Search Results (39,591)

Background/Objectives: Sciatica can adversely affect mental well-being; however, evidence regarding its psychological impact among Saudi women remains scarce, particularly concerning differential effects across specific mental health domains. This study examined the prevalence of sciatica and its associations with depression, anxiety, and stress among adult Saudi women. Methods: A cross-sectional online survey was conducted from February to March 2024 among Saudi women aged ≥18 years. Participants (n = 706) completed the Arabic Depression, Anxiety, and Stress Scale (DASS-21) and provided sociodemographic and health information. Sciatica status was based on self-report. Multivariable linear regression analyses identified independent predictors of each mental health domain. Results: Sciatica prevalence was 11.0% among 706 participants (mean age 29 ± 11 years; mean BMI 24 ± 6.5 kg/m²). Sciatica was the strongest independent predictor of stress (β = 6.87, 95% CI: 4.57–9.17, p < 0.001). No significant associations were observed with depression (β = 1.80, p = 0.183) or anxiety (β = 0.45, p = 0.481). Additional stress predictors included lower-back pain, diabetes, lower–middle income, and daily phone use >8 h, while bachelor-level education was protective. Arthritis independently predicted anxiety (β = 1.52, p = 0.008). Conclusions: In this convenience sample of Saudi women, sciatica was significantly associated with higher stress symptom scores, while associations with depression and anxiety did not reach statistical significance. The observed pattern suggests that stress screening and management should be considered within biopsychosocial care for sciatica patients, pending confirmation in prospective studies. Full article

Introduction: Type 2 diabetes mellitus predisposes patients to neuropathy, peripheral arterial disease, and diabetic foot ulcers, which may become infected and progress to osteomyelitis, increasing the risk of amputation. The growing prevalence of multidrug-resistant organisms complicates management. Photodynamic therapy (PDT), which combines a photosensitizer with light-emitting diode irradiation to generate reactive oxygen species, has emerged as a potential adjunctive antimicrobial strategy without inducing resistance. Objective: To describe clinical outcomes observed in patients with diabetic foot osteomyelitis treated with adjunctive photodynamic therapy (PDT), with emphasis on wound evolution, limb preservation, and healing time. Methods: This prospective case series included patients with osteomyelitis secondary to infected diabetic foot ulcers treated at a university hospital. Demographic and clinical data were collected from medical records. Serial photographic documentation was used to monitor wound progression and tissue response during therapy. Results: Sixteen patients with diabetic foot osteomyelitis were included. Complete healing was achieved in 13 patients (81.25%), while 2 patients (12.5%) remained under treatment with partial healing and 1 (6.25%) underwent major amputation. Among healed patients, healing time ranged from 19 to 546 days, with a median of 118 days. The number of photodynamic therapy sessions ranged from 2 to 12, depending on the clinical course of each case. Healing time varied among patients, and the hallux was the most frequent site of osteomyelitis. During follow-up, only one patient underwent major amputation, whereas the remaining patients either achieved complete healing or were still under treatment at the time of analysis. Healing time was comparable between insulin-dependent and non-insulin-dependent diabetes, although numerically shorter in the latter. Longer healing periods were associated with more treatment sessions. Conclusions: In this prospective uncontrolled case series, adjunctive PDT was associated with favorable clinical evolution in a subset of patients with diabetic foot osteomyelitis. However, because of the small sample size and the absence of a control group, these findings should be considered preliminary and hypothesis-generating. Full article

