Racial differences in metabolomic profiles may reflect underlying differences in social determinants of health by self-reported race and may be related to racial disparities in coronary heart disease ...(CHD) among women in the United States. However, the magnitude of differences in metabolomic profiles between Black and White women in the United States has not been well-described. It also remains unknown whether such differences are related to differences in CHD risk.
Plasma metabolomic profiles were analyzed using liquid chromatography-tandem mass spectrometry in the WHI-OS (Women's Health Initiative-Observational Study; 138 Black and 696 White women), WHI-HT trials (WHI-Hormone Therapy; 156 Black and 1138 White women), MESA (Multi-Ethnic Study of Atherosclerosis; 114 Black and 219 White women), JHS (Jackson Heart Study; 1465 Black women with 107 incident CHD cases), and NHS (Nurses' Health Study; 2506 White women with 136 incident CHD cases). First, linear regression models were used to estimate associations between self-reported race and 472 metabolites in WHI-OS (discovery); findings were replicated in WHI-HT and validated in MESA. Second, we used elastic net regression to construct a racial difference metabolomic pattern (RDMP) representing differences in the metabolomic patterns between Black and White women in the WHI-OS; the RDMP was validated in the WHI-HT and MESA. Third, using conditional logistic regressions in the WHI (717 CHD cases and 719 matched controls), we examined associations of metabolites with large differences in levels by race and the RDMP with risk of CHD, and the results were replicated in Black women from the JHS and White women from the NHS.
Of the 472 tested metabolites, levels of 259 (54.9%) metabolites, mostly lipid metabolites and amino acids, significantly differed between Black and White women in both WHI-OS and WHI-HT after adjusting for baseline characteristics, socioeconomic status, lifestyle factors, baseline health conditions, and medication use (false discovery rate <0.05); similar trends were observed in MESA. The RDMP, composed of 152 metabolites, was identified in the WHI-OS and showed significantly different distributions between Black and White women in the WHI-HT and MESA. Higher RDMP quartiles were associated with an increased risk of incident CHD (odds ratio=1.51 0.97-2.37 for the highest quartile comparing to the lowest;
=0.02), independent of self-reported race and known CHD risk factors. In race-stratified analyses, the RDMP-CHD associations were more pronounced in White women. Similar patterns were observed in Black women from the JHS and White women from the NHS.
Metabolomic profiles significantly and substantially differ between Black and White women and may be associated with CHD risk and racial disparities in US women.
Aim
Pleistocene climate and associated environmental changes have influenced phylogeographic patterns of many species. These not only depend on a species’ life history but also vary regionally. ...Consequently, populations of widespread species that occur in several biomes might display different evolutionary trajectories. We aimed to identify regional drivers of diversification in the common pheasant, a widely distributed ecological generalist.
Location
Asia.
Taxon
Common pheasant Phasianus colchicus.
Methods
Using a comprehensive geographical sampling of 204 individuals from the species’ entire range genotyped at seven nuclear and two mitochondrial loci, we reconstructed spatio‐temporal diversification and demographic history of the common pheasant. We applied Bayesian phylogenetic inference to describe phylogeographic structure, generated a species tree and inferred demographic history within and migration between lineages. Moreover, to establish a taxonomic framework, we conducted a species delimitation analysis.
Results
The common pheasant diversified during the Late Pleistocene into eight distinct lineages. It originated at the edge of the Qinghai–Tibetan plateau and spread to East and Central Asia. Only the widely distributed lowland lineage of East Asia displayed recent range expansion. Greater phylogeographic structure was identified elsewhere, with lineages showing no sign of recent demographic changes. One lineage in south‐central China is the result of long‐term isolation within a climatically stable but topographically complex region. In lineages from arid Central Asia and China, range expansions were impeded by repeated population fragmentation during dry glacial periods and by recent aridification.
