Search Results (1,528)

Type 1 diabetes mellitus is a major risk factor for both sarcopenia and osteoporosis, primarily due to the body’s inability to utilize glucose as a result of insulin deficiency. Impairments in insulin and glucose signaling can accelerate the decline in muscle and bone health. To investigate this interaction, we examined whether insulin deficiency exacerbates muscle and bone deterioration in Chrebp knockout (KO) mice. Male wild-type (WT) and KO mice, aged 18 weeks, were intraperitoneally treated with 200 mg/kg BW streptozotocin (STZ), which selectively destroys pancreatic beta cells, thereby inducing insulin deficiency. Two weeks after STZ administration, compared with STZ-treated WT mice, STZ-treated KO mice presented significantly greater reductions in body weight and gastrocnemius muscle weight (BW: WT-vehicle vs. WT-STZ; 2.58 [−1.23, 6.39] (p = 0.21); KO-vehicle vs. KO-STZ: 8.03 [5.23, 10.82]; GA muscle: WT vehicle vs. WT STZ: 0.084 [0.047, 0.12], p < 0.0001; KO vehicle vs. KO STZ: 0.084, [0.047, 0.12], p < 0.0001). The decrease in grip strength caused by STZ administration was greater in the KO mice than in the WT mice (mean differences [95% CIs]: WT vehicle—WT STZ, 49.6. [0.9, 98.4], p = 0.046; WT STZ—KO STZ: 71.40 [29.1, 113.7], p = 0.0059; KO vehicle—KO STZ: 84.3 [51.9, 116.8], p = 0.0003). Consistent with these findings, STZ administration reduced IGF-1 expression and increased atrogin mRNA levels, with the highest levels in STZ-treated KO mice. In skeletal muscle, the changes in IGF-1 and Atrogen induced by STZ administration were significantly greater in the KO group than in the WT group (IGF-1: WT vehicle—WT STZ: 0.19 [−0.072, 0.46], p = 0.17; KO vehicle—KO STZ: 0.79 [0.53, 1.06], p < 0.0001; Atrogen: WT vehicle—WT STZ: −2.7 [−3.01, −2.29], p < 0.0001; KO vehicle—KO STZ: −3.35 [−3.71, −2.99], p < 0.0001). The BMD in the Chrebp-deficient group was greater than that in the wild-type group (WT vehicle—KO vehicle: −5.2 [−8.4, −1.9], p = 0.0014); however, the administration of STZ significantly decreased the BMD only in the KO group (WT vehicle—WT STZ: p = 0.45, KO vehicle—KO STZ: 7.2 [3.9, 10.4], p < 0.0001). These results suggest that Chrebp deficiency combined with insulin deficiency aggravates sarcopenia and osteoporosis risk. Therefore, insulin and glucose signals are important for maintaining muscle and bone mass and function. However, further studies are needed to elucidate the mechanisms by which ChREBP deletion and insulin deficiency cause osteosarcopenia. Full article

Adolescents with Type 1 Diabetes Mellitus (T1DM) face a significantly increased risk of developing disordered eating behaviors (DEBs), a phenomenon that includes the deliberate omission of insulin, commonly referred to as diabulimia. The aim of this systematic review and meta-analysis was to determine the prevalence of diabulimia in adolescents with T1DM and consolidate the scientific evidence on this issue. Following PRISMA guidelines, observational studies published in English and Spanish involving adolescents aged 10 to 19 were identified through comprehensive searches in SCOPUS, LILACS, PubMed, Web of Science, and PsycINFO. After rigorous screening and eligibility assessment, 13 studies were included. Data were extracted independently, and meta-analyses were performed using random-effects models. Reported prevalence rates of DEB in T1DM varied widely among studies, ranging from 20.8% to 48%. The pooled prevalence in the final meta-analytic model was 11% (95% CI: 9–13%), with prevalence substantially higher in females (45%) than males (26%). These findings highlight not only the elevated risk of DEB and diabulimia among adolescents with T1DM but also considerable gender differences likely shaped by psychological, sociocultural, and biological factors. The lack of standardized diagnostic criteria for diabulimia remains a barrier to clinical management. Early detection and gender-sensitive preventive strategies are crucial for reducing complications and improving the quality of life in this vulnerable population. Full article

