On the diabetes-to-stomach side of the model, chronic hyperglycemia is presented as the initiating pressure. Excess glucose overloads mitochondrial electron transport, increases reactive oxygen species and activates pathways including NADPH oxidase. In diabetic animals, the review reports higher concentrations of lipid peroxidation products such as MDA and 4-HNE in gastric mucosa, reduced antioxidant enzyme activity, activation of the NF-κB inflammatory axis, an unfavorable balance between the anti-apoptotic protein Bcl-2 and pro-apoptotic Bax, and activation of caspase-9 and caspase-3. The resulting epithelial apoptosis, impaired cell proliferation and thinned lamina propria provide a plausible route from hyperglycemia to gland loss and mucosal atrophy. This evidence comes primarily from experimental models and does not establish the same sequence in human diabetes.

Advanced glycation end products, or AGEs, add another proposed route. High glucose promotes non-enzymatic glycation of long-lived matrix proteins including collagen and laminin, altering their cross-linking and physical properties. When AGEs engage the receptor for AGEs, or RAGE, they can activate NF-κB and MAPK signaling, stimulate NADPH oxidase and promote further reactive oxygen species. Animal studies summarized in the review associate elevated AGEs with structural disorders, while experimental findings connect RAGE signaling to impaired fibroblast function, reduced collagen synthesis and delayed healing. AGE cross-linking may also make the mucosa less compliant and more vulnerable to acid, bile and Helicobacter pylori. The authors describe this as a positive feedback loop in which oxidative stress and glycation reinforce one another, but they acknowledge that direct longitudinal evidence in patients remains limited.

Diabetes may also compromise the stomach’s blood supply and its capacity to repair. Diabetic microangiopathy affects the small vessels beneath the gastric mucosa, producing endothelial swelling, luminal narrowing, reduced perfusion density and chronic ischemia. The review cites measurements showing lower mucosal blood flow in people with diabetes than in healthy controls and patients with chronic superficial gastritis. Reduced nitric oxide bioavailability, increased asymmetric dimethylarginine and elevated von Willebrand factor can further disturb microcirculation and microthrombosis. Prolonged hypoxia stabilizes HIF-1α, which may initially support adaptation but, when chronically imbalanced, can sustain inflammatory signaling, reduce tight-junction proteins and hinder epithelial regeneration. Deficits in prostaglandin E2, epidermal growth factor and TGF-β signaling are also described as weakening mucus and bicarbonate protection and slowing the reconstruction of damaged epithelium.

Neurological complications add a gastric-motility component. Diabetic autonomic neuropathy can reduce vagal stimulation of acid-secreting parietal cells, disturb the balance between gastrin-secreting G cells and somatostatin-secreting D cells, and impair the protective role of ghrelin. Diabetic gastroparesis is characterized in the review by weak antral contractions, increased pyloric resistance and delayed emptying of solid food. Retention and reflux of bile- and enzyme-rich duodenal contents can damage epithelial tight junctions and cell membranes. Loss or dysfunction of interstitial cells of Cajal, the stomach’s electrical pacemaker cells, further disrupts contractions, and experimental work links oxidative stress, microvascular injury, pro-inflammatory macrophages and altered autophagy to their decline. Together, delayed emptying, bile reflux, mucosal injury, cellular loss and worsening motility are proposed to form a self-reinforcing sequence that can progress from chronic inflammation to gland atrophy and intestinal metaplasia.

Helicobacter pylori provides a potential meeting point between hyperglycemia, infection and atrophy. The review describes altered glycosylation of gastric mucins in a high-glucose environment, which may expose structures that improve bacterial adhesion, together with reduced acidity that weakens the stomach’s chemical defense. Diabetes-associated impairment of neutrophil chemotaxis, phagocytosis and intracellular killing may make early clearance less effective, while macrophage responses become more strongly skewed toward inflammation. H. pylori can also induce the immunosuppressive cytokine IL-37 through receptors including TLR2, TLR4 and NOD1. Its virulence factors, notably CagA from cag-positive strains, can amplify NADPH oxidase activity, oxidative damage and NF-κB signaling, potentially accelerating the sequence from gastritis to atrophy and metaplasia. These observations suggest that infection, immune dysfunction and high glucose may cooperate, but they do not show that every patient with diabetes follows this course or that eradication alone prevents atrophy.

In the reverse direction, atrophic gastritis may disturb glucose metabolism through several partially overlapping mechanisms. Loss of parietal cells reduces gastric acid and intrinsic factor, impairing the release and terminal-ileal absorption of vitamin B12 and reducing the conversion of dietary iron to a more soluble form. B12 deficiency can lead to hyperhomocysteinemia, which has been associated with oxidative stress, endothelial injury and insulin resistance. Preclinical evidence also links homocysteine to endoplasmic-reticulum stress, mitochondrial dysfunction and apoptosis in pancreatic beta cells. Iron deficiency may restrict mitochondrial complex IV activity and ATP production in insulin-sensitive tissues, potentially worsening insulin signaling and glucose-stimulated insulin secretion. These pathways are biologically coherent, but the review notes that much of the evidence is preclinical and that trials demonstrating improved glycemic control after correction of atrophic-gastritis-related deficiencies are scarce.

Changes in the gastric endocrine network offer a second potential route. Loss of acid removes negative feedback on antral G cells, producing marked hypergastrinemia, while impaired D-cell function may weaken somatostatin inhibition. Although moderate gastrin elevations can have metabolic or trophic effects under physiological conditions, the review proposes that sustained supraphysiological stimulation of CCK-B receptors on beta cells may desensitize insulin secretion, deplete functional reserves and interfere with beta-cell transcription factors. Atrophic gastritis affecting the gastric body and fundus can also destroy X/A-like cells, the main source of ghrelin, altering meal-related hunger signals and potentially removing ghrelin’s inhibitory influence on basal insulin secretion. Because ghrelin also affects skeletal-muscle mitochondrial function and inflammation, its loss may intersect with diabetic sarcopenia and insulin resistance. These consequences remain mechanistically inferred rather than demonstrated by prospective hormone-intervention trials.

Low gastric acidity can also permit small intestinal bacterial overgrowth, altering microbial metabolites and the gut-liver-pancreas axis. Lipopolysaccharide from Gram-negative bacteria may enter portal circulation, activate TLR4 and inflammatory pathways such as JNK and IKK/NF-κB, and contribute to systemic insulin resistance. Changes in short-chain fatty acids and bile-acid metabolism may affect intestinal barrier integrity and the incretin hormones GLP-1 and GIP. The review reports associations between overgrowth, dysbiosis, irregular glucose regulation and reduced post-meal incretin responses, but notes that microbial and short-chain-fatty-acid responses can be complex and cannot be reduced to a single pathway. A major shared mechanism in the proposed cycle is disruption of the PINK1/Parkin mitophagy pathway: experimental findings associate high glucose and inflammation with reduced Parkin activity, damaged mitochondrial accumulation, impaired autophagic flux and apoptosis in both gastric epithelium and pancreatic beta cells, while leaked mitochondrial DNA can further activate STING and NF-κB signaling.

