Search Results (1,049)

Background/Objectives: Achieving a balanced wholefood diet while stabilising glycaemic management is challenging for many people with type 2 diabetes (T2D) due to barriers such as food preparation skills, time, and medication effects. Diabetes-specific nutritional formulas (DSNFs) are nutritionally complete products designed to support glycaemic management and overall nutritional adequacy and may complement wholefood dietary approaches when these are not feasible or are insufficient. Despite growing clinical evidence of efficacy, practical guidance for routine use is limited. Methods: A multidisciplinary expert working group developed a Clinical Practice Guide (CPG) for integrating DSNFs into diabetes care. Development was informed by a literature review and iterative consensus among experts, including representatives of the Australian Diabetes Society, Australian Diabetes Educators Association, and the Royal Australian College of General Practitioners. Results: The CPG outlines a three-step pathway: (1) assess suitability (clinical indications, contraindications, preferences, cultural context); (2) tailor the approach (individual goals, dose/timing relative to weight and body composition goals and observed glycaemic patterns, integration with lifestyle care); and (3) monitor progress (baseline, 2–4 weeks to assess initial response, then 3, 6, and 12 months for glycaemic indices, weight/body composition where available, and medication review). Conclusions: This CPG provides practical, multidisciplinary guidance for the person-centred use of DSNFs as an adjunct to standard care, supporting translation of current evidence into clinical practice and promoting consistent, multidisciplinary implementation. Full article

Type 1 diabetes mellitus (T1D) is a common autoimmune disease during childhood with a substantial genetic component. Individual genome-wide association studies (GWAS) often have limited power and are predominantly based on European-ancestry populations. To provide a more robust synthesis of genetic associations, we conducted a meta-analysis using summary-level GWAS data from three independent pediatric T1D studies obtained from the NHGRI-EBI GWAS Catalog. Harmonized single-nucleotide polymorphisms (SNPs) shared across all datasets were analyzed using inverse-variance weighted fixed-effects and random-effects models, with between-study heterogeneity assessed using Cochran’s Q test and the $I^2$ statistic. Of the 4,297,702 million common SNPs analyzed, 3524 reached genome-wide significance ($p<5\times {10}^{-8}$), demonstrating strong and consistent associations with T1D risk. The most prominent signals clustered on chromosome 6, consistent with known immune-related loci, and included both risk-increasing and protective variants, in agreement with prior biological findings. Heterogeneity across studies was minimal, with $I^2$ values near $0\%$ for nearly all SNPs. These findings highlight robust and reproducible SNP-level associations with pediatric T1D, providing an updated foundation for functional follow-up and translational studies. Full article

Coxsackieviruses B are single-stranded RNA viruses belonging to the Enterovirus genus and are associated with various clinical outcomes, ranging from acute infections to chronic diseases, such as type 1 diabetes (T1D). It was previously shown that inoculation of Swiss albino mice with CVB4 by the intraperitoneal route induced both anti-CVB4 neutralizing and enhancing activities of serum. This study aimed to investigate the humoral immune response of mice inoculated with CVB4 by the mucosal route. Mice were inoculated orally or intranasally with CVB4, and the anti-CVB4 neutralizing activity of serum and saliva was assessed by a cell culture neutralization assay. Anti-enterovirus (EV) IgG and IgA antibodies were detected in serum and saliva, respectively, by ELISA. The serum-dependent enhancement of CVB4 infection in cultures of murine splenocytes was evaluated by detecting intracellular viral RNA using RT-qPCR. At day 45 post-inoculation, an anti-CVB4 neutralizing activity, the extent of which depends on the amount of inoculated infectious particles, was detected in the serum of mice exposed orally or intranasally. An increase in anti-CVB4 neutralizing activity was observed in the saliva of mice inoculated orally or intranasally during the follow-up. Oral or intranasal inoculation of CVB4 induced a systemic IgG and mucosal IgA response. In addition, serum from these mice harbored an anti-CVB4 enhancing activity in vitro. These data indicate that Swiss albino mice exposed to CVB4 via the mucosal route constitute a potentially useful model for testing strategies to promote the production of protective mucosal and systemic anti-CVB4 antibodies and for verifying whether or not enhanced antibodies are produced. Full article

