Search Results (15)

Background/Objective: Type 1 diabetes (T1D) is a complex autoimmune disease characterized by the destruction of insulin-producing pancreatic beta cells. The TAB2/SUMO4 locus has been implicated in T1D susceptibility through a biochemical mechanism involving NFκB. Given that alterations in NFκB activity have been linked to the etiology of T1D, this study evaluated the association between single nucleotide polymorphisms (SNPs) in the TAB2/SUMO4 region (rs6942381, rs237027, rs237025, and rs7896) and T1D in a population from southern Brazil. Methods: Two T1D groups, each comprising 150 with childhood-onset (aged ≤14 years) and 150 with adulthood-onset (aged >18 years) were compared with healthy controls (165 children aged ≤14 years and 150 adults aged >18 years, respectively). Genotyping of SNPs in the TAB2/SUMO4 region was performed using real-time PCR. Results: All polymorphisms were in Hardy–Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms in the TAB2/SUMO4 region did not differ among groups in either children or adults. The MAF of the children and adults controls are respectively for rs6942381 49.1% (95% CI 44–54%) and 48.0% (95% CI 42–52%), rs237027 12.4% (95% CI 9–16%) and 11.7% (95% CI 8–15%), rs237025 45.5% (95% CI 40–51%) and 46.0% (95% CI 41–52%) and rs7896 18.2% (95% CI 14–22%) and 24.3% (95% CI 19–29%). The haplotype frequencies were also similar between groups. The observed minor allele frequencies were similar to those reported in European populations. Conclusions: TAB2/SUMO4 locus polymorphisms (rs6942381, rs237027, rs237025, and rs7896) were not associated with childhood- or adulthood-onset T1D in the studied population. Full article

The COVID-19 pandemic disrupted diabetes care globally and created a complex bidirectional health crisis. Recent forecasting efforts using pre-pandemic data projected substantial increases in diabetes mortality through 2030, raising concerns about achieving Sustainable Development Goal (SDG) 3.4. However, these projections did not account for pandemic-related disruptions to health systems and chronic disease management. The newly released Global Burden of Disease (GBD) 2023 data, covering the pandemic period through 2023, now provide a comprehensive empirical reference for assessing COVID-19’s observed impact on diabetes trends. This perspective adopts a forecast reconciliation and interpretation approach by examining counterfactual pre-pandemic diabetes mortality projections alongside GBD 2023 data, thereby shedding light on how pandemic-era mortality diverged from pre-pandemic trajectories. Critically, we note that insulin-dependent diabetes mellitus (IDDM, Type 1) and non-insulin-dependent diabetes mellitus (NIDDM, Type 2) have distinct etiologies and pandemic vulnerabilities, a distinction this article addresses. The evidence is striking: by 2023, global diabetes deaths had already exceeded 2.0 million per year, surpassing the 2030 upper forecast bound of 1.91 million, seven years ahead of the forecast horizon. NIDDM was the primary driver, with deaths crossing 1.9 million per year in 2023. These findings underscore the urgent need to strengthen diabetes prevention and management strategies as the world recovers from the pandemic-era disruptions in health systems and chronic disease care. Full article

Background/Objectives: Diabetes mellitus (DM), especially insulin-dependent DM (IDDM), is strongly associated with adverse outcomes following percutaneous coronary intervention (PCI) failure. Polymer-free drug-eluting stents (PF-DESs) have emerged as a promising strategy to mitigate long-term coronary inflammation. This study aimed to evaluate the role of PF-DES, as compared to permanent-polymer DES (PP-DES) and biodegradable-polymer DES (BP-DES), in a real-world cohort of IDDM patients with obstructive coronary artery disease (CAD) undergoing PCI. Methods: IDDM patients with CAD who underwent PCI with DES at Parma University Hospital were divided into two study groups: PF-DES group vs. BP/PP-DES group. The primary endpoint was target vessel failure (TVF) at the 4-year follow-up. Survival analyses and propensity score matching (PSM) were performed to account for baseline differences. Results: A total of 170 IDDM patients with 215 treated lesions (31.6% PF-DES; 68.4% BP/PP-DES) were included. The PF-DES group experienced significantly lower rates of TVF (10.3% vs. 27.2%, p < 0.01, log rank p = 0.0072) compared with the BP/PP-DES group. PSM analysis confirmed the good clinical performance of PF-DES (HR 0.27, p < 0.01). Conclusions: In this PSM-based observational study, PF-DESs were associated with significantly lower rates of TVF compared with BP/PP-DESs in IDDM patients undergoing PCI for CAD. These suggest that PF-DES may represent a personalized PCI strategy for IDDM patients, with prognostic benefits that become increasingly pronounced as the clinical and anatomical risk profile worsens. Full article

