We compared fat storage in the abdominal region among individuals from 5 different ethnic–racial groups to determine whether fat storage is associated with disparities observed in metabolic syndrome ...and other obesity-associated diseases.
We collected data from 1794 participants in the Multiethnic Cohort Study (60–77 years old; of African, European white, Japanese, Latino, or Native Hawaiian ancestry) with body mass index values of 17.1–46.2 kg/m2. From May 2013 through April 2016, participants visited the study clinic to undergo body measurements, an interview, and a blood collection. Participants were evaluated by dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging. Among ethnic groups, we compared adiposity of the trunk, intra-abdominal visceral cavity, and liver, adjusting for total fat mass; we evaluated the association of adult weight change with abdominal adiposity; and we examined the prevalence of metabolic syndrome mediated by abdominal adiposity.
Relative amounts of trunk, visceral, and liver fat varied significantly with ethnicity—they were highest in Japanese Americans, lowest in African Americans, and intermediate in the other groups. Compared with African Americans, the mean visceral fat area was 45% and 73% greater in Japanese American men and women, respectively, and the mean measurements of liver fat were 61% and 122% greater in Japanese American men and women. The visceral and hepatic adiposity associated with weight gain since participants were 21 years old varied in a similar pattern among ethnic–racial groups. In the mediation analysis, visceral and liver fat jointly accounted for a statistically significant fraction of the difference in metabolic syndrome prevalence, compared with white persons, for African Americans, Japanese Americans, and Native Hawaiian women, independently of total fat mass.
In an analysis of data from the participants in the Multiethnic Cohort Study, we found extensive differences among ethnic–racial groups in the propensity to store fat intra-abdominally. This observation should be considered by clinicians in the prevention and early detection of metabolic disorders.
It has been recently hypothesized that many of the signals detected in genome-wide association studies (GWAS) to T2D and other diseases, despite being observed to common variants, might in fact ...result from causal mutations that are rare. One prediction of this hypothesis is that the allelic associations should be population-specific, as the causal mutations arose after the migrations that established different populations around the world. We selected 19 common variants found to be reproducibly associated to T2D risk in European populations and studied them in a large multiethnic case-control study (6,142 cases and 7,403 controls) among men and women from 5 racial/ethnic groups (European Americans, African Americans, Latinos, Japanese Americans, and Native Hawaiians). In analysis pooled across ethnic groups, the allelic associations were in the same direction as the original report for all 19 variants, and 14 of the 19 were significantly associated with risk. In summing the number of risk alleles for each individual, the per-allele associations were highly statistically significant (P<10(-4)) and similar in all populations (odds ratios 1.09-1.12) except in Japanese Americans the estimated effect per allele was larger than in the other populations (1.20; P(het) = 3.8×10(-4)). We did not observe ethnic differences in the distribution of risk that would explain the increased prevalence of type 2 diabetes in these groups as compared to European Americans. The consistency of allelic associations in diverse racial/ethnic groups is not predicted under the hypothesis of Goldstein regarding "synthetic associations" of rare mutations in T2D.
Background: As the proportion of visceral (VAT) to subcutaneous adipose tissue (SAT) may contribute to type 2 diabetes (T2D) development, we examined this relation in a cross-sectional design within ...the Multiethnic Cohort that includes Japanese Americans known to have high VAT. The aim was to understand how ectopic fat accumulation differs by glycemic status across ethnic groups with disparate rates of obesity, T2D, and propensity to accumulate VAT.Methods: In 2013–2016, 1,746 participants aged 69.2 (standard deviation, 2.7) years from five ethnic groups completed questionnaires, blood collections, and whole-body dual X-ray absorptiometry and abdominal magnetic resonance imaging scans. Participants with self-reported T2D and/or medication were classified as T2D, those with fasting glucose >125 and 100–125 mg/dL as undiagnosed cases (UT2D) and prediabetes (PT2D), respectively. Using linear regression, we estimated adjusted means of adiposity measures by T2D status.Results: Overall, 315 (18%) participants were classified as T2D, 158 (9%) as UT2D, 518 (30%) as PT2D, and 755 (43%) as normoglycemic (NG), with significant ethnic differences (P < 0.0001). In fully adjusted models, VAT, VAT/SAT, and percent liver fat increased significantly from NG, PT2D, UT2D, to T2D (P < 0.001). Across ethnic groups, the VAT/SAT ratio was lowest for NG participants and highest for T2D cases. Positive trends were observed in all groups except African Americans, with highest VAT/SAT in Japanese Americans.Conclusion: These findings indicate that VAT plays an important role in T2D etiology, in particular among Japanese Americans with high levels of ectopic adipose tissue, which drives the development of T2D to a greater degree than in other ethnic groups.
