Open research questions in Diabetes and associated disorders
133 unresolved questions extracted from the limitations and future-work sections of 479 Diabetes and associated disorders papers in our library. Each links back to the study that raised it.
What the literature leaves open
The study did not account for potential confounding factors, - The study relied on genetic variants associated with GD and antibody-mediated immune-response phenotypes, - The study used a limited number of genetic variants as instrumental variables
The causal relationship between antibody-mediated immune responses to infections and Graves’ disease: a bi-directional Mendelian randomization analysis · 2026 · DOIFurther investigation into the relationship between antibody-mediated immune responses and GD risk, - Examination of the potential influence of antibody-mediated immune responses on GD risk, - Investigation into the mechanisms underlying the association between GD and anti-polyomavirus 2 IgG seropositivity
The causal relationship between antibody-mediated immune responses to infections and Graves’ disease: a bi-directional Mendelian randomization analysis · 2026 · DOIfurther study of the role of Lyn-deficiency in disease initiation, - investigation of the effects of environmental factors on disease development, - comparison of the model to other mouse models of uveoretinitis
Spontaneous organ-specific eye autoimmune disease resulting from two engineered gene mutations compromising immune tolerance · 2026 · DOIThe gap in understanding how genetic compromises in multiple immune tolerance mechanisms confer susceptibility to autoimmune disease development. The need for a better understanding of the mechanisms of disease initiation. The lack of a comprehensive model of spontaneously developing organ-specific autoimmune disease.
Spontaneous organ-specific eye autoimmune disease resulting from two engineered gene mutations compromising immune tolerance · 2026 · DOICompared to HLA-A and HLA-B, relatively little is known about the participation of HLA-C-restricted T cells in T1D.
Islet-derived T cells from both mice and humans recognize conserved insulin A-chain peptides presented by HLA-C*03:04 · 2026 · DOIThis reinforces the link between emphysema, pulmonary TLT formation, and B cells; however, the exact mechanism involving B cells and pulmonary TLT in the development of emphysema remains elusive.
A mutation in PTPN6 associated to emphysema alters B-lymphocyte biology in humans and mice · 2026 · DOICell type–specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood.
Single-cell multiome and spatial profiling reveals pancreas cell type–specific gene regulatory programs of type 1 diabetes progression · 2025 · DOIFurthermore, the relationship between infection severity and new autoimmune disease risk has not been well examined.
Severity of acute SARS-CoV-2 infection and risk of new-onset autoimmune disease: A RECOVER initiative study in nationwide U.S. cohorts · 2025 · DOIThese findings indicate that HIF-1α plays a diminished role in controlling IL-10 production in NOD B cells and that IL-10 alone is insufficient to maintain immune tolerance.
Defects in Breg development and function have been identified in both human T1D and the non-obese diabetic (NOD) mouse, but whether these impairments reflect intrinsic B-cell abnormalities or microenvironmental changes associated with hyperglycemia and inflammation remains unclear.
Advances in restriction fragment length polymorphism (RFLP) analysis in the mid-1980s provided evidence that HLA-DQ genes were more strongly associated with T1D than HLA-DR,13–19 but direct sequencing data were lacking.
T1D incidence is increasing worldwide but it is poorly understood what activates autoreactive T-cells.
The impact of Parabacteroides distasonis colonization on the microbiome, metabolome, immune responses in SPF mice and diabetes onset in germ-free mice 4785 · 2025 · DOIHowever, how Ptpn22 impacts B cell dynamics during virus infection remains poorly understood.
While the exact cause remains unknown, studies in mouse models indicate that sympathetic denervation and macrophage depletion can halt T1D progression, suggesting a critical role for neuroimmune communication in the disease’s development.
Neuroimmune interactions in the pancreas in health and disease- Identifying the components of nerve-macrophage association 2911 · 2025 · DOIWhile preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.
Investigating the Interplay: Periodontal Disease and Type 1 Diabetes Mellitus—A Comprehensive Review of Clinical Studies · 2024 · DOIHowever, the precise trigger of autoimmunity and disease onset remain incompletely elucidated.
Extracellular vesicles (EVs) from β cells have been shown to carry protein and microRNAs (miRNAs), influencing cellular signaling and may contribute to the development of T1D but it remains to be addressed how senescence impacts β cell EV cargo.
Objective: Studies have shown an increased incidence of pediatric type 1 diabetes during the COVID-19 pandemic, but the detailed role of SARS-CoV-2 infection in the incidence increase in type 1 diabetes remains unclear.
Spatiotemporal association between COVID-19 incidence and type 1 diabetes incidence among children and adolescents: a register-based ecological study in Germany · 2024 · DOIHowever, further studies with large sample sizes and validation across different racial and ethnic populations are warranted.
Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB1*04:05-DQB1*04:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes · 2024 · DOIBackground The functional changes in alpha cells in patients with type 1 diabetes (T1D) with different residual beta cell functions remain poorly elucidated.
Abnormal late postprandial glucagon response in type 1 diabetes is a function of differences in stimulated C-peptide concentrations · 2024 · DOIAlthough several studies have indicated that fatty acid mitochondrial oxidation is critical for immune cell functions, contradictory findings have been reported.
Although several neutralizing Abs against a small number of HPIV3 F epitopes have been identified to date, relatively little is known about the Ab response to HPIV3 compared with other pathogens, such as influenza virus and SARS-CoV-2.
Potent HPIV3-neutralizing IGHV5-51 Antibodies Identified from Multiple Individuals Show L Chain and CDRH3 Promiscuity · 2024 · DOIThere is a need to determine the time to resolution of diabetic ketoacidosis and its predictors among adult diabetic patients in public hospitals of Northeast Ethiopia. There is a need to identify predictors of time to resolution of diabetic ketoacidosis.
Time to Resolution of Diabetic Ketoacidosis and Its Predictors among Adult Diabetic Patients in Public Hospitals of Northeast, Ethiopia · 2026 · DOIARTICLE 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 · DOILimited evidence from randomised trials in transplant recipients. Variability in trial duration and enrolment criteria. Incompletely and variably reported outcomes.
Comparison of incidence patterns and risk profiles of ST-elevation and non-ST-elevation myocardial infarction in type 1 diabetes in Finland: a nationwide cohort study · 2026 · DOI
Most-cited papers in Diabetes and associated disorders
- Seroconversion to Multiple Islet Autoantibodies and Risk of Progression to Diabetes in Children · JAMA · 2013 · 1,185 citations
- Type 1 diabetes: new perspectives on disease pathogenesis and treatment · The Lancet · 2001 · 1,069 citations
- ISLET-CELL ANTIBODIES IN DIABETES MELLITUS WITH AUTOIMMUNE POLYENDOCRINE DEFICIENCIES · The Lancet · 1974 · 1,056 citations
- Incidence of Diabetes in Youth in the United States · JAMA · 2007 · 779 citations
- The Burden of Diabetes Mellitus Among US Youth: Prevalence Estimates From the SEARCH for Diabetes in Youth Study · PEDIATRICS · 2006 · 601 citations
- The global spread of type 2 diabetes mellitus in children and adolescents · The Journal of Pediatrics · 2005 · 494 citations
- Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus before clinical onset of disease · The Lancet · 1994 · 445 citations
- DIABETES INCIDENCE AND PREVALENCE IN PIMA INDIANS: A 19-FOLD GREATER INCIDENCE THAN IN ROCHESTER, MINNESOTA · American Journal of Epidemiology · 1978 · 430 citations
- Prevalence of Diagnosed Diabetes in Adults by Diabetes Type — United States, 2016 · MMWR Morbidity and Mortality Weekly Report · 2018 · 382 citations
- Trends in Incidence of Type 1 and Type 2 Diabetes Among Youths — Selected Counties and Indian Reservations, United States, 2002–2015 · MMWR Morbidity and Mortality Weekly Report · 2020 · 347 citations
Most recent work
- Immune checkpoint inhibitor-associated diabetes mellitus: mechanisms, clinical manifestations, and management strategies · Frontiers in Endocrinology · 2026
- Regulatory T cell dysfunction and immunotherapeutic breakthroughs in type 1 diabetes · Frontiers in Endocrinology · 2026
- Imaging mass cytometry reveals functional and immunological changes during type 1 diabetes progression in human pancreata · Nature Metabolism · 2026
- Single-cell profiling of the lung immune cells of diabetes-tuberculosis comorbidity reveals reduced type-II interferon and elevated Th17 responses. · bioRxiv · 2026
- Thyroid autoimmunity and the subsequent development of islet and celiac autoimmunity in the TEDDY study · American Journal of Epidemiology · 2026
- Protection through early knowledge: clinical onset of type 1 diabetes in children and adolescents with and without early T1D detection programmes · BMC Pediatrics · 2026
- Screening Children for Early-Stage Type 1 Diabetes · JAMA · 2026
- Normal Saline Versus Ringer’s Lactate for Intravenous Fluid Therapy in Children with Diabetic Ketoacidosis: A Randomized Controlled Trial – Correspondence · Indian Journal of Pediatrics · 2026
- 20/ (fasting C-peptide × fasting plasma glucose) as a novel marker for insulin resistance in obese children and adolescents · Pediatric Research · 2026
- Methodological and statistical considerations in the assessment of GH-IGF-1 axis dysfunction and linear growth in children with type 1 diabetes mellitus · Heart Vessels and Transplantation · 2026
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