About

David Jacobs is the Mayo Professor of Public Health and a Professor in the Department of Epidemiology & Community Health. His research extensively focuses on cardiovascular health, particularly the development and progression of coronary artery disease and atherosclerosis. He has contributed to major longitudinal studies such as the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA), investigating risk factors and biomarkers related to heart disease and physical activity. Jacobs' work also addresses broader public health concerns including liver disease, insulin resistance, and the impact of lifestyle factors such as diet and physical activity on chronic disease risk. His research aligns with multiple United Nations Sustainable Development Goals, including those targeting poverty, hunger, health, education, gender equality, and climate action. Jacobs has been involved in numerous funded projects and has a prolific publication record, contributing to the understanding of disease mechanisms and prevention strategies in diverse populations.

Research topics

• Internal medicine
• Medicine
• Endocrinology
• Cardiology
• Surgery
• Gerontology
• Pediatrics
• Environmental health

Selected publications

• Association Between Body Mass Index and Breast Cancer Incidence in Non-Hispanic White and Black Women: Methodological Considerations From a Secondary Analysis of the Vitamin D and Omega-3 Trial Cohort

  Cureus · 2026-04-24

  articleOpen access

  Introduction: Obesity and age are established risk factors for breast cancer, but racial differences in the association between body mass index (BMI) and breast cancer incidence remain incompletely understood. This study examined the association between BMI and breast cancer incidence among non-Hispanic White and Black women in the VITamin D and OmegA-3 TriaL (VITAL) cohort and secondarily considered methodological issues that may arise when clinical trial data are analyzed observationally. Methods: We conducted a secondary observational analysis of women enrolled in the VITAL cohort, treating trial participants as a cohort rather than comparing randomized treatment arms. After excluding men and women of races/ethnicities other than non-Hispanic White or Black, 11,377 women aged 55-90 years at baseline with no previous history of breast cancer were included. Using SAS OnDemand software (SAS Institute, Cary, NC), we examined the association between BMI and the incidence of breast cancer with Cox proportional hazards regression models. Results: The study sample of 218 women with breast cancer included 84% non-Hispanic White women (n = 183) and 16% Black women (n = 35). Age and White race were each positively related to incident breast cancer in unadjusted models (both p < 0.001). There was a positive nonlinear relationship between BMI and breast cancer (p = 0.0072, df = 1, x2 = 7.23). On more detailed examination, the increasing breast cancer risk was found mainly across lower levels of BMI and younger ages in these non-Hispanic White and Black women. Conclusion: Breast cancer incidence showed a nonlinear association with BMI and age, increasing across lower ranges but attenuating at higher BMI levels and older ages. Because this was a secondary analysis of a selected trial cohort, the unexpected attenuation should be interpreted cautiously rather than as evidence of a physiologic plateau.

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• Adverse childhood family environment is associated with altered cardiovascular regulation during exercise among young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

  medRxiv · 2026-04-28

  articleOpen access

  ABSTRACT The purposes of this study were to determine whether adverse childhood family environment (ACFE) exposure is associated with altered hemodynamic responses to graded exercise in young adulthood, and whether this association was modified by sex and race in a large, population-based cohort. We hypothesized that ACFE exposure would be associated with an exaggerated exercise pressor response in young adulthood, independent of resting BP. We further hypothesized that the association between ACFE and the hemodynamic response to exercise would be stronger in females than males, and in Black versus White participants. Methods Exercising blood pressure (BP) and heart rate (HR) responses were recorded during graded exercise testing and ACFE exposure was assessed among 3,417 young adults (mean age = 25 ± 4 y; 44% female; 46% Black). Linear mixed-effects models that included participant-specific random intercepts and random slopes were used to assess the relation between ACFE exposure and exercising systolic (SBP), diastolic, and mean BP, pulse pressure (PP), pulse pressure index (PPI), heart rate (HR), and rate pressure product (RPP). All models were adjusted for resting values of the hemodynamic outcome, as well as age, sex, race, study center, body mass index, current hypertension medication use, smoking status, and alcohol consumption. Results Graded exercise hemodynamic responses were analyzed in 3,346–3,417 participants in the final models, providing 15,372–17,481 observations. Higher ACFE exposure was associated with lower SBP (β = −0.304 mmHg/ACFE, p = 0.033), HR (β = −0.485 bpm/ACFE, p <0.001), and RPP (β = −83.404 bpm·mmHg/ACFE, p =0.002) at the lowest workload, but steeper workload-related increases in SBP (interaction β = 0.044 mmHg·MET⁻¹·ACFE⁻¹, p =0.029), HR (β = 0.061 bpm·MET⁻¹·ACFE⁻¹, p <0.001), RPP (β = 10.16 bpm·mmHg·MET⁻¹·ACFE⁻¹, p =0.025), and PP (β = 0.052 mmHg·MET⁻¹·ACFE⁻¹, p =0.038) and PPI (β = 0.000232 units·MET⁻¹·ACFE⁻¹, p =0.018). These findings were robust to additional adjustment for central adiposity, exercise capacity, and maximal heart rate and heart rate recovery. Conclusion Our findings add nuanced evidence revealing that early adversity is associated with a demand-dependent shift in cardiovascular regulation, with attenuated responses at low demand, but more dramatic increases in pulsatile and myocardial load responses during progressive physiological stress.

