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Tobias, Deirdre

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Tobias

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Deirdre

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Tobias, Deirdre

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    Body-Mass Index and Mortality among Adults with Incident Type 2 Diabetes
    (New England Journal of Medicine (NEJM/MMS), 2014) Tobias, Deirdre; Pan, An; Jackson, Chandra L.; O'Reilly, Eilis J.; Ding, Eric L.; Willett, Walter; Manson, JoAnn; Hu, Frank
    Background: The relation between body weight and mortality among persons with type 2 diabetes remains unresolved, with some studies suggesting decreased mortality among overweight or obese persons as compared with normal-weight persons (an “obesity paradox”). Methods: We studied participants with incident diabetes from the Nurses’ Health Study (8970 participants) and Health Professionals Follow-up Study (2457 participants) who were free of cardiovascular disease and cancer at the time of a diagnosis of diabetes. Body weight shortly before diagnosis and height were used to calculate the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters). Multivariable Cox models were used to estimate the hazard ratios and 95% confidence intervals for mortality across BMI categories. Results: There were 3083 deaths during a mean period of 15.8 years of follow-up. A J-shaped association was observed across BMI categories (18.5 to 22.4, 22.5 to 24.9 [reference], 25.0 to 27.4, 27.5 to 29.9, 30.0 to 34.9, and ≥35.0) for all-cause mortality (hazard ratio, 1.29 [95% confidence interval {CI}, 1.05 to 1.59]; 1.00; 1.12 [95% CI, 0.98 to 1.29]; 1.09 [95% CI, 0.94 to 1.26]; 1.24 [95% CI, 1.08 to 1.42]; and 1.33 [95% CI, 1.14 to 1.55], respectively). This relationship was linear among participants who had never smoked (hazard ratios across BMI categories: 1.12, 1.00, 1.16, 1.21, 1.36, and 1.56, respectively) but was nonlinear among participants who had ever smoked (hazard ratios across BMI categories: 1.32, 1.00, 1.09, 1.04, 1.14, and 1.21) (P=0.04 for interaction). A direct linear trend was observed among participants younger than 65 years of age at the time of a diabetes diagnosis but not among those 65 years of age or older at the time of diagnosis (P<0.001 for interaction). Conclusions: We observed a J-shaped association between BMI and mortality among all partici- pants and among those who had ever smoked and a direct linear relationship among those who had never smoked. We found no evidence of lower mortality among patients with diabetes who were overweight or obese at diagnosis, as com- pared with their normal-weight counterparts, or of an obesity paradox.
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    Association between Vitamin D Genetic Risk Score and Cancer Risk in a Large Cohort of U.S. Women
    (MDPI, 2018) Chandler, Paulette; Tobias, Deirdre; Wang, Lu; Smith-Warner, Stephanie; Chasman, Daniel; Rose, Lynda; Giovannucci, Edward; Buring, Julie; Ridker, Paul; Cook, Nancy; Manson, JoAnn; Sesso, Howard
    Some observational studies suggest an inverse association between circulating 25-hydroxyvitamin D (25OHD) and cancer incidence and mortality. We conducted a Mendelian randomization analysis of the relationship between a vitamin D genetic risk score (GRS, range 0–10), comprised of five single nucleotide polymorphisms (SNPs) of vitamin D status in the DHCR7, CYP2R1 and GC genes and cancer risk among women. Analysis was performed in the Women’s Genome Health Study (WGHS), including 23,294 women of European ancestry who were cancer-free at baseline and followed for 20 years for incident cancer. In a subgroup of 1782 WGHS participants with 25OHD measures at baseline, the GRS was associated with circulating 25OHD mean (SD) = 67.8 (26.1) nmol/L, 56.9 (18.7) nmol/L in the lowest versus 73.2 (27.9) nmol/L in the highest quintile of the GRS (p trend < 0.0001 across quintiles). However, in age-adjusted Cox proportional hazards models, higher GRS (reflecting higher 25OHD levels) was not associated (cases; Hazard Ratio (HR) (95% Confidence Interval (CI)), p-value) with incident total cancer: (n = 3985; 1.01 (1.00–1.03), p = 0.17), breast (n = 1560; 1.02 (0.99–1.05), p = 0.21), colorectal (n = 329; 1.06 (1.00–1.13), p = 0.07), lung (n = 330; 1.00 (0.94–1.06), p = 0.89) or total cancer death (n = 770; 1.00 (0.96–1.04), p = 0.90). Results were similar in fully-adjusted models. A GRS for higher circulating 25OHD was not associated with cancer incidence or mortality.