Background/Objectives: The Prognostic Nutritional Index (PNI), which integrates serum albumin and lymphocyte count, reflects both nutritional and inflammatory status. However, its role in early renal function decline among patients with type 2 diabetes (T2D), particularly in relation to glycemic control, remains unclear. This study aimed to: (1) characterize the dose–response relationship between PNI and early renal function decline in type 2 diabetes using restricted cubic splines; (2) identify whether glycemic control (HbA1c) modifies the PNI–renal decline association; and (3) evaluate the clinical utility of combining PNI and HbA1c for risk stratification. Methods: We analyzed data from 1711 community-based participants with T2D who had preserved renal function at baseline. The PNI was calculated as serum albumin (g/L) + 5 × lymphocyte count (×10⁹/L). The primary outcome was a composite of rapid estimated glomerular filtration rate (eGFR) decline (>3 mL/min/1.73 m² per year) or incident chronic kidney disease (CKD) stage 3. Restricted cubic spline models, multivariable regression, and Johnson–Neyman analyses were used to examine non-linearity and effect modification by glycated hemoglobin (HbA1c). Results: A consistent inverse linear association was observed between PNI and the rate of eGFR decline (P for non-linearity > 0.05). Johnson–Neyman analysis further demonstrated that the protective association of PNI was statistically significant within an HbA1c range of 7.24% to 8.71%. Stratification by clinical cut-offs revealed a significant effect modification by glycemic status. The inverse linear association between PNI and renal risk was most pronounced under hyperglycemic stress, as evidenced by the markedly elevated incidence (50.0%) among individuals with both poor glycemic control (HbA1c ≥ 8%) and low PNI (<50). Conversely, under good glycemic control (HbA1c < 8%), this inverse association was substantially attenuated, with a lower incidence observed in the low-PNI subgroup (6.7%) than in the high-PNI subgroup (15.9%). These findings indicate that the protective role of PNI is conditional upon the glycemic milieu. Conclusions: The PNI demonstrates a stable linear association with early renal function decline in T2D, with its protective effect most pronounced at suboptimal HbA1c levels. Combining PNI and HbA1c effectively identifies a high-risk subgroup characterized by synergistic risk, underscoring the need for integrated nutritional and glycemic management. Full article

T cells play an important role in the development and progression of type 1 diabetes (T1D). Checkpoint receptors regulate T cell activity, and their expression may be linked to the cells’ metabolic state. This study aims to investigate the association between T regulatory (Treg) and T conventional (Tconv) cells expressing various checkpoint inhibitors and glucose metabolism in type 1 diabetes patients and healthy controls (HCs). The study included 28 participants, with 16 of them diagnosed with type 1 diabetes, while 12 constituted a healthy control group. Multicolor flow cytometry, spectrophotometric analysis, and bead-based multiplex assays were utilized for the analyses. The study revealed that the most significant difference in T cell subsets in peripheral blood concerned TIGIT. Compared to healthy subjects, the percentages of TIGIT+ Tregs and TIGIT+ Tconvs were lower in T1D patients. Interestingly, hyperglycemia in in vitro cultures reduced percentages of TIGIT+ Tregs and TIGIT+ Tconvs, and to some extent also CTLA-4+ Tregs. A decreased percentage of these subsets was, in turn, associated with reduced glucose uptake and lower activity of the enzymes responsible for various stages of glucose metabolism. The described associations suggest a negative influence of hyperglycemia in T1D on immune regulation via a TIGIT-dependent mechanism. Hyperglycemia seems to reduce the percentage of highly regulatory TIGIT+ Tregs both in vivo and in vitro, and it is associated with reduced glucose consumption by these cells. At the same time, a reduction in the percentage of TIGIT+ Tconvs under such conditions may facilitate higher activity of Tconvs, including aberrant autoimmune reactions. Full article