Background/objectives: Diabetes mellitus (DM) increases susceptibility to both cardiovascular and renal complications. Acute kidney injury (AKI) in the setting of acute coronary syndrome (ACS) is a frequent manifestation of acute cardiorenal syndrome (type 1); however, the impact of diabetes on the condition remains incompletely characterised. This study aimed to evaluate the real-world incidence, severity, and recurrence of AKI in individuals with ACS, focusing on the additional risk conferred by DM, and to assess the adequacy of post-discharge renal monitoring. Methods: We conducted a single-centre, retrospective observational study of 990 ACS admissions between July 2020 and June 2021 at the United Lincolnshire Hospitals NHS Trust. Acute kidney injury was defined using Kidney Disease Improving Global Outcomes criteria and stratified by severity. Outcome measures included incidence of AKI during admission, recurrence of AKI, and renal function monitoring within 12 months post-discharge. Results: Of 990 individuals recruited, 315 (31.8%) had DM. Overall, 14.2% individuals developed AKI during admission, being more frequently observed in those with DM (20.0% vs. 11.6%; RR 1.7, p < 0.001). Severe AKI (stage 3) was higher in those with diabetes (2.9% vs. 0.7%, p = 0.017). Recurrent AKI within 12 months occurred in 9.7%, with a higher incidence in those with DM (15.8% vs. 6.9%, p < 0.001). Post-discharge renal follow-up was performed in 88.7% of persons with AKI and similar in those with and without DM. Conclusions: Acute kidney injury is a common and serious complication of ACS, with DM substantially increasing the risk and severity of the condition during acute events and post-discharge. Despite this, individuals with DM receive similar monitoring in the post-discharge period. Improved systems for post-discharge renal monitoring and early initiation of protective therapies are required to mitigate long-term risk. Full article

Background: Diabetic ketoacidosis (DKA) is a serious acute complication of diabetes mellitus (DM) associated with significant morbidity, mortality, and healthcare burden worldwide. This study aimed to investigate population descriptors and clinical outcomes among adult and pediatric patients admitted with DKA at two tertiary medical centers in Riyadh, Saudi Arabia. Methods: We conducted a retrospective observational study that included adult and pediatric (≤15 years) patients admitted to emergency departments (EDs) and received care for DKA between 2018 and 2021. DKA severity was defined according to the American Diabetes Association (ADA) criteria, which rely on arterial/venous pH and serum bicarbonate (with anion gap supportive), as follows: mild (pH 7.25–7.30; HCO₃⁻ 15–18 mmol/L), moderate (pH 7.00–7.24; HCO₃⁻ 10–15 mmol/L), and severe (pH < 7.00; HCO₃⁻ < 10 mmol/L). Data were extracted from electronic medical records and analyzed descriptively. Results: A total of 373 patients were admitted to the EDs and received treatment for DKA throughout the study period. Adults constituted 71.6% (267/373), while children represented 28.4% (106/373) of the patients; the majority of adults (74.2%) had Type 1 DM (T1DM), while all pediatric patients had T1DM. More than half of the adult presentations met the criteria for severe DKA (55.8%; 149/267), whereas pediatric cases were most commonly moderate in severity (41.5%; 44/106). The most common precipitating factors across both age groups of patients with diabetes before the index DKA event were non-compliance with therapy and infection. Both groups demonstrated typical biochemical features of DKA, although pediatric patients presented with slightly lower bicarbonate and higher anion gaps (slightly greater metabolic acidosis) but with similar hydration status. Regarding patients’ outcomes, hyperkalemia was identified in 23.6% of adults and 24.5% of pediatric patients, while hypokalemia was documented in 20.2% of adults and 24.5% of pediatric patients, and adult patients experienced more acute kidney injuries than the other cohort (5.2% vs. 1.9%). In-hospital mortality was 0.8% (3/373) among all adults. Although pediatric patients experienced faster DKA resolution (median = 16.5 h; IQR, 11.7–25.8) compared to adult patients (23.7 h; 16.2–36.9), they had a longer hospital stay compared to adult patients, and a significant majority required ICU care (50.9%) at some point during their care. Conclusions: The increasing prevalence of DM in Saudi Arabia, especially among the youth, would lead to an increase in DKA burden unless effective preventive measures are taken. This study demonstrated that preventable causes, such as non-compliance with therapy and infection, were responsible for the high admission rates. Thus, comprehensive outpatient care can help strengthen care continuity and help decrease the burden on emergency and inpatient services. Full article