The review also identifies a shared immune and genetic background. HLA class II haplotypes such as DR3-DQ2 and DR4-DQ8 have been associated with susceptibility to both diseases, while anti-islet, anti-parietal-cell and intrinsic-factor antibodies occur in subsets of patients with diabetes. An imbalance between pro-inflammatory Th17 cells and regulatory T cells is another proposed link, with IL-17A activating NF-κB and STAT3-driven differentiation potentially contributing to injury of both gastric parietal cells and pancreatic beta cells. Yet the authors are explicit that none of the principal connecting nodes has been validated in a large prospective interventional study of comorbid patients. They call for longitudinal cohorts that repeatedly measure glucose control, gastroscopy, mucosal histology and biomarkers; dual-disease animal models and patient-derived gastric organoids; and simultaneous profiling of gastric and metabolic pathways. The review’s proposed antioxidant, hormonal, microecological and autophagy-based interventions are consequently early-stage research directions, not proven treatments for breaking the diabetes–gastritis cycle.

Subject of Research: Proposed bidirectional mechanisms linking diabetes mellitus and atrophic gastritis

Article Title: Diabetes mellitus and atrophic gastritis: progress in the study of interactive pathogenesis

Article References: Zhu, Z., Wang, L., Zhou, T., Che, Y., Shi, Y., Song, J., Zhang, Z., Xu, J., Tian, S., Qu, N., Lu, Y., Hao, Y., Zhang, J., Gao, H., & Lv, H. (2026). Diabetes mellitus and atrophic gastritis: progress in the study of interactive pathogenesis. Frontiers in Endocrinology, 17, Article 1955709. https://doi.org/10.3389/fendo.2026.1955709

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1955709

Keywords: diabetes mellitus, atrophic gastritis, hyperglycemia, gastric mucosa, oxidative stress, gut microbiome, insulin resistance, vitamin B12, gastroparesis, Helicobacter pylori, Diabetes, mellitus

The review’s abstract describes recent progress in identifying novel Cas orthologs and engineering Cas9 variants to improve editing fidelity, expand target ranges and reduce off-target effects. It also reports that structural and functional optimization of single-guide RNAs has improved target-binding affinity, stability and formation of the Cas9-sgRNA complex. High-fidelity Cas9 derivatives, base editors and prime editors are presented as enabling precise single-nucleotide substitutions and small insertions or deletions without producing double-stranded DNA breaks.

Delivery remains a central focus. According to the abstract, viral vectors, lipid nanoparticles and ribonucleoprotein electroporation have advanced CRISPR-mediated editing across in vitro, ex vivo and in vivo models. The review highlights therapeutic milestones reported for sickle cell disease, β-thalassemia and cystic fibrosis, where the abstract states that long-term clinical benefits have been documented. It also identifies a separate research role for CRISPR-Cas9 in diabetes: modeling disease mechanisms, identifying molecular pathways involved in glucose homeostasis and supporting development of cellular and gene-based therapies.

This is a review rather than a new clinical trial, laboratory study or protocol, and the available evidence consists of the article’s abstract and publisher information rather than the full text. The abstract does not provide study populations, sample sizes, quantitative editing efficiencies, delivery-performance measures, follow-up periods, safety outcomes or a systematic assessment of the cited clinical evidence. Consequently, the reported therapeutic milestones and broader translational claims are summarized here as the review’s conclusions; the available source does not support independent verification of their magnitude or applicability to individual patients.

Subject of Research: CRISPR-Cas9 genome editing technologies, delivery systems and therapeutic applications

Article Title: CRISPR–Cas9 genome editing: technological advances, delivery strategies and precision engineering of primary cells for therapeutic application in genetic disorders and diabetes mellitus

Article References: Islam, M. N., Islam, M. M., Feng, H., Bellah, S. F., Zaman Miah, M. M., & Hossain, M. S. (2026). CRISPR–Cas9 genome editing: technological advances, delivery strategies and precision engineering of primary cells for therapeutic application in genetic disorders and diabetes mellitus. Molecular Biology Reports, 53(1), Article 1589. https://doi.org/10.1007/s11033-026-12771-1

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12771-1

Keywords: CRISPR-Cas9, genome editing, base editing, prime editing, gene delivery, primary cells, genetic disorders, sickle cell disease, β-thalassemia, cystic fibrosis, diabetes mellitus, CRISPR

The case report describes an atypical pulmonary infection without the classic sulfur granules associated with pulmonary actinomycosis. The patient received four months of guideline-concordant penicillin therapy, yet the lesion showed no measurable reduction on imaging. Following multidisciplinary discussion and positron emission tomography-computed tomography to characterize the disease and identify other suspicious lesions, he underwent video-assisted thoracoscopic surgery with right upper lobectomy. Intraoperative pus culture and repeated high-abundance metagenomic sequencing confirmed S. odontolytica.

After surgery, the patient received an additional 24 weeks of oral amoxicillin-clavulanate. At six-month follow-up, the report states that he remained clinically and radiologically free of recurrence. The investigators concluded that combining special histochemical staining with metagenomic sequencing may assist diagnostic evaluation in sulfur granule-negative pulmonary actinomycosis that resembles lung cancer. They also reported that a low number of sequencing reads in bronchoalveolar lavage fluid did not exclude invasive infection complicated by an encapsulated abscess in this case.

These findings come from a single case and therefore do not establish the reliability of the diagnostic approach, define optimal timing for surgery, or demonstrate that resection plus prolonged antimicrobial treatment benefits similar patients generally. The case involved one patient with diabetes and a persistent pulmonary lesion initially considered highly suspicious for malignancy. Based on the available abstract, the proposed role of timely surgical resection and prolonged postoperative antimicrobial therapy remains limited to the selected case presented rather than validated as a broader treatment strategy.

Subject of Research: A single case of sulfur granule-negative pulmonary Schaalia odontolytica infection mimicking lung cancer.

Article Title: Sulfur granule‑negative pulmonary Schaalia odontolytica infection that mimics lung cancer with lack of radiological response to β‑lactam therapy: a case report

Article References: Li, G., Ye, B., Zhou, X., & Chen, G. (2026). Sulfur granule‑negative pulmonary Schaalia odontolytica infection that mimics lung cancer with lack of radiological response to β‑lactam therapy: a case report. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14494-x

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14494-x

Keywords: Schaalia odontolytica, pulmonary actinomycosis, case report, lung cancer mimic, metagenomic sequencing, bronchoalveolar lavage, penicillin therapy, surgical resection, amoxicillin-clavulanate, diabetes mellitus, Sulfur, granule

Trained enumerators interviewed participants face to face for approximately 20–30 minutes and administered a structured checklist covering 25 possible daily health complaints. The total score ranged from zero to 25 and was divided into three domains: sensory function or pain, body-system function, and activity participation. Participants were eligible if they were at least 15 years old, had diagnosed diabetes and reported a previous COVID-19 infection. Vaccination status was verified using electronic records from Indonesia’s SatuSehat platform and physical vaccination cards. Missing data were addressed through K-nearest-neighbours imputation with k = 5, producing an analytic sample of 420 participants. The count outcomes were modelled with negative binomial regression adjusted for sociodemographic and clinical variables.

