Qi Sun

Harvard Medical School | HMS

In epidemiological research, causal models incorporating potential mediators along a pathway are crucial for understanding how exposures influence health outcomes. This work is motivated by integrated epidemiological and blood biomarker studies, investigating the relationship between long-term adherence to a Mediterranean diet and cardiometabolic h...

A key challenge in differential abundance analysis of microbial samples is that the counts for each sample are compositional, resulting in biased comparisons of the absolute abundance across study groups. Normalization-based differential abundance analysis methods rely on external normalization factors that account for the compositionality by stand...

Although diet is a substantial determinant of the human gut microbiome, the interplay between specific foods and microbial community structure remains poorly understood. Coffee is a habitually consumed beverage with established metabolic and health benefits. We previously found that coffee is, among >150 items, the food showing the highest correlat...

Background A common genetic variant at the glutamate-ammonia ligase (GLUL) locus has been previously associated with an increased risk of coronary artery disease (CAD) as well as alterations of glutamic acid metabolism and the γ-glutamyl cycle in individuals with type 2 diabetes (T2D). Here we investigated whether less frequent variants in GLUL and...

Background Dietary strategies for type 2 diabetes (T2DM) prevention have mainly focused on solid foods and nutrients. Emanating evidence suggests that beverage consumption in adulthood may also influence T2DM development, whereas the role of beverages during adolescence remains unknow. Objective To examine adolescent beverages consumption, and the...

Since dietary intake is challenging to directly measure in large-scale cohort studies, we often rely on self-reported instruments (e.g., food frequency questionnaires, 24-hour recalls, and diet records) developed in nutritional epidemiology. Those self-reported instruments are prone to measurement errors, which can lead to inaccuracies in the calcu...

The effect of nonnutritive sweeteners (NNSs) on the body mass index [BMI (in kg/m 2)] of children and adolescents remains unclear despite rising consumption. Detailed systematic evaluations are warranted. We aimed to summarize evidence on NNS consumption and BMI sex-and age-specific absolute changes (kg/m 2) in pediatric populations, by NNS type, s...

Aims Circulating dimethylguanidino valeric acid (DMGV) was identified as a novel metabolite related to cardiorespiratory fitness and cardiometabolic abnormalities. Circulating DMGV levels are subjective to dietary modulation; however, studies on its associations with intakes of coronary heart disease (CHD)–related foods/nutrients are limited. We in...

Background and Aims Erythritol, a sugar alcohol (polyol), has recently been linked to the risks of major adverse cardiovascular events. We investigated whether plasma erythritol and other polyols (mannitol/sorbitol) were associated with the risk of incident coronary heart disease (CHD). Methods This prospective nested case-control study included 7...

Background Prospective associations between total and groups of ultra-processed foods (UPF) and cardiovascular disease (CVD) remained to be characterised. Our aim was to assess the association of total and group-specific UPF intakes with CVD, coronary heart disease (CHD), and stroke in three large prospective cohorts of US adults. Additionally, we...

Dietary haem iron intake is linked to an increased risk of type 2 diabetes (T2D), but the underlying plasma biomarkers are not well understood. We analysed data from 204,615 participants (79% females) in three large US cohorts over up to 36 years, examining the associations between iron intake and T2D risk. We also assessed plasma metabolic biomark...

Importance Lignans are phytoestrogens abundant in Western diets and may be associated with type 2 diabetes (T2D) risk. Objective To prospectively investigate associations between lignan intake and T2D incidence. Design, Setting, and Participants Population-based cohort study of US men and women enrolled in the Nurses’ Health Study (NHS, 1984-2018...

Background Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow‐up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shap...

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabo...

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scor...

Background In 2019, the EAT-Lancet Commission proposed a healthy dietary pattern that, along with reductions in food waste and improved agricultural practices, could feed the increasing global population sustainably. We developed a Planetary Health Diet Index (PHDI) to quantify adherence to the EAT-Lancet reference diet. Objectives We aimed to ass...