Introduction: The proteasome is a multicatalytic complex responsible for protein degradation and regulation of immune responses, and has been implicated in type 1 diabetes mellitus (T1DM) pathogenesis. Zinc (Zn²⁺) is essential for insulin granule biogenesis and modulates proteasomal activity. This study investigated associations between single-nucleotide polymorphisms (SNPs) in proteasomal subunits predicted to bind Zn²⁺ and T1DM susceptibility or related traits. Methods: This case–control study included 654 patients with T1DM and 573 subjects without DM from Southern Brazil. SNPs were selected through in silico analysis using MIB docking platform to identify Zn²⁺-interacting residues in proteasomal subunits. Five SNPs in proteasomal subunit genes—PSMA6 (rs1048990), PSMB6 (rs2304975), PSMB9 (rs17587), PSMC6 (rs2295825), and PSMD3 (rs3087852)—were genotyped using TaqMan assays. Results: The PSMC6 rs2295825C allele was associated with lower T1DM (OR = 0.77, 95% CI 0.61–0.97; p = 0.028) and diabetic retinopathy (DR; OR = 0.65; 95% CI 0.42–0.99; p = 0.048) risk, and a more favorable lipid profile (higher HDL-C, lower triglycerides) compared to the G/G genotype. The PSMB9 rs17587A/A genotype was linked to higher total cholesterol and HbA1c levels. The PSMA6 rs1048990G allele was linked to increased prevalence of diabetic kidney disease (DKD; OR = 1.75, 95% CI 1.02–2.99; p = 0.042), and the PSMD3 rs3087852A allele was associated with lower urinary albumin excretion. No significant associations were observed for the PSMB6 rs2304975 SNP. Conclusions: The PSMC6 rs2295825 SNP may confer protection against T1DM. The PSMC6 rs2295825, PSMB9 rs17587, PSMA6 rs1048990, and PSMD3 rs3087852 SNPs appear to influence lipid metabolism and diabetic microvascular complications. Full article

Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by the destruction of insulin-producing pancreatic β-cells by autoreactive T cells. Current treatments, including insulin replacement therapy and various immunotherapies, often modulate but fail to permanently halt the underlying autoimmune process or restore β-cell function. In this review, we examine T cell receptor (TCR)-based treatment strategies for T1DM. We focus on two main approaches: selective elimination of pathogenic autoreactive T cell clones and induction of immune tolerance using TCR-modified regulatory T cells (TCR-Tregs). We describe key islet autoantigens, including post-translationally modified neoantigens such as fusion insulin peptides, which are crucial for identifying pathogenic TCRs. Next, we will review methodologies for TCR detection and TCR-Treg generation, highlighting their mechanisms of action and impact on various immune cells, including dendritic cells, B cells, and macrophages. We will also examine the potential of CD8⁺T cell regulatory cells (CD8⁺Tregs). Finally, we will discuss the future of TCR-based therapy, emphasizing the need to optimize TCR affinity, ensure Tregs’ stability, and develop combination therapies. TCR-based therapy represents a revolutionary approach to restoring immune tolerance in T1DM, providing high specificity and reducing the risk of systemic immuno-suppression compared to traditional treatments. Full article