The participants had a median age of 60 years, and 70.2% were female. A total of 36.2% had received a COVID-19 vaccine before their infection. Joint or muscle pain was the most prevalent complaint, reported by 46.0% of participants, followed by visual impairment at 43.1% and fatigue at 24.3%. The multivariable results also identified associations between demographic or clinical characteristics and particular complaint domains. Female participants had a higher rate of total daily complaints than male participants, with an incidence rate ratio of 1.25 and a 95% confidence interval of 1.02–1.53. Participants with secondary education had a lower rate of body-system dysfunction, with an incidence rate ratio of 0.66, while the absence of other comorbidities was associated with a lower rate of sensory or pain complaints, with an incidence rate ratio of 0.84. The supplied abstract did not provide confidence intervals for these two domain-specific estimates.

Vaccination after the index COVID-19 infection was not significantly associated with a lower rate of complaints related to that infection. The estimated incidence rate ratio was 1.06, with a 95% confidence interval of 0.90–1.26, which includes no difference. This estimate does not show that vaccination after infection reduced complaints, but it also does not establish that vaccination before infection was superior to vaccination after infection. The significant pre-infection estimate and the non-significant post-infection estimate came from separate comparisons, and the reported confidence interval for the post-infection association includes both lower and higher values than one. The clearest finding was therefore the observed association between pre-infection vaccination status and the overall rate of daily complaints, rather than a demonstrated advantage of one vaccination timing over the other.

The study offers a primary-care view of health burdens reported by people with diabetes after COVID-19, a population for which evidence from low- and middle-income settings was described as limited. The authors proposed that vaccination promotion could be integrated into routine chronic-disease management in these settings, while calling for prospective confirmation of the association. Several features constrain that conclusion. The cross-sectional design assessed vaccination and infection histories retrospectively and collected the other data at a single time point, allowing the analysis to estimate rates but not establish temporal or causal relationships. The sample was drawn from one Indonesian province and included only people with self-reported prior infection, with no uninfected control group. Unmeasured differences between vaccinated and never-vaccinated participants could therefore contribute to the observed pattern, and the findings may not generalize to other populations or primary-care systems. Within these limitations, the study linked pre-infection vaccination with a lower overall burden of daily complaints among 420 Indonesian primary-care patients with diabetes after COVID-19.

Subject of Research: Association of pre-infection COVID-19 vaccination with daily health complaints among Indonesian primary-care patients with diabetes.

Article Title: Beyond the pandemic declaration: daily health complaints in diabetic COVID-19 survivors and the association with prior vaccination in Indonesian primary care

Article References: Machmud, P. B., Khatimah, H., Mahkota, R., Veronica, J., & Wijayanto, A. W. (2026). Beyond the pandemic declaration: daily health complaints in diabetic COVID-19 survivors and the association with prior vaccination in Indonesian primary care. BMC Public Health. https://doi.org/10.1186/s12889-026-30043-2

Image Credits: AI Generated

DOI: 10.1186/s12889-026-30043-2

Keywords: COVID-19 vaccination, diabetes mellitus, daily health complaints, post-COVID symptoms, cross-sectional study, primary care, Indonesia, long COVID, negative binomial regression, Beyond, pandemic, declaration

The review, published in BMC Cancer, examined observational research concerning factors associated with pancreatic cancer risk. It followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews and the Joanna Briggs Institute methodology. The authors searched PubMed/MEDLINE, Scopus, Web of Science, ProQuest and ScienceDirect from each database’s inception through 13 July 2026.

Two reviewers independently screened studies and extracted data, while methodological quality was appraised with Critical Appraisal Skills Programme checklists. The included studies had been published from 2001 through 2026, and the researchers synthesized the evidence using thematic analysis. Substance use was the most frequently investigated theme in the literature, followed by metabolic disorders, body weight and composition, dietary habits and pancreatic conditions.

Smoking, diabetes mellitus and chronic pancreatitis were among the factors most often reported across the included studies, alongside obesity-related measures, increasing age and family history of pancreatic cancer. The scope of the evidence therefore extends well beyond individual behavioral choices, incorporating metabolic, clinical and inherited factors as well as environmental and social domains. However, the number of studies examining a topic does not by itself establish causality or determine the strength of an association.

Across the 16 themes, the review identified evidence concerning clinical conditions, chronic inflammation, infectious agents, genetic factors, environmental exposures and medication-related exposures. These categories were represented in the literature but were generally studied less frequently than the principal themes. The review also included demographic characteristics, socioeconomic factors and psychosocial factors, showing that the assessed research extends beyond disease, lifestyle and inherited susceptibility alone.

As a scoping synthesis, the work maps the factors that have been investigated rather than pooling results into a single effect estimate. The authors’ conclusion is correspondingly cautious: the literature is extensive for several recurring factors, but important areas remain insufficiently characterized, particularly where exposure definitions and study methods vary. The review identifies two priorities for future research: greater use of prospective designs and standardized, clearly defined exposure assessment.

The authors state that more reliable pancreatic cancer risk stratification may be supported as the evidence base becomes clearer, but the review itself does not provide a new risk score, prove that the less-studied factors cause pancreatic cancer, or establish clinical benefit from any intervention. Its principal contribution is a detailed account of the current research landscape: six broad domains, 16 major themes and 130 observational studies show both where pancreatic cancer risk research is concentrated and where important questions remain less thoroughly examined.

Subject of Research: Scoping review of observational evidence on pancreatic cancer risk factors across behavioral, metabolic, clinical, genetic, environmental and social domains.

Article Title: Pancreatic cancer risk factors across behavioral, metabolic, clinical, genetic, environmental, and social domains: a scoping review

Article References: Ghanbari-Jahromi, M., Zare, Z., Jalali, F. S., Dastan, H., Sarikhani, Y., & Nematollahi, M. S. (2026). Pancreatic cancer risk factors across behavioral, metabolic, clinical, genetic, environmental, and social domains: a scoping review. BMC Cancer. https://doi.org/10.1186/s12885-026-16945-9

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16945-9

Keywords: pancreatic cancer, risk factors, scoping review, observational studies, smoking, diabetes mellitus, chronic pancreatitis, obesity, genetic factors, environmental exposures, social factors, thematic analysis

The research, led by Stefan Koning and colleagues at Leiden University Medical Center together with collaborators in The Hague and Copenhagen, enrolled 128 patients with peripheral artery disease, covering 144 treated limbs. Of these, 42 patients, or roughly a third, had diabetes mellitus, accounting for 48 limbs. The team performed quantitative indocyanine green near-infrared fluorescence imaging both before and after revascularization, measuring three time-based perfusion parameters that describe how quickly the fluorescent tracer arrives in the tissue of the foot, how fast it leaves, and how the signal builds up over time. In a subset of 67 patients suffering from chronic limb-threatening ischaemia, the most severe form of the disease, the researchers then checked whether the imaging findings predicted clinical improvement at six weeks.

