Publications

Long-term weight changes and risk of rheumatoid arthritis among women in a prospective cohort: a marginal structural model approach

Abstract Objective To examine the association of long-term weight change with RA risk in a large prospective cohort study. Methods The Nurses’ Health Study II started in 1989 (baseline); after exclusions, we studied 108 505 women 25–42 years old without RA. Incident RA was reported by participants and confirmed by medical record review. Body weight was reported biennially through 2015. We investigated two time-varying exposures: weight changes from baseline and from age 18; change was divided into five categories. We used a marginal structural model approach to account for time-varying weight change and covariates. Results Over 2 583 266 person-years, with a median follow-up time of 25.3 years, 541 women developed RA. Compared with women with stable weight from baseline, weight change was significantly associated with increased RA risk [weight gain 2–<10 kg: RR = 1.98 (95% CI 1.38, 2.85); 10–<20 kg: RR = 3.28 (95% CI 2.20, 4.89); ≥20 kg: RR = 3.81 (95% CI 2.39, 6.07); and weight loss >2 kg: RR = 2.05 (95% CI 1.28, 3.28)]. Weight gain of 10 kg or more from age 18 compared with stable weight was also associated with increased RA risk [10–< 20 kg: RR = 2.12 (95% CI 1.37, 3.27), ≥20 kg: RR = 2.31 (95% CI 1.50, 3.56)]. Consistent findings were observed for seropositive and seronegative RA. Conclusion Long-term weight gain was strongly associated with increased RA risk in women, with weight gain of ≥20 kg associated with more than a three-fold increased RA risk. Maintenance of healthy weight may be a strategy to prevent or delay RA.

Abstract MP31: Incident Type 2 Diabetes Onset Age and Duration, Mortality Risk, and Loss in Life Expectancy

Introduction: Evidence on the relationship between type 2 diabetes onset age, duration, and mortality risk has been influenced by limited follow-up, inadequate control for confounding, and inability to cover the full range of onset age, duration, and the full spectrum of major causes of death. Moreover, there are scarce data dissecting how type 2 diabetes onset age and duration shape life expectancy. Hypothesis We assessed the hypothesis that early onset of type 2 diabetes and longer disease duration may be associated with higher risk of all-cause and cause-specific mortality and greater loss in life expectancy. Methods: We prospectively followed 270,075 eligible participants in the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study longitudinal cohorts for up to 40 years. The exposures include type 2 diabetes onset age (<40, ≥40 to <50, ≥50 to <60, ≥60 to <70, ≥70 to <80, and ≥80 years) and duration (<10, ≥10 to <20, ≥20 to <30, and ≥30 years). Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for age and a wide spectrum of potential confounders. Results: We documented 73,076 deaths during 8,166,216 person-years of follow-up. In fully-adjusted analyses, incident early-onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), kidney disease (8.55, 1.98-36.9), and suggestively increased mortality from diabetes-related cancer (1.63, 0.94-2.83) and obesity-related cancer (1.63, 0.92-2.88). The relative risk elevations declined dramatically with each higher decade of age at type 2 diabetes diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Comparing individuals with early-onset type 2 diabetes to those without type 2 diabetes, their estimated multivariable-adjusted cumulative incidence of all-cause mortality at age 80 was 0.43 vs. 0.20, and the estimated life expectancy loss at age 40 was 2.5 years. Longer disease duration was associated with generally higher relative and absolute risk of mortality. Conclusions: Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy. The effect of early-onset type 2 diabetes on mortality risk is stronger than that of later-onset type 2 diabetes.