Background/Objectives: Rosiglitazone (RSG), a potent PPARγ agonist for type 2 diabetes mellitus (T2DM), induces adverse adipogenic effects that limit clinical use. We investigated whether emodin (1,3,8-trihydroxy-6-methylanthraquinone, EMO), a natural anthraquinone, mitigates RSG-induced complications while enhancing its insulin-sensitizing benefits in severe obesity. Methods: Male ob/ob mice with established obesity and diabetes were treated for 4 weeks with RSG (10 mg kg⁻¹ day⁻¹), EMO (200 or 400 mg kg⁻¹ day⁻¹) or their combination. Metabolic profiling, organ function, and adipose histology were analyzed. RNA sequencing and mechanistic studies (Western blot, RT-qPCR, luciferase assays) in inguinal subcutaneous adipose tissue (iSAT), epididymal white adipose tissue (eWAT), and 3T3-L1 adipocytes were used to define EMO’s actions. Results: EMO co-treatment dose-dependently reduced RSG-induced weight gain, visceral adiposity (iSAT and eWAT mass, p < 0.05), and ectopic lipid deposition while ameliorating hepatorenal dysfunction. EMO synergistically enhanced RSG’s glucose-lowering effects. Mechanistically, EMO suppressed sterol regulatory element-binding protein 1 (SREBP1)-mediated lipogenesis (Srebp1, Acc, Fasn, Scd1; p < 0.05) and enhanced PPARγ-peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)-driven thermogenesis via enhanced PPARγ transactivation and nuclear translocation. Thermogenic genes (Ucp1, Ppargc1a, Cidea; p < 0.05) were upregulated, with maximal uncoupling protein 1 (UCP1) induction in iSAT at 400 mg/kg EMO. Conclusions: EMO selectively enhances RSG’s glycemic benefits while attenuating its adipogenic effects in severe obesity by dual PPARγ modulation-inhibiting adipogenic pathways while amplifying thermogenesis. This strategy mitigates RSG’s adverse effects while improving insulin sensitivity, supporting the potential of EMO as a PPARγ adjunct therapy. Full article

Mitochondria are essential for β-cell function, coupling glucose metabolism to ATP production and insulin secretion. In diabetes, β-cell mitochondrial dysfunction arises from oxidative stress, impaired quality control and disrupted dynamics, leading to reduced oxidative phosphorylation, defective insulin release and progressive cell loss. Key transcriptional regulators link genetic susceptibility to mitochondrial dysfunction in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). These disruptions impair mitophagy, mitochondrial translation and redox homeostasis. Therapeutic strategies that restore mitochondrial function, including mitophagy enhancers, mitochondrial antioxidants, and transcriptional regulators, have shown potential in preserving β-cell integrity. As mitochondrial failure precedes β-cell loss, targeting mitochondrial pathways may represent a critical approach to modifying diabetes progression. Full article

Type 1 Diabetes Mellitus (T1D) can be related to various factors, including neonatal and perinatal conditions. This study investigated the impact of neonatal and perinatal factors—Apgar score, birth weight, feeding type, sex, and delivery type—on the risk of Type 1 Diabetes Mellitus and evaluated predictive models. A cohort of 327 patients was analyzed using correlations, General Linear Model, and artificial neural network. T1D patients showed higher birth weight, lower Apgar score, a predominance of formula feeding, and more cesarean deliveries. Diabetes risk showed a moderate positive correlation with birth weight class and nutrition type (p < 0.05) and a weak negative correlation with Apgar score (p < 0.05), while birth weight, birth weight class, and nutrition type were all weakly positively correlated with each other and with delivery type (p < 0.05). General linear model identified nutrition type, birth weight, and Apgar score as key predictors, with significant interactions among them (R² = 0.88). Artificial neural network achieved high accuracy (84.2%), AUC (0.95), sensitivity (89.1%), and specificity (76.7%). ANN successfully modeled the complex non-linear interactions among early-life factors, allowing it to discriminate between high-risk and low-risk cases, as evidenced by the low prediction errors (RMSE 0.31 and MAE 0.09) and strong agreement (Kappa 0.81). The models’ strong internal predictive performance points to potential applications in early T1D diagnosis and personalized management, although confirmation in larger and independent datasets is needed. Full article