Trimethylamine N-oxide (TMAO), a compound derived from diet and metabolism by the gut microbiome, has been associated with several chronic diseases, although the mechanisms of action are not well ...understood and few human studies have investigated microbes involved in its production.
Our study aims were 1) to investigate associations of TMAO and its precursors (choline, carnitine, and betaine) with inflammatory and cardiometabolic risk biomarkers; and 2) to identify fecal microbiome profiles associated with TMAO.
We conducted a cross-sectional analysis using data collected from 1653 participants (826 men and 827 women, aged 60–77 y) in the Multiethnic Cohort Study. Plasma concentrations of TMAO and its precursors were measured by LC-tandem MS. We also analyzed fasting blood for markers of inflammation, glucose and insulin, cholesterol, and triglycerides (TGs), and further measured blood pressure. Fecal microbiome composition was evaluated by sequencing the 16S ribosomal RNA gene V1–V3 region. Associations of TMAO and its precursors with disease risk biomarkers were assessed by multivariable linear regression, whereas associations between TMAO and the fecal microbiome were assessed by permutational multivariate ANOVA and hurdle regression models using the negative binomial distribution.
Median (IQR) concentration of plasma TMAO was 3.05 μmol/L (2.10–4.60 μmol/L). Higher concentrations of TMAO and carnitine, and lower concentrations of betaine, were associated with greater insulin resistance (all P < 0.02). Choline was associated with higher systolic blood pressure, TGs, lipopolysaccharide-binding protein, and lower HDL cholesterol (P ranging from <0.001 to 0.03), reflecting an adverse cardiometabolic risk profile. TMAO was associated with abundance of 13 genera (false discovery rate < 0.05), including Prevotella, Mitsuokella, Fusobacterium, Desulfovibrio, and bacteria belonging to the families Ruminococcaceae and Lachnospiraceae, as well as the methanogen Methanobrevibacter smithii.
Plasma TMAO concentrations were associated with a number of trimethylamine-producing bacterial taxa, and, along with its precursors, may contribute to inflammatory and cardiometabolic risk pathways.
Abstract
To investigate the association of alcohol intake with colorectal cancer risk according to race/ethnicity as well as sex, lifestyle-related factors, alcoholic beverage type, and anatomical ...subsite, we analyzed data from 190,698 black, Native Hawaiian, Japanese-American, Latino, and white persons in Hawaii and California in the Multiethnic Cohort Study, with 4,923 incident cases during a 16.7-year follow-up period (1993–2013). In multivariate Cox regression models, the hazard ratio was 1.16 (95% confidence interval (CI): 1.01, 1.34) for 15.0–29.9 g/day of alcohol and 1.28 (95% CI: 1.12, 1.45) for ≥30.0 g/day among men, and 1.06 (95% CI: 0.85, 1.32) and 1.15 (95% CI: 0.92, 1.43), respectively, among women, compared with nondrinkers (P for heterogeneity according to sex = 0.74). An increased risk was apparent among Native Hawaiians, Japanese Americans, Latinos, and white persons and among individuals with body mass index <25.0 (calculated as weight (kg)/height (m)2), never-users of nonsteroidal antiinflammatory drugs, and those with lower intake of dietary fiber and folate. Beer and wine, but not liquor, consumption was positively related to colorectal cancer risk. The association was stronger for rectum and left-colon tumors than for right-colon tumors. Our findings suggest that the positive association between alcohol and colorectal cancer varies according to race/ethnicity, lifestyle factors, alcoholic beverage type, and anatomical subsite of tumors.
