The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the ...Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP).
In 2013-16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100-125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders.
Among 1,702 participants (59.9-77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D.
T2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.
High-quality diets have been found to be beneficial in preventing long-term weight gain. However, concurrent changes in diet quality and body weight over time have rarely been reported. We examined ...the association between 10-year changes in diet quality and body weight in the Multiethnic Cohort Study. Analyses included 53 977 African Americans, Native Hawaiians, Japanese Americans, Latinos and Whites, who completed both baseline (1993–1996, 45–69 years) and 10-year follow-up (2003–2008) surveys including a FFQ and had no history of heart disease or cancer. Using multivariable regression, weight changes were regressed on changes in four diet quality indexes, Healthy Eating Index-2015, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet and Dietary Approaches to Stop Hypertension scores. Mean weight change over 10 years was 1·2 (sd 6·8) kg in men and 1·5 (sd 7·2) kg in women. Compared with stable diet quality (< 0·5 sd change), the greatest increase (≥ 1 sd increase) in the diet scores was associated with less weight gain (by 0·55–1·17 kg in men and 0·62–1·31 kg in women). Smaller weight gain with improvement in diet quality was found in most subgroups by race/ethnicity, baseline age and baseline BMI. The inverse association was stronger in younger age and higher BMI groups. Ten-year improvement in diet quality was associated with a smaller weight gain, which varied by race/ethnicity and baseline age and BMI. Our findings suggest that maintaining a high-quality diet and improving diet quality over time may prevent excessive weight gain.
This study investigated how diet quality changes over a ten-year period, assessed using the following four diet quality indexes, the Healthy Eating Index-2015 (HEI-2015), Alternative Healthy Eating ...Index-2010 (AHEI-2010), alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH), were related to mortality from cardiovascular disease (CVD) in the Multiethnic Cohort Study. The analysis included 61,361 participants who completed both the 1993-1996 baseline survey and the 2003-2008 10-year follow-up surveys. Over the mean follow-up period of 13 years after the 10-year survey, 4174 deaths from CVD were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox models. Increases in diet quality scores were associated with a reduced risk of CVD mortality for all indexes: HRs per one SD increment of 0.94 to 0.99 (HR (95% CI), 0.96 (0.92-1.01) for HEI-2015, 0.96 (0.91-1.01) for AHEI-2010, 0.99 (0.94-1.04) for aMED, and 0.94 (0.89-0.99) for DASH) in men and 0.88 to 0.92 (0.88 (0.84-0.92) for HEI-2015, 0.90 (0.85-0.95) for AHEI-2010, 0.89 (0.84-0.95) for aMED, and 0.92 (0.87-0.96) for DASH) in women. The inverse association generally did not vary by race and ethnicity, age, body mass index, smoking, and hypertension in each sex. Our findings suggest that improving diet quality and maintaining a high-quality diet over time may help reduce the risk of CVD mortality and could also be beneficial for those at higher risk of CVD.
Breast cancer is the most common cancer and the second‐leading cause of cancer‐related death among women. Inconsistent findings for the relationship between melatonin levels, sleep duration and ...breast cancer have been reported. We investigated the association of sleep duration at cohort entry and its interaction with body mass index (BMI) with risk of developing breast cancer in the large population‐based Multiethnic Cohort study. Among the 74,481 at‐risk participants, 5,790 breast cancer cases were identified during the study period. Although we detected no significant association between sleep duration and breast cancer incidence, higher risk estimates for short (HR = 1.03; 95% CI: 0.97–1.09) and long sleep (HR = 1.05; 95% CI: 0.95–1.15) compared to normal sleep (7–8 hr) were found. The patterns for models stratified by age, BMI, ethnicity and hormone receptor status were similar but did not indicate significant interaction effects. When examining the combined sleep duration and BMI interaction effect, in comparison to the normal BMI‐normal sleep group, risk estimates for underweight, overweight and obesity were similar across categories of sleep duration (≤6, 7–8, and ≥9 hr). The underweight‐normal sleep group had lower breast cancer incidence (HR = 0.66, 95% CI: 0.50–0.86), whereas the overweight‐short sleep, overweight‐normal sleep group and all obese women experienced elevated breast cancer incidence. The respective HRs for short, normal and long sleep among obese women were 1.35 (95% CI: 1.20–1.53), 1.27 (95% CI: 1.15–1.42) and 1.46 (95% CI: 1.21–1.76). Future perspectives need to examine the possibility that sleep quality, variations in circadian rhythm and melatonin are involved in breast cancer etiology.
What's new?