Main conclusions
Spatio‐temporal phylogeographic frameworks of widespread taxa such as the common pheasant provide valuable opportunities to identify divergent drivers of regional diversification. Our results suggest that diversification and population histories in the eight distinct evolutionary lineages were shaped by regionally variable effects of past climate and associated environmental changes. The evolutionary history of the common pheasant is best reflected by its being split into three species.
Type 2 diabetes is a major public health concern in the United States and worldwide. The dietary inflammatory index (DII) and the energy-adjusted DII (E-DII) are tools that assess dietary ...inflammation. Previous evidence suggests that obesity can modify the association between inflammation and disease.
The aim of this study was to evaluate the association between the DII/E-DII and incident diabetes in self-identified Hispanic women from the Women's Health Initiative (WHI). The secondary aim was to evaluate whether obesity modifies the association between the DII/E-DII scores and incident diabetes.
Participants were from the WHI Observational Study and the Clinical Trial Components (except women from the treatment arm in the Dietary Modification Trial) conducted among postmenopausal women in the United States. DII/E-DII scores were calculated from a self-administered food frequency questionnaire at baseline that included 122 food items, of which 12 are representative of Hispanic eating patterns.
Participants included 3,849 postmenopausal women who self-identified as Hispanic that were recruited for the WHI from 1993 to 1998 at 40 US clinical centers.
The outcome was incident diabetes.
Cox regression models were used to assess the association between DII/E-DII and incident diabetes. Models were adjusted for age at baseline, lifestyle-related risk factors, known type 2 diabetes mellitus (T2DM) risk factors, and neighborhood socioeconomic status. Interaction was tested between the DII/E-DII scores and obesity.
The incidence of diabetes was 13.1% after a median follow-up of 13 years. Higher E-DII scores were associated with a higher risk of incident diabetes (hazard ratio HR, 1.09; 95% confidence interval CI, 1.04-1.14). There was no interaction between E-DII scores and obesity (P = 0.73).
Pro-inflammatory diets, as measured by higher E-DII scores, were associated with a higher risk of incident diabetes. Future research is needed for understanding how the inflammatory potential of diets can be decreased.
Insulin Sensitivity and Insulin Secretion Determined by Homeostasis Model Assessment and Risk of Diabetes in a Multiethnic
Cohort of Women
The Women's Health Initiative Observational Study
Yiqing ...Song , MD, SCD 1 ,
JoAnn E. Manson , MD, DRPH 1 2 ,
Lesley Tinker , PHD, RD 3 ,
Barbara V. Howard , PHD 4 ,
Lewis H. Kuller , MD, DRPH 5 ,
Lauren Nathan , MD 6 ,
Nader Rifai , PHD 7 and
Simin Liu , MD, SCD 1 2 8 9
1 Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
2 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
3 Public Health Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
4 MedStar Research Institute, Washington, D.C.
5 Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
6 Department of Obstetrics and Gynecology, University of California, Los Angeles, Los Angeles, California
7 Children's Hospital, Boston, Massachusetts
8 Department of Epidemiology, University of California, Los Angeles, School of Public Health, Los Angeles, California
9 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
Address correspondence and reprint requests to Prof. Simin Liu, Department of Epidemiology, UCLA School of Public Health,
Box 951772, 650 Charles E. Young Dr. South, Los Angeles, CA 90095. E-mail: siminliu{at}ucla.edu
Abstract
OBJECTIVE — The homeostasis model assessment (HOMA), based on plasma levels of fasting glucose and insulin, has been widely validated
and applied for quantifying insulin resistance and β-cell function. However, prospective data regarding its relation to diabetes
risk in ethnically diverse populations are limited.
RESEARCH DESIGN AND METHODS — Among 82,069 women who were aged 50–79 years, free of cardiovascular disease or diabetes, and participating in the Women's
Health Initiative Observational Study, we conducted a nested case-control study to prospectively examine the relations of
HOMA of insulin resistance (HOMA-IR) and β-cell function (HOMA-B) with diabetes risk. During a median follow-up period of
5.9 years, 1,584 diabetic patients were matched with 2,198 control subjects by age, ethnicity, clinical center, time of blood
draw, and follow-up time.