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• Plasma lactate and its association with adiposity and biomarkers of cardiometabolic risk

  Nutrition Metabolism and Cardiovascular Diseases · 2025-11-08 · 1 citations

  article
  PublisherDOI

• Arterial Stiffness in Heart‐Healthy Indigenous Tsimane Forager‐Horticulturalists

  Journal of the American Heart Association · 2025-07-14

  articleOpen access

  BACKGROUND: Little is known about arterial stiffness in rural subsistence populations that experience few cardiovascular risk factors. We conducted a cross-sectional study comparing 3 arterial stiffness metrics among Tsimane forager-horticulturalists with 2 representative US cohorts. METHODS: Arterial elasticity (the inverse of stiffness) markers C1 (large artery elasticity) and C2 (small artery elasticity) were measured using a tonometry device among 490 Tsimane adults (mean age, 51.2±10.1 years; 55% women), and compared with 6294 multiethnic US adults (mean age, 62.0±10.2 years; 52% women) from MESA (Multi-Ethnic Study of Atherosclerosis). Carotid-femoral pulse wave velocity was assessed using the foot-to-foot method in a smaller Tsimane sample (n=94) and compared with 3086 predominantly White US adults (mean age, 46.1±8.7 years; 54% women) from the FHS Gen3 (Framingham Heart Study Third Generation). RESULTS: Tsimane participants exhibited superior arterial health compared with US cohorts, with higher elasticity (C1/C2) and lower stiffness (carotid-femoral pulse wave velocity). Their C1 (mean 22.8±12.2 mL/mm Hg×10) and C2 (mean 7.5±4.0 mL/mm Hg×100) were 47.3% and 35.7% higher than MESA participants by age 40 years, respectively, and differences remained sustained throughout adulthood. Compared with participants in FHS Gen3, the carotid-femoral pulse wave velocity in Tsimane participants (mean 6.2±1.2 m/s) was 33.9% lower and showed a minimal age-related increase, with carotid-femoral pulse wave velocity only higher by age 70+ (β=1.74±0.38; reference <40 years). Tsimane participants with ≥2 comorbidities (hypertension, obesity, and diabetes) had ≈25% higher arterial elasticity than healthy Americans with no comorbidities. CONCLUSIONS: Tsimane forager-farmers of the Bolivian Amazon demonstrate substantially lower arterial stiffness throughout adulthood than more urbanized and sedentary populations, and the differences are only partially explained by conventional cardiometabolic risk factors.

  PublisherDOI

• Dietary metabolic signatures and cardiometabolic risk

  UNC Libraries · 2025-07-26

  articleOpen access

  AIMS: Observational studies of diet in cardiometabolic-cardiovascular disease (CM-CVD) focus on self-reported consumption of food or dietary pattern, with limited information on individual metabolic responses to dietary intake linked to CM-CVD. Here, machine learning approaches were used to identify individual metabolic patterns related to diet and relation to long-term CM-CVD in early adulthood. METHODS AND RESULTS: In 2259 White and Black adults (age 32.1 &plusmn; 3.6 years, 45% women, 44% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, multivariate models were employed to identify metabolite signatures of food group and composite dietary intake across 17 food groups, 2 nutrient groups, and healthy eating index-2015 (HEI2015) diet quality score. A broad array of metabolites associated with diet were uncovered, reflecting food-related components/catabolites (e.g. fish and long-chain unsaturated triacylglycerols), interactions with host features (microbiome), or pathways broadly implicated in CM-CVD (e.g. ceramide/sphingomyelin lipid metabolism). To integrate diet with metabolism, penalized machine learning models were used to define a metabolite signature linked to a putative CM-CVD-adverse diet (e.g. high in red/processed meat, refined grains), which was subsequently associated with long-term diabetes and CVD risk numerically more strongly than HEI2015 in CARDIA [e.g. diabetes: standardized hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.32-1.97, P &lt; 0.0001; CVD: HR: 1.55, 95% CI: 1.12-2.14, P = 0.008], with associations replicated for diabetes (P &lt; 0.0001) in the Framingham Heart Study. CONCLUSION: Metabolic signatures of diet are associated with long-term CM-CVD independent of lifestyle and traditional risk factors. Metabolomics improves precision to identify adverse consequences and pathways of diet-related CM-CVD.