Type 1 Diabetes (T1D) is thought to result from the interaction of genetic and environmental factors, with different studies highlighting a potential role for the gut microbiota and its metabolites in modulating immune responses and disease development. We hypothesized that patients with T1D exhibited altered levels of circulating bacterial metabolites compared with healthy controls (HC), and that these metabolite profiles were associated with key demographic, clinical, and analytical features of the disease. A total of 91 T1D patients and 58 HC were recruited. Plasma samples were collected and analyzed with gas chromatography coupled to mass spectrometry for the detection of the metabolites: short-chain fatty acids (SCFAs: acetate [AA], propionate [PA], isobutyrate [IBA], butyrate [BA], isovalerate [IVA], valerate [VA], and methyl valerate [MVA]), medium-chain fatty acids (MCFAs: hexanoate [HxA] and heptanoate [HpA]) and para-cresol (p-cresol). We also calculated the ratios between the different SCFAs with AA. T1D patients showed significantly higher circulating AA levels than HC, along with reduced PA/AA and IBA/AA ratios, indicating an altered SCFA profile. SCFA diversity was lower in T1D patients, with reduced detection of BA, and total SCFA levels were increased mainly due to elevated AA. AA levels were higher and SCFA ratios lower in women with T1D compared with healthy women, while p-cresol levels were higher in men with T1D than in healthy men. In T1D patients, AA levels positively correlated with HbA1c, whereas PA/AA, IBA/AA, and BA/AA ratios showed negative correlations, particularly in women. MV/AA and non-AA/AA ratios were inversely associated with glucose levels, again, mainly in women. p-cresol levels correlated positively with age and ferritin and were higher in T1D patients with liver dysfunction or hypertension. Therefore, we can conclude that T1D is associated with a marked alteration in circulating gut-derived metabolites, characterized by increased AA levels, particularly in women, and an imbalance in SCFA ratios that correlates with glycemic control. These findings, together with the associations observed for p-cresol and metabolic comorbidities, support a role for the gut microbiota–host metabolic axis in T1D. Full article

Autoimmune type 1 diabetes (T1D) results from the failure of the physiologic regulatory mechanisms that are designed to maintain immune tolerance to pancreatic beta cells. Consequently, the design of strategies to restore tolerance to beta cell antigens is an attractive objective of translational research. We have designed ultrasmall nanoparticles (NPs) loaded with a proinsulin (PI) fusion protein and an agonist for the aryl hydrocarbon receptor (AhR), a transcription factor promoting tolerance induction by different immune cells. We report that a 4 week-treatment with these NPs in non-obese diabetic (NOD) mice starting at disease onset induces temporary and sometimes durable disease remission. Mechanistically, short-term NP treatment induces a rapid depletion of islet infiltrates with a dramatic reduction in the number of CD8⁺ T cells and dendritic cells. This is accompanied by the emergence of B lymphocytes producing IL-10. In the rare mice that undergo durable disease remission, the disappearance of islet infiltrates is associated with the emergence of Foxp3⁺ CD4⁺ regulatory T cells, IFN-γ-producing memory T cells in the spleen, and draining lymph nodes (LNs). We conclude that treatment with these NPs could be of interest in the treatment of recent-onset autoimmune diabetes, but is unlikely to be sufficient for the induction of long-term remission as a stand-alone therapy. Full article