Urinary concentrations of bisphenol A and phthalate metabolites and weight change: a prospective investigation in US women

Abstract 016: Artificially Sweetened Beverage Consumption, Plasma Metabolomics, And Risk Of Type 2 Diabetes Among US Adults

Introduction: The relationship between artificially sweetened beverage (ASB) intake and type 2 diabetes (T2D) risk remains inconclusive. Few studies have evaluated whether circulating metabolites that reflect ASB consumption may unveil potential mechanisms underlying the association between ASB consumption and T2D risk. Hypothesis: We hypothesized that a novel metabolomic profile reflecting habitual ASB consumption would positively associate with incident T2D among US adults. Methods: We quantified 120 plasma metabolites with liquid chromatography-mass spectroscopy in N=3,424 Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-up Study (HPFS) discovery cohort participants, and N=1,870 Framingham Heart Study (FHS) replication cohort participants. Habitual ASB consumption (servings/day; low-calorie cola or other carbonated beverages) was estimated from food frequency questionnaires at the time of blood draw. We used elastic net regression with 10-fold-cross-validation to age- and body mass index- adjusted metabolite levels to identify a metabolite profile associated with higher ASB consumption (ln-transformed). We then derived the continuous ASB metabolomic score as the weighted sum of these metabolites and replicated the analysis in an internal testing set and FHS. Finally, we evaluated the association of quartiles (Q) of the ASB-derived metabolomic score in NHS/NHSII/HPFS and FHS cohorts with incident T2D risk after blood draw (baseline for analysis) using Cox regression models to estimate hazard ratios (HR) and 95% confidence interval (CI), adjusted for demographics, lifestyle, diet, and body mass index at blood draw. Results: The ASB-derived metabolomic profile included 61 metabolites, primarily lipids and amino acids (Pearson correlation coefficients [ r ] between ASB self-reported intake and metabolomic score: r=0.08 [95% CI: 0.05, 0.11; p <0.0001] and r=0.09 [95% CI: 0.04, 0.14; p =0.001], for discovery and replication, respectively). Mean follow-up was 20 and 16 years from blood draw, including 359 and 241 confirmed incident T2D cases for NHS/NHSII/HPFS and FHS, respectively. Compared with participants in the lowest quartile of the ASB-derived metabolomic profile, higher quartiles were incrementally and significantly at higher T2D risk in NHS/NHSII/HPFS (HR [CI] for Q2, Q3, Q4 vs. Q1: 1.45 [1.04, 2.02], 1.83 [1.33, 2.52], 1.62 [1.18, 2.22], respectively; p-trend =0.003) and FHS (1.76 [1.24, 2.48], 1.82 [1.28, 2.58], 2.45 [1.77, 3.40], respectively; p-trend <0.0001). Conclusions: A robust metabolomic profile of ASB intake was not identified, yet the objective and replicable ASB-derived metabolomic profile was associated with higher incident T2D risk. The identified metabolites may reflect ASB intake, western dietary patterns, underlying metabolic health, and/or T2D-related pathophysiology.

Practical enzymic synthesis of adenosine 5'-0-(3-thiotriphosphate) (ATP-.gamma.-S)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPractical enzymic synthesis of adenosine 5'-0-(3-thiotriphosphate) (ATP-.gamma.-S)Obsidiana Abril, Debbie C. Crans, and George M. WhitesidesCite this: J. Org. Chem. 1984, 49, 8, 1360–1364Publication Date (Print):April 1, 1984Publication History Published online1 May 2002Published inissue 1 April 1984https://pubs.acs.org/doi/10.1021/jo00182a009https://doi.org/10.1021/jo00182a009research-articleACS PublicationsRequest reuse permissionsArticle Views331Altmetric-Citations14LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Urea Cycle Metabolites and Atrial Fibrillation or Heart Failure Risk: Two Case-Control Studies in the PREDIMED Trial