Indocyanine green is a well-established fluorescent tracer that binds to plasma proteins and circulates with the blood. When illuminated by a near-infrared light source, it emits fluorescence that can be captured by specialized cameras, allowing clinicians to visualize perfusion beneath the skin surface without ionizing radiation. Because the technique is dynamic, it does not merely show whether blood vessels are open, as an angiogram does, but whether blood is actually reaching and washing through the microcirculation of the foot, the capillary beds where oxygen delivery ultimately matters. This distinction is crucial, because a technically successful operation on a large artery does not guarantee that the smallest vessels of a diabetic foot can respond.

The preoperative findings were already revealing. Before any intervention, patients with diabetes showed faster inflow and outflow of the tracer than patients without diabetes at most levels of measurement, with the notable exception of the crural level, the region of the lower leg where the arteries branch toward the ankle and foot. This counterintuitive observation suggests that the diabetic foot microcirculation behaves differently even at baseline, a phenomenon the authors link to the complex interplay of neuropathy, microvascular dysfunction and calcified, often rigid vessels that characterize diabetic vascular disease. Rather than simply being more blocked, the diabetic circulation appears to be differently regulated, which may explain why conventional anatomical assessments so often fail to predict outcomes in this group.

The postoperative picture was where the divide became dramatic. After revascularization, only two of the nine perfusion parameters improved significantly in the diabetes group, with p-values below 0.001, whereas six of nine parameters improved in the non-diabetes group, with p-values ranging from 0.027 to below 0.001. In plain terms, opening the arteries produced a far richer physiological response in patients without diabetes. Their feet flushed with restored blood flow across nearly every measurable dimension, while the diabetic feet showed a muted, partial recovery. The imaging was, in effect, capturing the difference between a circulation that can respond to restored supply and one whose microvascular machinery has been damaged by years of metabolic disease.

The clinical correlation strengthened the case. Among the 67 patients with chronic limb-threatening ischaemia, 50 experienced clinical improvement at six weeks, 34 without diabetes and 16 with diabetes, while 14 did not improve, including 8 with diabetes and 6 without, and 3 were lost to follow-up. In the patients who did improve, perfusion rose significantly across all measured parameters in the non-diabetic group, with p-values from 0.08 to below 0.001, but not in the diabetic group. Overall, 85 percent of non-diabetic chronic limb-threatening ischaemia patients improved clinically, compared with 66 percent of diabetic patients, a trend that approached but did not reach statistical significance with a p-value of 0.073. The numbers are small, and the authors are careful to describe the difference as a trend, but the direction is consistent with everything the perfusion imaging showed.

These findings matter because current decision-making in limb-threatening ischaemia relies heavily on the Wound, Ischemia and foot Infection classification system maintained by the Society for Vascular Surgery, which grades the severity of wounds, the degree of ischemia and the presence of infection to predict the likelihood of limb salvage. What that system cannot do is tell a surgeon whether an individual diabetic foot, once reperfused, has enough residual microvascular capacity to heal. The Leiden study suggests that quantitative near-infrared fluorescence imaging could fill that gap, offering a functional, dynamic readout of tissue-level perfusion both before the operation, to set expectations, and immediately after, to verify whether the revascularization has actually changed anything at the capillary level.

The implications for personalized treatment are considerable. If diabetic patients demonstrate reduced perfusion responsiveness after technically successful revascularization, surgeons might use that information to plan adjunctive therapies, to select different revascularization targets, to intensify wound care and offloading, or to have earlier and more honest conversations about prognosis and the risk of amputation. Conversely, a diabetic patient whose postoperative imaging shows a robust perfusion response might be reassured and followed less intensively. The technology itself is relatively practical: indocyanine green is already approved and widely used, the imaging sessions are quick, and the radiation-free nature of near-infrared imaging makes repeated measurements feasible, even at the bedside.

The study, approved by the Medical Research Ethics Committee of Leiden University Medical Center under number G21.087 and conducted in accordance with the Declaration of Helsinki, was co-funded through the Dutch public-private partnership program Health~Holland under the RULER and IMPULSE projects, with additional support from the European Union’s Horizon Europe program through the RETINA project. The work, published open access on 9 September 2026, arrives amid growing recognition that diabetes transforms peripheral artery disease from a plumbing problem into a disease of the smallest vessels and the nerves that regulate them. Diabetic patients face higher rates of neuropathy, more extensive ischemia and dramatically elevated amputation risk, and the study provides direct visual evidence of why.

For now, the authors position their results as a step toward tailored strategies for the highest-risk group rather than a finished clinical tool. The message, however, is unmistakable: restoring flow through a large artery is only half the battle. What ultimately saves a limb is blood arriving where it is needed, in the skin and tissue of the foot, and for the first time surgeons can watch that happen, in glowing green, seconds after injecting a tracer. As near-infrared fluorescence imaging matures, the day may come when every revascularization is followed by a real-time perfusion check, turning an invisible microvascular failure into something a surgeon can see, measure and act upon before the wound, or the limb, is lost.

Subject of Research: Quantitative ICG near-infrared fluorescence imaging of foot perfusion before and after revascularization in peripheral artery disease patients with and without diabetes mellitus

Article Title: Assessment of foot perfusion before and after revascularization using quantitative ICG near-infrared fluorescence imaging in patients with and without diabetes mellitus

Article References: Koning, S., Peul, R. C., Kruiswijk, M. W., Tange, F. P., van Schaik, J., Schepers, A., Brouwers, J. J. W. M., van Rijswijk, C. S. P., van der Bogt, K. E. A., Eiberg, J. P., Vahrmeijer, A. L., Hamming, J. F., van den Hoven, P., & van der Vorst, J. R. (2026). Assessment of foot perfusion before and after revascularization using quantitative ICG near-infrared fluorescence imaging in patients with and without diabetes mellitus. BMC Medical Imaging. https://doi.org/10.1186/s12880-026-02682-9

Image Credits: AI Generated

DOI: 10.1186/s12880-026-02682-9

Keywords: peripheral artery disease, diabetes mellitus, indocyanine green, near-infrared fluorescence imaging, foot perfusion, revascularization, chronic limb-threatening ischaemia, microcirculation, vascular surgery, WIfI classification, amputation risk, BMC Medical Imaging

The headline figure from the survey is a self-reported tuberculosis prevalence of approximately 150 per 100,000 population, a figure expressed in the study as 150 per lakh, the South Asian unit of one hundred thousand. While that number sits within the broad range of official estimates for the country, what makes the study valuable is not simply the prevalence estimate itself but the parallel measurement of six well-established vulnerability factors that make individuals more likely to progress from latent infection to active disease. These are HIV infection, current smoking, silicosis, occupational exposure to silica dust, diabetes mellitus, and a persistent cough lasting more than two weeks, the classic warning symptom that should trigger diagnostic evaluation.

