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Open research questions in Diabetes and associated disorders

35 unresolved questions extracted from the limitations and future-work sections of 383 Diabetes and associated disorders papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread globally, knowledge accumulated rapidly through publications that were frequently based on preliminary or sometimes conflicting evidence, yet these papers played a critical role in shaping evolving medical, research and societal responses.

    SARS-CoV-2 and diabetes: a post-pandemic reappraisal · 2026 · DOI

  • Many studies on the incidence of newly diagnosed T1D during the pandemic period yield conflicting results: some sug- gest an increase in incidence, while others report a decrease or no change compared to pre-pandemic levels [4, 8, 11, 12].

    Ketoacidosis in new-onset type 1 diabetes: return to pre-COVID-19 pandemic reality? · 2026 · DOI

  • Because little is known about the emergence of islet autoantibodies in AOT1D, we conducted a retrospective study using electronic medical records from the United States Military Health System and longitudinal serum samples from 169 individuals with AOT1D and 40 healthy controls obtained from the Department of Defense Serum Repository.

    Predictive Autoantibodies Before the Diagnosis of Type I Diabetes in Adults · 2026 · DOI

  • Further studies involving larger, multi-ethnic popula- tions are warranted to confirm the observed association between IP6K3 SNP rs791903 and HT. Future research should also include comprehensive genetic analyses of the IP6K3 locus and adjacent immune-related regions, as well as functional studies to clarify the potential biologi- cal mechanisms underlying the observed association with anti-TPO antibody levels. A preliminary version of this work was previously pre- sented as an e-poster at ALEXMED (DOI: h t t p s : / / d o i . o r g / 1 0 . 2 1 6 0 8 / a l e x p o . 2 0 2 4 . 3 4 4 5 9 2 . 2 0 3 2 ) as part of academic requirements. The current manuscript represents a sub- stantially expanded and fully developed version of the study. Authors’ contributions S.M. and E.N. conceptualized the study, led the data collection process, and drafted the initial manuscript. T.E. contributed to the study design. H.B. and Nassar et al. The Egyptian Journal of Internal Medicine (2026) 38:80 E.N. performed data analysis, and participated in the interpretation of the results. S.M. reviewed and edited the manuscript. E.N. contributed to the literature review, and provided critical revisions. All authors read and approved the final manuscript.

    Association of IP6K3 gene SNP rs791903 and Hashimoto’s thyroiditis in a cohort of Egyptian patients · 2026 · DOI

  • Background: While observational studies have highlighted a potential link between diabetes and oral lichen planus (OLP), the causal relationship remains unclear, and it is uncertain which specific form of diabetes might promote OLP development.

    Effect of type 1 diabetes on oral lichen planus mediated by IL-10 · 2026 · DOI

  • However, due to the observational design, the absence of matching for key confounders, and the lack of data on important covariates such as BMI, dietary intake and sun exposure, the findings support only associations and cannot establish causality. Finally, the effects of vitamin D supplementation on patients with T1DM were not investigated.

    A study of 25‑(OH)D <sub>3</sub> levels in children with type 1 diabetes mellitus and its influencing factors · 2026 · DOI

  • ligible patients to have type II diabetes and active antihyperglyce- mic therapy helps reduce misclassification of pharmacologic exposure, but treatment persistence could not be assessed.

    Association between semaglutide use and thyroid eye disease-related outcomes in autoimmune thyroiditis with type II diabetes · 2026 · DOI

  • Therefore, the intrinsic activation of STAT3, responsiveness to IL-21, and stability of FoxP3 in patient- derived Tregs remain to be directly validated. The contributions of these cells to T1D pathogenesis and their interactions with T cells warrant further exploration.

    Aberrant IL-21/STAT3 signaling disrupts regulatory T cell function and CD4+ T cell homeostasis in children with type 1 diabetes · 2026 · DOI

  • ARTICLE IN PRESS ARTICLE IN PRESS ACCEPTED MANUSCRIPT This study has several limitations. Using secondary data, we were unable to assess certain predictors of time to DKA resolution, including admission pH, potassium levels, and adherence to treatment protocols. The analysis focused on the number of DKA episodes rather than individual patients, so those with multiple episodes may have been included more than once, potentially affecting results due to varying clinical characteristics and treatment responses. Data on baseline or chronic medications, including SGLT-2 inhibitors, were unavailable, limiting adjustment for potential confounders. Furthermore, missing physiological data—such as pH, bicarbonate, anion gap, creatinine, and lactate prevented adjustment for these variables, despite guidelines recommending pH >7.3, bicarbonate ≥18 mmol/L, and anion gap closure as standard criteria for DKA resolution.