Diabetes mellitus (DM) continues to be a global world health problem. Despite medical advances, both DM and chronic kidney disease (CKD) remain global health issues with high mortality and limited options to prevent end-stage renal failure. Current therapies encompass five classes of drugs: (1) angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin II receptor blockers (AIIRB); (2) sodium-glucose-transporter 2 (SGLT2) inhibitors; (3) glucagon-like peptide-1 receptor agonists (GLP-1 RA); and (4) an antagonist of type 1 endothelin receptor (ET1R) with proven efficacy to reduce albuminuria and proteinuria. (5) The mineralocorticoid receptor antagonist (MRA) finerenone has been tested in RCTs as a kidney protective agent. In our review, we summarize many of the principal trials that have generated evidence in this regard. Many novel agents—many of them proven not only for DM management but also for the treatment of obesity with or without DM or heart failure (HF)—are now in development and may be added to the five classical pillars: other non-steroidal MRA (balcinrenone); aldosterone synthase inhibitors (baxdrostat and vicadrostat); other GLP-1 RA (tirzepatide, survodutide, retatrutide, and cagrilintide); ET1 R antagonists, (zibotentan); and soluble guanylate cyclase activators (avenciguat). These new agents aim to slow disease progression further and reduce cardiovascular risk. Future strategies rely on integrated, patient-centered approaches and personalized therapy to curb renal disease and its related complications. Full article

Diabetes mellitus and chronic venous disease (CVD) are multifactorial, long-lasting diseases. Although usually considered separately, they often coexist, and individuals with diabetes are more prone to CVD development. Despite different etiology, CVD and diabetic vascular complications share several pathomechanisms, and oxidative stress is one of them. In this study the antioxidative potential of two venoactive flavonoids—diosmin and hesperidin—in the course of type 1 diabetes was compared for the first time. Type 1 diabetic rats were treated with diosmin or hesperidin, each at two doses, 50 and 100 mg/kg, for four weeks. In order to evaluate the antioxidative potential of tested compounds, the antioxidative enzyme activity (superoxide dismutase, catalase and glutathione peroxidase), thiols homeostasis, oxidative status markers (total antioxidative response—TAR, total oxidative status and oxidative stress index—OSI), and oxidative damage markers (advanced oxidation protein products and malondialdehyde) in the serum were measured. Diabetes caused disturbance in the serological redox homeostasis, especially by decreasing enzyme activity and TAR while increasing levels of oxidative damage markers and OSI, increasing advanced glycation end products (AGEs) levels, as well as altering carbohydrate and lipid metabolism. Flavonoids improved the majority of lipid metabolism markers and reduced AGEs with no effect on glycemia. In the context of oxidative stress, their effect was moderate and dose-dependent, and better potency of hesperidin over diosmin was noted, both in individual and multivariate analyses of the parameters. The collective analysis of all parameters led to the conclusion that both diosmin and hesperidin can be considered complementary agents averting negative impact of diabetes due to their multi-faceted actions, including antioxidative properties. Full article

Background/Objectives: Skeletal muscle–derived myokines have emerged as pivotal mediators of the muscle–brain axis, linking peripheral metabolic regulation with central nervous system function. These molecules may influence skeletal muscle maintenance, neuroplasticity, neuroinflammation, and cognitive performance, and their dysregulation is increasingly associated with metabolic and cognitive impairment. In obesity (OB) and type 2 diabetes mellitus (T2DM), dysregulated myokine profiles characterized by reduced levels of irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B (CTSB) have been reported and may contribute to the development of both sarcopenia and cognitive impairment. This review aims to summarize current evidence on myokine alterations in OB and T2DM and to evaluate how exercise- and nutrition-based interventions may modulate the muscle–brain axis to support metabolic and cognitive health. Methods: This narrative review synthesizes experimental, clinical, and translational studies examining (1) alterations in circulating myokines in OB and T2DM, (2) associations between myokines, skeletal muscle function, and neurocognitive outcomes, and (3) the modulatory effects of exercise and specific nutrients on myokine-mediated muscle–brain communication. Results: Available evidence indicates that OB and T2DM are frequently accompanied by reduced circulating levels of beneficial myokines such as irisin, BDNF, and CTSB, which may impair skeletal muscle integrity and contribute to cognitive decline. Restoring favorable myokine signaling through physical activity appears to enhance skeletal muscle maintenance, neuroplasticity, and metabolic homeostasis. Emerging data further suggest that selected nutrients can mimic or potentiate some exercise-induced myokine responses, thereby supporting both muscle and brain function. Collectively, these findings imply that combined exercise and nutrition strategies may exert synergistic or additive effects by reinforcing inter-organ communication along the muscle–brain axis. Conclusions: This review outlines current evidence on myokine alterations observed in OB and T2DM and discusses how exercise- and nutrition-based approaches may modulate the muscle–brain axis to mitigate metabolic dysfunction and preserve cognitive health. Targeting beneficial myokine pathways through tailored lifestyle interventions represents a promising avenue to support both skeletal muscle and neurocognitive function in individuals with metabolic disease. Full article