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• No Evidence of Metabolomic Disruptions From Real‐World Intakes of Aspartame or Saccharin: The Coronary Artery Risk Development in Young Adults Study

  Journal of Diabetes · 2025-08-01

  articleOpen access

  BACKGROUND: Artificial sweeteners have become ubiquitous additives in the food supply, and yet the safety of their regular consumption remains controversial. The present study examined whether intakes of aspartame or saccharin are related to aberrations in the plasma metabolome indicating disruptions in metabolism. METHODS: A cohort of 2160 male and female participants, mean age 32.1 years, was included in the analysis. Liquid chromatography and mass-spectrometry assessed 549 unique plasma metabolites. Diet was assessed using a validated questionnaire that allowed for estimation of aspartame and saccharin intakes. A generalized linear regression model evaluated associations of saccharin or aspartame intake with plasma metabolites with adjustment for potential confounders and multiple comparisons. Multiple sensitivity analyses and propensity score matching were conducted. RESULTS: Heavy aspartame intake (≥ 5 servings/day) was associated with plasma levels (per SD) of saccharin (β = 0.90; q = 9.0E-36), myo-inositol (β = 0.27; q = 3.7E-04), caffeine (β = 0.31; q = 4.1E-04), and five metabolites of caffeine including 1,7-dimethyluric acid (β = 0.37; q = 7.1E-06), 1-methylurate (β = 0.36; q = 7.1E-06), 5-acetylamino-6-amino-3-methyluracil (β = 0.38; q = 3.2E-6), theophylline (β = 0.36; q = 9.1E-06), and 1-methylxanthine (β = 0.32; q = 2.0E-03). Saccharin intake was associated with plasma levels of saccharin alone (β = 0.29; q = 1.8E-10). No associations with sugars, carbohydrates, lipids, amino acids, or other metabolites that would suggest metabolic perturbations were observed with either artificial sweetener; sensitivity analyses supported these findings. CONCLUSIONS: In the largest metabolomics study to date, no link was found between metabolic disruptions and either aspartame or saccharin intake. We cannot exclude the possibility that more extreme intakes may be related to metabolic disruptions among consumers of artificial sweeteners.

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• Cardiometabolic Health and Bariatric Surgery: A 25-Year Longitudinal Cohort Study in CARDIA Participants

  Annals of Surgery Open · 2025-09-01 · 1 citations

  articleOpen access

  Objective: Compare longitudinal cardiometabolic health outcomes among individuals who underwent bariatric surgery (BarS) with nonsurgical controls. Background: BarS is well-established for inducing profound weight loss and improving cardiometabolic health, but it remains unclear whether patients achieve long-term cardiometabolic health consistent with the attained lower weight status. Methods: Cohort study participants who underwent any BarS procedure between 1987 and 2021 (n = 94) were paired with sex- and body mass index (BMI)-matched nonsurgical controls (n = 282) at the nearest postoperative cohort exam visit (2.8 ± 1.7 years following surgery). A mixed model tested differences between BarS cases and nonsurgical matched controls, adjusting for age, sex, race, field center, and maximal education attainment. Intermediate cardiometabolic endpoints and incident diabetes and metabolic syndrome, were examined at follow-up exam visits. Results: Approximately 7.5 years following their procedures, those who underwent BarS showed higher BMIs than matched controls (+2.8 kg/m 2 ); however, the BarS group showed significantly lower mean fasting levels of glucose (−6.5 mg/dL; P = 0.03), insulin (−2.75 μU/mL; P = 0.01), low density lipoprotein cholesterol (−20.0 mg/dL; P &lt; 0.001), C-reactive protein (log-transformed) (−0.42; P = 0.002), homeostasis model assessment-estimated insulin resistance (−0.75; P = 0.02), and higher mean high density lipoprotein cholesterol (+11.4 mg/dL; P &lt; 0.001) compared to matched controls. BarS cases showed lower incidence of diabetes (1.8% vs 11.7%; P = 0.007) and nominally lower MetS (13.7% vs 22.3%; P = 0.23). Conclusions: We found no evidence of lasting adverse cardiometabolic health consequences of severe obesity in a sample of cohort participants who underwent a BarS procedure. On average, BarS cases showed features of better cardiometabolic health than postoperative-matched nonsurgical controls who followed a more moderate trajectory of obesity.