We previously developed a prediction score for MRI-quantified abdominal visceral adipose tissue (VAT) based on concurrent measurements of height, body mass index (BMI), and nine blood biomarkers, for ...optimal performance in five racial/ethnic groups. Here we evaluated the VAT score for prediction of future VAT and examined if enhancement with additional biomarkers, lifestyle behavior information, and medical history improves the prediction. We examined 500 participants from the Multiethnic Cohort (MEC) with detailed data (age 50-66) collected 10 years prior to their MRI assessment of VAT. We generated three forecasted VAT prediction models: first by applying the original VAT equation to the past data on the predictors ("original"), second by refitting the past data on anthropometry and biomarkers ("refit"), and third by building a new prediction model based on the past data enhanced with lifestyle and medical history ("enhanced"). We compared the forecasted prediction scores to future VAT using the coefficient of determination (R.sup.2). In independent nested case-control data in MEC, we applied the concurrent and forecasted VAT models to assess association of the scores with subsequent incident breast cancer (950 pairs) and colorectal cancer (831 pairs). Compared to the VAT prediction by the concurrent VAT score (R.sup.2 = 0.70 in men, 0.68 in women), the forecasted original VAT score (R.sup.2 = 0.54, 0.48) performed better than past anthropometry alone (R.sup.2 = 0.47, 0.40) or two published scores (VAI, METS-VF). The forecasted refit (R.sup.2 = 0.61, 0.51) and enhanced (R.sup.2 = 0.62, 0.55) VAT scores each showed slight improvements. Similar to the concurrent VAT score, the forecasted VAT scores were associated with breast cancer, but not colorectal cancer. Both the refit score (adjusted OR for tertile 3 vs. 1 = 1.27; 95% CI: 1.00-1.62) and enhanced score (1.27; 0.99-1.62) were associated with breast cancer independently of BMI. Predicted VAT from midlife data can be used as a surrogate to assess the effect of VAT on incident diseases associated with obesity, as illustrated for postmenopausal breast cancer.
Visceral adipose tissue (VAT) may play a greater role than subcutaneous fat in increasing cancer risk but is poorly estimated in epidemiologic studies.
We developed a VAT prediction score by ...regression equations averaged across 100 least absolute shrinkage and selection operator models in a cross-sectional study of 1,801 older adults in the Multiethnic Cohort (MEC). The score was then used as proxy for VAT in case-control studies of postmenopausal breast (950 case-control pairs) and colorectal (831 case-control pairs) cancer in an independent sample in MEC. Abdominal MRI-derived VAT; circulating biomarkers of metabolic, hormonal, and inflammation dysfunctions; and ORs for incident cancer adjusted for BMI and other risk factors were assessed.
The final score, composed of nine biomarkers, BMI, and height, explained 11% and 15% more of the variance in VAT than BMI alone in men and women, respectively. The area under the receiver operator curve for VAT >150 cm
was 0.90 in men and 0.86 in women. The VAT score was associated with risk of breast cancer OR (95% confidence interval CI) by increasing tertiles: 1.00, 1.09 (0.86-1.39), 1.48 (1.16-1.89);
= 0.002 but not with colorectal cancer (
= 0.84), although an association 1.00, 0.98 (0.68-1.39), 1.24 (0.88-1.76);
= 0.08 was suggested for this cancer after excluding cases that occurred within 7 years of blood draw (
= 0.06).
The VAT score predicted risks of postmenopausal breast cancer and can be used for risk assessment in diverse populations.
These findings provide specific evidence for a role of VAT in breast cancer.
Variation in gut microbial community structure is partly attributed to variations in diet. A priori dietary indexes capture diet quality and have been associated with chronic disease risk.
The aim of ...this study was to examine the association of diet quality, as assessed by the Healthy Eating Index, Alternative Healthy Eating Index-2010, alternate Mediterranean Diet, and the Dietary Approaches to Stop Hypertension Trial, with measures of fecal microbial community structure assessed in the Adiposity Phenotype Study (APS), an ethnically diverse study population with varied food intakes.
Multiethnic Cohort Study members completed a validated quantitative food frequency questionnaire (QFFQ) at cohort entry (1993–1996) and, for the APS subset, at clinic visit (2013–2015), when they also provided a stool sample. DNA was extracted from stool, and the V1-V3 region of the 16S rRNA gene was amplified and sequenced. Dietary index scores were computed based on the QFFQ and an extensive nutritional database. Using linear regression adjusted for relevant covariates, we estimated associations of dietary quality with microbiome measures and computed adjusted mean values of microbial measures by tertiles of dietary index scores.