The rationale for mapping these factors together stems from a growing recognition in TB control strategy that comorbidities and occupational exposures in otherwise uninfected individuals create pockets of heightened susceptibility. HIV infection dramatically increases the risk that latent Mycobacterium tuberculosis infection will activate, because the virus depletes the CD4-positive T cells that normally keep the bacillus in check. Diabetes mellitus, which has tripled in prevalence across India in recent decades, impairs immune function in ways that roughly double or triple TB risk. Smoking damages the mucociliary clearance mechanisms of the airways, while silica dust exposure and established silicosis disrupt macrophage function in the lungs, the very cells responsible for engulfing and destroying tubercle bacilli. Each of these conditions, on its own, marks a population that could benefit from more intensive screening.

To build the dataset, the researchers designed a multi-stage random sampling framework that aimed to capture a genuinely representative slice of rural life. In each of the six districts, two administrative blocks were selected at random, and within each block, villages were again chosen randomly. Rather than sampling individual households within those villages, the team employed a universal sampling technique, meaning every household in the selected villages was approached for participation. This choice matters methodologically, because universal sampling within clusters avoids the selection biases that can creep in when enumerators choose which homes to visit, and it maximizes coverage of populations that are often missed by facility-based surveillance, such as people who never seek care or who cannot easily travel to a clinic.

Data collection relied on a pre-tested semi-structured questionnaire administered through face-to-face interviews at every eligible household. Pre-testing the instrument is a standard but crucial step, since it allows researchers to identify ambiguous wording, translation problems, or questions that respondents consistently misunderstand before the full survey begins. The interviews captured demographic details alongside self-reported TB status and the selected vulnerability factors. Descriptive statistical analysis was then performed, with results expressed as frequencies and percentages. The final sample comprised 52 percent males and 47 percent females, with 77 percent of the population aged 15 years or older, an age distribution that aligns with the typical demographic structure of rural India and ensures that adult prevalence patterns are well represented.

The measured prevalence of the vulnerability factors reveals a layered risk landscape. HIV-reactive individuals made up 0.9 percent of the surveyed population, current smokers accounted for 5 percent, silicosis was reported at 1.2 percent, occupational exposure to silica dust at 1.1 percent, diabetes mellitus at 1.4 percent, and a cough lasting more than two weeks at 4 percent. Each of these percentages, multiplied across a rural population of hundreds of millions nationally, translates into enormous numbers of people. The 4 percent reporting persistent cough is particularly significant for programmatic purposes, because cough of more than two weeks is the cardinal symptom that NTEP screening algorithms use as a trigger for sputum testing and, increasingly, molecular diagnostics such as the GeneXpert platform.

It is worth pausing on the relationship between these factors and the biology of TB progression. An estimated quarter of the world’s population carries latent TB infection, in which the bacteria sit dormant within granulomas in the lungs, held in check by the immune system. Progression to active disease occurs in roughly 5 to 10 percent of latently infected individuals over a lifetime, but that risk is not evenly distributed. In a person living with HIV, the annual risk of developing active TB can be more than tenfold higher than in an immunocompetent person. In someone with untreated diabetes, the risk is estimated at two to three times baseline. In silicosis, the granuloma-forming macrophages that normally wall off the infection are progressively destroyed by silica particles, creating an environment where tubercle bacilli can flourish, and TB risk in silicotics has been reported to be several times that of the general population.

The implications for active case finding are the study’s central contribution. Passive case finding, in which patients are diagnosed only after they present themselves to a health facility, has long been known to miss a substantial fraction of TB cases, particularly in rural and underserved areas where access barriers, stigma, and low health literacy suppress care-seeking. Active case finding, by contrast, sends screening into communities, identifying infectious individuals earlier in their disease course, interrupting transmission chains, and reducing the duration for which untreated patients spread the bacillus through coughing. The NTEP has embraced targeted active case finding, but targeting requires maps. Knowing which villages and which demographic or occupational groups carry elevated vulnerability allows program managers to concentrate expensive screening resources where they will yield the most diagnosed cases rather than distributing them uniformly.

The study’s multipronged approach, simultaneously measuring six vulnerability factors in a single massive cohort, is what distinguishes it from narrower prevalence surveys. Many earlier studies in India have examined one comorbidity at a time, for instance diabetes prevalence among TB patients or smoking rates in a single district. By capturing the full profile in one coordinated effort, the authors provide a denominator-based picture: for every vulnerability factor, program planners can now estimate how many people in comparable rural settings carry that risk marker. The very large sample size, exceeding eighty thousand individuals, gives the descriptive estimates considerable stability, which is essential when those estimates are used to project resource needs for screening campaigns, diagnostic capacity, and drug supplies.

Certain limitations are inherent to the design and deserve honest acknowledgment. The study relies on self-reported TB status and self-reported conditions, which means some cases may be undercounted if respondents were unaware of their infection or reluctant to disclose it, while clinical confirmation such as sputum microscopy or molecular testing was not performed as part of the survey itself. Self-reported diabetes likewise may miss undiagnosed cases, a substantial concern in India where a large share of people with diabetes are believed to be unaware of their condition. Despite these caveats, the scale and design of the survey make it a valuable strategic asset. As India pursues its goal of TB elimination, studies of this kind demonstrate that the path forward runs through granular, community-level surveillance of both the disease and the conditions that fuel it, turning the abstract arithmetic of a national epidemic into an actionable map of who needs screening, where, and why.

Subject of Research: Self-reported tuberculosis prevalence and associated vulnerability factors in rural populations across six districts of India

Article Title: Self-reported prevalence of tuberculosis and selected associated vulnerability factors among rural populations in six districts of India: A community-based cross-sectional study

Article References: Anand, P. K., Singh, M., Banerjee, P., Sahay, S., Bangar, S., Ghosh, B. R., Chalga, M. S., Pappu, A., Das, V., Gupta, S., Kumar, A., & Pandey, D. (2026). Self-reported prevalence of tuberculosis and selected associated vulnerability factors among rural populations in six districts of India: A community-based cross-sectional study. PLOS One, 21(10), e0360758. https://doi.org/10.1371/journal.pone.0360758

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0360758

Keywords: tuberculosis, India, prevalence, HIV, diabetes mellitus, silicosis, smoking, silica dust exposure, active case finding, National Tuberculosis Elimination Programme, cross-sectional study, rural health

The research, led by Narayane Ramkumar of the Indira Gandhi Institute of Dental Sciences at Sri Balaji Vidyapeeth in Puducherry, together with Hanumanth Sankar and Premalatha T, surveyed 380 medical professionals across India. The group included interns, postgraduate students, private practitioners, government practitioners, and medical faculty. Between June and December 2022, participants completed a structured, pre-tested questionnaire distributed electronically through Google Forms, with responses scored on a five-point Likert scale and combined into composite awareness scores for each periodontal–systemic domain. The instrument showed satisfactory internal consistency, with a Cronbach’s alpha of 0.836 across its thirteen knowledge and awareness items.

The headline number is almost paradoxical. A full 90.5 percent of respondents said they refer patients to dentists during their clinical practice — a figure that sounds reassuring until you learn why. Only 1.1 percent of those referrals were made because of knowledge of periodontal–systemic associations. In other words, doctors send patients to the dentist when they see something wrong in the mouth, not because they understand that the mouth may be driving disease elsewhere in the body. Referrals were overwhelmingly triggered by visible clinical manifestations such as intraoral lesions, gingival inflammation, and oral malodor rather than by any appreciation of the underlying biology linking periodontal inflammation to systemic illness.

