Metabolomics profiles of type 2 diabetes and insulin resistance and their associations with total mortality.

Plant-based diet quality and the risk of total and disease-specific mortality: A population-based prospective study

Objective: To investigate associations of butter and plant-based oil intakes with risk of total and cause-specific mortality. Participants: 221,054 women and men from the Nurses’ Health Study (1990-2018), Nurses’ Health Study II (1991-2018), and Health Professionals Follow-up Study (1990-2018) were included, all of whom were free of cancer, cardiovascular disease (CVD), diabetes, or neurodegenerative disease at baseline. Exposure: We assessed dietary intake repeatedly using validated semiquantitative food frequency questionnaires every 4 years. Primary exposures included total butter (butter added at the table and from baking and frying) and plant-based oil intake (safflower, soybean, corn, canola, and olive oil). Main Outcome: We identified deaths through the National Death Index and other sources. A physician classified the cause of death based on all available records. Total mortality was the primary outcome, and mortality due to cancer and CVD were secondary outcomes. Results: During up to 28 years of follow-up, we documented 41,618 deaths, including 11,380 from cancer and 9,114 from CVD. After adjusting for confounding factors, the highest butter intake was associated with an 18% higher risk of total mortality compared to the lowest intake (HR: 1.18; 95% CI: 1.10-1.25; P trend <0.001). Conversely, the highest plant-based oil intake was linked to an 18% lower risk of total mortality (HR: 0.82; 95% CI: 0.76-0.89; P trend <0.001). Higher olive, soybean, and canola oil intakes were also significantly associated with lower total mortality (all P trend <0.001). For every 10 g/day increase in plant-based oil intake, cancer mortality risk decreased by 11% (HR: 0.89; 95% CI: 0.85-0.94; P trend <0.001), and CVD mortality risk by 6% (HR: 0.94; 95% CI: 0.89-0.99; P trend = 0.03). Higher butter intake was associated with increased cancer mortality (HRper10g/day: 1.12; 95% CI: 1.04-1.20; P trend <0.001), but not with CVD mortality ( P trend =0.61). Replacing 10 g/day of butter with plant-based oils was associated with a 19% reduction in total mortality (HR: 0.81; 95% CI: 0.77-0.85; P trend <0.001) and a 20% reduction in cancer mortality (HR: 0.80; 95% CI: 0.74-0.88; P trend <0.001). Conclusion: A higher intake of butter is associated with higher mortality, while a higher intake of plant-based oil is associated with lower mortality. Substituting butter with plant-based oils may confer substantial benefits for preventing premature deaths.

BackgroundNumerous studies have suggested that fasting plasma glucose (FPG) was associated with the risk of mortality. However, relationship on longitudinal changes of FPG with the risk of mortality remained inconsistent.MethodsWe examined the association of FPG at baseline and its longitudinal changes with risk of mortality based on a cohort study in Yinzhou, China, during 2010–2018. Cox regression models and competing risk models were separately used to examine the association of FPG levels and long‐term fluctuation with risk of total and cause‐specific mortality.ResultsSubjects who had an impaired fasting glucose or diabetes suffered a higher risk of total mortality than subjects who had a normal fasting glucose (HRs and 95% CIs: 1.17 [1.01–1.35], 1.30 [1.10–1.53], respectively). The HR for total mortality was 1.54 (95% CI: 1.29–1.84) and for cancer mortality was 1.41 (95% CI: 1.04–1.92) in the highest quartile of coefficient of variation of FPG. Trajectory analysis indicated that subjects with a significantly changed FPG suffered a higher risk of total mortality.ConclusionAccording to this cohort study, we found that long‐term fluctuation of FPG was significantly associated with the risk of total and cancer mortality. Our findings suggest that long‐term fluctuation of FPG could be used as an efficient indicator for predicting the subsequent risk of mortality.

Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with risk of mortality is of public health interest. We examined associations between consumption of SSBs and ASBs with risk of total and cause-specific mortality among 37 716 men from the Health Professional's Follow-up study (from 1986 to 2014) and 80 647 women from the Nurses' Health study (from 1980 to 2014) who were free from chronic diseases at baseline. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals. We documented 36 436 deaths (7896 cardiovascular disease [CVD] and 12 380 cancer deaths) during 3 415 564 person-years of follow-up. After adjusting for major diet and lifestyle factors, consumption of SSBs was associated with a higher risk of total mortality; pooled hazard ratios (95% confidence intervals) across categories (<1/mo, 1-4/mo, 2-6/week, 1-<2/d, and ≥2/d) were 1.00 (reference), 1.01 (0.98, 1.04), 1.06 (1.03, 1.09), 1.14 (1.09, 1.19), and 1.21 (1.13, 1.28; P trend <0.0001). The association was observed for CVD mortality (hazard ratio comparing extreme categories was 1.31 [95% confidence interval, 1.15, 1.50], P trend <0.0001) and cancer mortality (1.16 [1.04, 1.29], P trend =0.0004). ASBs were associated with total and CVD mortality in the highest intake category only; pooled hazard ratios (95% confidence interval) across categories were 1.00 (reference), 0.96 (0.93, 0.99), 0.97 (0.95, 1.00), 0.98 (0.94, 1.03), and 1.04 (1.02, 1.12; P trend = 0.01) for total mortality and 1.00 (reference), 0.93 (0.87, 1.00), 0.95 (0.89, 1.00), 1.02 (0.94, 1.12), and 1.13 (1.02, 1.25; P trend = 0.02) for CVD mortality. In cohort-specific analysis, ASBs were associated with mortality in NHS (Nurses' Health Study) but not in HPFS (Health Professionals Follow-up Study) ( P interaction, 0.01). ASBs were not associated with cancer mortality in either cohort. Consumption of SSBs was positively associated with mortality primarily through CVD mortality and showed a graded association with dose. The positive association between high intake levels of ASBs and total and CVD mortality observed among women requires further confirmation.

BackgroundAlthough studies have demonstrated that both lifestyles and subjective well-being (SWB) are associated with mortality risk, the joint effects of a healthy lifestyle and SWB on the risk of mortality are unclear. This study aimed to explore the combined impact of lifestyles and SWB on total mortality among the older Chinese population.MethodsData were obtained from the Chinese Longitudinal Healthy Longevity Survey conducted from 2002 to 2018. A total of 13,282 participants aged ≥ 65 years were included. SWB was measured by an eight-item tool covering life satisfaction, optimism, conscientiousness, anxiety, loneliness, personal control, feeling useless, and happiness. A total healthy lifestyle score was calculated by summing across five lifestyle factors (smoking, drinking, exercise, dietary diversity and body mass index), ranging from 0 to 5, and was categorized into the following groups: healthy (4–5 points), intermediate (2–3 points) and unhealthy (0–1 point). Cox proportional regression analyses were carried out adjusting for demographic characteristics and other potential confounders.ResultsIn total, 8549 (64.4%) deaths were reported during the follow-up period. Compared with the higher healthy lifestyle score, the hazard ratios (HRs) for all-cause mortality for the intermediate and unhealthy lifestyle scores were 1.11 (1.04–1.17) and 1.17 (1.09–1.26), respectively, independent of SWB. A similar relationship between SWB and total mortality was observed, independent of lifestyle factors. The participants who had worse SWB experienced a 1.19 (1.14–1.25) higher risk of total mortality in comparison with those who had better SWB after adjusting for lifestyles. Combinations of unhealthy lifestyle scores and poor SWB were associated with an increased risk of total mortality, and the highest risk was found among participants with a healthy lifestyle score of 0–1 and worse SWB (HR = 1.41, 95% CI = 1.28–1.55).ConclusionsA stronger risk of total mortality was found when worse SWB and unhealthy lifestyle occurred together, suggesting that a comprehensive approach to healthy lifestyle and SWB might be a potential strategy to improve longevity.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12877-025-06345-2.

