Person:

Sun, Qi

Despite the well-established observation that substitution of saturated fats for carbohydrates or unsaturated fats increases low-density lipoprotein (LDL) cholesterol in humans and animal models, the relationship of saturated fat intake to risk for atherosclerotic cardiovascular disease in humans remains controversial. A critical question is what macronutrient should be used to replace saturated fat. Substituting polyunsaturated fat for saturated fat reduces LDL cholesterol and the total cholesterol to high-density lipoprotein cholesterol ratio. However, replacement of saturated fat by carbohydrates, particularly refined carbohydrates and added sugars, increases levels of triglyceride and small LDL particles and reduces high-density lipoprotein cholesterol, effects that are of particular concern in the context of the increased prevalence of obesity and insulin resistance. Epidemiologic studies and randomized clinical trials have provided consistent evidence that replacing saturated fat with polyunsaturated fat, but not carbohydrates, is beneficial for coronary heart disease. Therefore, dietary recommendations should emphasize substitution of polyunsaturated fat and minimally processed grains for saturated fat.

Background: While increasing data on bacterial evolution in controlled environments are available, our understanding of bacterial genome evolution in natural environments is limited. We thus performed full genome analyses on four Listeria monocytogenes, including human and food isolates from both a 1988 case of sporadic listeriosis and a 2000 listeriosis outbreak, which had been linked to contaminated food from a single processing facility. All four isolates had been shown to have identical subtypes, suggesting that a specific L. monocytogenes strain persisted in this processing plant over at least 12 years. While a genome sequence for the 1988 food isolate has been reported, we sequenced the genomes of the 1988 human isolate as well as a human and a food isolate from the 2000 outbreak to allow for comparative genome analyses. Results: The two L. monocytogenes isolates from 1988 and the two isolates from 2000 had highly similar genome backbone sequences with very few single nucleotide (nt) polymorphisms (1 – 8 SNPs/isolate; confirmed by re-sequencing). While no genome rearrangements were identified in the backbone genome of the four isolates, a 42 kb prophage inserted in the chromosomal comK gene showed evidence for major genome rearrangements. The human-food isolate pair from each 1988 and 2000 had identical prophage sequence; however, there were significant differences in the prophage sequences between the 1988 and 2000 isolates. Diversification of this prophage appears to have been caused by multiple homologous recombination events or possibly prophage replacement. In addition, only the 2000 human isolate contained a plasmid, suggesting plasmid loss or acquisition events. Surprisingly, besides the polymorphisms found in the comK prophage, a single SNP in the tRNA Thr-4 prophage represents the only SNP that differentiates the 1988 isolates from the 2000 isolates. Conclusion: Our data support the hypothesis that the 2000 human listeriosis outbreak was caused by a L. monocytogenes strain that persisted in a food processing facility over 12 years and show that genome sequencing is a valuable and feasible tool for retrospective epidemiological analyses. Short-term evolution of L. monocytogenes in non-controlled environments appears to involve limited diversification beyond plasmid gain or loss and prophage diversification, highlighting the importance of phages in bacterial evolution.

Objectives: To summarise evidence on the association between white rice consumption and risk of type 2 diabetes and to quantify the potential dose-response relation. Design: Meta-analysis of prospective cohort studies. Data sources: Searches of Medline and Embase databases for articles published up to January 2012 using keywords that included both rice intake and diabetes; further searches of references of included original studies. Study selection: Included studies were prospective cohort studies that reported risk estimates for type 2 diabetes by rice intake levels. Data synthesis: Relative risks were pooled using a random effects model; dose-response relations were evaluated using data from all rice intake categories in each study. Results: Four articles were identified that included seven distinct prospective cohort analyses in Asian and Western populations for this study. A total of 13 284 incident cases of type 2 diabetes were ascertained among 352 384 participants with follow-up periods ranging from 4 to 22 years. Asian (Chinese and Japanese) populations had much higher white rice consumption levels than did Western populations (average intake levels were three to four servings/day versus one to two servings/week). The pooled relative risk was 1.55 (95% confidence interval 1.20 to 2.01) comparing the highest with the lowest category of white rice intake in Asian populations, whereas the corresponding relative risk was 1.12 (0.94 to 1.33) in Western populations (P for interaction=0.038). In the total population, the dose-response meta-analysis indicated that for each serving per day increment of white rice intake, the relative risk of type 2 diabetes was 1.11 (1.08 to 1.14) (P for linear trend<0.001). Conclusion: Higher consumption of white rice is associated with a significantly increased risk of type 2 diabetes, especially in Asian (Chinese and Japanese) populations.

