Showing papers by "Frank B. Hu published in 2015"

The Epidemiology of Obesity: A Big Picture

Abstract: The epidemic of overweight and obesity presents a major challenge to chronic disease prevention and health across the life course around the world. Fueled by economic growth, industrialization, mechanized transport, urbanization, an increasingly sedentary lifestyle, and a nutritional transition to processed foods and high-calorie diets over the last 30 years, many countries have witnessed the prevalence of obesity in its citizens double and even quadruple. A rising prevalence of childhood obesity, in particular, forebodes a staggering burden of disease in individuals and healthcare systems in the decades to come. A complex, multifactorial disease, with genetic, behavioral, socioeconomic, and environmental origins, obesity raises the risk of debilitating morbidity and mortality. Relying primarily on epidemiologic evidence published within the last decade, this non-exhaustive review discusses the extent of the obesity epidemic, its risk factors-known and novel-, sequelae, and economic impact across the globe.

Type 2 diabetes mellitus.

Abstract: Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN.

Sleep Duration and Risk of Type 2 Diabetes: A Meta-analysis of Prospective Studies

Abstract: OBJECTIVE It remains unclear how many hours of sleep are associated with the lowest risk of type 2 diabetes. This meta-analysis was performed to assess the dose-response relationship between sleep duration and risk of type 2 diabetes. RESEARCH DESIGN AND METHODS PubMed and Embase were searched up to 20 March 2014 for prospective observational studies that assessed the relationship of sleep duration and risk of type 2 diabetes. Both semiparametric and parametric methods were used. RESULTS Ten articles with 11 reports were eligible for inclusion in the meta-analysis. A total of 18,443 incident cases of type 2 diabetes were ascertained among 482,502 participants with follow-up periods ranging from 2.5 to 16 years. A U-shaped dose-response relationship was observed between sleep duration and risk of type 2 diabetes, with the lowest risk observed at a sleep duration category of 7–8 h per day. Compared with 7-h sleep duration per day, the pooled relative risks for type 2 diabetes were 1.09 (95% CI 1.04–1.15) for each 1-h shorter sleep duration among individuals who slept CONCLUSIONS Our dose-response meta-analysis of prospective studies shows a U-shaped relationship between sleep duration and risk of type 2 diabetes, with the lowest type 2 diabetes risk at 7–8 h per day of sleep duration. Both short and long sleep duration are associated with a significantly increased risk of type 2 diabetes, underscoring the importance of appropriate sleep duration in the delay or prevention of type 2 diabetes.

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

Association of Cardiometabolic Multimorbidity With Mortality

Abstract: IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci

Abstract: We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.

Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial: A Randomized Clinical Trial.

Abstract: Importance Breast cancer is the leading cause of female cancer burden, and its incidence has increased by more than 20% worldwide since 2008. Some observational studies have suggested that the Mediterranean diet may reduce the risk of breast cancer. Objective To evaluate the effect of 2 interventions with Mediterranean diet vs the advice to follow a low-fat diet (control) on breast cancer incidence. Design, Setting, and Participants The PREDIMED study is a 1:1:1 randomized, single-blind, controlled field trial conducted at primary health care centers in Spain. From 2003 to 2009, 4282 women aged 60 to 80 years and at high cardiovascular disease risk were recruited after invitation by their primary care physicians. Interventions Participants were randomly allocated to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Main Outcomes and Measures Breast cancer incidence was a prespecified secondary outcome of the trial for women without a prior history of breast cancer (n = 4152). Results After a median follow-up of 4.8 years, we identified 35 confirmed incident cases of breast cancer. Observed rates (per 1000 person-years) were 1.1 for the Mediterranean diet with extra-virgin olive oil group, 1.8 for the Mediterranean diet with nuts group, and 2.9 for the control group. The multivariable-adjusted hazard ratios vs the control group were 0.31 (95% CI, 0.13-0.77) for the Mediterranean diet with extra-virgin olive oil group and 0.53 (95% CI, 0.23-1.26) for the Mediterranean diet with nuts group. In analyses with yearly cumulative updated dietary exposures, the hazard ratio for each additional 5% of calories from extra-virgin olive oil was 0.72 (95% CI, 0.57-0.90). Conclusions and Relevance This is the first randomized trial finding an effect of a long-term dietary intervention on breast cancer incidence. Our results suggest a beneficial effect of a Mediterranean diet supplemented with extra-virgin olive oil in the primary prevention of breast cancer. These results come from a secondary analysis of a previous trial and are based on few incident cases and, therefore, need to be confirmed in longer-term and larger studies. Trial Registration ISRCTN.org Identifier: ISRCTN35739639

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

Abstract: Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Changes in Intake of Fruits and Vegetables and Weight Change in United States Men and Women Followed for Up to 24 Years: Analysis from Three Prospective Cohort Studies.