We investigated whether the peripheral co-administration of leptin and liraglutide (a glucagon-like peptide-1 receptor agonist) improved glucose metabolism in a mouse model of insulin-dependent diabetes mellitus (IDDM). Twelve-week-old male C57BL/6J mice were injected intraperitoneally with a high dose of streptozotocin to induce IDDM or vehicle-treated. Mice with IDDM were divided into four groups: leptin treatment alone (LEP), liraglutide treatment alone (LIRA), co-administration of leptin and liraglutide treatment (LEP+LIRA), untreated mice (UNT). Vehicle-treated mice were the healthy controls (HC). The blood glucose (BG) levels were measured, and a glucose tolerance test (GTT) was performed to compare the five groups. Leptin was administered peripherally at 20 μg/day using an osmotic pump, while liraglutide was administered subcutaneously at 1000 μg/kg/day. Monotherapy with leptin or liraglutide significantly improved glucose metabolism, as assessed by comparing BG levels and GTTs with those of the UNT group. Mice in the LEP+LIRA group showed even greater improvements in glucose metabolism than the monotherapy groups. Notably, glucose metabolism in the LEP+LIRA group improved comparably with the HC group. Thus, the peripheral co-administration of leptin and liraglutide effectively improved glucose metabolism in mice with IDDM without the use of insulin. Full article

The iterative decreasing dimension method (IDDM) is an iterative method used to solve the linear algebraic system $Ax=f$. Such systems are important in modeling many problems in applied sciences. For a number of reasons, such as estimated measurements made for modeling, errors arising from floating point calculations, and approximation methods used for solutions, it becomes necessary to study intervals in the solutions of systems of linear equations. The objective of this paper is to utilize IDDM to achieve resolution in the interval linear system (ILS). During the calculations, the Kaucher space is considered an extended classical interval space. The solutions of Barth-Nuding and Hansen interval linear systems, which are commonly used in the literature to test the solutions of ILSs, are obtained with the interval iterative decreasing dimension method for interval linear systems (I-IDDM). Since IDDM is a variation method of Gaussian elimination, a comparative analysis of the results with the interval Gaussian elimination method (I-GEM) is performed. It has been demonstrated that our approach, I-IDDM, produces better outcomes than I-GEM. I-IDDM is also used to investigate the analog circuit problem, where interval analysis is crucial. Full article

Preclinical biomedical models are a fundamental tool to improve the knowledge and management of diseases, particularly in diabetes mellitus (DM) since, currently, the pathophysiological and molecular mechanisms involved in its development are not fully clarified, and there is no treatment to cure DM. This review will focus on the features, advantages and limitations of some of the most used DM models in rats, such as the spontaneous models: Bio-Breeding Diabetes-Prone (BB-DP) and LEW.1AR1-iddm, as representative models of type 1 DM (DM-1); the Zucker diabetic fatty (ZDF) and Goto-kakizaki (GK) rats, as representative models of type 2 DM (DM-2); and other models induced by surgical, dietary and pharmacological—alloxan and streptozotocin—procedures. Given the variety of DM models in rats, as well as the non-uniformity in the protocols and the absence of all the manifestation of the long-term multifactorial complications of DM in humans, the researchers must choose the one that best suits the final objectives of the study. These circumstances, added to the fact that most of the experimental research in the literature is focused on the study of the early phase of DM, makes it necessary to develop long-term studies closer to DM in humans. In this review, a recently published rat DM model induced by streptozotocin injection with chronic exogenous administration of insulin to reduce hyperglycaemia has also been included in an attempt to mimic the chronic phase of DM in humans. Full article

Camel milk is known for its exceptional medical uses. It has been used since ancient times to treat infant diarrhea, hepatitis, insulin-dependent diabetes (IDDM), lactose intolerance, alcohol-induced liver damage, allergies, and autism. It has the power to treat several diseases, with cancer being the most significant. This study investigated the evolutionary relationship, physiochemical characteristics, and comparative genomic analysis of the casein gene family (CSN1S1, CSN2, CSN1S2, and CSN3) in Camelus ferus. Molecular phylogenetics showing the camelid species clustered casein nucleotide sequences into four groups: CSN1S1, CSN2, CSN1S2, and CSN3. The casein proteins from camels were evaluated and found to be unstable, thermostable, and hydrophilic. CSN1S2, CSN2, and CSN3 were acidic, but CSN1S1 was basic. CSN1S1 showed positive selection for one amino acid (Q), CSN1S2 and CSN2 for three (T, K, Q), and CSN3 showed no positive selection. We also compared high-milk-output species such as cattle (Bos Tarus) and low-milk-yield species such as sheep (Ovies Aries) with camels (Camel ferus) and discovered that YY1 sites are more frequent in sheep than in camels and very low in cattle. We concluded that the ratio of YY1 sites in these species may affect milk production. Full article

