weight-loss program. METHODS: The study analyzed data from the Innovative Approaches to Diet, Exercise and Activity (IDEA) study. RESULTS: If all participants consumed a breakfast meal 5 to 7 times/week over 18 months, they would have regained 2.95 kg of body weight on average (95% CI: 2.01 to 3.96), which is 0.59 kg (95% CI: -0.86 to -0.32) lower than if all participants consumed breakfast 0 to 4 times/week. If all participants consumed a post-dinner snack 0 to 2 times/week, they would have regained 2.86 kg of body weight on average (95% CI: 0.99 to 5.25), which is 0.83 kg (95% CI: -1.06 to -0.59) lower than if all consumed a post-dinner snack 3 to 7 times/week. CONCLUSIONS: Regular breakfast consumption and minimizing post-dinner snacking may modestly mitigate weight and body fat regain over 18 months after initial weight loss.

Characterizing the microbiome of patients with myeloproliferative neoplasms during a Mediterranean diet intervention.

Myeloproliferative neoplasms (MPNs) are a class of rare hematological malignancies that result in the overproduction of myeloid lineage cells. These malignancies result in increased cytokine production and inflammation, which correlate with worsened symptom burden and prognosis. Other than bone marrow transplantation, there is no cure for myeloproliferative neoplasms. As such, treatments focus on reducing thrombotic risk, inflammation, and symptom burden. Because current pharmacological treatments carry significant side effects, there is a need to explore low-risk therapies that may modulate inflammation and alleviate symptom burden. One potential way to achieve this is adherence to a Mediterranean (MED) diet, which is rich in anti-inflammatory foods, reduces inflammatory biomarkers, and beneficially alters the gut microbiome. We performed a 15-week clinical trial of 28 individuals with MPN who were randomized to dietary counseling based on either a Mediterranean diet or standard U.S. Guidelines for Americans. Our primary objective was to determine whether MPN patients could adopt a Mediterranean eating pattern when supported with dietician counseling. As exploratory endpoints, we investigated the impact of diet and inflammation on the gut microbiome. Using shotgun metagenomic sequencing, we found that microbiome diversity and composition were stable throughout the study duration in both cohorts. Furthermore, we discovered significant differences in the microbiomes between MPN subtypes, such as increased beta-dispersion in subjects with myelofibrosis. Lastly, we found several significant correlations between the abundance of multiple bacterial taxa and cytokine levels. Together, this study provides insight into the interaction between diet, inflammation, and the gut microbiome. IMPORTANCE The gut microbiome serves as an interface between the host and the diet. Diet and the gut microbiome both play important roles in managing inflammation, which is a key aspect of myeloproliferative neoplasm (MPN). Studies have shown that a Mediterranean (MED) diet can reduce inflammation. Therefore, we longitudinally characterized the gut microbiomes of MPN patients in response to Mediterranean or standard 2020 US Guidelines for Americans dietary counseling to determine whether there were microbiome-associated changes in inflammation. We did not find significant changes in the gut microbiome associated with diet, but we did find several associations with inflammation. This research paves the way for future studies by identifying potential mechanistic targets implicated in inflammation within the MPN gut microbiome.

Measures of MRI Brain Biomarkers in Middle Age According to Average Modified Mediterranean Diet Scores Throughout Young and Middle Adulthood.

BACKGROUND: The Mediterranean diet (MedDiet) has been linked with better cognitive function and brain integrity. OBJECTIVE: To examine the association of modified Mediterranean diet (mMedDiet) scores from early through middle adulthood in relation to volumetric and microstructural midlife MRI brain measures. Assess the association of mMedDiet and brain measures with four cognitive domains. If variables are correlated, determine if brain measures mediate the relationship between mMedDiet and cognition. METHODS: 618 participants (mean age 25.4±3.5 at year 0) of the Coronary Artery Risk Development in Young Adults (CARDIA) study were included. Cumulative average mMedDiet scores were calculated by averaging scores from years 0, 7, and 20. MRI scans were obtained at years 25 and 30. General linear models were used to examine the association between mMedDiet and brain measures. RESULTS: Higher cumulative average mMedDiet scores were associated with better microstructural white matter (WM) integrity measured by fractional anisotropy (FA) at years 25 and 30 (all ptrend <0.05). Higher mMedDiet scores at year 7 were associated with higher WM FA at year 25 (ß= 0.003, ptrend = 0.03). Higher mMedDiet scores at year 20 associated with higher WM FA at years 25 (ß= 0.0005, ptrend = 0.002) and 30 (ß= 0.0003, ptrend = 0.02). mMedDiet scores were not associated with brain volumes. Higher mMedDiet scores and WM FA were both correlated with better executive function, processing speed, and global cognition (all ptrend <0.05). WM FA did not mediate the association between mMedDiet scores and cognition. CONCLUSIONS: mMedDiet scores may be associated with microstructural WM integrity at midlife.