Background: Diabetes mellitus is frequently associated with complications and comorbidities that often require hospitalization and the use of multiple medications for effective management. However, the simultaneous use of these treatments significantly increases the risk of potential drug–drug interactions (pDDIs). Objectives: This study assessed the prevalence, levels, and associated predictors of pDDIs among hospitalized participants with type 2 diabetes mellitus (T2DM) and evaluated their clinical relevance and implications for monitoring and management. Methods: This retrospective cross-sectional study included 430 inpatients with T2DM at Universitas Indonesia Hospital, Indonesia. Lexicomp^® Lexi-Interact™ software Wolters Kluwer was used to analyze and classify pDDIs based on severity, risk rating, and documentation levels. Additionally, logistic regression analysis was conducted to identify the predictors of pDDIs, and the study assessed the clinical relevance of major pDDIs. Results: Of the total participants, 84.7% (n = 364) experienced pDDIs, with 1642 interactions identified. Moderate interactions accounted for 77.5% (n = 1273), whereas major interactions constituted 12.2% (n = 201). The most common risk rating was category C (77.5%, n = 1187), and the predominant evidence support level was ‘fair’ (64.8%, n = 1064). Multivariate logistic regression analysis showed a significant association between pDDIs and of 7–12 medications used (OR = 30.1; p < 0.001), and hospital stays ≥4 days (OR = 9.7; p = 0.001). Major pDDIs were significantly linked to ≥13 medications (OR = 5.5; p = 0.002), ≥4 days hospitalization (OR = 11.3; p < 0.001), and urinary tract infections (OR = 3.5; p = 0.02). Participants with major pDDIs exhibited hypoglycemia, hyperglycemia, electrolyte imbalances, and reduced therapeutic responses. Conclusions: The findings indicate a high prevalence of pDDIs among participants with T2DM, highlighting the impact of polypharmacy, prolonged hospitalization, and comorbidities. Implementing software-based screening, close monitoring, and targeted interventions are essential to reduce adverse clinical outcomes and enhance patient safety. Full article

Experimental diabetes models induced by streptozotocin (STZ) and alloxan are widely used in preclinical research; however, direct standardized comparisons in female rodents remain limited. The present study evaluated multiple chemical induction protocols in female Wistar rats, including STZ (40 and 65 mg/kg), STZ at the same doses combined with nicotinamide (110 mg/kg), and alloxan (130 mg/kg). Glycemic progression, oral glucose tolerance test, body weight evolution, oxidative stress markers, and multi-organ histopathology were assessed over a 14-day period. High-dose STZ (65 mg/kg) and alloxan produced rapid, sustained hyperglycemia (p < 0.0001), significant body weight reduction, increased lipid peroxidation (elevated MDA), nitric oxide overproduction, thiol depletion, and pronounced pancreatic and renal structural damage. In contrast, STZ–nicotinamide protocols generated moderate but stable hyperglycemia with partial preservation of islet architecture, attenuated oxidative imbalance, and improved systemic tolerability. Oral glucose tolerance test confirmed impaired glucose handling in the STZ–nicotinamide group, consistent with a type 2 diabetes-like phenotype rather than complete insulin deficiency. These results demonstrate that induction strategy critically determines metabolic stability, oxidative stress burden, and tissue remodeling patterns, supporting model selection according to specific experimental objectives. Full article

Background: Gestational diabetes mellitus (GDM) is a common metabolic disorder characterized by glucose intolerance and associated with adverse maternal and fetal outcomes. Emerging evidence suggests that oxidative stress and hypoxia-related pathways may contribute to its pathophysiology. This study aimed to evaluate the diagnostic performance of serum sestrin-2 (SESN-2) and hypoxia-inducible factor-1alpha (HIF-1α) as potential biomarkers in GDM. Methods: In this case–control study, 100 pregnant women (50 with GDM and 50 controls) were enrolled. Serum SESN-2 and HIF-1α levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: Patients with GDM showed significantly higher body mass index, glucose levels, glycated hemoglobin (HbA1c), insulin, and C-reactive protein (CRP) (all p < 0.05). SESN-2 and HIF-1α levels were significantly elevated (both p < 0.0001). Receiver operating characteristic (ROC) analysis showed area-under-the-curve (AUC) values of 0.799 for SESN-2 and 0.769 for HIF-1α, which increased to 0.909 when combined. Both biomarkers were independently associated with GDM in multivariable analysis. Conclusions: SESN-2 and HIF-1α levels are elevated in GDM and are associated with its presence. These biomarkers demonstrated moderate diagnostic performance, and their combined use improved discrimination; however, they should be considered complementary rather than standalone diagnostic tools. Given the cross-sectional design, the findings reflect associations rather than predictive relationships, and further prospective studies are required to clarify their clinical utility. Full article