OBJECTIVES: To prospectively analyze the associations between urea cycle metabolites and incident atrial fibrillation (AF) or heart failure (HF), and to evaluate the effect of a Mediterranean diet (MD) intervention on such associations. METHODS: We designed two nested case-control studies within the PREDIMED trial, a randomized controlled trial aimed to evaluate the effect of two MD interventions, supplemented with either extra virgin olive oil (EVOO) or nuts, on cardiovascular disease (CVD). Fasting blood samples were collected at baseline and urea cycle metabolites (arginine, citrulline, and ornithine) and methylarginines (asymmetric dimethylarginine/symmetric dimethylarginine ratio (ADMA/SDMA ratio)) were determined using liquid chromatography tandem mass spectrometry. We used conditional logistic regression models, adjusted for potential confounders, to analyze the associations between the metabolites and incident AF or HF. Potential interactions between metabolites and intervention (MD groups vs control group) were tested with the likelihood ratio test. RESULTS: The study population comprised a total of 1241 participants (509 cases) for AF case-control and 824 participants (326 cases) for HF case-control. Arginine was inversely associated with incident AF (OR per SD 0.83, 95% CI 0.73; 0.94) and HF (OR per SD 0.82, 95% CI 0.69; 0.97). Whereas ADMA/SDMA ratio was positively associated with AF (OR per SD 1.19, 95% CI 1.02; 1.41) but not with HF risk. A statistically significant interaction (P = 0.044) was found between arginine and intervention on HF risk. The lower risk of HF associated with arginine was only observed in participants of the MD groups (EVOO + nuts). CONCLUSIONS: The results of the present study suggest that urea cycle metabolites, arginine and ADMA/SDMA ratio specifically, could be involved in AF and HF pathophysiology. Moreover, the dietary intervention may modify the association between arginine and HF. FUNDING SOURCES: National Institutes of Health (NIH), Spanish Government Official Agency for funding biomedical research-Instituto de Salud Carlos III (ISCIII) and CIBEROBN

Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus

Diameter dependence of the Raman<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mi>D</mml:mi></mml:math>-band in isolated single-wall carbon nanotubes

Raman D-band spectra are reported for several different SWNTs using two different laser energies ${(E}_{\mathrm{laser}}=1.58$ and 2.41 eV). At a fixed ${E}_{\mathrm{laser}},$ individual isolated SWNTs exhibit different diameter-dependent D-band frequencies ${\ensuremath{\omega}}_{D}$ around an average value. For both semiconducting and metallic tubes, ${\ensuremath{\omega}}_{D}$ decreases with decreasing nanotube diameter, though ${\ensuremath{\omega}}_{D}$ for isolated metallic SWNTs is higher than for isolated semiconducting SWNTs. The average D-band frequency depends linearly on ${E}_{\mathrm{laser}},$ as previously observed for SWNT bundles, suggesting that the D-band in SWNTs is activated by defects or by the finite size of the SWNTs.

Association Between a Genetic Variant Related to Glutamic Acid Metabolism and Coronary Heart Disease in Individuals With Type 2 Diabetes

A single-nucleotide polymorphism (rs10911021) was identified that was significantly associated with CHD among persons with diabetes but not in those without diabetes and was functionally related to glutamic acid metabolism, suggesting a mechanistic link.

An agenda-setting paper on data sharing platforms: euCanSHare workshop

Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.

Strain localization within a fluid-saturated fault gouge layer during seismic shear

No abstract is provided for this article.

Inflammatory Markers and Risk of Developing Type 2 Diabetes in Women

We conducted a prospective, nested, case-control study of inflammatory markers as predictors of type 2 diabetes among 32,826 women who provided blood samples in 1989 through 1990 in the Nurses’ Health Study. Among women free of diabetes, cardiovascular disease, or cancer at baseline, 737 had developed diabetes by 2000. Control women (n = 785) were selected matched on age, fasting status, race, and BMI for cases in the top BMI decile. Baseline levels of tumor necrosis factor (TNF)-α receptor 2, interleukin (IL)-6, and C-reactive protein (CRP) were significantly higher among case than control subjects (all P ≤ 0.001). After adjusting for BMI and other lifestyle factors, all three biomarkers significantly predicted diabetes risk; the odds ratios (ORs) comparing extreme quintiles were 1.64 (95% CI 1.10–2.45) for TNF-αR2, 1.91 (1.27–2.86) for IL-6, and 4.36 (2.80–6.80) for CRP (P for trend &amp;lt;0.001 for all biomarkers). In a multivariate model simultaneously including the three biomarkers, only CRP levels were significantly associated with risk of diabetes (OR comparing extreme quintiles of CRP = 3.99, P for trend &amp;lt;0.001). These data support the role of inflammation in the pathogenesis of type 2 diabetes. Elevated CRP levels are a strong independent predictor of type 2 diabetes and may mediate associations of TNF-αR2 and IL-6 with type 2 diabetes.