RESULTS — Baseline levels of fasting glucose, insulin, and HOMA-IR were each significantly higher among case compared with control
subjects, while HOMA-B was lower (all P values <0.0001). After adjustment for matching factors and diabetes risk factors, all four markers were significantly associated
with diabetes risk; the estimated relative risks per SD increment were 3.54 (95% CI 3.02–4.13) for fasting glucose, 2.25 (1.99–2.54)
for fasting insulin, 3.40 (2.95–3.92) for HOMA-IR, and 0.57(0.51–0.63) for HOMA-B. While no statistically significant multiplicative
interactions were observed between these markers and ethnicity, the associations of both HOMA-IR and HOMA-B with diabetes
risk remained significant and robust in each ethnic group, including whites, blacks, Hispanics, and Asians/Pacific Islanders.
When evaluated jointly, the relations of HOMA-IR and HOMA-B with diabetes risk appeared to be independent and additive. HOMA-IR
was more strongly associated with an increased risk than were other markers after we excluded those with fasting glucose ≥126
mg/dl at baseline.
CONCLUSIONS — High HOMA-IR and low HOMA-B were independently and consistently associated with an increased diabetes risk in a multiethnic
cohort of U.S. postmenopausal women. These data suggest the value of HOMA indexes for diabetes risk in epidemiologic studies.
HOMA, homeostasis model assessment
HOMA-B, HOMA of β-cell function
HOMA-IR, HOMA of insulin resistance
IGT, impaired glucose tolerance
NGT, normal glucose tolerance
WHI-OS, Women's Health Initiative Observational Study
Footnotes
Published ahead of print at http://care.diabetesjournals.org on 27 April 2007. DOI: 10.2337/dc07-0358.
Additional information for this article, as well as a list of WHI investigators, can be viewed in an online appendix at http://dx.doi.org/10.2337/dc07-0358 .
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
Accepted April 14, 2007.
Received February 20, 2007.
DIABETES CARE
Abstract only Introduction: There are known sex and race differences in the risk of incident ischemic stroke (IS) associated with diabetes mellitus (DM), but the mechanism is unclear. To explore the ...role of impaired glucose metabolism in such differences, we aimed to determine if there are differences in the risk of IS across increasing fasting blood glucose (FBG) by race/sex subgroups. Methods: We analyzed data from black and white adults age ≥45 years at baseline (2003-2007) without a history of stroke from the Reasons for Geographic And Racial Differences in Stroke Study, a national longitudinal cohort. Data on age, race, sex, FBG, and DM medications was collected at baseline, and IS events were ascertained by phone every 6 months with physician adjudication of suspected events through September 2018. Cox proportional hazards regression was used to assess the association between FBG (<100 (ref), 100-125, 126-150, >150 mg/dL) and IS in sex/race groups (white women (WW), black women (BW), white men (WM), black men (BM)), stratified by DM medication use (DM medication use vs. no DM medication use) after adjustment for demographics, comorbidities, education, and income . Results: Of the 20,338 participants, mean age was 64.5(SD 9.3) years, 38.7% were black, 55.4% were women and 16.2% were using DM medications. There were 954 events. Of those on DM medication, the association between FBG and IS varied by race/sex (adjusted hazard ratios for FBG > 150 compared to FBG <100: WW 3.30 (95% CI 1.20, 9.10), BW 2.02 (95%CI 1.06, 3.87), BM 1.24 (95%CI 0.63, 2.46), WM 1.08 (95%CI 0.53, 2.17), p=0.08). Among those not on diabetes medications, IS risk across FBG did not vary by race/sex (p=0.36) (Table). Conclusions: Among those using diabetes medications, the magnitude of the association of increasing FBG with incident IS is highest among white women compared with other race/sex subgroups, suggesting possible race and sex differences in the role of impaired glucose metabolism in stroke risk.
Although diet response prediction for cardiometabolic risk factors (CRFs) has been demonstrated using single genetic variants and main-effect genetic risk scores, little investigation has gone into ...the development of genome-wide diet response scores.