To date, the potential relationship between melatonin levels, sleep duration, and breast cancer remains unclear. This large ethnically diverse population‐based cohort study provides the first results on sleep duration and breast cancer among individuals of white, African American, Japanese American, Native Hawaiian, and Latino origin. Although sleep duration was not significantly associated with breast cancer incidence, the authors used a novel approach to examine the interaction effect of body mass index and sleep duration on breast cancer risk. In the combined BMI‐sleep analyses, participants with overweight or obesity had a higher breast cancer risk across all sleep categories.
Although the contribution of air pollution to lung cancer risk is well characterized, few studies have been conducted in racially, ethnically, and socioeconomically diverse populations.
To examine ...the association between traffic-related air pollution and risk of lung cancer in a racially, ethnically, and socioeconomically diverse cohort.
Among 97,288 California participants of the Multiethnic Cohort Study, we used Cox proportional hazards regression to examine associations between time-varying traffic-related air pollutants (gaseous and particulate matter pollutants and regional benzene) and lung cancer risk (
= 2,796 cases; average follow-up = 17 yr), adjusting for demographics, lifetime smoking, occupation, neighborhood socioeconomic status (nSES), and lifestyle factors. Subgroup analyses were conducted for race, ethnicity, nSES, and other factors.
Among all participants, lung cancer risk was positively associated with nitrogen oxide (hazard ratio HR, 1.15 per 50 ppb; 95% confidence interval CI, 0.99-1.33), nitrogen dioxide (HR, 1.12 per 20 ppb; 95% CI, 0.95-1.32), fine particulate matter with aerodynamic diameter <2.5 μm (HR, 1.20 per 10 μg/m
; 95% CI, 1.01-1.43), carbon monoxide (HR, 1.29 per 1,000 ppb; 95% CI, 0.99-1.67), and regional benzene (HR, 1.17 per 1 ppb; 95% CI, 1.02-1.34) exposures. These patterns of associations were driven by associations among African American and Latino American groups. There was no formal evidence for heterogeneity of effects by nSES (
heterogeneity > 0.21), although participants residing in low-SES neighborhoods had increased lung cancer risk associated with nitrogen oxides, and no association was observed among those in high-SES neighborhoods.
These findings in a large multiethnic population reflect an association between lung cancer and the mixture of traffic-related air pollution and not a particular individual pollutant. They are consistent with the adverse effects of air pollution that have been described in less racially, ethnically, and socioeconomically diverse populations. Our results also suggest an increased risk of lung cancer among those residing in low-SES neighborhoods.
Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute to T2D risk, the functional effects of the mtDNA ...polymorphisms and the therapeutic potential of mitochondrial-derived peptides at the mtDNA polymorphisms are underexplored. Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D. In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization
. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.
Endometrial cancer is the second most common cancer among female cancer survivors in the United States. Cardiovascular disease is the leading cause of death among endometrial cancer survivors. ...Studies that examine long-term cardiovascular outcomes among endometrial cancer survivors are critical.
Cohorts of 2648 endometrial cancer survivors diagnosed between 1997 and 2012 and 10 503 age-matched women from the general population were identified. Cardiovascular disease diagnoses were identified from electronic medical records and statewide ambulatory surgery and statewide inpatient data. Cox regression models were used to estimate hazard ratios (HRs) at one to five years, more than five to 10 years, and more than 10 years after cancer diagnosis.
Between one and five years after diagnosis, increased cardiovascular risks among endometrial cancer survivors were observed for phlebitis, thrombophlebitis, and thromboembolism (HR = 2.07, 99% confidence interval CI = 1.57 to 2.72), pulmonary heart disease (HR = 1.74, 99% CI = 1.26 to 2.40), and atrial fibrillation (HR = 1.50, 99% CI = 1.07 to 2.11). At more than five to 10 years, some elevated risk persisted for cardiovascular diseases. Compared with patients who had surgery, patients who additionally had radiation therapy and/or chemotherapy were at increased risk for heart and circulatory system disorders between one and five years after cancer diagnosis. Older age and obesity were also risk factors for hypertension and heart disease among endometrial cancer survivors.
Endometrial cancer survivors are at higher risk for various adverse long-term cardiovascular outcomes compared with women from the general population. This study suggests that increased monitoring for cardiovascular diseases may be necessary for endometrial cancer patients for 10 years after cancer diagnosis.
