Type 2 diabetes (T2D) stems from metabolic dysregulation, and body cell mass (BCM) comprises the principal physiological substrate of basal metabolic rate (BMR); however, the as-sociation between BCM and diabetes is still unclear. This study examined the relationship of percentage body cell mass (PBCM) with insulin resistance (IR) and T2D, and evaluated the mediators of this association.

This study utilized data from U.S. adults in the National Health and Nutrition Survey (1999-2004). Weighted multivariate regression, restricted cubic spline analysis, subgroup analyses, and sensitivity analysis were employed to investigate the relationship of PBCM with T2D risk biomarkers, IR and T2D. The potential mediating role of body mass index (BMI) was explored.

A total of 2,923 participants aged 18 years or older were included. Preliminary analysis demonstrated an inverse association between PBCM and biomarkers of T2D risk. Further analyses revealed that higher PBCM was associated with lower odds of IR (OR = 0.91, 95% CI: 0.88-0.94, p <0.001) and T2D (OR = 0.89, 95% CI: 0.84-0.94, p <0.001) in the fully adjusted model. Mediation analysis indicated that BMI mediated 70.6% (95% CI: 55.1%-88.9%, p <0.001) of the total effect of PBCM on IR, and 29.9% (95% CI: 14.2%-65.9%, p <0.001) of that on T2D, respectively.

PBCM was negatively associated with the prevalence of IR and T2D. Mediation analyses demonstrated a mediating effect of BMI, suggesting that PBCM might be related to IR and T2D, potentially mediated by BMI.

A woman in her early 50s presented with a 4-month history of erythema and scaling of the limbs, weight loss, anasarca and chronic foul-smelling diarrhoea, suggestive of nutritional dermatosis with steatorrhoea due to malabsorption. She was non-obese and had no prior history of diabetes or exocrine deficiency. During admission, she experienced abdominal pain and hyperglycaemia consistent with diabetic ketoacidosis. CT of the abdomen revealed a diffusely enlarged, entirely fatty pancreas with preserved shape and a dilated main pancreatic duct containing intraductal calculi, indicating lipomatous pseudohypertrophy (LPH) with chronic calcific pancreatitis (CCP). Clinical and imaging findings confirmed exocrine insufficiency, while coexisting diabetes mellitus, which can be attributed to CCP, suggested a type 3 c diabetes mellitus. She developed sepsis and despite intensive medical management, she died of refractory septic shock. Enlarged pancreatic volume distinguishes LPH from the usual degenerative fatty replacement commonly seen in older patients or patients with obesity or diabetes.

A woman in her early 70s with a history of diabetes mellitus, hypertension and prior right mastectomy for breast carcinoma presented with community-acquired pneumonia (CAP), septic shock and multi-organ dysfunction syndrome. Despite empirical antibiotic therapy and supportive care, her condition worsened. Bronchoalveolar lavage and blood cultures revealed Saprochaete capitata, a rare opportunistic fungal pathogen. She was started on intravenous voriconazole, resulting in gradual clinical improvement. The patient was discharged in a stable condition after a prolonged hospital stay. S. capitata infections are uncommon but can cause life-threatening disease, particularly in immunocompromised hosts. This case highlights the need to consider rare fungal pathogens in patients with severe CAP who do not respond to standard antimicrobial therapy, especially in those with underlying malignancy or prior immunosuppression.

Autoimmune polyglandular syndrome type 3 (APS-3) is the coexistence of autoimmune thyroid disease (AITD) with type 1 diabetes (T1D) or other autoimmune diseases, after exclusion of adrenal insufficiency. We aimed to evaluate the prevalence, timeline and features of APS-3 in children and adolescents with T1D.

We studied 439 T1D paediatric patients who were diagnosed and followed up over 16 years using annual biochemical and autoantibody profile evaluations.

The prevalence of APS-3a (T1D+AITD) was 23.5%, with significant female predominance (54.4%, P = 0.007). The vast majority had Hashimoto's thyroiditis (96.0%), while Graves' disease represented only 4.0%. Coincidence of T1D and AITD diagnosis was recorded in 49.5%. The frequency of diabetic ketoacidosis in patients diagnosed with AITD before the onset of T1D (63.6%) was similar to that in patients with isolated T1D (61.7%). Overlapping of APS-3 subtypes were identified, including celiac disease (n=4), autoimmune hepatitis (n=1), atrophic gastritis (n=1) (APS-3b), vitiligo (n=1), psoriasis (n=1) (APS-3c) and Sjögren's syndrome (n=1) (APS-3d).