The exact clinical course and factors associated with persistent endocrine immune-related adverse events (irAEs) are not well-established. Elucidation of these information will aid irAEs screening and follow-up planning for patients on immunotherapy. We analysed the clinical course of endocrine irAEs including thyroid and pituitary dysfunction and insulin-dependent diabetes mellitus (IDDM), identified factors associated with persistent thyroid dysfunction, and determined the association between endocrine irAEs and survival parameters. This retrospective observational study enrolled patients with metastatic cancer who underwent anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 treatment and developed endocrine irAE at the National University Cancer Institute, Singapore, between June 2015 and December 2020. Sixty-six patients with endocrine irAE were evaluated, with a median follow-up time of 15.7 months. The median time to onset of thyroid dysfunction, pituitary dysfunction, and IDDM was 1.8 months (range: 0.3–15.8 months), 6.8 months (range: 1.5–27.3 months), and 7.8 months (range: 1.4–9.1 months), respectively. Positive thyroperoxidase antibodies (TPOAb) and/ or thyroglobulin antibodies (TgAb) status at the time of thyroid dysfunction was associated with persistent thyroid dysfunction (OR 11.6, 95% CI 1.3–570.8, p = 0.02; OR 8.8, 95% CI 1.3–106.9, p = 0.01, respectively). All patients with pituitary irAE had central hypocortisolism. All patients with IDDM had grade 4 irAE. Patients with endocrine irAE had longer median survival times. Endocrine irAEs were associated with non-progressive disease. The screening and follow-up approach for endocrine irAEs should be tailored according to each endocrinopathy’s clinical course. Early screening is imperative given its wide median time to onset. Full article

The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes (T1D). Previously, we have shown that combination with anti-TCR/anti-TNF-α antibody-based therapy re-established normoglycemia and increased proteinic arginine-dimethylation in the spleen, yet not in the pancreas. High blood glucose is often associated with elevated formation of advanced glycation end-products (AGEs) which act via their receptor (RAGE). Both anti-TCR and anti-TNF-α are inhibitors of RAGE. The aim of the present work was to investigate potential biochemical changes of anti-TCR/anti-TNF-α therapy in the LEW.1AR1-iddm rat. We determined by stable-isotope dilution gas chromatography-mass spectrometry (GC-MS) the content of free and proteinic AGEs and the N^ε-monomethylation of lysine (Lys) residues in proteins of pancreas, kidney, liver, spleen and lymph nodes of normoglycemic control (ngCo, n = 6), acute diabetic (acT1D, n = 6), chronic diabetic (chT1D, n = 4), and cured (cuT1D, n = 4) rats after anti-TCR/anti-TNF-α therapy. Analyzed biomarkers included Lys and its metabolites N^ε-carboxymethyl lysine (CML), furosine and N^ε-monomethyl lysine (MML). Other amino acids were also determined. Statistical methods including ANOVA, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to evaluate the effects. Most statistical differences between the study groups were observed for spleen, pancreas and kidney, with liver and lymph nodes showing no such differences. In the pancreas, the groups differed with respect to proteinic furosine (p = 0.0289) and free CML (p = 0.0023). In the kidneys, the groups differed with respect to proteinic furosine (p = 0.0076) and CML (p = 0.0270). In the spleen, group differences were found for proteinic furosine (p = 0.0114) and free furosine (p = 0.0368), as well as for proteinic CML (p = 0.0502) and proteinic MML (p = 0.0191). The acT1D rats had lower furosine, CML and MML levels in the spleen than the rats in all other groups. This observation corresponds to the lower citrullination levels previously measured in these rats. PCA revealed diametric associations between PC1 and PC2 for spleen (r = −0.8271, p < 0.0001) compared to pancreas (r = 0.5805, p = 0.0073) and kidney (r = 0.8692, p < 0.0001). These findings underscore the importance of the spleen in this animal model of human T1D. OPLS-DA showed that in total sixteen amino acids differed in the experimental groups. Full article