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    Duration of Reproductive Life Span, Age at Menarche, and Age at Menopause Are Associated With Risk of Cardiovascular Disease in Women
    (John Wiley and Sons Inc., 2017) Ley, Sylvia; Li, Yanping; Tobias, Deirdre; Manson, JoAnn; Rosner, Bernard; Hu, Frank; Rexrode, Kathryn
    Background: Although the timing of menarche and menopause may be associated with cardiovascular disease (CVD), the entire reproductive life span has not been considered comprehensively as risk for CVD. We investigate the associations of reproductive life span duration and ages at menarche and menopause, induced by natural means or surgical bilateral oophorectomy, with incident CVD in women. Methods and Results: Prospective cohort study of 73 814 Nurses' Health Study following participants without CVD, defined as incident coronary heart disease or stroke, from 1980 through 2012. Duration of reproductive life span was generated by subtracting age at menarche from age at menopause. A shorter reproductive life span was associated with a higher risk of incident CVD after multivariable adjustment (relative risk, 1.32 [95% confidence interval, 1.16–1.49] comparing duration <30 with ≥42 years; P trend<0.0001). Early age at menopause was associated with higher multivariable‐adjusted CVD risk (1.32 [1.16–1.51] comparing age <40 with 50 to <55 years; P trend<0.0001), with excess risk for both natural and surgical menopause. Compared with women with menarche at 13 years, the multivariable‐adjusted CVD risk for early menarche at ≤10 years was 1.22 (1.09–1.36). The association between reproductive life span and CVD remained significant in sensitivity analyses excluding women who experienced extreme early age at menarche or who used hormone therapy. Conclusions: A shorter duration of reproductive life span is associated with a higher risk of CVD, which is likely driven by the timing of menopause induced either naturally or surgically. Extremely early age at menarche is also associated with a higher risk of CVD.
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    Does Being Overweight Really Reduce Mortality?
    (2013) Tobias, Deirdre; Hu, Frank
    There is indisputable evidence from epidemiologic and clinical studies that being overweight and obese elevates the risk of developing debilitating and costly chronic diseases, including hypertension, hypercholesterolemia, type 2 diabetes, cardiovascular diseases (CVD), and cancer (1). Nonetheless, the relationship between body mass index (BMI) and mortality remains the subject of much debate. A recent meta-analysis concluded that compared to those of normal weight (BMI<25.0), overweight individuals (BMI 25.0–29.9) had a significantly lower mortality risk (2). Even Class 1 obesity (BMI 30–34.9) was associated with marginally reduced mortality. In this Perspective, we discuss why this finding is likely to be an artifact of methodological limitations and what the clinical and public health implications may be.
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    Prepregnancy Dietary Protein Intake, Major Dietary Protein Sources, and the Risk of Gestational Diabetes Mellitus: A prospective cohort study
    (American Diabetes Association, 2013) Bao, Wei; Bowers, Katherine; Tobias, Deirdre; Hu, Frank; Zhang, Cuilin
    OBJECTIVE Dietary protein is an important modulator of glucose metabolism. However, studies regarding the association between dietary protein intake and gestational diabetes mellitus (GDM) risk are sparse. This study was to examine the association. RESEARCH DESIGN AND METHODS Our study included 21,457 singleton pregnancies reported among 15,294 participants of the Nurses' Health Study II cohort between 1991 and 2001. Included pregnancies were free of chronic diseases before pregnancy or previous GDM. Generalized estimating equations were used to estimate the relative risks (RRs) and 95% CIs. RESULTS After adjustment for age, parity, nondietary and dietary factors, and BMI, multivariable RRs (95% CIs) comparing the highest with lowest quintiles were 1.49 (1.03–2.17) for animal protein intake and 0.69 (0.50–0.97) for vegetable protein intake. The substitution of 5% energy from vegetable protein for animal protein was associated with a 51% lower risk of GDM (RR [95% CI], 0.49 [0.29–0.84]). For major dietary protein sources, multivariable RRs (95% CIs) comparing the highest with the lowest quintiles were 2.05 (1.55–2.73) for total red meat and 0.73 (0.56–0.95) for nuts, respectively. The substitution of red meat with poultry, fish, nuts, or legumes showed a significantly lower risk of GDM. CONCLUSIONS Higher intake of animal protein, in particular red meat, was significantly associated with a greater risk of GDM. By contrast, higher intake of vegetable protein, specifically nuts, was associated with a significantly lower risk. Substitution of vegetable protein for animal protein, as well as substitution of some healthy protein sources for red meat, was associated with a lower risk of GDM.