Introduction: Moderate alcohol intake is associated with reduced risk of ischemic heart disease and total mortality but might have a detrimental role in several other diseases (in particular some cancers). The association of moderate alcohol intake with reduced total mortality has therefore been questioned. Hypothesis: Alcohol intake have a non-linear association with cardiovascular (CV) and total mortality. Methods: Using harmonised data from the cohorts in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project, the association of alcohol intake with risk of cardiovascular disease and total mortality was assessed using multivariable Cox regression. Multiple imputation (n=10) was used to accommodate missing data for covariates. Results: 67.4% of the populations studied were drinkers (median intake among drinkers 11 g/day of ethanol, no missing data). Their mortality was observed over median follow-up of 13.8 yrs and covariates (age, sex, smoking, hypertension, diabetes, history of CVD, BMI and level of education) were available for 19 cohorts (1 from Australia and 18 from Europe), including 197,113 individuals (mean age 51±12 y, 60% men, no missing data) and 36,730 deaths (12,644 coronary or cerebrovascular). Former drinkers (2.8%) were excluded from the reference group, which thus comprised habitual teetotallers only (17.7%). Because of missing data, we failed to distinguish between teetotallers and former drinkers in n=24,036 (12.2%) non-drinkers; these individuals were analysed separately but not included in the reference group. In comparison with the reference group, intake of alcohol up to 5 g/day was associated with a 10.5% (95%CI: 6.7% to 14.2%) reduction in the risk of total mortality and 11.8% (5.2% to 17.9%) in the risk of CV mortality; intake between 5 and 10 g/day with a 6.5% (2.0% to 11.0%) and a 3.4% (0.3% to 15.5%) reduction, respectively, while intake over 20 g/day was associated with a 14.5% (9.6% to 19.7%) increase in risk of total mortality and a 6.3% (-1.5% to 14.7%) rise in the risk of CV mortality. Findings were similar in men and women and according to level of education, whereas they were heterogeneous across Countries, with greater protection by alcohol observed in Italy and France and lowest in Australia. The reduced risk of mortality associated with alcohol in moderation was more marked when the beverage of preference was wine rather than beer or spirits; the increased risk associated with heavy intake appeared in individuals whose beverage of preference was beer or spirits. Conclusions: Using a large multi Country cohort, we confirmed that intake of more than 2 alcoholic units per day is associated with a detrimental health effect, while intake of alcohol in moderation (up to 1 unit per day) is associated with reduced risk of CV and total mortality, with small variations according to Country and type of alcoholic beverage.

Long-term data describing small abdominal aortic aneurysms (AAAs) and increasing infrarenal aortic diameters and their relationship to future surgical repair, total mortality, and incident cardiovascular disease (CVD) events, particularly among women, are sparse. In 1992 to 1993, 4734 Cardiovascular Health Study participants > or = 65 years old had an abdominal aortic ultrasound evaluation. Of those screened, 416 had an AAA (infrarenal aortic diameter > or = 3.0 cm or an infrarenal/suprarenal ratio > or = 1.2). By 2002, there were 56 surgical AAA repairs and 10 AAA-related deaths. A single ultrasound screening demonstrated that aneurysm dilation > or = 3 cm identified 68% of all AAA repairs over the next 10 years and 6 of the 10 AAA-related deaths in 4% of the total population and that a > or = 2.5-cm dilation identified 91% of all AAA repairs and 9 of the 10 deaths in 10% of the total population. With adjusted Cox proportional hazard models, AAAs were associated with a higher risk of total mortality (hazard ratio 1.44, 95% confidence interval 1.25 to 1.66) and incident CVD events (hazard ratio 1.52, 95% confidence interval 1.25 to 1.85). Compared with diameters < 2.0 cm, infrarenal aortic diameters 2.0 to < 3.0 cm were associated with increased risk of incident CVD events in women and total mortality in men. This study suggests that a 1-time screening of the abdominal aorta can acceptably identify individuals with a clinically significant AAA. Infrarenal aortic diameters > 2.0 cm are associated with a significantly increased risk of future CVD events and total mortality.