Adolescent dairy product consumption and risk of type 2 diabetes in middle-aged women

Localization of plastic deformation

The localization of plastic deformation into a shear band is discussed as an instability of plastic flow and a precursor to rupture. Experimental observations are reviewed, a general theoretical framework is presented, and specific calculations of critical conditions are carried out for a variety of material models. The interplay between features of inelastic constitutive description, especially deviations from normality and vertex-like yielding, and the onset of localization is emphasized.

Load-Independent Friction: MoO₃ Nanocrystal Lubricants

The behavior of the model lubricant system molybdenum disulfide (MoS2) has been characterized as a function of thermal oxidation on the atomic to nanometer scales with scanning tunneling microscopy (STM) and atomic force microscopy (AFM) in ultrahigh vacuum (UHV). STM studies of single-crystal MoS2 surfaces showed that the initial stages of thermal oxidation produce atomic-scale pits and then molybdenum oxide (MoO3) nanocrystals 1−5 nm in diameter. The densities of pits and MoO3 nanocrystals and the size of MoO3 nanocrystals increased with increasing oxidation time. UHV AFM friction measurements made on these same samples exhibited a direct relationship between defect density and friction for short oxidation times. After longer oxidation times when well-defined MoO3 nanocrystals were present, load-independent friction was observed. A model, which involves adhesion of MoO3 nanocrystals to the AFM probe tip end, has been developed to explain this first observation of load-independent friction. The implications of these results are discussed.

The stress field and energy of a three-dimensional dislocation loop at a crack tip

The self stress field and self energy are estimated for a planar 3D dislocation loop emanating from a half-plane crack tip. While the problem is of greatest interest for analysis of shear loops nucleating from the crack tip in the concentrated stress field there due to applied loadings, it is addressed here in the interest of tractability for 3D prismatic loops lying in the same plane as the crack. Exact elastic calculations for that case are based on recent developments of 3D crack weight function theory and specific results are given for induced stress fields, intensity factors and energy of semicircular and rectangular prismatic dislocation loops. Also, self stresses and energy expressions are derived for the 2D case of a line dislocation lying parallel to the crack for arbitrary Burgers vector type and general orientation of the dislocated plane relative to the crack plane, and those results are used together with the 3D prismatic loop results to estimate approximately the self energy for 3D shear dislocation loops emanating from the tip on planes inclined to the crack plane. Energy results are given in terms of a correction factor m to the usual estimate of energy for an emergent crack tip loop as half the energy of a full loop (identified as the emergent loop and its image relative to the crack tip) in an uncracked solid. That is, if the energy of a full circular loop of radius r in an uncracked solid is 2πrA 0 1n ( 8r e2r0 ), with r 0 = core cut-off and A 0 = energy factor, then the energy of a semicircular loop of radius r emerging from the crack tip is shown to take the form πrA 0 In ( 8mr e2r0 ) and the constant m is calculated here as 2.2 for a prismatic loop ahead of a crack and estimated approximately to range from about 1.2 to 1.9 for representative shear loops inclined to the crack plane. The self energy exceeds the half-full-loop value, corresponding to m = 1, and it is observed that this effect increases by √m the predicted loads to nucleate a dislocation loop of the assumed shape from a crack tip.