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    Birth weight and later life adherence to unhealthy lifestyles in predicting type 2 diabetes: prospective cohort study
    (BMJ Publishing Group Ltd., 2015) Li, Yanping; Ley, Sylvia; Tobias, Deirdre; Chiuve, Stephanie; VanderWeele, Tyler; Rich-Edwards, Janet; Curhan, Gary; Willett, Walter; Manson, JoAnn; Hu, Frank; Qi, Lu
    Objectives To prospectively assess the joint association of birth weight and established lifestyle risk factors in adulthood with incident type 2 diabetes and to quantitatively decompose the attributing effects to birth weight only, to adulthood lifestyle only, and to their interaction. Design: Prospective cohort study. Setting: Health Professionals Follow-up Study (1986-2010), Nurses’ Health Study (1980-2010), and Nurses’ Health Study II (1991-2011). Participants: 149 794 men and women without diabetes, cardiovascular disease, or cancer at baseline. Main outcome measure Incident cases of type 2 diabetes, identified through self report and validated by a supplementary questionnaire. Unhealthy lifestyle was defined on the basis of body mass index, smoking, physical activity, alcohol consumption, and the alternate healthy eating index. Results: During 20-30 years of follow-up, 11 709 new cases of type 2 diabetes were documented. The multivariate adjusted relative risk of type 2 diabetes was 1.45 (95% confidence interval 1.32 to 1.59) per kg lower birth weight and 2.10 (1.71 to 2.58) per unhealthy lifestyle factor. The relative risk of type 2 diabetes associated with a combination of per kg lower birth weight and per unhealthy lifestyle factor was 2.86 (2.26 to 3.63), which was more than the addition of the risk associated with each individual factor, indicating a significant interaction on an additive scale (P for interaction<0.001). The attributable proportions of joint effect were 22% (95% confidence interval 18.3% to 26.4%) to lower birth weight alone, 59% (57.1% to 61.5%) to unhealthy lifestyle alone, and 18% (13.9% to 21.3%) to their interaction. Conclusion: Most cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle, but simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases.
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    Adherence to healthy lifestyle and risk of gestational diabetes mellitus: prospective cohort study
    (BMJ Publishing Group Ltd., 2014) Zhang, Cuilin; Tobias, Deirdre; Chavarro, Jorge; Bao, Wei; Wang, Dong; Ley, Sylvia; Hu, Frank
    Objective: To quantify the association between a combination of healthy lifestyle factors before pregnancy (healthy body weight, healthy diet, regular exercise, and not smoking) and the risk of gestational diabetes. Design: Prospective cohort study. Setting: Nurses’ Health Study II, United States. Participants: 20 136 singleton live births in 14 437 women without chronic disease. Main outcome measure Self reported incident gestational diabetes diagnosed by a physician, validated by medical records in a previous study. Results: Incident first time gestational diabetes was reported in 823 pregnancies. Each lifestyle factor measured was independently and significantly associated with risk of gestational diabetes. The combination of three low risk factors (non-smoker, ≥150 minutes a week of moderate to vigorous physical activity, and healthy eating (top two fifths of Alternate Healthy Eating Index-2010 adherence score)) was associated with a 41% lower risk of gestational diabetes compared with all other pregnancies (relative risk 0.59, 95% confidence interval 0.48 to 0.71). Addition of body mass index (BMI) <25 before pregnancy (giving a combination of four low risk factors) was associated with a 52% lower risk of gestational diabetes compared with all other pregnancies (relative risk 0.48, 0.38 to 0.61). Compared with pregnancies in women who did not meet any of the low risk lifestyle factors, those meeting all four criteria had an 83% lower risk of gestational diabetes (relative risk 0.17, 0.12 to 0.25). The population attributable risk percentage of the four risk factors in combination (smoking, inactivity, overweight, and poor diet) was 47.5% (95% confidence interval 35.6% to 56.6%). A similar population attributable risk percentage (49.2%) was observed when the distributions of the four low risk factors from the US National Health and Nutrition Examination Survey (2007-10) data were applied to the calculation. Conclusions: Adherence to a low risk lifestyle before pregnancy is associated with a low risk of gestational diabetes and could be an effective strategy for the prevention of gestational diabetes.
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    Effect of Low-Fat vs. Other Diet Interventions on Long-Term Weight Change in Adults: A Systematic Review and Meta-Analysis
    (2015) Tobias, Deirdre; Chen, Mu; Manson, JoAnn; Ludwig, David; Willett, Walter; Hu, Frank
    Background: The effectiveness of low-fat diets for long-term weight loss has been debated for decades, with dozens of randomized trials (RCTs) and recent reviews giving mixed results. Methods: We conducted a random effects meta-analysis of RCTs to estimate the long-term effect of low-fat vs. higher fat dietary interventions on weight loss. Our search included RCTs conducted in adult populations reporting weight change outcomes at ≥1 year, comparing low-fat with higher fat interventions, published through July 2014. The primary outcome measure was mean difference in weight change between interventions. Findings: Fifty-three studies met inclusion criteria representing 68,128 participants. In the setting of weight loss trials, low-carbohydrate interventions led to significantly greater weight loss than low-fat interventions (n comparisons=18; weighted mean difference [WMD]=1.15 kg, 95% CI=0.52 to 1.79; I2=10%). Low-fat did not lead to differences in weight change compared with other moderate fat weight loss interventions (n=19; WMD=0.36, 95% CI=-0.66 to 1.37; I2=82%), and were superior only when compared with “usual diet” (n=8; WMD=-5.41, 95% CI=-7.29 to −3.54; I2=68%). Similarly, non-weight loss trials and weight maintenance trials, for which there were no low-carbohydrate comparisons, had similar effects for low-fat vs moderate fat interventions, and were superior compared with “usual diet”. Weight loss trials achieving a greater difference in fat intake at follow-up significantly favored the higher fat dietary interventions, as indicated by difference of ≥5% of calories from fat (n=18; WMD=1.04, 95% CI=0.06 to 2.03; I2=78%) or by difference in change serum triglycerides of ≥5 mg/dL (n=17; WMD=1.38, 95% CI=0.50 to 2.25; I2=62%). Interpretation These findings suggest that the long-term effect of low-fat diets on body weight depends on the intensity of intervention in the comparison group. When compared to dietary interventions of similar intensity, evidence from RCTs does not support low-fat diets over other dietary interventions.