Background and Clinical Significance: Overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in children is a rare but life-threatening metabolic emergency. The coexistence of hyperosmolality and ketoacidosis increases neurologic vulnerability and complicates fluid and insulin management. Early identification and osmolality-guided therapy are essential to prevent cerebral edema and other complications. This case describes a 5-year-old boy with new-onset type 1 diabetes mellitus (T1D) presenting with DKA/HHS overlap two weeks after influenza vaccination—an unusual temporal association without proven causality. Case Presentation: A previously healthy 5-year-old presented with progressive polyuria, polydipsia, nocturnal enuresis, fatigue, and drowsiness. Two weeks earlier, he had received the influenza vaccine. Examination revealed moderate dehydration without Kussmaul respiration or altered consciousness. Laboratory evaluation showed glucose 45.9 mmol/L (826 mg/dL; reference 3.9–7.8 mmol/L), venous pH 7.29 (reference 7.35–7.45), bicarbonate 12 mmol/L (reference 22–26 mmol/L), moderate ketonuria, and measured serum osmolality 344 mOsm/kg (reference 275–295 mOsm/kg), fulfilling diagnostic criteria for DKA/HHS overlap. After an initial 20 mL/kg 0.9% NaCl bolus, fluids were adjusted to maintenance plus approximately 10% deficit using 0.45–0.75% NaCl according to sodium/osmolality trajectory. Intravenous insulin (approximately 0.03–0.05 IU/kg/h) was initiated once blood glucose no longer decreased adequately with fluids alone and had stabilized near 22.4 mmol/L (≈400 mg/dL). Dextrose was added when glucose reached 13.9 mmol/L (250 mg/dL) to avoid rapid osmolar shifts. Hourly neurological and biochemical monitoring ensured a glucose decline of 2.8–4.2 mmol/L/h (50–75 mg/dL/h) and osmolality decrease ≤3 mOsm/kg/h. The patient recovered fully without cerebral edema or neurologic sequelae. IA-2 antibody positivity with low C-peptide and markedly elevated HbA1c confirmed new-onset T1D. Conclusions: This case highlights the diagnostic and therapeutic challenges of pediatric DKA/HHS overlap. Osmolality-based management, conservative insulin initiation, and vigilant monitoring are crucial for preventing complications. The temporal proximity to influenza vaccination remains incidental. Full article

Background/Objectives: Modifiable lifestyle factors, particularly diet, are important for preventing type 2 diabetes (T2D); however, the evidence regarding this from prospective studies is limited in the Asian population. We therefore evaluated whether a diet-inclusive healthy lifestyle score (HLS) predicts incident T2D in a community-based cohort. Methods: We analyzed 7185 T2D-free adults from the KoGES Ansan–Ansung cohort, constructing the HLS (range: 0–5) based on five lifestyle factors: non-smoking, ≥30 min/day of moderate-to-vigorous physical activity, low-risk alcohol consumption (≤40 g/day for men; ≤20 g/day for women), BMI of 18.5–24.9 kg/m², and a healthy diet, defined as a healthy plant-based diet index within the top 40th percentile. Cox proportional hazards regression models were employed to examine the association between HLS and incident T2D risk. Results: During a median follow-up of 17.5 years, 1223 cases of T2D were identified. Compared to individuals with a score of 0 or 1, those with a score of 5 had a 56% lower risk of T2D after adjustment for potential confounders (HR: 0.44, 95% CI: 0.32–0.62), and these associations remained consistent across subgroups stratified by age, sex, family history of T2D, hypertension, and residential area. However, the association was stronger among non-users of anti-diabetic medication than among users. Conclusions: Adherence to a healthier lifestyle, as indicated by a higher HLS, was significantly associated with a reduced risk of developing T2D among Korean adults. These findings underscore the importance of promoting integrated healthy lifestyle behaviors to prevent T2D. Full article

Hypoglycemia is associated with cardiovascular events reflected by platelet abnormalities. We hypothesized that sequential endothelial changes may occur during hypoglycemia that may enhance cardiovascular risk. In type 2 diabetes (T2D) (n = 23) and controls (n = 23), blood SOMAscan proteomic analysis of endothelial proteins at baseline, insulin-induced hypoglycemia and post hypoglycemia to 24 h were examined using repeated-measures linear mixed modeling with a prospective parallel study design. Most endothelial proteins that changed over time did not differ between groups. Baseline levels of P-selectin, plasminogen activator inhibitor-1 (PAI-1; serpine-1), E-selectin and angiopoietin-1 (ANGPT1) were significantly higher, whilst cadherin-5 was lower in T2D. Several proteins exhibited changes versus baseline in both T2D and controls. Under hypoglycemia, decreases in cadherin-5 and soluble angiopoietin-1 receptor (sTie-2) were observed, with increased P-selectin, intercellular adhesion molecule-3 (ICAM3), ANGPT1 and PAI-1. Post hypoglycemia, decreased cadherin-5 and ICAM5 were observed at 2 h and PAI-1 at 4 h, as well as increases in P-selectin at 30 min, 1 h and 24 h and ICAM3 at 24 h. Post hypoglycemia, E-selectin, P-selectin and ICAM3 were significantly lower in T2D patients at 2 h, while PAI-1 was significantly lower at 4 h and ICAM3 was significantly lower at 24 h. Baseline endothelial proteins differed between T2D and controls, which may suggest local endothelial inflammatory activation leading to a pro-thrombotic, destabilized vascular phenotype characteristic of diabetic vasculopathy. Hypoglycemia may exacerbate this towards a pro-adhesive and pro-thrombotic phenotype, worsening endothelial dysfunction. Full article