That biology is anything but speculative. The idea dates back to 1891, when Walter Miller proposed the focal infection theory, suggesting that oral microbes could disseminate to distant body sites and contribute to disease. The modern era of what researchers call periodontal medicine began in 1996, when Steven Offenbacher coined the term to describe the connection between periodontal illness and systemic conditions. Since then, evidence has accumulated that chronic periodontal inflammation raises the body’s overall inflammatory burden through bacteremia, the dissemination of pro-inflammatory cytokines and bacterial endotoxins, and immune responses triggered by periodontal pathogens. These mechanisms are implicated in endothelial dysfunction, atherosclerotic plaque formation, and metabolic dysregulation — and periodontal pathogens such as Porphyromonas gingivalis have even been identified within atherosclerotic plaques themselves.

The associations run in both directions in some of medicine’s most common conditions. Diabetes and periodontitis form a classic bidirectional loop: hyperglycemia damages periodontal tissues and impairs immune responses, while periodontal inflammation worsens insulin resistance and glycemic control. Research by G.W. Taylor and colleagues indicated that severe periodontitis may act as a risk factor for poor glycemic control, and that treating gum disease may improve diabetes outcomes. Periodontal infection has also been linked to adverse pregnancy outcomes, with Offenbacher’s team reporting it as a potential risk factor for preterm low birth weight, and experimental work by J.G. Collins showing that P. gingivalis infection can reduce fetal weight in animal models through inflammatory mediator responses. Respiratory disease enters the picture too: oral pathogens including Pseudomonas species, Staphylococcus aureus, and members of the Enterobacteriaceae family can colonize dental plaque and be aspirated into the lungs, particularly in immunocompromised patients, and periodontal pathogens have been implicated in rheumatoid arthritis through their capacity to trigger systemic immune responses.

Against that backdrop, the survey results are sobering. Awareness of periodontal disease symptoms was reasonably high, reported by 86.6 percent of participants, with gingival bleeding the most frequently identified sign at 33.4 percent, followed by tooth mobility at 23.7 percent, gingival pain at 19.2 percent, tooth migration at 13.2 percent, and malodor at 10.5 percent. A chi-square test found a statistically significant association between professional category and the primary symptom identified, with p less than 0.001, showing that symptom recognition varies meaningfully across career stages. But recognizing a bleeding gum is not the same as understanding what it might signal about the heart, the pancreas, or the placenta.

The composite awareness scores told a more nuanced story. One-way ANOVA revealed significant differences among professional groups for three specific domains: diabetes mellitus, adverse pregnancy outcomes, and polycystic ovary syndrome, with p values of 0.016, 0.002, and 0.015 respectively. Tukey’s post-hoc analysis showed that government practitioners scored significantly higher than interns on both the diabetes and pregnancy domains, while medical faculty outperformed interns on the PCOS domain. Interns consistently posted the lowest mean scores — 3.20 for diabetes, 3.20 for pregnancy, and 3.25 for PCOS on the five-point scale — compared with government practitioners at 3.87, 3.75, and 3.59 respectively. The pattern suggests that clinical experience and continuing education build awareness over time, but that early-career doctors are entering practice with significant blind spots.

The authors attribute this gradient largely to gaps in undergraduate medical education, where oral health is typically underemphasized. Medical curricula focus extensively on systemic diseases while devoting minimal attention to the mouth, and structured teaching on periodontal–systemic relationships, practical training in basic oral examination, and interdisciplinary learning with dental students are all scarce. The authors caution, however, that the survey did not directly measure participants’ prior oral-health training or curriculum content, and that the cross-sectional design cannot establish whether education, experience, or other factors caused the observed differences. Other limitations deserve note as well: the convenience sampling method may have introduced selection bias, self-reported data are vulnerable to recall and social-desirability bias, and because recruitment flowed through WhatsApp groups and professional networks, a conventional response rate could not be calculated.

The PCOS finding is particularly intriguing because it touches one of the newest frontiers in periodontal medicine. Recent studies indicate that the chronic inflammation and oxidative stress characteristic of periodontal disease may contribute to the metabolic and hormonal imbalances seen in polycystic ovary syndrome. That medical faculty showed greater awareness of this emerging link than interns likely reflects their exposure to recent research findings and continuing medical education — but the overall variability across all groups underscores how unevenly new evidence percolates through the medical workforce, even for associations that could reshape how conditions like PCOS are managed.

The practical implications extend well beyond the classroom. The authors argue that physicians managing patients with diabetes or cardiovascular disease could incorporate oral health assessment into routine clinical evaluation, potentially improving overall disease management, while closer collaboration between dentists and obstetricians could help reduce the risk of preterm birth and low birth weight. At the policy level, they call for oral health assessments to be embedded in routine medical check-ups, structured referral protocols between medical and dental professionals, and public health initiatives targeting both providers and patients. Future research, they suggest, should test whether educational interventions and interdisciplinary training actually improve referral practices and patient outcomes — and identify the barriers that still keep medicine and dentistry, two professions caring for the same patient, so strikingly apart.

Subject of Research: Medical professionals' knowledge and awareness of the relationship between periodontal disease and systemic conditions such as diabetes, cardiovascular disease, and adverse pregnancy outcomes

Article Title: Knowledge, awareness, and attitudes of medical professionals toward the periodontal–systemic disease relationship: a cross-sectional study

Article References: Ramkumar, N., Sankar, H., & T, P. (2026). Knowledge, awareness, and attitudes of medical professionals toward the periodontal–systemic disease relationship: a cross-sectional study. Frontiers in Oral Health, 7, Article 1931494. https://doi.org/10.3389/froh.2026.1931494

Image Credits: AI Generated

DOI: 10.3389/froh.2026.1931494

Keywords: periodontal disease, systemic health, medical professionals, diabetes mellitus, cardiovascular disease, adverse pregnancy outcomes, PCOS, cross-sectional study, oral health education, referral practices, periodontal medicine, India

The study, published in BMC Geriatrics by a team from Nantong University’s School of Nursing and Rehabilitation and the Affiliated Hospital of Nantong University, set out to answer a question that has grown increasingly urgent as populations age: does multimorbidity — the coexistence of multiple chronic diseases — add information about dementia risk beyond what any single diagnosis provides? The researchers screened participants using the Revised Hasegawa Dementia Scale, a widely used cognitive assessment tool, and classified suspected dementia based on those scores. Eight chronic diseases were evaluated from participants’ medical histories, and the team then modeled both individual diseases and selected two- and three-disease combinations using logistic regression.