    Time to Resolution of Diabetic Ketoacidosis and Its Predictors among Adult Diabetic Patients in Public Hospitals of Northeast, Ethiopia · 2026 · DOI

  • Alpha-1-acid glycoprotein (AGP), alpha-1-antitrypsin (AAT), and C-reactive protein (CRP) have been proposed as markers related to inflammatory processes in T2DM; however, their combined assessment remains insufficiently characterized.

    Assessment of alpha-1-acid glycoprotein (AGP) and alpha-1-antitrypsin (AAT) in patients with type 2 diabetes mellitus · 2025 · DOI

  • SBC is associated with and leads to obesity and chronic diseases, nonetheless the role of SBC in development of autoimmune disorders such as latent autoimmune diabetes in adults (LADA) has not been addressed adequately among the different ethnic groups.

    Sugary beverages consumption and latent autoimmune diabetes in adults: systematic review and meta-analysis · 2020 · DOI

  • We present a 15-year-old Caucasian boy with an exceptional coincidence of a rare monogenic metabolic disease - alkaptonuria (AKU) and a cluster of autoimmune disorders: type 1 diabetes (T1DM), autoimmune thyroiditis (AIT), vitiligo, insulin infusion induced lipoatrophy and immunoglobulin A deficiency (IgAD) Alkaptonuria and type 1 diabetes in a child, especially in such an interesting coincidence with other autoimmune conditions, has not been reported so far.

    Alkaptonuria in a boy with type 1 diabetes mellitus, vitiligo, autoimmune thyroiditis and immunoglobulin A deficiency – a case report · 2016 · DOI

  • The organ-specificity of islet-cell antibodies has not yet been established by absorption and subcellular fractionation studies, but the fact that this immuno- fluorescence does not involve pancreatic exocrine tissue and was not invariably found together with any of the other known tissue antibodies, also the un- doubted organ-specificity of thyroid, gastric, and adrenal antibodies, lend some credibility to such a hypothesis.

    ISLET-CELL ANTIBODIES IN DIABETES MELLITUS WITH AUTOIMMUNE POLYENDOCRINE DEFICIENCIES · 1974 · DOI

  • Low‐grade inflammation may contribute to CAN development, but the exact inflammatory factors associated with CAN remain unclear.

    Severity of Cardiovascular Autonomic Neuropathy Is Linked to Increasing Levels of Circulating Proinflammatory Cytokines · 2026 · DOI

  • Recent epidemiologic studies indicate that adult-onset type 1 diabetes (AOT1D) is more common than childhood-onset type 1 diabetes, yet it remains clinically underrecognized.

    Predictive Autoantibodies Before the Diagnosis of Type I Diabetes in Adults · 2026 · DOI

  • Results and discussion:The analyzed studies indicate a progressive increase in the incidence of type 1 diabetes in young people across different regions of the world, although the exact causes are not yet fully understood.

    Incidência do diabetes tipo 1 em jovens e os desafios para o diagnóstico precoce: revisão integrativa da literatura · 2026 · DOI

  • Background: Previous studies suggested an important role of impairments in T cell subsets in different stages during type 1 diabetes (T1D) development, while data regarding CD25high T cells and transforming growth factor b1 (TGFβ1), both T regulatory associated, remains controversial.

    Changes in CD4+CD25HIGH T cells and TGFb1 levels in different stages of adult-onset type 1 diabetes · 2024 · DOI

  • BACKGROUND: The prevalence of antibodies to pancreatic islets in monogenic diabetes remains unknown and the incidence estimation is difficult as the occurrence of autoantibodies in patient is one of the well-known exclusion criteria for further genetic diagnostics.

    Humoral response markers in GCK MODY · 2016 · DOI

  • A set of variables that synthesize a diabetic's profile could be included in a dedicated model and facilitate the early detection of infections; other aspects, such as continuous self-monitoring and personalized medical records, should be examined in this direction.

    Proof of concept for the role of glycemic control in the early detection of infections in diabetics · 2012 · DOI

  • The etiology of type 1 diabetes (T1D) remains unknown, but a growing body of evidence points to infectious agents and/or components of early childhood diet.

    The Environmental Determinants of Diabetes in the Young (TEDDY) Study · 2008 · DOI

  • 3-1% of all episodes of DKA, and its aetiology, pathophysiology, and ideal method of treatment are poorly understood.

    ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents · 2004 · DOI

  • lO,l1 Of this large group of bio- chemically and serologically distinct organisms only a few have been well defined and identified; most re- main poorly characterised.

    ISLET-CELL ANTIBODIES IN DIABETES MELLITUS WITH AUTOIMMUNE POLYENDOCRINE DEFICIENCIES · 1974 · DOI

  • We would conclude that our results provide further evidence of an association between infection and juvenile diabetes, but the aetiological significance of these findings remains uncertain.

    Seasonal Incidence of Diabetes Mellitus · 1969 · DOI

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35 open questions have been extracted from the limitations and future-work passages of 383 Diabetes and associated disorders papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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