Background/Objectives: Diabetes mellitus (DM) is a major global health concern, yet limited research has examined how sociodemographic factors and physical activity (PA) influence glycaemic control within specific national contexts. This pilot study explored associations between sociodemographic and behavioral factors and glycaemic regulation among adults with DM in Croatia. Methods: A cross-sectional study was conducted at a national reference center, including 95 adults with type 1 or type 2 diabetes. Data on demographics, clinical characteristics, and PA were obtained through questionnaires and medical records. Descriptive statistics, Welch’s t-tests, χ² tests, correlations, and regression analyses were applied to identify predictors of HbA1c and diabetes-related complications. Glycaemic control was categorized as optimal (HbA1c ≤ 7.5%) or suboptimal (>7.5%) according to the pragmatic clinical threshold commonly used in DM management. Results: Mean HbA1c was 6.9% (SD = 1.3), with 33.7% of participants above 7.5%. Higher education (β = −0.48, p = 0.013) and participation in strength or balance exercises (β = −0.32, p = 0.041) were associated with lower HbA1c, whereas longer disease duration (β = 0.03, p = 0.004) and type 2 diabetes (β = 0.38, p = 0.030) predicted higher HbA1c. In logistic regression, age predicted cardiovascular comorbidities (OR = 1.12, 95% CI 1.02–1.23, p = 0.019). The interaction between PA and place of residence (urban vs. rural) showed a non-significant trend (p = 0.061). Conclusions: Glycaemic control in Croatian adults with diabetes was associated with educational level and engagement in strength and balance exercises, while longer disease duration, older age, and type 2 diabetes were linked to poorer regulation and more complications. These findings underscore the importance of structured exercise and patient education in diabetes management, although larger, prospective studies with standardized PA-intensity measures are required to confirm and extend these results. Full article

Background/Objectives: Diabetes mellitus (DM) in pregnancy, including type 1 (T1DM), type 2 (T2DM), and gestational DM (GDM), represents an increasing health burden due to its maternal and fetal complications. Despite the increment in the global prevalence estimates of DM in pregnancy, in Romania, it has not been comprehensively described. This study aimed to analyze the prevalence and dynamics of DM in pregnancy in Romania between 2014 and 2024, using national databases, and to identify prevention strategies for reducing maternal and fetal complications. Methods: Data were obtained from the Romanian National Public Health Institute through two distinct sources: Database 1, consisting of reports from public and medical units associated with the National Health Insurance House and Database 2, based on the reports from general practitioners. Pregnancies complicated by DM were assessed by type, age group, and environmental settlement. Additional data were extracted on pregnancies with insufficient prenatal care and those of socially vulnerable individuals. Results: From 2014 to 2024, the prevalence of DM in pregnancy in Romania was consistently lower than European and global estimates, ranging from 1.01‰ to 3.08‰ in Database 1 and from 0.84‰ to 5.88‰ in Database 2, respectively. GDM accounted for the majority of cases, accounting for 65–88% of reported DM in pregnancy. The highest incidence was observed in the 20–39 years age group, with a growing proportion in women aged ≥40 years. Urban-rural disparities decreased over the decade, with rural cases reaching parity by 2024. Vulnerable populations included adolescents, women with insufficient prenatal care, and those with social risk factors, predominantly from rural areas. Conclusions: Although the reported prevalence of DM in pregnancy in Romania is lower than international figures, the true burden is likely underestimated. GDM remains the leading type of DM in pregnancy, mirroring global trends. Strengthening the reporting system, standardizing diagnostic criteria, and targeting high-risk groups through preconceptional counselling, lifestyle interventions, advanced monitoring technologies, and improving social support through the involved authorities are crucial steps to reduce maternal and fetal morbidity. Full article