Insulin-dependent diabetes mellitus (IDDM) is a metabolic condition that induces blood glucose levels to rise due to insulin deficiency and the formation of reactive oxygen species (ROS). The purpose of this study is to assess how efficient the antioxidant extracts Tribulus terrestris (TT) and metformin (MET) are in reducing oxidative stress and histopathology produced by streptozotocin in rat hepatocytes. The 36 male rats weighing 170–190 g of this study were randomly sorted into 6 groups. The first group was considered a normal control group, and the second and third groups were normal and remedy with MET and TT extract, respectively. The fourth group was positive diabetic, and the fifth and sixth groups were diabetic rats that were treated with MET and TT extract, respectively. Lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST), and glutathione (GSH) were detected, and the histopathology of the liver was evaluated after 8 weeks of treatment. Compared to regulation, morphological changes in the liver were found in diabetic animals, with a rise in LPO and a change in GSH levels as well as CAT and GST activities. The oxidative stress and histological architecture of the hepatocytes caused by hyperglycemia were improved as a result of therapy in the rats with MET and TT extract. Because of its antioxidant activities, diabetic rats with TT extract are more effective than MET in normoglycemia and hepatocyte reconditioning. Beneficial intervention tends to benefit primarily from direct ROS scavenging and CAT, GST, and GSH regeneration. Full article

Immune checkpoint inhibitor (ICI)-induced insulin-dependent diabetes mellitus (IDDM) is a rare but potentially fatal immune-related adverse event (irAE). In this multicentre retrospective cohort study, we describe the characteristics of ICI-induced IDDM in patients treated across five Canadian cancer centres, as well as their tumor response rates and survival. In 34 patients identified, 25 (74%) were male and 19 (56%) had melanoma. All patients received anti-programed death 1 (anti-PD1) or anti-programmed death ligand-1 (anti-PD-L1)-based therapy. From ICI initiation, median time to onset of IDDM was 2.4 months (95% CI 1.1–3.6). Patients treated with anti-PD1/PD-L1 in combination with an anti-cytotoxic T lymphocyte antigen 4 antibody developed IDDM earlier compared with patients on monotherapy (1.4 vs. 3.9 months, p = 0.05). Diabetic ketoacidosis occurred in 21 (62%) patients. Amongst 30 patients evaluable for response, 10 (33%) had a complete response and another 10 (33%) had a partial response. Median overall survival was not reached (95% CI NE; median follow-up 31.7 months). All patients remained insulin-dependent at the end of follow-up. We observed that ICI-induced IDDM is an irreversible irAE and may be associated with a high response rate and prolonged survival. Full article

Long-read data is a great tool to discover new active transposable elements (TEs). However, no ready-to-use tools were available to gather this information from low coverage ONT datasets. Here, we developed a novel pipeline, nanotei, that allows detection of TE-contained structural variants, including individual TE transpositions. We exploited this pipeline to identify TE insertion in the Arabidopsis thaliana genome. Using nanotei, we identified tens of TE copies, including ones for the well-characterized ONSEN retrotransposon family that were hidden in genome assembly gaps. The results demonstrate that some TEs are inaccessible for analysis with the current A. thaliana (TAIR10.1) genome assembly. We further explored the mobilome of the ddm1 mutant with elevated TE activity. Nanotei captured all TEs previously known to be active in ddm1 and also identified transposition of non-autonomous TEs. Of them, one non-autonomous TE derived from (AT5TE33540) belongs to TR-GAG retrotransposons with a single open reading frame (ORF) encoding the GAG protein. These results provide the first direct evidence that TR-GAGs and other non-autonomous LTR retrotransposons can transpose in the plant genome, albeit in the absence of most of the encoded proteins. In summary, nanotei is a useful tool to detect active TEs and their insertions in plant genomes using low-coverage data from Nanopore genome sequencing. Full article

Background: Diabetic vasculopathy plays an important role in the pathophysiology of coronary artery disease (CAD) with oxidative stress as a strong mediator. This study aims to elucidate the underlying pathomechanisms of diabetic cardiac vasculopathy leading to coronary disease with an emphasis on the role of oxidative stress. Therefore, novel insights into antioxidant pathways might contribute to new strategies in the treatment and prevention of diabetic CAD. Methods: In 20 patients with insulin-dependent or non-insulin dependent diabetes mellitus (IDDM/NIDDM) and 39 non-diabetic (CTR) patients, myocardial markers of oxidative stress, vasoactive proteins, endothelial nitric oxide synthase (eNOS), activated phosphorylated eNOS (p-eNOS), and antioxidant enzymes, e.g., tetrahydrobiopterin generating dihydrofolate reductase (DHFR), heme oxygenase (HO-1), as well as serum markers of inflammation, e.g., E-selectin, interleukin-6 (IL-6), and lipid metabolism, e.g., high- and low-density lipoptrotein (HDL- and LDL-cholesterol) were determined in specimens of right atrial tissue and in blood samples from type 2 diabetic and non-diabetic patients undergoing coronary artery bypass graft (CABG) surgery. Results: IDDM/NIDDM increased markers of inflammation (e.g., E-selectin, p = 0.005 and IL-6, p = 0.051), decreased the phosphorylated myocardial p-eNOS (p = 0.032), upregulated the myocardial stress response protein HO-1 (p = 0.018), and enhanced the serum LDL-/HDL-cholesterol ratio (p = 0.019). However, the oxidative stress markers in the myocardium and the expression of vasoactive proteins (eNOS, DHFR) showed only marginal adverse changes in patients with IDDM/NIDDM. Conclusion: Dyslipidemia and myocardial inflammation seem to be the major determinants of diabetic CAD complications. Dysregulation in pro-oxidative enzymes might be attributable to the severity of CAD and oxidative stress levels in all included patients undergoing CABG. Full article

