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Open research questions in Diet, Metabolism, and Disease

111 gap statements mined from Diet, Metabolism, and Disease papers in our 4.5M-paper local library, which holds 530 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • This scoping review also identified several key gaps in the literature including a lack of diversity in study samples, an almost-exclusive focus on heteronormative sugaring arrangements, and a lack of studies involving those who participate in sugaring in the research development and/or implementation.

    Sugar coated connections: A scoping review of sugar dating · 2026 · DOI

  • However, the molecular mechanisms underlying these effects remain poorly understood.

    Prefrontal Cortex Dysregulation of Amino Acid–Glucose Homeostasis Links High-Fat and/or High-Fructose Intake to Cognitive Deficits in Male Mice · 2026 · DOI

  • Excessive fructose consumption is increasingly linked to obesity, diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease, yet its impact on brown adipocytes remains poorly defined.

    Fructose impairs brown adipogenesis by promoting thyroid hormone resistance in differentiated brown adipocytes · 2026 · DOI

  • Emerging evidence has linked high dietary fructose intake with adverse health outcomes, yet its role in colitis-associated colorectal cancer (CAC) remains underexplored.

    Dietary targeting of CNBP to rein in the EREG-EGFR cascade and restore homeostasis in colitis-associated colorectal cancer · 2026 · DOI

  • High Resolution Image Download MS PowerPoint Slide Excessive fructose intake drives intestinal aging and impairs intestinal stem cell (ISC) function, yet effective therapeutic interventions remain elusive.

    Astragaloside IV Alleviates Fructose-Induced Intestinal Metabolic Senescence by Targeting Ketohexokinase Asn261/Ala226 to Preserve Intestinal Stem Cell Homeostasis · 2025 · DOI

  • The impact of Se on insulin resistance has not been evaluated in large prospective studies, so no firm conclusions can yet be drawn.

    STUDY OF THE CAUSAL ROLE OF SELENIUM IN THE DEVELOPMENT OF TYPE 2 DIABETES IN A HIGH-FRUCTOSE DIET MODEL IN WISTAR RAT · 2025 · DOI

  • Although long-term epidemiological data are limited, a recent study demonstrated that sucrose intake increased the risk for hypertension in women.

    Cardiovascular Effects of Sucrose in Experimental Animals and Humans · 2025 · DOI

  • Although a biosynthetic pathway from starch to fructose-6-phosphate has been well established in metabolic engineering studies, the downstream enzymatic route leading to the biosynthesis of sorbitol from this intermediate has not yet been elucidated in the literature.

    Development of an in vitro multi-enzyme system for efficient one-pot biosynthesis of sorbitol from fructose-6-phosphate · 2025 · DOI

  • The role of carbohydrates in diabetes risk is of particular interest due to conflicting results.

    Types of dietary sugars and carbohydrates, cardiometabolic risk factors, and risk of diabetes: a cohort study from the general Danish population · 2025 · DOI

  • The burden of type 2 diabetes mellitus (T2DM) associated with a diet high in SSBs on a global scale remain unclear.

    Global trends and age-period-cohort analysis for the disability adjusted life years and mortality of type 2 diabetes mellitus due to diet high in sugar-sweetened beverages · 2025 · DOI

  • However, the relationship between acute HS and kidney injury caused by endogenous fructose remains unclear.

    Acute heat stress upregulates Akr1b3 through Nrf-2 to increase endogenous fructose leading to kidney injury · 2024 · DOI

  • Essential amino acids (EAAs) and endurance exercise training (ET) improve abnormal metabolism in various disease conditions, yet their combined effect and metabolic mechanism remain unclear.

    Endurance training and essential amino acid intervention synergize to ameliorate fructose-induced metabolic dysfunction in mice · 2024 · DOI

  • However, caloric restriction's effects on thyroid hormone signaling during MetS remains unclear.

    Caloric Restriction Improves Hepatic Thyroid Hormone Signaling During Metabolic Syndrome · 2024 · DOI

  • However, it remains unclear if heavy alcohol use contributes to the development of type 2 diabetes in an aged population.

    Effects of Heavy Alcohol Use on Fasting Glucose and Insulin Resistance in Mid-Life Adults · 2024 · DOI

  • Appropriate strategies to achieve these recommendations for the general public, however, remain unclear.