Importance Sleep duration and moderate-to-vigorous physical activity (MVPA) are associated with healthy aging, but the associations of sedentary behaviors and light-intensity physical activity (LPA) with healthy aging are still unclear. Objective To examine the independent association of sedentary behaviors and LPA with healthy aging, and to estim...

Background Accurate quantification of sodium intake based on self‐reported dietary assessments has been a persistent challenge. We aimed to apply machine‐learning (ML) algorithms to predict 24‐hour urinary sodium excretion from self‐reported questionnaire information. Methods and Results We analyzed 3454 participants from the NHS (Nurses' Health S...

Importance Plant-based diets are increasing in popularity due, in part, to their health benefits for selected cardiometabolic diseases as well as favorable environmental impact. Little is known about how such a diet is related to gout risk. Objective To examine associations between adherence to a plant-based diet (including healthy and unhealthy v...

Background Ultra-processed foods (UPFs) are emerging as a risk factor for colorectal cancer (CRC), yet how post-diagnostic UPF intake may impact CRC prognosis remains unexplored. Methods Data collected from food frequency questionnaires were used to estimate intakes of total UPFs and UPF subgroups (serving/d) at least 6 months but less than 4 year...

Background: While prostate cancer is the second leading cause of cancer death in U.S. males, most men with prostate cancer die from other causes. We prospectively examined the potential benefits of adhering to established healthy dietary patterns on overall and cause-specific mortality among men living with prostate cancer. Methods: We studied men...

Introduction: Lignans are polyphenolic compounds abundant in plant-based foods such as seeds, whole grains, and certain fruits and vegetables and may lead to better metabolic health. It remains elucidated regarding the role of lignan consumption in the etiology of premature deaths among diabetes patients. Hypothesis: We hypothesize that a higher in...

Background: Plasma metabolites have been associated with type 2 diabetes (T2D) risk and may reflect metabolic homeostasis as a result of the interplay among diet, genetics, and the gut microbiome. Hypothesis: We hypothesized that specific multi-metabolite signatures can characterize the adherence and metabolic response to various dietary patterns a...

Introduction: Early time-restricted eating (TRE) has been recently suggested as an effective dietary intervention strategy to improve risk factors of coronary heart disease (CHD), whereas late TRE may be related to poor cardiometabolic health. Metabolomic pathways linking the adherence to habitual TREs depending on the time of the day and CHD risk...

Background: Olive oil intake is inversely associated with the risk of chronic diseases and mortality. However, it is unclear whether there is an association between olive oil intake and weight changes; because it is an energy-dense food concerns have been raised that high intake may contribute to weight gain. Therefore, we aimed to determine the as...

Introduction: Chronic disruption of circadian rhythms is linked to weight gain and metabolic dysregulation. Time-restricted eating (TRE), a form of intermittent fasting, has shown effectiveness in improving short-term weight loss and energy homeostasis. However, associations between habitual adherence to TRE and long-term weight change remain under...

Background: Childhood obesity has become a public health challenge globally, with increasing prevalence worldwide. Existing studies have indicated a potential link between maternal macronutrients intake and subsequent weight changes in their offspring during childhood. However, the long-term relationship between maternal macronutrient consumption a...

Introduction: Gestational diabetes mellitus (GDM) is associated with higher lifetime cardiovascular disease (CVD) risk in women, even without subsequent type 2 diabetes (T2D). Dysregulation of lipid and amino acid metabolism precedes CVD and has been associated with T2D in women with GDM history. However, the precise metabolic pathways contributing...

Introduction: Evidence on the relationship between type 2 diabetes onset age, duration, and mortality risk has been influenced by limited follow-up, inadequate control for confounding, and inability to cover the full range of onset age, duration, and the full spectrum of major causes of death. Moreover, there are scarce data dissecting how type 2 d...

Background Protein intake plays an important role in maintaining the health status of older adults. However, few epidemiologic studies examined midlife protein intake in relation to healthy aging. Objectives The objective of this study was to evaluate the long-term role of dietary protein intake in healthy aging among female participants in the pr...