Health-related quality of life (HRQOL) is an essential measure that is used to assess the effect of chronic disease management on the health status of an individual. Previous studies have identified various instruments used in the measuring of diabetes-specific health-related quality of life (HRQOL). The aim of this paper is to provide a systematic review of the various instruments used for the diabetes-specific measure of HRQOL, and place emphasis on its content and measurement properties. Methods Preferred Reporting Items for Systematic Reviews and Meta analyses (PRISMA) guidelines was used. A systematic search strategy was used to identify publications reporting diabetes HRQOL measures. The search terms used were: “diabetes quality of life”, “measurements”, and “instruments”. The database that was searched includes PubMed, Science Direct, CINAHL, and Medline. Articles written in the English language and published from January 1990 to December 2020 were included. Those articles that did not measure HRQOL for diabetic patients were excluded. Results: A total of seventeen instruments met the inclusion criteria and included in the review. The appraisal of diabetes scale (ADS), Audit of Diabetes-Dependent QOL measure (ADDQOL), Diabetes Health Profile (DHP), and Problem Areas in Diabetes (PAID) are more suitable for single-scale questionnaires when investigating one or more specific aspects of diabetes-specific quality of life (QOL). The ADDQOL, ADS, Diabetes Impact Measurement Scales (DIMS), Diabetes Quality of Life Clinical Trial Questionnaire (DQLCTQ-R), Malay Version of Diabetes Quality of Life (DQOL), Iranian Diabetes Quality of Life (IRDQOL), Brief Clinical Inventory, and PAID are relevant measures of HRQOL for insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM) patients. The Asian Diabetes Quality of Life AsianDQOL, The Chinese Short Version of DQOL, Elderly Diabetes Burden Scale (EDBS), Malay Version of Diabetes Quality of Life (DQOL), are relevant measures of HRQOL for NIDDM patients. Only two instruments assess for responsiveness, namely PAID and DQLCTQ-R. In PAID, the effect sizes ranged from 0.32 to 0.65 for interventions. The DQLCTQ-R four domains were responsive to clinical change in metabolic control. Based on this review ADDQOL, DSQOLS, and EDBS psychometric properties are sufficient. Conclusion: Most studies did not check for responsiveness, and future studies should prioritize responsiveness to change, which was not included in the psychometric finding of the reviewed instruments. Full article

Type 1 diabetes (T1DM) is a chronic autoimmune disease, with a strong genetic background, leading to a gradual loss of pancreatic beta-cells, which secrete insulin and control glucose homeostasis. Patients with T1DM require life-long substitution with insulin and are at high risk for development of severe secondary complications. The incidence of T1DM has been continuously growing in the last decades, indicating an important contribution of environmental factors. Accumulating data indicates that sphingolipids may be crucially involved in T1DM development. The serum lipidome of T1DM patients is characterized by significantly altered sphingolipid composition compared to nondiabetic, healthy probands. Recently, several polymorphisms in the genes encoding the enzymatic machinery for sphingolipid production have been identified in T1DM individuals. Evidence gained from studies in rodent islets and beta-cells exposed to cytokines indicates dysregulation of the sphingolipid biosynthetic pathway and impaired function of several sphingolipids. Moreover, a number of glycosphingolipids have been suggested to act as beta-cell autoantigens. Studies in animal models of autoimmune diabetes, such as the Non Obese Diabetic (NOD) mouse and the LEW.1AR1-iddm (IDDM) rat, indicate a crucial role of sphingolipids in immune cell trafficking, islet infiltration and diabetes development. In this review, the up-to-date status on the findings about sphingolipids in T1DM will be provided, the under-investigated research areas will be identified and perspectives for future studies will be given. Full article