OBJECTIVE Epidemiological studies have repeatedly investigated the association between depression and metabolic syndrome (MetS). However, the results have been inconsistent. This meta-analysis aimed to summarize the current evidence from cross-sectional and prospective cohort studies that evaluated this association. RESEARCH DESIGN AND METHODS MEDLINE, EMBASE, and PsycINFO databases were searched for articles published up to January 2012. Cross-sectional and cohort studies that reported an association between the two conditions in adults were included. Data on prevalence, incidence, unadjusted or adjusted odds ratio (OR), and 95% CI were extracted or provided by the authors. The pooled OR was calculated separately for cross-sectional and cohort studies using random-effects models. The I2 statistic was used to assess heterogeneity. RESULTS The search yielded 29 cross-sectional studies (n = 155,333): 27 studies reported unadjusted OR with a pooled estimate of 1.42 (95% CI 1.28–1.57; I2 = 55.1%); 11 studies reported adjusted OR with depression as the outcome (1.27 [1.07–1.57]; I2 = 60.9%), and 12 studies reported adjusted OR with MetS as the outcome (1.34 [1.18–1.51]; I2 = 0%). Eleven cohort studies were found (2 studies reported both directions): 9 studies (n = 26,936 with 2,316 new-onset depression case subjects) reported adjusted OR with depression as the outcome (1.49 [1.19–1.87]; I2 = 56.8%), 4 studies (n = 3,834 with 350 MetS case subjects) reported adjusted OR with MetS as the outcome (1.52 [1.20–1.91]; I2 = 0%). CONCLUSIONS Our results indicate a bidirectional association between depression and MetS. These results support early detection and management of depression among patients with MetS and vice versa.

Background: Magnesium is associated with lower risk of sudden cardiac death, possibly through antiarrhythmic mechanisms. Magnesium influences endothelial function, inflammation, blood pressure, and diabetes, but a direct relation with coronary heart disease (CHD) risk has not been established. Methods and Results: We prospectively examined the association between dietary and plasma magnesium and risk of CHD among women in the Nurses' Health Study. The association for magnesium intake was examined among 86 323 women free of disease in 1980. Information on magnesium intake and lifestyle factors was ascertained every 2 to 4 years through questionnaires. Through 2008, 3614 cases of CHD (2511 nonfatal/1103 fatal) were documented. For plasma magnesium, we conducted a nested case–control analysis, with 458 cases of incident CHD (400 nonfatal/58 fatal) matched to controls (1:1) on age, smoking, fasting status, and date of blood sampling. Higher magnesium intake was not associated with lower risk of total CHD (P‐linear trend=0.12) or nonfatal CHD (P‐linear trend=0.88) in multivariable models. However, magnesium intake was inversely associated with risk of fatal CHD. The RR comparing quintile 5 to quintile 1 of magnesium intake was 0.61 (95% CI, 0.45 to 0.84; P‐linear trend=0.003). The association between magnesium intake and risk of fatal CHD appeared to be mediated partially by hypertension. Plasma magnesium levels above 2.0 mg/dL were associated with lower risk of CHD, although not independent of other cardiovascular biomarkers (RR, 0.67; 95% CI, 0.44 to 1.04). Conclusions: Dietary and plasma magnesium were not associated with total CHD incidence in this population of women. Dietary magnesium intake was inversely associated with fatal CHD, which may be mediated in part by hypertension.

OBJECTIVE: The aim of this study is to investigate the intake of zinc in relation to risk of type 2 diabetes in U.S. women. RESEARCH DESIGN AND METHODS: Dietary intakes of zinc and other nutrients were assessed and updated using a validated food frequency questionnaire from 1980 to 2002 among 82,297 women who were aged 33–60 years at baseline in 1980 and followed up to 2004 in the Nurses' Health Study. RESULTS: During the 24 years of follow-up, 6,030 incident cases of type 2 diabetes were ascertained. After adjustment of lifestyle and dietary risk factors, the relative risks (RRs) (95% CI) of type 2 diabetes comparing the highest with the lowest quintiles were 0.90 (0.82–0.99) (Ptrend = 0.04) for total zinc intake and 0.92 (0.84–1.00) (Ptrend = 0.009) for dietary zinc intake from food sources, respectively. We further found an inverse association for dietary zinc to heme iron ratio. After multivariate adjustment of covariates, the RRs (95% CI) across quintiles of this ratio were 1.0 (reference), 0.93 (0.86–1.01), 0.86 (0.79–0.94), 0.82 (0.75–0.90), and 0.72 (0.66–0.80), respectively (Ptrend < 0.0001). CONCLUSIONS: Higher zinc intake may be associated with a slightly lower risk of type 2 diabetes in women. More studies are warranted to confirm this association and to explore potential mechanisms.

Background: Prospective data regarding persistent organic pollutants (POPs) and risk of type 2 diabetes (T2D) are limited, and the results for individual POPs are not entirely consistent across studies. Objectives: We prospectively examined plasma POP concentrations in relation to incident T2D and summarized existing evidence in a meta-analysis. Methods: Plasma polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and hexachlorobenzene (HCB) concentrations were measured in 1,095 women who were free of diabetes at blood draw in 1989–1990 and participated in two case–control studies in the Nurses’ Health Study. We identified 48 incident T2D cases through 30 June 2008. We conducted a literature search in PubMed and EMBASE through December 2011 to identify prospective studies on POPs in relation to diabetes. We used a fixed-effects model to summarize results. Results: After multivariable adjustment, plasma HCB concentration was positively associated with incident T2D [pooled odds ratio (OR) 3.59 (95% CI: 1.49, 8.64, p({trend})= 0.003) comparing extreme tertiles]. Other POPs were not significantly associated with diabetes. After pooling our results with those of six published prospective studies that included 842 diabetes cases in total, we found that HCB and total PCBs both were associated with diabetes: the pooled ORs were 2.00 (95% CI: 1.13, 3.53; I(^2)= 21.4%, p({heterogeneity})= 0.28) and 1.70 (95% CI: 1.28, 2.27; I(^2)= 16.3%, p(_{heterogeneity})= 0.30) for HCB and total PCBs, respectively. Conclusions: These findings support an association between POP exposure and the risk of T2D.