We sought to leverage the multistudy setup of the Women’s Health Initiative cohort to generate and test genetic scores for the response of 6 CRFs (BMI, systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, and fasting glucose) to dietary fat.
A genome-wide interaction study was undertaken for each CRF in women (n ∼ 9000) not participating in the dietary modification (DM) trial, which focused on the reduction of dietary fat. Genetic scores based on these analyses were developed using a pruning-and-thresholding approach and tested for the prediction of 1-y CRF changes as well as long-term chronic disease development in DM trial participants (n ∼ 5000).
Only 1 of these genetic scores, for LDL cholesterol, predicted changes in the associated CRF. This 1760-variant score explained 3.7% (95% CI: 0.09, 11.9) of the variance in 1-y LDL cholesterol changes in the intervention arm but was unassociated with changes in the control arm. In contrast, a main-effect genetic risk score for LDL cholesterol was not useful for predicting dietary fat response. Further investigation of this score with respect to downstream disease outcomes revealed suggestive differential associations across DM trial arms, especially with respect to coronary heart disease and stroke subtypes.
These results lay the foundation for the combination of many genome-wide gene-diet interactions for diet response prediction while highlighting the need for further research and larger samples in order to achieve robust biomarkers for use in personalized nutrition.
Familial dysalbuminemic hyperthyroxinemia (FDH) is a rare autosomal dominant disorder whose clinical characteristics remain incompletely understood, we investigated the role of albumin gene mutation ...in relation to miscarriage rate in a large pedigree of FDH followed up for 4 years.
The proband and extended family with unexplained miscarriage and hyperthyroxinemia were identified and genotypes in candidate genes and thyroid function tests (TFTs), including changes in TFTs during pregnancy were comprehensively assessed. We also evaluated the development and growth of children in this large FDH pedigree during four years follow-up.
The R218S variant in the albumin gene was identified in the proband and her relatives with hyperthyroxinemia who were diagnosed as FDH. Among the family members who underwent TFTs, 11 of 17 (65%) had similar changes in levels of thyroid hormone, with an estimated FDH heritability of 86%. Moreover, 32% (95% CI 16-54%) of FDH women experienced miscarriages at a rate that was substantially higher than the spontaneous abortion rate reported in the general population in China (7-14%). During the follow-up, results revealed that free triiodothyronine (fT3) and thyroid stimulating hormone (TSH) levels were normal during the entire gestational period; comparing to their age-adjusted peers, both FDH affected and FDH unaffected children in this pedigree appeared to have lower body weight and height.
Albumin gene variant (R218S) not only causes FDH but also may be associated with a higher risk of miscarriages, although the growth of their children appears not to be affected by the age of 2 years.
BACKGROUND Much uncertainty exists about the role of dietary glycemic index and glycemic load in the development of type 2 diabetes mellitus, especially in populations that traditionally subsist on a ...diet high in carbohydrates. METHODS We observed a cohort of 64 227 Chinese women with no history of diabetes or other chronic disease at baseline for 4.6 years. In-person interviews were conducted to collect data on dietary habits, physical activity, and other relevant information using a validated questionnaire. Incident diabetes cases were identified via in-person follow-up. Associations between dietary carbohydrate intake, glycemic index, and glycemic load and diabetes incidence were evaluated using multivariable Cox proportional hazards models. RESULTS We identified 1608 incident cases of type 2 diabetes mellitus in 297 755 person-years of follow-up. Dietary carbohydrate intake and consumption of rice were positively associated with risk of developing type 2 diabetes mellitus. The multivariable-adjusted estimates of relative risk comparing the highest vs the lowest quintiles of intake were 1.28 (95% confidence interval, 1.09-1.50) for carbohydrates and 1.78 (95% confidence interval, 1.48-2.15) for rice. The relative risk for increasing quintiles of intake was 1.00, 1.04, 1.02, 1.09, and 1.21 (95% confidence interval, 1.03-1.43) for dietary glycemic index and 1.00, 1.06, 0.97, 1.23, and 1.34 (95% confidence interval, 1.13-1.58) for dietary glycemic load. CONCLUSION High intake of foods with a high glycemic index and glycemic load, especially rice, the main carbohydrate-contributing food in this population, may increase the risk of type 2 diabetes mellitus in Chinese women.Arch Intern Med. 2007;167(21):2310-2316-->
Although gestational diabetes mellitus and delivering high-birthweight infants are known to predict a higher risk of future type 2 diabetes mellitus, the association of hypertensive disorders of ...pregnancy and other adverse pregnancy outcomes with type 2 diabetes mellitus is not well established.