In type 1 diabetes (T1D) in non-obese diabetic (NOD) mice, dendritic cells (DCs) exhibit a Stat5b mutation that impairs regulatory T cell (Tregs) numbers and suppressive function. To correct this defect, we generated transgenic NOD mice expressing constitutively active Stat5b (NOD.Stat5b-CA) in DCs, which conferred protection from diabetes that was associated with an expanded Treg population and a marked reduction in CD8⁺ T cell frequencies in secondary lymphoid organs. However, the phenotypic characteristics and underlying mechanisms to eliminate CD8⁺ T cells in NOD.Stat5b-CA mice are unknown. In this study, we found that the frequency of Tregs was significantly higher in the thymus and peripheral lymphoid organs of NOD.Stat5b-CA mice compared with NOD mice. Tregs in the peripheral lymphoid organs exhibited increased expression of activation markers CD69 and OX40, alongside reduced CD62L. We also found that CD8⁺ T cell frequencies were reduced in the peripheral organs but not in the thymus of NOD.Stat5b-CA mice, while CD4⁺ T cell frequencies remained unchanged across all organs. Furthermore, NOD.Stat5b-CA mice exhibited a reduced frequency of central Tregs (CD62L^high CD44^low) and increased frequency of effector Tregs (CD62L^low CD44^high) under steady-state conditions compared to NOD mice. Notably, Tregs from NOD.Stat5b-CA mice displayed enhanced cytotoxic activity, evidenced by increased expression of perforin, granzyme B, and Fas ligand, potentially mediating CD8⁺ T cell frequency reduction. Collectively, these findings highlight a novel role for Stat5b-CA.DC-educated Tregs in modulating immune responses by eliminating peripheral pathogenic CD8⁺ T cells via cytotoxic pathways, thereby contributing to immune regulation in NOD.Stat5b-CA mice. Full article

Objectives: This study aimed to investigate the association between optical coherence tomography angiography (OCTA) parameters and cardiovascular (CV) risk scores in individuals with type 1 diabetes (T1D). Methods: A cross-sectional analysis of a large-scale prospective OCTA trial cohort (ClinicalTrials.gov NCT03422965) was performed. Demographic, systemic, and ocular data—including OCTA imaging—were collected. T1D participants were stratified into three CV risk categories: moderate (MR), high (HR), and very high risk (VHR). Individualized predictions for fatal and non-fatal CV events at 5 and 10 years were calculated using the STENO T1 Risk Engine calculator. Results: A total of 501 individuals (1 eye/patient; 397 T1D, 104 controls) were included. Subjects with MR (n = 37), HR (n = 152) and VHR (n = 208) exhibited significantly reduced vessel density (VD) (20.9 ± 1.3 vs. 20.2 ± 1.6 vs. 19.3 ± 1.8 mm⁻¹, p < 0.05), perfusion density (PD) (0.37 ± 0.02 vs. 0.36 ± 0.02 vs. 0.35 ± 0.02%, p < 0.05) and foveal avascular zone circularity (0.69 ± 0.06 vs. 0.65 ± 0.07 vs. 0.63 ± 0.09, p < 0.05). Statistically significant negative correlations were observed between CV risk and OCTA parameters including VD, PD, and retinal nerve fiber layer thickness, while central macular thickness (CMT) showed a positive correlation (p < 0.05). Notably, CMT was significantly associated with 5-year CV risk. Conclusions: OCTA-derived metrics, particularly reduced retinal VD and PD, are associated with elevated CV risk scores in T1D patients. These findings suggest that OCTA may serve as a valuable non-invasive tool for identifying individuals with increased CV risk scores. Full article