Context: Whether a healthy lifestyle may be associated with longer telomere length is largely unknown. Objectives: To examine healthy lifestyle practices, which are primary prevention measures against major age-related chronic diseases, in relation to leukocyte telomere length. Design and Setting Cross-sectional analysis in the Nurses' Health Study (NHS). Participants: The population consisted of 5,862 women who participated in multiple prospective case-control studies within the NHS cohort. Z scores of leukocyte telomere length were derived within each case-control study. Based on prior work, we defined low-risk or healthy categories for five major modifiable factors assessed in 1988 or 1990: non-current smoking, maintaining a healthy body weight (body mass index in 18.5–24.9 kg/m(^2)), engaging in regular moderate or vigorous physical activities ((\geq)150 minutes/week), drinking alcohol in moderation (1 drink/week to <2 drinks/day), and eating a healthy diet (Alternate Healthy Eating Index score in top 50%). We calculated difference (%) of the z scores contrasting low-risk groups with reference groups to evaluate the association of interest. Results: Although none of the individual low-risk factors was significantly associated with larger leukocyte telomere length z scores, we observed a significant, positive relationship between the number of low-risk factors and the z scores. In comparison with women who had zero low-risk factors (1.9% of the total population) and were, therefore, considered the least healthy group, the leukocyte telomere length z scores were 16.4%, 22.1%, 28.7%, 22.6%, and 31.2% (P for trend = 0.015) higher for women who had 1 to 5 low-risk factors, respectively. Conclusions: Adherence to a healthy lifestyle, defined by major modifiable risk factors, was associated with longer telomere length in leukocytes.

The association between regional fat mass distribution and cardiometabolic risk factors has been inconsistent in the literature, and data for ethnic minority groups, such as non-Hispanic blacks and Hispanics, are lacking. We aimed to examine this association among 8802 US residents who participated in the 1999-2004 US National Health and Nutrition Examination Survey (NHANES). Body composition was measured using dual-energy X-ray absorptiometry (DXA). Leg fat indices included leg fat mass (FM), leg fat mass percent (FM%), leg to whole body FM ratio (leg/whole) and leg to trunk FM ratio (leg/trunk). We evaluated the correlation between leg fat indices and adiposity-related risk factors, as well as the association of these indices with metabolic syndrome (MetS). After adjusting for covariates including age, gender, and trunk FM or trunk FM%, higher leg FM and leg FM% were, in general, correlated favorably with adiposity-related risk factors and associated with lower odds of MetS in all ethnicities, including non-Hispanic whites and blacks and Hispanic groups. In addition, in all multivariate-adjusted models, leg/whole and leg/trunk ratios were strongly associated with lower levels of most risk factors and decreased odds of MetS in these ethnicities (all odds ratios comparing extreme quintiles < 0.1). Our results show that leg fat accumulation is inversely associated with adiposity-related biological factors and risk of MetS in both whites and ethnic groups, suggesting that regional fat distribution plays an important role in the etiology of adiposity-related diseases in these populations.

IGF-I shares structural homology and in vitro metabolic activity with insulin. Laboratory models suggest that IGF-I and its binding proteins IGFBP-1 and IGFBP-2 have potentially beneficial effects on diabetes risk, whereas IGFBP-3 may have adverse effects. We therefore conducted a prospective nested case-control investigation of incident diabetes (n = 742 case subjects matched 1:1 to control subjects) and its associations with IGF-axis protein levels in the Nurses’ Health Study, a cohort of middle-aged women. The median time to diabetes was 9 years. Statistical analyses were adjusted for multiple risk factors, including insulin and C-reactive protein. Diabetes risk was fivefold lower among women with baseline IGFBP-2 levels in the top versus bottom quintile (odds ratio [OR]q5–q1 = 0.17 [95% CI 0.08–0.35]; P trend < 0.0001) and was also negatively associated with IGFBP-1 levels (ORq5–q1 = 0.37 [0.18–0.73]; P trend = 0.0009). IGFBP-3 was positively associated with diabetes (ORq5–q1 = 2.05 [1.20–3.51]; P trend = 0.002). Diabetes was not associated with total IGF-I levels, but free IGF-I and diabetes had a significant association that varied (P interaction = 0.003) by insulin levels above the median (ORq5–q1 = 0.48 [0.26–0.90]; P trend = 0.0001) versus below the median (ORq5–q1 = 2.52 [1.05–6.06]; P trend < 0.05). Thus, this prospective study found strong associations of incident diabetes with baseline levels of three IGFBPs and free IGF-I, consistent with hypotheses that the IGF axis might influence diabetes risk.