Coffee Consumption and Type 2 Diabetes Mellitus

Letters17 August 2004Coffee Consumption and Type 2 Diabetes MellitusFrank B. Hu, MD, PhD, Walter C. Willett, MD, DrPH, and JoAnn E. Manson, MD, DrPHFrank B. Hu, MD, PhDFrom Harvard School of Public Health and Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115.Search for more papers by this author, Walter C. Willett, MD, DrPHFrom Harvard School of Public Health and Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115.Search for more papers by this author, and JoAnn E. Manson, MD, DrPHFrom Harvard School of Public Health and Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-4-200408170-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Louria asked whether nut consumption confounded the inverse association between coffee consumption and type 2 diabetes mellitus in our study. We reran the analyses controlling for nut intake; the results remained virtually unchanged, suggesting that this confounding is unlikely to explain our findings.Dr. Schaefer also raised the issue of confounding by other dietary and lifestyle factors. However, coffee consumption tends to be associated with smoking, unhealthy diet, and less exercise. Thus, such confounding would have biased the relationship between coffee consumption and type 2 diabetes mellitus toward a positive association. In an ecological analysis, Dr. Schaefer ... Author, Article, and Disclosure InformationAffiliations: From Harvard School of Public Health and Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCoffee Consumption and Risk for Type 2 Diabetes Mellitus Eduardo Salazar-Martinez , Walter C. Willett , Alberto Ascherio , JoAnn E. Manson , Michael F. Leitzmann , Meir J. Stampfer , and Frank B. Hu Coffee Consumption and Type 2 Diabetes Mellitus Donald B. Louria Coffee Consumption and Type 2 Diabetes Mellitus Benjamin Schaefer Coffee Consumption and Type 2 Diabetes Mellitus Federico Soriguer , Gemma Rojo-Martínez , and Isabel Esteva de Antonio Coffee Consumption and Type 2 Diabetes Mellitus John H. Glaser and Sheila K. Glaser Coffee Consumption and Type 2 Diabetes Mellitus Donald A. Gerber Metrics 17 August 2004Volume 141, Issue 4Page: 323-324KeywordsCoffeeExerciseFactor analysisFoodGlucoseGlucose intoleranceInsulinMilkOral glucose tolerance testType 2 diabetes ePublished: 17 August 2004 Issue Published: 17 August 2004 CopyrightCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...

Lower hemoglobin levels associate with lower body mass index and healthier metabolic profile

Hemoglobin (Hb) is the main carrier of oxygen. In general, high-end Hb levels within the normal range are considered beneficial for health 1 . However, activation of the hypoxia response has been shown to protect mice against metabolic dysfunction 2-4 . We used Hb levels as an indicator for oxygenation status and studied its association with &gt;170 anthropometric and metabolic parameters in two Finnish birth cohorts both in cross-sectional and longitudinal design (max n = 7,175). Here we show a positive linear association between Hb levels and body mass index (BMI). Subjects with the lower Hb levels had better glucose tolerance, lower cholesterol and blood pressure levels, less adverse metabolite profiles and lower inflammatory load. Notably, these associations were not only mediated by the lower BMI, and the effect size of many of them increased with age. Polygenic risk score (PRS) analyses indicated shared genetic determinants between Hb levels and BMI, insulin, triglyceride and HDL cholesterol levels. Mendelian randomization (MR) analyses could not demonstrate causal relationships between Hb and metabolic parameters. However, manipulation of Hb levels by venesection in mice showed evidence for causal associations with body weight and metabolic parameters. Our findings suggest that lower-end normal Hb levels may be favorable for systemic metabolism involving mild chronic activation of the hypoxia response. Therefore modulation of Hb levels could be a novel strategy towards maintenance of metabolic health.

Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10−107) and stratified analyses (all P &amp;lt; 3.3 × 10−30). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the &amp;lt;55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the &amp;lt;55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.