Abstract Context The distribution of body fat has been linked to circulating levels of lipids and sex steroid hormones. The cholesterol metabolite and endogenous selective estrogen receptor ...modulator, 27-hydroxychlolesterol (27HC), may be influenced by adiposity phenotypes, particularly among females. No study has examined the relationships of 27HC with adiposity phenotypes. Objective To investigate the associations of 27HC and steroid hormones with detailed adiposity phenotypes among a multiethnic population of postmenopausal women. Methods A cross-sectional study was conducted among 912 postmenopausal women from the Multiethnic Cohort Adiposity Phenotype study. Multivariable linear regression examined the associations of circulating levels of 27HC, steroid hormones, and sex hormone–binding globulin (SHBG) with detailed adiposity phenotypes, adjusting for demographics, lifestyle factors, diabetes status, and use of lipid-lowering drugs. Subgroup analyses were conducted across race and ethnicity. Results Total fat mass (P trend = .003), subcutaneous adipose tissue (SAT) (P trend = .006), and superficial subcutaneous adipose tissue (P trend = 4.41 × 10−4) were inversely associated with circulating 27HC levels. In contrast, visceral adipose tissue (VAT) (P trend = .003) and liver fat (P trend = .005) were positively associated with 27HC levels. All adiposity phenotypes were associated with higher levels of free estradiol and testosterone and lower levels of SHBG. Generally, similar patterns of associations were observed across race and ethnicity. Conclusion Adiposity phenotypes, such as SAT, VAT, and liver fat, were differentially associated with circulating 27HC, while consistent directions of associations were seen for circulating hormones among postmenopausal women. Future studies are warranted to further understand the biology and relationships of 27HC and adiposity-related diseases.
Ultrafine particles (UFP; diameter less than or equal to 100 nm) may reach the brain via systemic circulation or the olfactory tract and have been implicated in the risk of brain tumors. The effects ...of airport-related UFP on the risk of brain tumors are not known. Here we determined the association between airport-related UFP and risk of incident malignant brain cancer (
= 155) and meningioma (
= 420) diagnosed during 16.4 years of follow-up among 75,936 men and women residing in Los Angeles County from the Multiethnic Cohort study. UFP exposure from aircrafts was estimated for participants who lived within a 53 km × 43 km grid area around the Los Angeles International Airport (LAX) from date of cohort entry (1993-1996) through December 31, 2013. Cox proportional hazards models were used to estimate the effects of time-varying, airport-related UFP exposure on risk of malignant brain cancer and meningioma, adjusting for sex, race/ethnicity, education, and neighborhood socioeconomic status. Malignant brain cancer risk in all subjects combined increased 12% 95% confidence interval (CI), 0.98-1.27 per interquartile range (IQR) of airport-related UFP exposure (∼6,700 particles/cm
) for subjects with any address in the grid area surrounding the LAX airport. In race/ethnicity-stratified analyses, African Americans, the subgroup who had the highest exposure, showed a HR of 1.32 (95% CI, 1.07-1.64) for malignant brain cancer per IQR in UFP exposure. UFP exposure was not related to risk of meningioma overall or by race/ethnicity. These results support the hypothesis that airport-related UFP exposure may be a risk factor for malignant brain cancers. SIGNIFICANCE: Malignant brain cancer risk increases with airport-related UFP exposure, particularly among African Americans, suggesting UFP exposure may be a modifiable risk factor for malignant brain cancer.
Purpose
The purpose of the study was to investigate the association of type 2 diabetes (T2D) with survival of breast cancer (BC) patients across five ethnic groups within the Multiethnic Cohort ...study.
Methods
Between recruitment in 1993–1996 and 2013, 7570 incident BC cases were identified through SEER cancer registries in Hawaii and California. T2D diagnosed before BC was ascertained in 1013 women from self-reports and confirmed by administrative data sources. Covariate information was collected by questionnaire. Cox regression analysis with age as the time metric and BMI as time-varying exposure was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for BC-specific and all-cause survival while adjusting for known prognostic factors.
Results
In total, 2119 all-cause and 730 BC-specific deaths were recorded with corresponding 5-year survival rates of 86 and 93%. T2D was not a significant predictor of BC-specific survival (HR 0.84; 95% CI 0.65–1.09), but mortality was 36% lower for those with < 7 years of T2D than a longer history of T2D. On the other hand, all-cause mortality was higher in women with T2D (HR 1.23; 95% CI 1.08–1.40), especially in women with T2D of ≥ 7 years duration (HR 1.27; 95% CI 1.07–1.49). In women receiving none or either chemotherapy or radiation but not both, T2D predicted higher all-cause mortality (
P
interaction
= 0.004). Variations in the association of T2D with mortality across ethnic groups were small.
Conclusions
T2D was associated with higher all-cause but not BC-specific mortality among women with BC in the Multiethnic Cohort study. However, T2D affected survival in cases who did not receive both radiation and chemotherapy.
PDF