APS-3a is common in the paediatric T1D population and is often diagnosed at its clinical onset. The overlaps with gastrointestinal and connective tissue pathology highlight the unpredictable natural course of autoimmunity, underscoring the necessity for lifelong regular monitoring.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus and a leading cause of chronic kidney disease and end-stage renal disease. Although current therapeutic strategies can delay disease progression, they remain insufficient to reverse established renal injury. Plant-derived flavonoids, a class of natural polyphenolic compounds, have attracted increasing attention due to their diverse pharmacological properties. This structured narrative review summarizes the major molecular mechanisms underlying the protective effects of plant-derived flavonoids against DN. A comprehensive literature search was conducted in PubMed, Web of Science, and MEDLINE from database inception through December 25, 2025. A total of 251 relevant studies were included (54 in vitro only, 107 in vivo only, and 90 involving both). The evidence indicates that plant-derived flavonoids may exert renoprotective effects through diverse mechanisms, including the modulation of inflammation, oxidative stress, fibrosis, autophagy, apoptosis, ferroptosis, and microRNA (miRNA)-mediated regulatory pathways. Collectively, these flavonoids, such as kaempferol, quercetin, puerarin, and (-)-epigallocatechin-3-gallate (EGCG), demonstrate multi-target therapeutic potential against DN and may serve as promising adjunctive agents for disease management. However, the current evidence is predominantly derived from preclinical studies, and well-designed randomized controlled trials are required to further validate their efficacy and safety and to facilitate clinical translation.

Type 2 diabetes mellitus (T2DM) and insomnia represent two of the most prevalent and interacting chronic conditions in global clinical medicine, sharing overlapping pathophysiological substrates involving dysregulated immune activation, impaired circadian rhythm, and systemic metabolic dysfunction. Despite epidemiological evidence documenting the high co-occurrence of insomnia in T2DM populations and converging mechanistic insights implicating shared inflammatory pathways, no prior study has integrated genome-wide genetic profiling, inflammatory immunophenotyping, and pathway-based analysis within a unified framework explicitly designed to characterize the infection susceptibility consequences of this comorbidity. This study fills that gap through a prospective case-control design enrolling 180 T2DM patients with comorbid insomnia, 180 T2DM patients without insomnia, and 120 healthy controls, recruited from three tertiary care centers. Peripheral blood samples were subjected to genome-wide SNP genotyping (Illumina MEGA array), a 40-analyte multiplex cytokine and chemokine panel, flow cytometric immunophenotyping of 12 peripheral blood mononuclear cell subsets, and polysomnographic sleep architecture assessment. Pathway-based analysis integrating Gene Ontology, KEGG, and STRING protein interaction networks identified 10 significantly enriched pathways, with the NF-kB signaling, NLRP3 inflammasome, and toll-like receptor pathways showing the strongest co-activation in the T2DM-insomnia group. The infection-free survival analysis demonstrated that T2DM-insomnia patients had a 52-week cumulative infection incidence 3.8-fold higher than healthy controls and 2.1-fold higher than T2DM-only patients. Mediation analysis identified IL-6, TNF-alpha, NF-kB pathway activation, and regulatory T-cell depletion as significant mediators of the insomnia-to-infection susceptibility pathway, collectively accounting for 64 % of the total indirect effect. Logistic regression models adjusted for age, sex, BMI, medication use, and glycaemic control documented significantly elevated odds of urinary tract infection, respiratory infection, skin and soft tissue infection, and sepsis in T2DM-insomnia patients compared with T2DM-only patients. These findings establish a convergent genetic-inflammatory signature unique to T2DM-insomnia comorbidity that mechanistically underlies heightened infection susceptibility and worse clinical outcomes.

Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy, closely related to insulin resistance and altered fatty acid metabolism. However, evidence on mid-pregnancy fatty acid profiles and GDM risk remains limited and inconsistent. We comprehensively characterized mid-pregnancy circulating fatty acid profiles and their derived patterns in relation to GDM risk in a matched case-control study.

Based on a prospective cohort study conducted in Shenzhen, China, we performed a 1:2 matched case-control study including 290 GDM cases and 580 normal glucose tolerance controls, matched by maternal age and pre-pregnancy BMI. Conditional logistic regression was used to examine associations between individual fatty acids and GDM risk. Multivariable linear regression with cluster-robust standard errors was applied to assess associations with oral glucose tolerance test glucose levels. Principal component analysis was further used to identify fatty acid patterns.