Abstract: Background Current dietary guidelines recommend eating a variety of fruits and vegetables. However, based on nutrient composition, some particular fruits and vegetables may be more or less beneficial for maintaining or achieving a healthy weight. We hypothesized that greater consumption of fruits and vegetables with a higher fiber content or lower glycemic load would be more strongly associated with a healthy weight. Methods and Findings We examined the association between change in intake of specific fruits and vegetables and change in weight in three large, prospective cohorts of 133,468 United States men and women. From 1986 to 2010, these associations were examined within multiple 4-y time intervals, adjusting for simultaneous changes in other lifestyle factors, including other aspects of diet, smoking status, and physical activity. Results were combined using a random effects meta-analysis. Increased intake of fruits was inversely associated with 4-y weight change: total fruits -0.53 lb per daily serving (95% CI -0.61, -0.44), berries -1.11 lb (95% CI -1.45, -0.78), and apples/pears -1.24 lb (95% CI -1.62, -0.86). Increased intake of several vegetables was also inversely associated with weight change: total vegetables -0.25 lb per daily serving (95% CI -0.35, -0.14), tofu/soy -2.47 lb (95% CI, -3.09 to -1.85 lb) and cauliflower -1.37 lb (95% CI -2.27, -0.47). On the other hand, increased intake of starchy vegetables, including corn, peas, and potatoes, was associated with weight gain. Vegetables having both higher fiber and lower glycemic load were more strongly inversely associated with weight change compared with lower-fiber, higher-glycemic-load vegetables (p < 0.0001). Despite the measurement of key confounders in our analyses, the potential for residual confounding cannot be ruled out, and although our food frequency questionnaire specified portion size, the assessment of diet using any method will have measurement error. Conclusions Increased consumption of fruits and non-starchy vegetables is inversely associated with weight change, with important differences by type suggesting that other characteristics of these foods influence the magnitude of their association with weight change.

Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of prospective observational studies

Abstract: Backgrounds: Considerable evidence suggests that adiposity, measured by body mass index, is implicated in carcinogenesis. While adult weigh gain has diverse advantages over body mass index in measuring adiposity, systematic reviews on adult weight gain and risks of major cancers are lacking. Methods: PubMed and Embase were searched from the inception to May, 2014 to identify prospective observational studies investigating the relationship between adult weight gain and incident cancers of the breast, prostate, and colorectum. Dose-response meta-analyses were performed using a random-effects model to estimate summary relative risk (RR) and 95% confidence interval (CI) for each cancer type. Results: In the linear dose-response estimating cancer risk associated with 5kg increase in adult weight gain, a statistically significant direct association was found only for postmenopausal breast cancer and colon cancer. The summary RR was 1.11 (95% CI=1.08-1.13, I2=22%, seven studies with 4,570 cases, range=0-35kg) for postmenopausal breast cancer; 0.99 (95% CI=0.95-1.03, I2=36%, three studies with 2,409 cases, range=0-27.5kg) for premenopausal breast cancer. Etiologic heterogeneity by menopausal status at diagnosis was statistically significant (Pheterogeneity=0.001). The summary RR for colon cancer was 1.06 (95% CI=1.03-1.10, I2=0%, four studies with 2,909 cases, range=0-29kg). While there was no evidence of heterogeneity by sex (Pheterogeneity=0.17), the association was statistically significant only among men. No evidence of a linear association was indicated for prostate cancer (RR=0.98, 95% CI=0.94-1.02, four studies with 6,882 cases, range=0-25kg) and for its subtypes (localized: RR=0.96, 95% CI=0.92-1.00, I2=38%; advanced: RR=1.04, 95% CI=0.99-1.09, I2=0%). Conclusions: Avoiding adult weight gain itself may confer protection against postmenopausal breast cancer and colon cancer. As preventing weight gain is relatively more feasible than losing weight, clinicians and public health policies may prioritize weight maintenance throughout adulthood to reduce the burden of postmenopausal breast cancer and colon cancer.