This study aimed to examine the associations between different types of adverse pregnancy outcomes and incident type 2 diabetes mellitus among postmenopausal women.
The Women's Health Initiative, a nationwide cohort of postmenopausal women, collected self-reported history of adverse pregnancy outcomes, including gestational diabetes mellitus, hypertensive disorders of pregnancy, preterm birth, and delivering low- birthweight (<2500 g) or high-birthweight (>4500 g) infants. Participants were followed up annually for self-reported incident type 2 diabetes mellitus treated with medication from baseline (1993-1998) to March 2021. This study used logistic regression to examine the associations of any and individual adverse pregnancy outcomes with diabetes mellitus. Stratified analyses were performed to assess effect modification by body mass index, race and ethnicity, education, parity, breastfeeding, and age at first birth.
This analysis included 49,717 women without a history of diabetes mellitus at enrollment who had a least 1 pregnancy and responded to the questionnaire about adverse pregnancy outcomes. After adjusting for body mass index, demographic, lifestyle, and reproductive factors, gestational diabetes mellitus (odds ratio, 2.26; 95% confidence interval, 1.94-2.63), high birthweight (odds ratio, 1.30; 95% confidence interval, 1.18-1.44), and hypertensive disorders of pregnancy (odds ratio, 1.18; 95% confidence interval, 1.08-1.30) were independently associated with higher odds of type 2 diabetes mellitus, whereas preterm birth and low birthweight were not associated with diabetes mellitus risk. A history of ≥2 adverse pregnancy outcomes was associated with higher odds of type 2 diabetes mellitus (odds ratio, 1.55; 95% confidence interval, 1.28-1.88). This study further observed higher odds of type 2 diabetes mellitus (odds ratio, 3.69; 95% confidence interval, 2.38-5.70) among women with a history of both gestational diabetes mellitus and hypertensive disorders of pregnancy than those without any adverse pregnancy outcomes.
Postmenopausal women with a history of gestational diabetes mellitus, those delivering high-birthweight infants, or those with hypertensive disorders of pregnancy are at risk of future type 2 diabetes mellitus. In addition, women with ≥2 conditions had an augmented risk and might be prioritized for screening and prevention efforts for type 2 diabetes mellitus.
In the present study, one of the new generation of host molecules, cucurbit(6)uril (CB(6)), was immobilized onto silica (CB(6)/SiO2) by a sol–gel approach. CB(6)/SiO2 was characterized by NMR ...spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and elemental analysis. It was used as a high‐performance liquid chromatographic stationary phase and its chromatographic performance was systematically investigated with different types of analytes as probes. The results revealed that the CB(6)/SiO2 stationary phase exhibited weak hydrophobic and strong hydrophilic properties. Hence, the variables for hydrophilic interaction liquid chromatography, including components and pH of the mobile phase, were further investigated to explore the retention mechanism of this CB(6)/SiO2 stationary phase. For less polar analytes, both hydrophobic and hydrophilic interactions could contribute to the retention, while for polar analytes, hydrophilic interaction may be predominant. Compared to the tetraethoxylsilane‐coated SiO2 stationary phases, the CB(6)/SiO2 stationary phase exhibited a different retention behavior toward basic analytes with excellent stability. It is a novel promising hydrophilic interaction liquid chromatography stationary phase.
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