The headline numbers are striking. Among the 2,458 participants, 559 — or 22.7 percent — had suspected dementia. Multimorbidity was more common in that group: 38.8 percent of participants with suspected dementia had two or more chronic diseases, compared with 31.6 percent of those without suspected dementia. The gap widened further at higher disease counts, with three or more diseases present in 15.6 percent of the suspected-dementia group versus 9.7 percent of the rest. While such cross-sectional figures cannot establish that the diseases cause cognitive decline, they paint a consistent picture in which the burden of coexisting conditions tracks closely with cognitive impairment in older adults.

After full statistical adjustment for confounding factors, two individual diseases stood out. Diabetes mellitus was associated with higher odds of suspected dementia, with an odds ratio of 1.33 and a 95 percent confidence interval of 1.03 to 1.70 — a modest but statistically reliable elevation. Ear disease showed an even stronger association, with an odds ratio of 1.57 (95 percent confidence interval 1.06 to 2.33). The diabetes finding aligns with a substantial body of research linking impaired glucose metabolism, insulin resistance, and microvascular damage to cognitive decline. The ear disease association is more intriguing and fits into a growing literature connecting hearing loss and auditory disorders with dementia risk, possibly through social isolation, cognitive load from sensory deprivation, or shared underlying vascular and neurodegenerative processes.

The study’s most distinctive contribution, however, lies in its treatment of disease combinations rather than isolated diagnoses. Among pairwise combinations, the coexistence of hypertension and ear disease was associated with higher odds of suspected dementia, with an odds ratio of 1.83 (95 percent confidence interval 1.09 to 3.10). This suggests that the joint presence of a vascular condition and a sensory disorder may mark a risk profile that neither condition fully captures on its own. The researchers went further, applying Firth penalized logistic regression when sparse data or statistical separation occurred — a technique that stabilizes estimates when certain disease combinations are rare in the sample — and secondary analyses extended the approach to three-disease combinations as well.

Beyond simple co-occurrence, the team formally explored disease interactions on two statistical scales. Additive interaction was assessed using the relative excess risk due to interaction, the attributable proportion due to interaction, and the synergy index, while multiplicative interaction was tested within the regression models themselves. These are complementary questions: additive interaction asks whether the combined effect of two diseases exceeds the sum of their individual effects in absolute terms, which matters for public health burden, whereas multiplicative interaction asks whether their joint effect exceeds what would be predicted by multiplying their separate effects, which matters for biological mechanism. The secondary analyses characterized associations involving these interactions, adding a layer of nuance that most multimorbidity studies omit.

The study also broke new ground by examining how neuropsychiatric symptoms vary among people with suspected dementia. Using the Neuropsychiatric Inventory Questionnaire, the researchers performed a latent class analysis — a statistical method that identifies unobserved subgroups within a population based on patterns of observed characteristics. This analysis identified distinct symptom profiles among participants with suspected dementia, and notably, broader somatic disease associations were observed in two of these classes: one characterized by sleep and appetite disturbance, and another marked by agitation and irritability. In other words, the relationship between physical disease burden and dementia may not be uniform across symptom presentations; people whose dementia manifests as disrupted sleep, poor appetite, or agitated behavior showed wider links to coexisting chronic conditions than other symptom groups.

Methodologically, the team took several steps to strengthen a cross-sectional design that is inherently vulnerable to bias. Missing covariate data were handled using multiple imputation, a standard approach that fills in gaps by drawing from the observed data distribution while preserving uncertainty. The study was registered with the Chinese Clinical Trial Registry under identifier ChiCTR1900020923, and the protocol was reviewed and approved by the Ethics Committee of the Affiliated Hospital of Nantong University, with all participants providing signed informed consent in accordance with the Declaration of Helsinki.

For clinicians and researchers, the implications point toward a shift in how dementia risk is conceptualized in aging populations. Rather than treating chronic diseases as independent, additive risk factors, the findings suggest that the composition of a patient’s disease portfolio — which conditions coexist, and in what pairings — may carry information that disease counts alone do not. A patient with hypertension and ear disease may warrant closer cognitive monitoring than disease counts would suggest, and neuropsychiatric symptom profiles may help identify subgroups in which somatic disease burden plays a larger role. This resonates with a broader movement in geriatric medicine toward treating multimorbidity as a system-level phenomenon rather than a simple accumulation of diagnoses.

The authors are careful about the limits of their evidence. As a cross-sectional study, it captures a single moment in time and cannot determine whether the chronic diseases preceded the cognitive decline, followed it, or share common upstream causes. The analysis covered eight chronic diseases drawn from medical history, and the researchers themselves note that larger prospective studies incorporating a broader range of chronic conditions are needed to confirm the findings. Still, in a field where most risk models treat conditions one at a time, the demonstration that specific disease combinations — and even symptom-specific subgroups of dementia — carry distinct statistical signals offers a concrete, testable direction for future research into how the body’s accumulating conditions shape the aging brain.

Subject of Research: Associations between chronic disease combinations and suspected dementia in older adults

Article Title: Association between selected disease combinations and suspected dementia: a community-based cross-sectional study

Article References: Wei, R., Xu, Z., Ni, J., Cao, Y., Chen, T., Zhang, F., & Zhu, X. (2026). Association between selected disease combinations and suspected dementia: a community-based cross-sectional study. BMC Geriatrics. https://doi.org/10.1186/s12877-026-08437-z

Image Credits: AI Generated

DOI: 10.1186/s12877-026-08437-z

Keywords: dementia, multimorbidity, chronic disease, diabetes mellitus, hypertension, ear disease, older adults, cross-sectional study, latent class analysis, neuropsychiatric symptoms, BMC Geriatrics, Nantong

The epidemiological picture is striking. Across population studies, diabetes is associated with a two- to four-fold increase in both the incidence and recurrence of urinary tract infections. A meta-analysis encompassing 15 studies and 827,948 individuals with type 2 diabetes estimated a prevalence of roughly 11.5 percent, while asymptomatic bacteriuria, the silent presence of bacteria in the bladder without symptoms, has been reported in 23.7 percent of type 2 diabetes patients. More recent studies suggest the burden may be even higher in certain populations, with prevalence reaching up to 39.3 percent and overall risk nearly doubled compared with people without diabetes. Recurrence is a defining feature: reported rates range from approximately 23 to 37 percent, and diabetes has been identified as an independent risk factor for progression from a first episode of cystitis to recurrent disease.

The microbiology is equally revealing. Uropathogenic Escherichia coli remains the dominant cause of uncomplicated infections in diabetic and non-diabetic patients alike, accounting for roughly 60 to 71 percent of isolates across studies. But in diabetes the spectrum broadens considerably: Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus species, Enterobacter species, and, less frequently, Candida albicans all appear more often. Critically, patients with diabetes carry a higher prevalence of antimicrobial-resistant pathogens, including extended-spectrum beta-lactamase (ESBL)-producing strains of E. coli and K. pneumoniae. One comparative study cited in the review found resistance to at least one antimicrobial agent in 92.5 percent of isolates from diabetic patients versus 75.0 percent from non-diabetic controls, with particularly large gaps for amoxicillin (85.0 versus 67.5 percent), amoxicillin/clavulanic acid (57.5 versus 37.5 percent), ciprofloxacin (38.8 versus 20.0 percent), and ceftriaxone (25.0 versus 7.5 percent).