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Abstract: Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

Relation of Smoking With Total Mortality and Cardiovascular Events Among Patients With Diabetes Mellitus: A Meta-Analysis and Systematic Review.

Abstract: Background—The prevalence of smoking in diabetic patients remains high, and reliable quantification of the excess mortality and morbidity risks associated with smoking is important for diabetes management. We performed a systematic review and meta-analysis of prospective cohort studies to evaluate the relation of active smoking with risk of total mortality and cardiovascular events among diabetic patients. Methods and Results—We searched Medline and Embase databases through May 2015, and multivariate-adjusted relative risks were pooled by using random-effects models. A total of 89 cohort studies were included. The pooled adjusted relative risk (95% confidence interval) associated with smoking was 1.55 (1.46–1.64) for total mortality (48 studies with 1 132 700 participants and 109 966 deaths), and 1.49 (1.29–1.71) for cardiovascular mortality (13 studies with 37 550 participants and 3163 deaths). The pooled relative risk (95% confidence interval) was 1.44 (1.34–1.54) for total cardiovascular disease (16 st...

Advances in the Science, Treatment, and Prevention of the Disease of Obesity: Reflections From a Diabetes Care Editors' Expert Forum.

Abstract: As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular disease, and numerous other detrimental conditions. The prevalence of obesity in U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although this trend may be leveling off, obesity and its individual, societal, and economic costs remain of grave concern. In June 2014, a Diabetes Care Editors' Expert Forum convened to review the state of obesity research and discuss the latest prevention initiatives and behavioral, medical, and surgical therapies. This article, an outgrowth of the forum, offers an expansive view of the obesity epidemic, beginning with a discussion of its root causes. Recent insights into the genetic and physiological factors that influence body weight are reviewed, as are the pathophysiology of obesity-related metabolic dysfunction and the concept of metabolically healthy obesity. The authors address the crucial question of how much weight loss is necessary to yield meaningful benefits. They describe the challenges of behavioral modification and predictors of its success. The effects of diabetes pharmacotherapies on body weight are reviewed, including potential weight-neutral combination therapies. The authors also summarize the evidence for safety and efficacy of pharmacotherapeutic and surgical obesity treatments. The article concludes with an impassioned call for researchers, clinicians, governmental agencies, health policymakers, and health-related industries to collectively embrace the urgent mandate to improve prevention and treatment and for society at large to acknowledge and manage obesity as a serious disease.

Changes in Diet Quality Scores and Risk of Cardiovascular Disease Among US Men and Women

Abstract: Background —Adherence to several diet quality scores including the Alternative Healthy Eating Index (AHEI), Alternative Mediterranean diet score (AMED), and Dietary Approach to Stop Hypertension (DASH) has been associated with lower risk of cardiovascular disease (CVD), but little is known about how changes in these scores over time influence subsequent CVD risk. Methods and Results —We analyzed the association between 4-year changes in three diet quality scores (AHEI, AMED, and DASH) and subsequent CVD risk among 29,343 men in the Health Professionals Follow-up Study and 51,195 women in the Nurses9 Health Study (1986-2010). During 1,394,702 person-years of follow up, we documented 11,793 CVD cases. Compared with participants whose diet quality remained relatively stable in each 4-year period, those with the greatest improvement in diet quality scores had a 7%-8% lower CVD risk in the subsequent 4-year period (pooled hazard ratio, 0.92 [95% confidence interval (CI): 0.87-0.99] for AHEI; 0.93 [95% CI: 0.85-1.02] for AMED; and 0.93 [95% CI: 0.87-0.99] for DASH; all P-trend<0.05). In the long term, increasing the diet scores from baseline to the first 4-year follow up was associated with lower CVD risk during the next 20 years (7% [95% CI: 1% to 12%] for AHEI and 9% [95% CI: 3% to 14%] for AMED). A decrease in diet quality scores was associated with significantly elevated risk of CVD in subsequent time periods. Conclusions —Improving adherence to diet quality scores over time is associated with significantly lower CVD risk both in the short term and the long term.