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    Association of N-Linked Glycoprotein Acetyls and Colorectal Cancer Incidence and Mortality
    (Public Library of Science, 2016) Chandler, Paulette; Akinkuolie, Akintunde O.; Tobias, Deirdre; Lawler, Patrick R.; Li, Chungying; Moorthy, M. Vinayaga; Wang, Lu; Duprez, Daniel A.; Jacobs, David R.; Glynn, Robert; Otvos, James; Connelly, Margery A.; Post, Wendy S.; Ridker, Paul; Manson, JoAnn; Buring, Julie; Lee, I-Min; Mora, Samia
    Background: Acute phase proteins highlight the dynamic interaction between inflammation and oncogenesis. GlycA, a novel nuclear magnetic resonance (NMR) inflammatory marker that identifies primarily circulating N-acetyl glycan groups attached to acute phase proteins, may be a future CRC risk biomarker. Methods: We examined the association between GlycA and incident CRC and mortality in two prospective cohorts (N = 34,320); Discovery cohort: 27,495 participants from Women's Health Study (WHS); Replication cohort: 6,784 participants from Multi-Ethnic Study of Atherosclerosis (MESA). Multivariable Cox models were adjusted for clinical risk factors and compared GlycA to acute phase proteins (high-sensitivity C-reactive protein [hsCRP], fibrinogen, and soluble intercellular adhesion molecule-1 [sICAM-1]). Results: In WHS (median follow-up 19 years, 337 cases, 103 deaths), adjusted HRs (95% CIs) per SD increment of GlycA for CRC incidence and mortality were 1.19 (1.06–1.35; p = 0.004) and 1.24 (1.00–1.55; p = 0.05), respectively. We replicated findings in MESA (median follow-up 11 years, 70 cases, 23 deaths); HRs (95% CIs) per SD of GlycA for CRC incidence and mortality were 1.32 (1.06–1.65; p = 0.01) and 1.54 (1.06–2.23; p = 0.02), respectively, adjusting for age, sex, and race. Pooled analysis, adjusted HR (95% CI) per SD of GlycA for CRC incidence and mortality was 1.26 (1.15–1.39; p = 1 x 10−6). Other acute phase proteins (hsCRP, fibrinogen, and sICAM-1) had weaker or no association with CRC incidence, while only fibrinogen and GlycA were associated with CRC mortality. Conclusions: The clinical utility of GlycA to personalize CRC therapies or prevention warrants further study. Trial Registration ClinicalTrials.gov: WHS NCT00000479, MESA NCT00005487
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    Prepregnancy Consumption of Fruits and Fruit Juices and the Risk of Gestational Diabetes Mellitus
    (American Diabetes Association, 2012) Chen, Liwei; Hu, Frank; Yeung, Edwina; Tobias, Deirdre; Willett, Walter; Zhang, Cuilin
    OBJECTIVE Examine the association of prepregnancy habitual consumption of fruits and fruit juices and gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS A prospective study among women with at least one singleton pregnancy in the Nurses’ Health Study II from 1991 to 2001. RESULTS Among 13,475 women, 860 reported a first diagnosis of GDM. The adjusted relative risks (RRs) for GDM from the lowest to highest quintile of whole fruit consumption were 1.00 (referent), 0.80 (95% CI 0.65–0.98), 0.90 (0.73–1.10), 0.80 (0.64–1.00), and 0.93 (0.76–1.16), respectively. The corresponding RRs for fruit juice were 1.00, 0.82 (0.66–1.01), 0.78 (0.63–0.96), 0.84 (0.68–1.04), and 1.00 (0.81–1.23). CONCLUSIONS These data suggest that prepregnancy higher consumption of whole fruits is not associated with an increased GDM risk. The association between fruit juices and GDM risk appears to be nonlinear.