Background Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume co...

BACKGROUND The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified ana...

Our objective was to evaluate the role of dietary carbohydrate quality in healthy aging among women in the Nurses’ Health Study (NHS). We included 29,635 NHS participants aged <60 years old in 1984. Total carbohydrate, refined carbohydrate, dietary glycemic index (GI), dietary fiber intake and carbohydrate from fruits, vegetables, whole and refined...

Context Psychological distress has been linked to diabetes risk. Few population-based, epidemiologic studies have investigated the potential molecular mechanisms (e.g., metabolic dysregulation) underlying this association. Objective To evaluate the association between a metabolomic signature for psychological distress and diabetes risk. Methods W...

Current guidelines for cardiometabolic disease prevention recommend increasing dietary unsaturated fat intake while reducing saturated fats. However, standard cardiometabolic risk markers may not fully capture the metabolic benefits. Here, we demonstrate that a deep lipidomics-based multi-lipid score (MLS) accurately reflects the metabolic impact o...

Since dietary intake is hard to directly measure in large-scale cohort studies, we often rely on self-reported instruments (e.g., food frequency questionnaires, diet recall surveys, and diet diary methods) developed in nutritional epidemiology. Those self-reported instruments are prone to measurement errors. The measurement errors eventually lead t...

Background: The plant-based Portfolio dietary pattern includes recognized cholesterol-lowering foods (ie, plant protein, nuts, viscous fiber, phytosterols, and plant monounsaturated fats) shown to improve several cardiovascular disease (CVD) risk factors in randomized controlled trials. However, there is limited evidence on the role of long-term ad...

Background Plant-based dietary patterns are gaining more attention due to their potential in reducing the risk of developing major chronic diseases, including type 2 diabetes (T2D), cardiovascular disease (CVD), cancer, and mortality, while an up-to-date comprehensive quantitative review is lacking. This study aimed to summarize the existing prospe...

Objective To comprehensively examine the associations between changes in carbohydrate intake and weight change at four year intervals. Design Prospective cohort study. Setting Nurses’ Health Study (1986-2010), Nurses’ Health Study II (1991-2015), and Health Professionals Follow-Up Study (1986-2014). Participants 136 432 men and women aged 65 yea...

Objectives To identify indolepropionate (IPA)-predicting gut microbiota species, investigate potential diet–microbiota interactions, and examine the prospective associations of circulating IPA concentrations with type 2 diabetes (T2D) and coronary heart disease (CHD) risk in free-living individuals. Design We included 287 men from the Men’s Lifest...

Experimental studies reported biochemical actions underpinning aging processes and mortality, but the relevant metabolic alterations in humans are not well understood. Here we examine the associations of 243 plasma metabolites with mortality and longevity (attaining age 85 years) in 11,634 US (median follow-up of 22.6 years, with 4288 deaths) and 1...

Background: Evening chronotype may promote adherence to an unhealthy lifestyle and increase type 2 diabetes risk. Objective: To evaluate the role of modifiable lifestyle behaviors in the association between chronotype and diabetes risk. Design: Prospective cohort study. Setting: Nurses' Health Study II. Participants: 63 676 nurses aged 45...

Background: Evidence regarding the potential health effects of dietary amino acids glutamine and glutamate among individuals with type 2 diabetes (T2D) is limited. Objectives: The aim was to examine dietary glutamine and glutamate in relation to subsequent risk of cardiovascular disease (CVD) and mortality among individuals with T2D. Methods:...

Objective: We examined whether intake of methyl donor nutrients, including vitamins B2, B6, and B12 and folate, from foods and/or supplements is associated with type 2 diabetes risk. Research design and methods: We included 203,644 women and men from the Nurses' Health Study (1984-2016), Nurses' Health Study 2 (1991-2017), and Health Professiona...

Studying human dietary intake may help us identify effective measures to treat or prevent many chronic diseases whose natural histories are influenced by nutritional factors. Here, by examining five cohorts with dietary intake data collected on different time scales, we show that the food intake profile varies substantially across individuals and o...