Association of Coffee Consumption With Total and Cause-Specific Mortality in 3 Large Prospective Cohorts

Abstract: Background The association between consumption of caffeinated and decaffeinated coffee and risk of mortality remains inconclusive. Methods and results We examined the associations of consumption of total, caffeinated, and decaffeinated coffee with risk of subsequent total and cause-specific mortality among 74,890 women in the Nurses' Health Study (NHS), 93,054 women in the Nurses' Health Study II, and 40,557 men in the Health Professionals Follow-up Study. Coffee consumption was assessed at baseline using a semiquantitative food frequency questionnaire. During 4,690,072 person-years of follow-up, 19,524 women and 12,432 men died. Consumption of total, caffeinated, and decaffeinated coffee were nonlinearly associated with mortality. Compared with nondrinkers, coffee consumption of 1 to 5 cups per day was associated with lower risk of mortality, whereas coffee consumption of more than 5 cups per day was not associated with risk of mortality. However, when restricting to never smokers compared with nondrinkers, the hazard ratios (and 95% confidence intervals) of mortality were 0.94 (0.89-0.99) for 1.0 or less cup per day, 0.92 (0.87-0.97) for 1.1 to 3.0 cups per day, 0.85 (0.79-0.92) for 3.1 to 5.0 cup per day, and 0.88 (0.78-0.99) for more than 5.0 cup per day (P value for nonlinearity = 0.32; P value for trend Conclusions Higher consumption of total coffee, caffeinated coffee, and decaffeinated coffee was associated with lower risk of total mortality.

Comparison of Methods to Account for Implausible Reporting of Energy Intake in Epidemiologic Studies

Abstract: In a recent article in the American Journal of Epidemiology by Mendez et al. (Am J Epidemiol. 2011;173(4):448–458), the use of alternative approaches to the exclusion of implausible energy intakes led to significantly different cross-sectional associations between diet and body mass index (BMI), whereas the use of a simpler recommended criteria ( 3,500 kcal/day) yielded no meaningful change. However, these findings might have been due to exclusions made based on weight, a primary determinant of BMI. Using data from 52,110 women in the Nurses' Health Study (1990), we reproduced the cross-sectional findings of Mendez et al. and compared the results from the recommended method with those from 2 weight-dependent alternative methods (the Goldberg method and predicted total energy expenditure method). The same 3 exclusion criteria were then used to examine dietary variables prospectively in relation to change in BMI, which is not a direct function of attained weight. We found similar associations using the 3 methods. In a separate cross-sectional analysis using biomarkers of dietary factors, we found similar correlations for intakes of fatty acids (n = 439) and carotenoids and retinol (n = 1,293) using the 3 methods for exclusions. These results do not support the general conclusion that use of exclusion criteria based on the alternative methods might confer an advantage over the recommended exclusion method.

Association between dietary whole grain intake and risk of mortality: two large prospective studies in US men and women.

Abstract: Importance Higher intake of whole grains has been associated with a lower risk of major chronic diseases, such as type 2 diabetes mellitus and cardiovascular disease (CVD), although limited prospective evidence exists regarding whole grains’ association with mortality. Objective To examine the association between dietary whole grain consumption and risk of mortality. Design, Setting, and Participants We investigated 74 341 women from the Nurses’ Health Study (1984–2010) and 43 744 men from the Health Professionals Follow-Up Study (1986–2010), 2 large prospective cohort studies. All patients were free of CVD and cancer at baseline. Main Outcomes and Measures Hazard ratios (HRs) for total mortality and mortality due to CVD and cancer according to quintiles of whole grain consumption, which was updated every 2 or 4 years by using validated food frequency questionnaires. Results We documented 26 920 deaths during 2 727 006 person-years of follow-up. After multivariate adjustment for potential confounders, including age, smoking, body mass index, physical activity, and modified Alternate Healthy Eating Index score, higher whole grain intake was associated with lower total and CVD mortality but not cancer mortality: the pooled HRs for quintiles 1 through 5, respectively, of whole grain intake were 1 (reference), 0.99 (95% CI, 0.95-1.02), 0.98 (95% CI, 0.95-1.02), 0.97 (95% CI, 0.93-1.01), and 0.91 (95% CI, 0.88-0.95) for total mortality ( P fortrend P fortrend P fortrend = .43). We further estimated that every serving (28 g/d) of whole grain consumption was associated with a 5% (95% CI, 2%-7%) lower total morality or a 9% (95% CI, 4%-13%) lower CVD mortality, whereas the same intake level was nonsignificantly associated with lower cancer mortality (HR, 0.98; 95% CI, 0.94-1.02). Similar inverse associations were observed between bran intake and CVD mortality, with a pooled HR of 0.80 (95% CI, 0.73-0.87; P fortrend Conclusions and Relevance These data indicate that higher whole grain consumption is associated with lower total and CVD mortality in US men and women, independent of other dietary and lifestyle factors. These results are in line with recommendations that promote increased whole grain consumption to facilitate disease prevention.