The 858 men and 877 women of white, Japanese American, Latino, Native Hawaiian, and African American ancestry had a mean age of 69.2 years at stool collection. Alpha diversity according to the Shannon index increased by 1–2% across tertiles of all 4 diet indexes measured at clinic visit. The mean relative abundance of the phylum Actinobacteria was 13–19% lower with higher diet quality across all 4 indexes (difference between tertile 3 and tertile 1 divided by tertile 1). Of the 104 bacterial genera tested, 21 (primarily from the phylum Firmicutes) were positively associated with at least 1 index after Bonferroni adjustment.
Diet quality was strongly associated with fecal microbial alpha diversity and beta diversity and several genera previously associated with human health.
Abstract
Background
Diabetes has been proposed to be a risk factor for and a consequence of pancreatic cancer (PC). The relationship between recent-onset diabetes and PC is not well understood, and ...data in minorities are sparse. We examined the relationships between recent-onset diabetes and PC incidence in African Americans and Latinos in the Multiethnic Cohort.
Methods
A total of 48 995 African Americans and Latinos without prior diabetes and cancer at baseline (1993–1996) were included in the study. Questionnaires, Medicare data, and California hospital discharge files were used to identify new diabetes diagnoses. Cox regressions were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer associated with diabetes and with diabetes duration.
Results
A total of 15 833 (32.3%) participants developed diabetes between baseline and 2013. A total of 408 incident PC cases were identified during follow-up. Diabetes was associated with PC (HRage75 = 2.39, 95% CI = 1.91 to 2.98). Individuals with recent-onset diabetes (within three or fewer years of PC diagnosis) had a greater risk compared with those with long-term diabetes across all ages. The HRage75 for recent-onset diabetes was 4.08 (95% CI = 2.76 to 6.03) in Latinos and 3.38 (95% CI = 2.30 to 4.98) in African Americans.
Conclusions
Diabetes was associated with a more than twofold higher risk of PC in African Americans and Latinos, but recent-onset diabetes was associated with a 2.3-fold greater increase in risk of PC than long-standing diabetes. Our findings support the hypothesis that recent-onset diabetes is a manifestation of PC and that long-standing diabetes is a risk factor for this malignancy.
Latinos are the largest minority group in the United States. We assessed cancer mortality by birthplace and generation status of Mexican Latinos in the Multiethnic Cohort.
We included 26 751 Latinos ...of Mexican origin and 6093 non-Latino Whites aged 45-74 years at cohort entry (1993-1996) from the California Multiethnic Cohort component. The Mexican Latinos comprised 42% first-generation Mexico-born immigrants, 42% second-generation (28% US-born with both parents Mexico-born and 14% US-born with 1 parent US-born and 1 parent Mexico-born), and 16% third-generation or more who were US-born with both parents US-born. Multivariable Cox models were used to calculate covariate adjusted hazard ratios and 95% confidence intervals for overall and site-specific cancer mortality by birthplace and generation status. All statistical tests were 2-sided.
Cancer death rate was highest among the US-born with 1 parent US-born and 1 parent Mexico-born (age-adjusted rate = 471.0 per 100 000 person-years) and US-born with both parents US-born (age-adjusted rate = 469.0 per 100 000 person-years) groups. The US-born with both parents Mexico-born group had a 30% (hazard ratio = 1.30, 95% confidence interval = 1.18 to 1.44) higher risk of cancer death than the first-generation Mexico-born immigrants group, showing US birthplace was associated with an elevated cancer mortality. For cancer-specific mortality, US birthplace was positively associated with colorectal, liver and lung, and ovarian cancer (P values ranged from .04 to .005). Among US-born Mexican Latinos, generation status was not statistically significantly associated with overall cancer or site-specific cancer mortality.
Our findings suggest that US birthplace is a risk factor for cancer death in Mexican Americans. Identification of the contributing factors is important to curtail patterns of increasing cancer mortality in US-born Mexican Latinos.
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