BACKGROUND The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial. OBJECTIVES This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF. METHODS We used participant-...

Obesity has been associated with increased risk of morbidity and mortality as well as decreased odds of healthy aging. Physical activity is often prescribed to reduce body weight by increasing energy use, but the amount of weight loss is highly variable. Our gut microbiome may play a role in this variability through its influence on energy balance...

Background The gut microbiome regulates host energy balance and adiposity-related metabolic consequences, but it remains unknown how the gut microbiome modulates body weight response to physical activity (PA). Methods Nested in the Health Professionals Follow-up Study, a subcohort of 307 healthy men (mean[SD] age, 70[4] years) provided stool and b...

Introduction Chronotype refers to one’s inclination to earlier or later sleeping times. Late chronotype has been linked to increased diabetes risk, which may be mediated through adherence to unhealthy lifestyle. This study aimed to evaluate the interplay among chronotype, lifestyle factors, and diabetes risk. Methods In 2009, 63,594 diabetes-free...

Objective: The Mediterranean diet is associated with lower risks for type 2 diabetes (T2D) and cardiovascular disease in certain populations, although data among diverse groups are limited. This study evaluated cross-sectional and prospective associations between a novel South Asian Mediterranean-style (SAM) diet and cardiometabolic risk among US...

Background: Associations between per- and polyfluoroalkyl substances (PFAS) and blood lipid levels in humans were mixed. Objectives: The objective of this meta-analysis was to summarize associations between PFAS and blood lipids in adults. Methods: A literature search was conducted on PubMed and Web of Science for articles published through 13...

Objective To investigate the intake of specific types of beverages in relation to mortality and cardiovascular disease (CVD) outcomes among adults with type 2 diabetes. Design Prospective cohort study. Setting Health professionals in the United States. Participants 15 486 men and women with a diagnosis of type 2 diabetes at baseline and during f...

Background: Multiple studies have independently investigated associations between the consumption of individual beverage types and specific plasma biomarkers, with type 2 diabetes (T2D) risk. However, as individuals do not consume single beverage types exclusively, and plasma biomarkers do not act in isolation, it remains unclear how patterns of b...

Background: High unprocessed and minimally processed food (UMP) intake has been associated with high-quality diets, while the opposite has been shown for ultra-processed food (UPF). Nevertheless, the association between UMP and UPF consumption and diet-quality over the long-term warrants further examination. Objective: This study aimed to assess...

Objective: We examined the relationship between ultra-processed food (UPF) intake and type 2 diabetes (T2D) risk among 3 large U.S. cohorts, conducted a meta-analysis of prospective cohort studies, and assessed meta-evidence quality. Research design and methods: We included 71,871 women from the Nurses' Health Study, 87,918 women from the Nurses...

Introduction: Ultra-processed foods (UPF) are associated with cardiovascular disease (CVD) in European populations. Evidence is limited from U.S. populations, for specific UPF subgroups, and in the diet quality context. Hypothesis: We hypothesized that U.S. women with higher UPF intake have higher CVD risk and evaluated this association by UPF subg...

Introduction: Recent evidence suggests that intake of ultra-processed foods (UPF) is related to unfavorable cardio-metabolic risk profiles among generally healthy populations. However, evidence on the relationship between UPF intake and cardiovascular disease (CVD) among patients with type 2 diabetes (T2D) is lacking. Hypothesis: We assessed the hy...

Introduction: Recent evidence suggests that dietary proteins modulate the microbial composition and metabolite production to influence host physiology. Gut-microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors, phenylacetylglutamine (PAGln) and p-tolyl (cresol) sulfate, have been recently implicated as atherogenic...

The association of PFASs with blood lipids, lipoproteins and apolipoproteins, and coronary heart disease (CHD) risk are inconsistent in previous studies. The aim of current study is to examine the potential association between plasma PFASs, blood lipoproteins and their subspecies defined by apolipoproteins, and whether PFASs are associated with CHD...