Timely recognition of type 1 diabetes (T1D) in children and adolescents is crucial to prevent acute complications such as diabetic ketoacidosis (DKA). This narrative review examines the pathophysiology, clinical presentation, and diagnostic challenges of childhood T1D, including the young age of onset, clinician training gaps, and overlapping symptomatology between T1D and other common pediatric illnesses. Despite increased awareness, a significant proportion of children still present with DKA at diagnosis due to misinterpretation of symptoms, such as polydipsia, polyuria, and weight loss. This work emphasizes the importance of early recognition, timely intervention, and the use of structured management algorithms for primary care clinicians. Strategies to reduce DKA incidence, based on existing literature, successful real-world examples, and current guidelines, include enhanced screening for high-risk populations, educational initiatives, and improved diagnostic protocols. By implementing systematic approaches and public health campaigns, healthcare providers can improve early T1D detection and prevent severe DKA complications, ultimately enhancing patient outcomes and reducing long-term morbidity. Full article

Accurate prediction of Blood Glucose (BG) levels is essential for effective diabetes management and the prevention of adverse glycemic events. This study introduces a novel designed hybrid Gated Recurrent Unit-Transformer (GRU-Transformer) model tailored to forecast BG levels at 15, 30, 45, and 60 min horizons using only Continuous Glucose Monitoring (CGM) data as input. The proposed approach integrates advanced CGM feature extraction step. The extracted features are statistically the mean, the median, the maximum, the entropy, the autocorrelation and the Detrended Fluctuation Analysis (DFA). In addition, in order to define more enhanced and specific features, the custom 3-points monotonicity score, the sinusoidal time encoding, and the workday/weekend binary features are proposed in this work. This approach enables the model to capture physiological dynamics and contextual temporal patterns of Type 1 Diabetes (T1D) with great accuracy. To thoroughly assess the performance of the proposed method, we relied on several well-established metrics, including Root Mean Squared Error (RMSE), Coefficient of Determination (R²), Mean Absolute Error (MAE), Mean Absolute Percentage Error (MAPE), and Root Mean Squared Percentage Error (RMSPE). Experimental results demonstrate that the proposed method achieves superior predictive accuracy for both short-term (15–30 min) and long-term (45–60 min) forecasting. Specifically, the model attained the lowest average RMSE values, with 4.00 mg/dL, 6.65 mg/dL, 7.96 mg/dL, and 8.91 mg/dL and yielding consistently high R² scores for the respective prediction horizons. This new method distinguishes itself by continuously exceeding current prediction models, reinforcing its potential for real-time CGM and clinical decision support. Its high accuracy and adaptability make it a favorable tool for improving diabetes management and personalized glycemic control. Full article

Type 2 diabetes mellitus (T2DM) is a highly prevalent disease characterized by chronic hyperglycemia, commonly associated with intake of a high-calorie diet (HCD). Although numerous T2DM murine models have been developed using C57BL/6 mice, BALB/c mice typically fail to develop the disease under the same conditions. We hypothesized that diets optimized for C57BL/6 mice may be insufficient to induce T2DM in BALB/c mice. Female BALB/c and C57BL/6 mice (n = 48 each) were fed either a specific high-calorie diet (HCD) or a standard diet (SD) for ten weeks. BALB/c mice fed a specific HCD exhibited developed persistent hyperglycemia (112.6 mg/dL ± 3.4) from week 1 through week 10, while SD-fed controls maintained normal glucose levels (84.2 mg/dL ± 2.8). HCD-fed BALB/c mice showed elevated serum insulin (39.09 pg/dL ± 25.94), triglycerides (290.8 mg/dL ± 139.5), HOMA index (7.68 ± 1.49) and high post-challenge glucose along with visceral adiposity, hepatic steatosis, and pancreatic alterations. SD-fed BALB/c mice showed no such changes. Similar findings were observed in C57BL/6 mice, used as a positive disease-control group. This model demonstrates that a properly formulated HCD can induce T2DM in BALB/c mice, enabling the study of genes and molecules associated with diabetes susceptibility without requiring genetic or chemical manipulation. Full article