Why does hyperglycemia so profoundly reshape infection risk? The review lays out a layered mechanistic explanation. Chronic high blood glucose spills into the urine as glucosuria once plasma levels exceed the renal reabsorption threshold, creating a nutrient-rich environment that fuels bacterial growth. Simultaneously, hyperglycemia impairs innate and adaptive immune defenses: neutrophils show reduced chemotaxis, phagocytosis, and oxidative burst, while the antimicrobial peptide psoriasin, which normally controls bacterial growth at mucosal surfaces, is downregulated. Diabetic autonomic neuropathy adds a mechanical dimension, causing incomplete bladder emptying and urinary stasis that facilitate bacterial colonization. Hyperglycemia also disrupts the uroepithelial barrier itself, weakening intercellular junctions and altering receptor expression in ways that promote bacterial adhesion and deeper tissue invasion.

The bacterial side of the story is just as dynamic. UPEC initiates infection by adhering to uroepithelial cells through type 1 and P pili, with the FimH adhesin at the tip of type 1 pili driving bacterial internalization and the formation of intracellular bacterial communities that shield the pathogen from both immune attack and antibiotics. P pili, particularly class II variants, are associated with upper urinary tract colonization and heightened renal inflammation under diabetic conditions. UPEC also deploys an arsenal of virulence factors, including hemolysin A, cytotoxic necrotizing factor 1, the curli fiber protein CsgA, the serum resistance protein TraT, and group 2 capsule factors, which together promote tissue damage, biofilm formation, and immune evasion. Experimental work suggests that elevated glucose acts as both a metabolic substrate and a signaling cue, upregulating virulence-associated genes and enhancing biofilm production, which in turn increases tolerance to antibiotics and host defenses.

Perhaps the most clinically consequential insight is the bidirectional feedback loop between infection and glycemia. When a urinary tract infection takes hold, the body’s stress response releases counterregulatory hormones that increase hepatic glucose production and reduce insulin sensitivity, driving blood sugar upward. Inflammatory processes accompanying the infection further aggravate insulin resistance, and persistent low-grade inflammation can intensify this effect, particularly in patients with impaired renal function. The practical implication is that an unexplained rise in blood glucose in a diabetic patient should prompt consideration of an occult urinary infection, and conversely, that treating the infection is inseparable from restoring metabolic control. Hospitalized patients typically require structured glucose monitoring and insulin-centered regimens, with careful adjustment based on glucose trends and clinical status.

The review also tackles a modern therapeutic dilemma: sodium-glucose cotransporter 2 (SGLT2) inhibitors. These widely prescribed drugs deliberately induce glucosuria, sometimes exceeding 60 to 70 grams of urinary glucose per day in patients with preserved renal function, to improve glycemic control and deliver cardiovascular and renal benefits. The concern is obvious: does pharmacologically sweetened urine cultivate infection? The evidence is nuanced. Randomized controlled trials and meta-analyses generally show no significant increase in urinary tract infection risk with SGLT2 inhibitors, while observational studies suggest only a modest elevation that appears driven more by impaired kidney function and prior genitourinary infections than by glycemic status alone. In contrast, genital infection risk is consistently and markedly increased, more than threefold, particularly in women and those with a history of such infections, though these episodes are typically mild and respond well to standard treatment. The authors note that experimental studies supporting a role for urinary glucose in bacterial growth and UPEC virulence do not fully align with clinical observations from patients on SGLT2 inhibitors, leaving the contribution of glucosuria itself incompletely understood.

Clinical presentation adds another layer of complexity. While diabetic patients may experience classic symptoms such as dysuria, urinary frequency, and lower abdominal pain, atypical or muted symptoms are common and can delay diagnosis. When infection does take hold, it is more likely to escalate: the review catalogs a higher incidence of acute pyelonephritis, renal abscesses, emphysematous cystitis and pyelonephritis, and urosepsis in diabetic populations. These severe outcomes are attributed primarily to hyperglycemia-induced immune impairment, glucosuria, urinary stasis from neuropathy, and chronic inflammation rather than to diabetes type itself. Notably, patients over 45 years of age appear particularly susceptible, and type 2 diabetes is associated with more frequent infections than type 1, most likely because of higher rates of obesity, insulin resistance, poorer glycemic control, and chronic complications rather than the diabetes type per se.

Looking forward, the authors identify several promising therapeutic frontiers. Because hyperglycemia both impairs host defenses and enhances bacterial virulence, optimized glycemic control remains foundational, potentially reducing glucosuria-associated bacterial growth and partially restoring antimicrobial peptide expression. Targeting biofilm formation, which drives persistence and recurrence especially under hyperglycemic conditions, offers another avenue, as does modulating host immune responses, including interference with the AGE-RAGE-NF-kappa-B inflammatory axis that sustains tissue damage without effective pathogen clearance. Anti-virulence therapies that disarm bacterial toxins, adhesion factors, and immune evasion mechanisms could reduce pathogenicity without imposing the selective pressure that fuels antibiotic resistance. For multidrug-resistant UPEC strains carrying blaCTX-M, blaTEM, and blaSHV beta-lactamase genes, the review highlights bacteriophage therapy, microbiome-based interventions, and probiotic strategies as promising adjuncts, and points to genomics, transcriptomics, and metabolomics as tools for uncovering novel targets in hyperglycemia-driven immune dysfunction.

The review is candid about the limits of current knowledge. Most mechanistic evidence derives from in vitro experiments and animal models, while human studies remain predominantly observational, making it difficult to isolate the independent effect of hyperglycemia from coexisting diabetic complications, immune dysfunction, and structural abnormalities of the urinary tract. Heterogeneity in study populations, diagnostic criteria, and definitions of recurrent infection further complicates cross-study comparison. Yet the clinical message is unambiguous: urinary tract infections in diabetes demand integrated management that treats the infection promptly with culture-guided antimicrobials while simultaneously stabilizing blood glucose, with particular vigilance in patients with advanced kidney disease who may swing between hyperglycemia and hypoglycemia. As antimicrobial resistance continues to climb, understanding the molecular dialogue between a sugar-laden urinary tract and an adaptable pathogen may prove essential to protecting one of medicine’s most vulnerable populations.

Subject of Research: The bidirectional relationship between diabetes mellitus and urinary tract infections, covering epidemiology, UPEC pathogenesis, glucosuria, immune dysfunction, and management strategies

Article Title: Urinary tract infections in diabetes: clinical significance and management approaches

Article References: Zalewska-Piątek, B., Nagórka, M., & Piątek, R. (2026). Urinary tract infections in diabetes: clinical significance and management approaches. Acta Biochimica Polonica, 73, Article 17198. https://doi.org/10.3389/abp.2026.17198

Image Credits: AI Generated

DOI: 10.3389/abp.2026.17198

Keywords: diabetes mellitus, urinary tract infections, uropathogenic Escherichia coli, hyperglycemia, glucosuria, SGLT2 inhibitors, antimicrobial resistance, biofilms, immune dysfunction, glycemic control, ESBL, bacteriophage therapy