    Dietary recommendations for reducing free sugar intakes: A pilot study investigating effects following advice to substitute sweet high-sugar foods with different alternatives · 2024 · DOI

  • Limited research shows that African Americans have higher fructose malabsorption prevalence than others.

    Disproportionately higher cardiovascular disease risk and incidence with high fructose corn syrup sweetened beverage intake among black young adults–the CARDIA study · 2024 · DOI

  • Higher consumption of sugary beverages (SB) has been associated with type 2 diabetes (T2D), but whether these associations are modified by physical activity remains unclear.

    Associations of sugary beverage intake with type 2 diabetes and the role of physical activity: a prospective cohort study · 2024 · DOI

  • However, non-obese murine models recapitulating these features are lacking to study the mechanisms underlying the development of metabolic dysregulations in lean children.

    Protein restriction associated with high fat induces metabolic dysregulation without obesity in juvenile mice · 2024 · DOI

  • The need for a comprehensive understanding of carbohydrate metabolism to improve diagnosis, treatment, and prevention strategies in clinical medicine.

    CARBOHYDRATES: STRUCTURE, METABOLISM AND CLINICAL SIGNIFICANCE IN HUMAN HEALTH · 2026 · DOI

  • The limited natural abundance and inefficiency of traditional production methods are significant challenges. Further improvements in productivity and industrial feasibility are needed.

    Engineering strategies for the biosynthesis of rare sugars in microbial cell factories · 2026 · DOI

  • Future studies should examine the effects of fructose on other brain regions and behavioral outcomes. Future studies should investigate the mechanisms underlying the effects of fructose on CA1 synaptic ultrastructure. Future studies should examine the effects of fructose on synaptic function and plasticity.

    Selective alterations in CA1 spine morphology following dietary fructose intake · 2026 · DOI

  • The effects of fructose on hippocampal synaptic architecture remain unclear. Prior studies have focused on the effects of fructose on metabolic outcomes and have not examined the effects on synaptic ultrastructure.

    Selective alterations in CA1 spine morphology following dietary fructose intake · 2026 · DOI

  • The pilot study presented here aimed to extend this original study through the additional investigation of three different types of dietary advice based on food substitutions.

    Dietary recommendations for reducing free sugar intakes: A pilot study investigating effects following advice to substitute sweet high-sugar foods with different alternatives · 2024 · DOI

  • Further research on the importance of glycemic index and glycemic load in dietary planning. Emerging therapies targeting carbohydrate metabolism pathways for treating diabetes and related conditions.

    CARBOHYDRATES: STRUCTURE, METABOLISM AND CLINICAL SIGNIFICANCE IN HUMAN HEALTH · 2026 · DOI

  • Developing more efficient microbial cell factories through multi-level engineering strategies. Exploring novel applications of rare sugars in the food and pharmaceutical industries.

    Engineering strategies for the biosynthesis of rare sugars in microbial cell factories · 2026 · DOI

Most-cited papers in Diet, Metabolism, and Disease

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Open questions raised by papers listed on this page include: (1) The molecular mechanisms underlying these effects remain poorly understood (“Prefrontal Cortex Dysregulation of Amino Acid–Glucose Homeostasis Links…”, 2026); (2) Emerging evidence has linked high dietary fructose intake with adverse health outcomes, yet its role in colitis-associated colorectal cancer (CAC) remains underexplored (“Dietary targeting of CNBP to rein in the EREG-EGFR cascade and restore…”, 2026); (3) Further improvements in productivity and industrial feasibility are needed (“Engineering strategies for the biosynthesis of rare sugars in microbial cell…”, 2026); (4) Future studies should examine the effects of fructose on other brain regions and behavioral outcomes (“Selective alterations in CA1 spine morphology following dietary fructose intake”, 2026); (5) High Resolution Image Download MS PowerPoint Slide Excessive fructose intake drives intestinal aging and impairs intestinal stem cell (ISC) function, yet effective therapeutic interventions remain elusive (“Astragaloside IV Alleviates Fructose-Induced Intestinal Metabolic Senescence by…”, 2025). 111 gap statements have been mined from Diet, Metabolism, and Disease papers in our 4.5M-paper local library, which holds 530 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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