Medium-chain saturated fatty acids, including C12:0 and C14:0, were inversely associated with GDM risk and post-load glucose levels. The highest quartile of C12:0 was associated with a 48% lower GDM risk. Total odd-chain fatty acids also showed a protective association. In contrast, very-long-chain saturated fatty acids, particularly C22:0 and C24:0, were positively associated with GDM risk and post-load glucose, with the highest quartile of C22:0 associated with a more than two-fold higher risk. Among polyunsaturated fatty acids, ALA was associated with lower GDM risk, whereas DHA was associated with higher risk. Principal component analysis identified a fatty acid pattern characterized by higher C24:0, C22:0, and C18:1n-9 and lower C18:3n-3, C17:0, and C18:2n-6, which was associated with increased GDM risk and elevated post-load glucose.

Mid-pregnancy circulating fatty acid profiles were associated with GDM risk and glycemic levels. Fatty acid pattern analysis provides a complementary perspective to individual fatty acid associations, offering an integrated view of fatty acid metabolism in pregnancy.

Celiac plexus neurolysis (CPN) ablates the celiac ganglia using dehydrated (99%) ethanol, typically for palliation of upper abdominal pain. The sympathetic nervous system contributes to hepatic glucose production and suppression of insulin secretion, so disruption of these pathways may alter glycemic regulation. Glycemic outcomes are described in 6 patients with Type 2 diabetes mellitus who underwent CPN for chronic abdominal pain over a 9-year period. All 6 procedures were technically successful without 30-day adverse events, and no hypoglycemic episodes occurred during follow-up. At 6 and 12 months, all 6 patients showed reductions in HbA1c (mean change: -1.3% and -1.1%, respectively) and fasting glucose (mean change: -44.0 mg/dL and -52.2 mg/dL, respectively). Of the 4 insulin-treated patients, 2 discontinued insulin entirely and 2 had their insulin dose reduced. These hypothesis-generating findings suggest CPN may have an incidental effect on glycemic control warranting prospective evaluation.

Objective. The link between ultrafast heart period (HP) dynamics and baroreflex is poorly analyzed, especially in pathologies altering autonomic regulation. This study assesses this link via heart rate fragmentation (HRF) analysis in type 2 diabetes mellitus (T2DM) with or without cardiac autonomic neuropathy (CAN).Approach. Sixty-four individuals with T2DM, divided into those with CAN (DM_CAN, n=28, 55-62 yrs, 17 males) and without CAN (DM_noCAN, n=36, 49-61 yrs, 19 males), were evaluated at supine resting (REST) and during active standing (STAND). HRF was calculated using sequences of four consecutive HPs categorized as words with zero (W₀), one (W₁), two (W₂), three (W₃) and total (PIP) inflection points. Baroreflex control was assessed from HP and systolic arterial pressure (SAP) variabilities cross-spectral analyses in low frequency (LF) and high frequency (HF) bands and via sequence method (SEQ). Also squared coherence between HP and SAP in LF and HF bands, namely K²_HP-SAP(LF) and K²_HP-SAP(HF), and percentage of baroreflex sequences (%_SEQ) were assessed.Main results. W₃was higher in DM_CANat REST compared to DM_noCANand W₃increased in STAND for both groups. At REST %_SEQand K²_HP-SAP(HF) were positively associated with W₀and W₁, while they were negatively associated with W₃and PIP. During STAND K²_HP-SAP(LF), %_SEQand α_SEQwere negatively correlated with PIP and W₃.Significance. Greater presence of inflection points in 4-beat words was associated with a less effective baroreflex, thus suggesting that an impaired baroreflex augmented the likelihood of fast HP changes in DM_CAN.

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options and poor clinical outcomes. This study evaluated folic acid-functionalized solid lipid nanoparticles co-loaded with docetaxel and erlotinib (FA-DOC/ERL-SLNs) as an oral targeted therapy for TNBC. FA-DOC/ERL-SLNs exhibited the lowest IC₅₀ values of 0.82 ± 0.05 μM and 0.92 ± 0.03 μM in MDA-MB-231 and 4T1 cells, respectively, with enhanced cellular uptake compared with free drugs and non-targeted SLNs. The formulation also induced higher apoptosis (apoptosis indices of 1.42 and 1.45), greater G2/M cell-cycle arrest, autophagy inhibition, and reduced clonogenicity and migration. Pharmacokinetic studies demonstrated markedly improved oral bioavailability, with AUC₀-t increasing from 1.03 to 45.69 μg·h/mL for docetaxel and from 18.30 to 87.76 μg·h/mL for erlotinib. In 4T1 tumor-bearing mice, FA-DOC/ERL-SLNs reduced tumor volume by approximately 1.5-fold compared with non-targeted SLNs and 2.5-3.0-fold compared with free drugs, without significant body weight loss or systemic toxicity. These findings demonstrate that FA-DOC/ERL-SLNs enhance the efficacy and safety of oral docetaxel-erlotinib combination therapy and represent a promising targeted nanocarrier platform for TNBC treatment.