  PublisherDOI

• Abstract 4365077: Subclinical Inflammatory Biomarker Profiles and Associations with Future Chronic Inflammatory-Related Disease and Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis

  Circulation · 2025-11-03

  article

  Background: Inflammation is associated with cardiovascular diseases (CVD). We previously described Chronic Inflammatory-Related Disease (ChrIRD), a composite of non-cardiovascular, non-diabetes, and non-cancer pathologies, both infectious and non-infectious, with a common basis of inflammation. ChrIRD had a bidirectional association with CVD, was predated by elevated inflammatory biomarker levels, and portended high mortality. ChrIRD represents a unique opportunity to study underlying inflammatory processes that link clinical inflammatory disease and CVD. Research Questions: We hypothesize that a subclinical biochemical profile consistent with inflammasome activity is associated with future ChrIRD and CVD while profiles of other inflammatory pathways associated with atherogenesis may associate differentially. Methods: In 2000-2002 the Multi-Ethnic Study of Atherosclerosis (MESA) enrolled 6,814 participants aged 45-84 and free of overt CVD. ChrIRD diagnosis was based on review of hospital and death ICD codes. Incident CVD was adjudicated by review of medical records. Inflammation biomarker levels were measured in baseline blood samples and categorized as associated primarily with inflammasome activity, adaptive immune system activation, thrombosis, or endothelial dysfunction. We performed separate age, race, sex adjusted proportional hazards regressions for these baseline biomarker groups and future ChrIRD, future CVD, and mortality. Results: Participants had mean age 62±10 years and 47% were male. Baseline biomarker associations are summarized in Table 1. Each outcome occurred in about 20% of participants. Biomarkers associated with inflammasome activity and adaptive immune system activity were associated with future ChrIRD, CVD, and mortality. Among biomarkers associated with thrombosis, only PAI-1 was associated with future ChrIRD and CVD but not mortality. For endothelial dysfunction, matrix metalloproteinases were not associated whereas cellular adhesion markers ICAM and E-Selectin were associated with ChrIRD, CVD, and mortality. Conclusions: Subclinical biochemical profiles consistent with increased inflammasome activity and various inflammatory mechanisms associated with atherogenesis predict both future ChrIRD and CVD.

  PublisherDOI

• Prediabetes transitions to normoglycaemia or type 2 diabetes and associated risk factors in the Obesity, Diabetes and Cardiovascular Disease Collaboration: an individual-level pooled analysis of 19 prospective cohort studies

  The Lancet Global Health · 2025-08-20 · 13 citations

  articleOpen access

  BACKGROUND: With the increasing global burden of type 2 diabetes, prevention strategies that target prediabetes, a state of hyperglycaemia that puts individuals at high risk of type 2 diabetes, are required. We aimed to estimate global rates of transition from prediabetes to normoglycaemia or type 2 diabetes, stratified by age, sex, and race and ethnicity. We also aimed to quantify the effect of modifiable and non-modifiable risk factors on these transitions. METHODS: In this pooled analysis of individual-level data, we included original data from 19 prospective cohort studies conducted in Asia (Iran and Japan), Australia, Europe (Spain and Sweden), North America (USA and Mexico), and South America (Venezuela). We applied discrete-time hidden Markov models to estimate rates and ratios of prediabetes transitions to type 2 diabetes and normoglycaemia specific to age, sex, and race and ethnicity. We used Fine-Gray competing risk models to derive cohort-specific subhazard ratios (SHRs) for potential risk factors influencing these transitions. We subsequently pooled these SHRs using a random-effects meta-analysis. In subgroup analyses stratified by age, sex, race and ethnicity, and recruitment period, we used multivariate Cox models to investigate the degree of heterogeneity between studies. FINDINGS: 76 092 participants (39 842 [52·3%] women and 36 250 [47·6%] men; mean age 51·1 years [SD 12·7]) with available data on glycaemic status from at least one follow-up visit were included in the analysis, of whom 56 837 (74·7%) had normoglycaemia and 19 255 (25·3%) had prediabetes. Median follow-up was 9·8 years (IQR 5·8-12·5). Within 10 years, individuals with prediabetes had a 12·5% probability of progressing to type 2 diabetes, whereas the probability of reverting to normoglycaemia was 36·1%. However, in the highest fasting plasma glucose quartile, the probability of progression increased to 16·1% and reversion decreased to 13·4%. Male sex, older age (≥55 years), and Latinx populations were associated with an increased risk of transitioning to type 2 diabetes. Risk factors that significantly reduced prediabetes reversion to normoglycaemia were overweight (SHR 0·88 [95% CI 0·76-0·99]), obesity (0·66 [0·52-0·81]), elevated waist-to-height ratio (0·82 [0·70-0·95]), elevated waist-to-hip ratio (0·79 [0·68-0·91]), and reduced HDL concentration (0·72 [0·59-0·84]). INTERPRETATION: Our findings highlight that reversion to normoglycaemia was more common than progression to type 2 diabetes among individuals with prediabetes, and that these transitions were strongly influenced by modifiable risk factors. The increased risk of progression with advancing age and among men underscores the importance of early identification and targeted interventions in population groups at high risk of type 2 diabetes. Furthermore, the elevated progression risk in individuals with higher fasting plasma glucose concentrations at baseline reinforces the need for timely detection and intervention during this crucial clinical window. FUNDING: Deakin University Postgraduate Research Scholarship.