Alternate Healthy Eating Index 2010 and risk of chronic obstructive pulmonary disease among US women and men: prospective study.

Abstract: Objective To investigate the association between the Alternate Healthy Eating Index 2010 (AHEI-2010)—a measure of diet quality—and the risk of chronic obstructive pulmonary disease (COPD). Design Prospective cohort study. Setting Participants in the Nurses’ Health Study and the Health Professionals Follow-up Study, United States. Participants 73 228 female nurses from 1984 to 2000 and 47 026 men from 1986 to 1998, who completed biennial questionnaires. Main outcome measures The primary outcome was the self report of newly diagnosed COPD. Multivariable Cox proportional hazards models were adjusted for age, physical activity, body mass index, total energy intake, smoking, second hand tobacco exposure (only in the Nurses’ Health Study), race/ethnicity, physician visits, US region, spouse’s highest educational attainment (only in the Nurses’ Health Study), and menopausal status (only in the Nurses’ Health Study). Results Over the study period, 723 cases of newly diagnosed COPD occurred in women and 167 in men. In the pooled analysis, a significant negative association was seen between the risk of newly diagnosed COPD and fifths of the AHEI-2010: hazard ratios were 0.81 (95% confidence interval 0.51 to 1.29) for the second fifth, 0.98 (0.80 to 1.18) for the third fifth, 0.74 (0.59 to 0.92) for the fourth fifth, and 0.67 (0.53 to 0.85) for participants who ate the healthiest diet according to the AHEI-2010 (that is, were in the highest fifth), compared with those who ate the less healthy diet (participants in the lowest fifth). Similar findings were observed among ex-smokers and current smokers. Conclusions A higher AHEI-2010 diet score (reflecting high intakes of whole grains, polyunsaturated fatty acids, nuts, and long chain omega-3 fats and low intakes of red/processed meats, refined grains, and sugar sweetened drinks) was associated with a lower risk of COPD in both women and men. These findings support the importance of a healthy diet in multi-interventional programs to prevent COPD.

Posttraumatic stress disorder and incidence of type 2 diabetes mellitus in a sample of women: a 22-year longitudinal study.

Abstract: Importance Posttraumatic stress disorder (PTSD) is a common, debilitating mental disorder that has been associated with type 2 diabetes mellitus (T2D) and its risk factors, including obesity, in cross-sectional studies. If PTSD increases risk of incident T2D, enhanced surveillance in high-risk populations may be warranted. Objective To conduct one of the first longitudinal studies of PTSD and incidence of T2D in a civilian sample of women. Design, Setting, and Participants The Nurses’ Health Study II, a US longitudinal cohort of women (N = 49 739). We examined the association between PTSD symptoms and T2D incidence over a 22-year follow-up period. Main Outcomes and Measures Type 2 diabetes, self-reported and confirmed with self-report of diagnostic test results, symptoms, and medications, a method previously validated by physician medical record review. Posttraumatic stress disorder was assessed by the Short Screening Scale for DSM-IV PTSD. We examined longitudinal assessments of body mass index, smoking, alcohol intake, diet quality, physical activity, and antidepressant use as mediators of possible increased risk of T2D for women with PTSD. The study hypothesis was formulated prior to PTSD ascertainment. Results Symptoms of PTSD were associated in a dose-response fashion with T2D incidence (1-3 symptoms: hazard ratio, 1.4 [95% CI, 1.2-1.6]; 4 or 5 symptoms; hazard ratio, 1.5 [95% CI, 1.3-1.7]; 6 or 7 symptoms: hazard ratio, 1.8 [95% CI, 1.5-2.1]). Antidepressant use and a higher body mass index associated with PTSD accounted for nearly half of the increased risk of T2D for women with PTSD. Smoking, diet quality, alcohol intake, and physical activity did not further account for increased risk of T2D for women with PTSD. Conclusions and Relevance Women with the highest number of PTSD symptoms had a nearly 2-fold increased risk of T2D over follow-up than women with no trauma exposure. Health professionals treating women with PTSD should be aware that these patients are at risk of increased body mass index and T2D. Comprehensive PTSD treatment should be expanded to address the health behaviors that contribute to obesity and chronic disease in affected populations.