Adhering to a Healthy Lifestyle Attenuates the Risk of Total Mortality Related to Cardiometabolic Diseases: A Prospective UK Biobank Cohort Study

The relationship between butter and plant-based oil intakes and mortality remains unclear, with conflicting results from previous studies. Long-term dietary assessments are needed to clarify these associations. To investigate associations of butter and plant-based oil intakes with risk of total and cause-specific mortality among US adults. This prospective population-based cohort study used data from 3 large cohorts: the Nurses' Health Study (1990-2023), the Nurses' Health Study II (1991-2023), and the Health Professionals Follow-up Study (1990-2023). Women and men who were free of cancer, cardiovascular disease (CVD), diabetes, or neurodegenerative disease at baseline were included. Primary exposures included intakes of butter (butter added at the table and from cooking) and plant-based oil (safflower, soybean, corn, canola, and olive oil). Diet was assessed by validated semiquantitative food frequency questionnaires every 4 years. Total mortality was the primary outcome, and mortality due to cancer and CVD were secondary outcomes. Deaths were identified through the National Death Index and other sources. A physician classified the cause of death based on death certificates and medical records. During up to 33 years of follow-up among 221 054 adults (mean [SD] age at baseline: 56.1 [7.1] years for Nurses' Health Study, 36.1 [4.7] years for Nurses' Health Study II, and 56.3 [9.3] years for Health Professionals Follow-up Study), 50 932 deaths were documented, with 12 241 due to cancer and 11 240 due to CVD. Participants were categorized into quartiles based on their butter or plant-based oil intake. After adjusting for potential confounders, the highest butter intake was associated with a 15% higher risk of total mortality compared to the lowest intake (hazard ratio [HR], 1.15; 95% CI, 1.08-1.22; P for trend < .001). In contrast, the highest intake of total plant-based oils compared to the lowest intake was associated with a 16% lower total mortality (HR, 0.84; 95% CI, 0.79-0.90; P for trend < .001). There was a statistically significant association between higher intakes of canola, soybean, and olive oils and lower total mortality, with HRs per 5-g/d increment of 0.85 (95% CI, 0.78-0.92), 0.94 (95% CI, 0.91-0.96), and 0.92 (95% CI, 0.91-0.94), respectively (all P for trend < .001). Every 10-g/d increment in plant-based oils intake was associated with an 11% lower risk of cancer mortality (HR, 0.89; 95% CI, 0.85-0.94; P for trend < .001) and a 6% lower risk of CVD mortality (HR, 0.94; 95% CI, 0.89-0.99; P for trend = .03), whereas a higher intake of butter was associated with higher cancer mortality (HR, 1.12; 95% CI, 1.04-1.20; P for trend < .001). Substituting 10-g/d intake of total butter with an equivalent amount of total plant-based oils was associated with an estimated 17% reduction in total mortality (HR, 0.83; 95% CI, 0.79-0.86; P < .001) and a 17% reduction in cancer mortality (HR, 0.83; 95% CI, 0.76-0.90; P < .001). In this cohort study, higher intake of butter was associated with increased mortality, while higher plant-based oils intake was associated with lower mortality. Substituting butter with plant-based oils may confer substantial benefits for preventing premature deaths.

Associations among dietary fat, cholesterol intake and total mortality remain controversial, and most available data cover Western populations. The aim of this study was to assess associations for dietary fat and cholesterol in relation to total mortality in Koreans. This study used data from three prospective Korean Genome and Epidemiology studies (conducted between June 2001 and December 2013). A total of 194,295 middle-aged and older Korean adults were included. Dietary fat intake was classified into quintiles. Dietary cholesterol intake was categorized into three groups based on cholesterol intake as follows: <200mg, 200-299mg and ≥300mg. A multivariable Cox frailty model with random effects was applied to calculate hazard ratios (HR) and 95% confidence intervals (CIs) after adjusting for confounders. We documented 3866 deaths across a mean (min-max) follow-up period of 8.15years (3-13years). Higher fat intake was associated with lower total mortality (Q5 vs. Q1, HR 0.82 [95% CI 0.69, 0.98]; p trend<0.01) after adjusting for age, sex, body mass index, alcohol, smoking, exercise and total calorie and protein (%) intake. Higher dietary cholesterol intake (≥300mg/day) was associated with a higher risk of total mortality (HR 1.19 [95% CI 1.04, 1.37]) than lower cholesterol intake (<200mg/day) in the multivariate model. In Koreans, high dietary fat intake is associated with a lower risk of total mortality, while dietary cholesterol intake above 300mg/day is associated with a higher risk of total mortality.