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• Thirty-Year Glycemic Trajectories From Young Adulthood Through Middle Age

  JAMA Network Open · 2025-06-26 · 2 citations

  articleOpen access

  Importance: Type 2 diabetes prevalence is increasing, and currently 24% of young adults have prediabetes. Little is known regarding timing and progression from normoglycemia to diabetes starting in young adulthood. Objective: To examine glycemic trajectories from young adulthood through middle age. Design, Setting, and Participants: This cohort study used sequence analysis to identify patterns of glycemic trajectories across 30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a large, diverse, population-based cohort of young adults from 4 national community sites with repeated measures of fasting plasma glucose (FPG). Sequence analysis reduces the various glycemic trajectories that individuals may follow over time into common trajectory clusters. The CARDIA study enrolled adults aged 18 to 30 years from 1985 to 1986, with groups balanced on Black and White race, sex, age, and educational level. Data through year 30 (2015-2016) were used, excluding participants with baseline diabetes, those missing the first 2 FPG values, and those missing 6 or more FPG values. Data analysis was performed from July 2023 to October 2024. Main Outcomes and Measures: Clusters of common glycemic trajectory patterns. Results: Among the 4684 study participants (2553 [54.5%] female), 1278 unique glycemic trajectories were identified across 30 years. A total of 3420 participants (73.0%) had trajectories classifiable into 9 common patterns of glycemic trajectory: stable normoglycemia; 5 patterns of impaired fasting glucose (IFG) not progressing to diabetes, including a brief period of low IFG regressing to normoglycemia at younger (mean [SD] age at IFG, 35.9 [6.6] years) and older ages (mean [SD] age at IFG, 46.8 [3.7] years), younger-onset sustained IFG (mean [SD] age at IFG, 38.6 [5.0] years), older-onset sustained low IFG (mean [SD] age at IFG, 51.7 [5.1] years), and older-onset sustained high IFG (mean [SD] age at IFG, 41.9 [8.8] years); and 3 patterns of diabetes, including young onset (mean [SD] age at diabetes, 34.8 [3.6] years), middle-age onset (mean [SD] age at diabetes, 43.6 [4.4] years), and older onset (mean [SD] age at diabetes, 52.4 [3.8] years). Conclusions and Relevance: This cohort study revealed substantial heterogeneity in glycemic trajectories across 30 years of follow-up. Clusters that represented IFG during young adulthood did not demonstrate progression to diabetes, and clusters that represented diabetes lacked prior IFG during young adulthood. These data suggest the need for strategies beyond simply screening for IFG during young adulthood to identify and target diabetes prevention for young adults.

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Recent grants

• NIH Grant R01HL098382

  NIH · $2.7M · 2015

• NIH Grant R01HL071121

  NIH · $210k · 2004

• NIH Grant R56HL053560

  NIH · $494k · 2010

• NIH Grant R01HL053560

  NIH · $10.7M · 2017

• NIH Grant N01HC048048

  NIH · $6.0M · 2003

Frequent coauthors

• France Bellisle

  1155 shared

• Philip C. Calder

  NIHR Southampton Biomedical Research Centre

  1155 shared

• John C. Mathers

  Newcastle University

  1154 shared

• O Kennedy

  1154 shared

• Chris J. Seal

  F-star (United Kingdom)

  1154 shared

• Susan J. Whiting

  University of Saskatchewan

  1154 shared

• Weeks Zdravics

  Université Sorbonne Paris Nord

  1116 shared

• Jonathan Norton

  Saskatoon Medical Imaging

  1116 shared

Awards & honors

• Member, Delta Omega Honorary Society in Public Health