Reducing the global burden of type 2 diabetes by improving the quality of staple foods: The Global Nutrition and Epidemiologic Transition Initiative.

Abstract: The prevalence of type 2 diabetes has been reaching epidemic proportions across the globe, affecting low/middle-income and developed countries. Two main contributors to this burden are the reduction in mortality from infectious conditions and concomitant negative changes in lifestyles, including diet. We aimed to depict the current state of type 2 diabetes worldwide in light of the undergoing epidemiologic and nutrition transition, and to posit that a key factor in the nutrition transition has been the shift in the type and processing of staple foods, from less processed traditional foods to highly refined and processed carbohydrate sources. We showed data from 11 countries participating in the Global Nutrition and Epidemiologic Transition Initiative, a collaborative effort across countries at various stages of the nutrition-epidemiologic transition whose mission is to reduce diabetes by improving the quality of staple foods through culturally-appropriate interventions. We depicted the epidemiologic transition using demographic and mortality data from the World Health Organization, and the nutrition transition using data from the Food and Agriculture Organization food balance sheets. Main staple foods (maize, rice, wheat, pulses, and roots) differed by country, with most countries undergoing a shift in principal contributors to energy consumption from grains in the past 50 years. Notably, rice and wheat products accounted for over half of the contribution to energy consumption from staple grains, while the trends for contribution from roots and pulses generally decreased in most countries. Global Nutrition and Epidemiologic Transition Initiative countries with pilot data have documented key barriers and motivators to increase intake of high-quality staple foods. Global research efforts to identify and promote intake of culturally-acceptable high-quality staple foods could be crucial in preventing diabetes. These efforts may be valuable in shaping future research, community interventions, and public health and nutritional policies.

Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci

Abstract: Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians.

Birth weight and later life adherence to unhealthy lifestyles in predicting type 2 diabetes: prospective cohort study.

Abstract: 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 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.

Higher plasma betatrophin/ANGPTL8 level in Type 2 Diabetes subjects does not correlate with blood glucose or insulin resistance

Abstract: Betatrophin/ANGPTL8 is a newly identified hormone produced in liver and adipose tissue that has been shown to be induced as a result of insulin resistance and regulates lipid metabolism. Little is known about betatrophin level in humans and its association with T2D and metabolic risk factors. Plasma level of betatrophin was measured by ELISA in 1603 subjects: 1047 non-diabetic and 556 T2D subjects and its associations with metabolic risk factors in both non-diabetic and T2D were also studied. Our data show a significant difference in betatrophin levels between non-diabetic (731.3 (59.5–10625.0) pg/ml) and T2D (1710.5 (197.4–12361.1) p < 0.001. Betatrophin was positively correlated with age, BMI, waist/hip ratio, FBG, HbA1C, HOMA-IR and TG in the non-diabetic subjects. However, no association was observed with BMI, FBG, HbA1C or HOMA-IR in T2D subjects. TC and LDL showed negative association with betatrophin in T2D subjects. Multivariate analysis showed that subjects in the highest tertile of betatrophin had higher odds of having T2D (odd ratio [OR] = 6.15, 95% confidence interval [CI] = (3.15 – 12.01). Our data show strong positive associations between betatrophin and FBG and insulin resistance in non-diabetic subjects. However, correlations with FBG and insulin resistance were diminished in T2D subjects.

Curbing the Diabetes Pandemic: The Need for Global Policy Solutions.

Abstract: disease of the affluent, with lower socioeconomic groups being disproportionately affected in high-income countries and with 77% of the world’s diabetic population living in low- and middle-income countries It is also no longer predominantly a disease of older persons, with almost half of the people with diabetes in the 40- to 59-year age range Low- and middle-income countries face the added challenge of dealing with a dual burden of disease, as they are seeing an increase in obesity and diabetes levels, while still grappling with undernutrition and infectious diseases 3 In 2013, diabetes was associated with US $548 billion in health care expenditures globally 1 This figure is