Several epidemiologic investigations have suggested that weight loss is associated with increased mortality risk but have not examined whether the weight loss was intentional or unintentional. The authors examined whether the association between weight loss and mortality differs by whether the weight loss was intentional or unintentional as part of the Iowa Women's Health Study, a prospective cohort study of health risk factors in postmenopausal women. Women aged 55-69 years completed questions about intentional and unintentional weight losses since age 18 years via mail survey in 1992 and were followed through 1995. One or more intentional weight loss episodes of 20 or more pounds (> or =9.1 kg) during adulthood was not significantly associated with higher total or cardiovascular disease mortality risk compared with never losing > or =20 pounds. One or more unintentional weight loss episodes of 20 or more pounds was associated with a 26-57% higher total mortality risk and a 51-114% higher cardiovascular disease mortality risk, compared with never losing 20 or more pounds. Associations between unintentional weight loss and increased mortality risk were confined mostly to women with prevalent disease, hypertension, or diabetes. Patterns of association did not vary by overweight status. These findings suggest that the association between weight loss and increased mortality risk observed in epidemiologic studies may be due to unintentional weight loss that reflects existing disease and not due to intentional weight loss.

Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study

Breast cancer survivors often have a reduced digestive capacity to digest whole grains due to cancer treatment. The purpose of this study was to investigate the independent and joint associations of whole grain and refined grain consumption with total mortality among breast cancer survivors. We studied a cohort of 3081 female breast cancer survivors who provided demographic, dietary, and lifestyle data at baseline, year 1 and year 4. Mortality was assessed via semi-annual telephone interviews and confirmed by the National Death Index (NDI) and death certificates. We assessed the associations of whole grain and refined grain with incident of mortalities using Cox proportional hazards models. Increased whole grain consumption was marginally associated with an increased risk of total mortality (p = 0.07) but was not significantly associated with breast cancer-specific mortality (p = 0.55). An increased intake of refined grains was associated with an increased risk of both total (HR = 1.74; 95% CI,1.17 to 2.59) and breast cancer-specific mortality (HR = 1.16; 95% CI, 1.08 to 1.26). Furthermore, we examined the joint associations of whole grain and refined grain with total mortality. Among those with a high consumption of refined grain, those with high consumption of whole grain had a higher risk of total mortality (HR = 1.52, 95% CI, 1.07 to 2.14) than those with a low consumption of whole grain. Increased consumption of whole grains may exacerbate the adverse associations of refined grain with mortality among breast cancer survivors. Our findings indicate the need to revisit current dietary guidelines for breast cancer survivors regarding whole grain intake.

A healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity. In four large cohorts with 13,056 individuals and 28-year follow-up, we assessed five healthy lifestyle factors, used liquid chromatography mass spectrometry to profile plasma metabolites, and ascertained deaths with death certificates. The unique healthy lifestyle metabolomic signature was identified using an elastic regression. Multivariable Cox regressions were used to assess associations of the signature with mortality and longevity. The identified healthy lifestyle metabolomic signature was reflective of lipid metabolism pathways. Shorter and more saturated triacylglycerol and diacylglycerol metabolite sets were inversely associated with the healthy lifestyle score, whereas cholesteryl ester and phosphatidylcholine plasmalogen sets were positively associated. Participants with a higher healthy lifestyle metabolomic signature had a 17% lower risk of all-cause mortality, 19% for cardiovascular disease mortality, and 17% for cancer mortality and were 25% more likely to reach longevity. The healthy lifestyle metabolomic signature explained 38% of the association between the self-reported healthy lifestyle score and total mortality risk and 49% of the association with longevity. This study identifies a metabolomic signature that measures adherence to a healthy lifestyle and shows prediction of total and cause-specific mortality and longevity. This work was funded by the NIH, CIHR, AHA, Novo Nordisk Foundation, and SciLifeLab.

P1566Identification of the cardiovascular threshold limit for serum uric acid. Analysis from a general Italian population