Intermittent fasting confers protection in diverse diseases through various mechanisms, including the clearance of senescent and pathogenic cells, modulation of tissue inflammation and enhancement of stem/progenitor cell niche and functionality. Our previous study demonstrated the beneficial impact of alternate-day fasting (ADF) on xerostomia and sialadenitis, along with an improvement in salivary gland ductal compartments, where salivary gland progenitor cells reside, in non-obese diabetic mice, a spontaneous model of Sjögren’s syndrome (SS). In the present study, we induced SS-associated hyposalivation in KRT5^CreERT2; R26^tdTomato lineage tracing mice by immunizing them with submandibular gland proteins from wild-type C57BL/6 mice. ADF alleviated salivary gland hypofunction, which was accompanied by decreased expression of the senescent cell marker p16^INK4a, reduced protein levels of anti-apoptotic proteins BCL-2, BCL-XL, and MCL-1, and attenuated NLRP3 inflammasome activity in the submandibular glands, particularly within the ductal compartments, of this inducible model. Furthermore, immunofluorescence staining of submandibular gland sections revealed the expression of the acinar cell marker aquaporin 5 in a small subset of Keratin 5⁺ cells in 2 of 9 mice that were subjected to ADF, whereas no such cells were detected in the control mice. Taken together, these findings indicate that ADF favorably modulates the salivary gland progenitor cell niche, potentially by promoting apoptosis-mediated senescent cell clearance, suppressing NLRP3 inflammasome signaling, and promoting Keratin 5⁺ progenitor cell-derived acinar cell replenishment, thereby contributing to the structural and functional restoration of damaged salivary glands in autoimmune exocrinopathy. Full article

We showed recently that the adenosine system and nitric oxide (NO) can interact differently in the control of renal function in normoglycaemia (NG) versus streptozotocin-induced diabetes (DM). Herein, we investigated if this relationship is modulated by dietary betaine (Bet, food compound possessing antioxidant and anti-inflammatory properties), to examine if adenosine receptor signalling in NG and DM females is altered by chronic Bet supplementation. The effects of intravenous infusion of theophylline, non-selective adenosine receptor antagonist, were examined in anaesthetised Sprague–Dawley female rats, pretreated for 2 weeks with Bet alone or combined with 4-day NO synthesis blockade with L-NAME (Bet + L-NAME). Renal blood flow (RBF, ultrasound artery probe), perfusion of the cortex, outer (OM-BF) and inner medulla (IM-BF; laser-Doppler technique), and tissue NO signal (selective electrode) were determined along with renal excretion. Bet and Bet + L-NAME decreased baseline RBF irrespective of glycaemia, whereas Bet lowered (NG) or elevated (DM) basal OM-BF; Bet + L-NAME treatment abolished these effects. Baseline sodium excretion decreased after Bet and Bet + L-NAME in NG only. Bet modified theophylline effects: IM-BF was lowered in DM rats, while tissue NO changes shown in the control were modified: NO increased in NG and decreased in DM. In NG, these effects were abolished by Bet + L-NAME. Bet pretreatment did not alter diuresis, natriuresis and kaliuresis, but after Bet + L-NAME these parameters increased (NG) or decreased (DM). Dietary Bet has the potential to affect renal medullary blood circulation; however, the eventual effect depends on glycaemia. Bet can modify renal functional changes induced by the interplay of the adenosine and NO systems, both in rats with normoglycaemia and streptozotocin diabetes. Full article

Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of diabetes mellitus which affects individuals with both type 1 and type 2 diabetes mellitus (T2DM), presenting with sensory loss, pain, and progressive nerve dysfunction. DPN pathogenesis is multifactorial: chronic hyperglycemia activates the polyol, hexosamine, and protein kinase C (PKC) pathways, increases advanced glycation end-products, and drives oxidative stress, mitochondrial dysfunction, inflammation, and impaired neurotrophic signaling. In addition to hyperglycemia-driven mechanisms, dyslipidemia and microvascular insufficiency exacerbate neural ischemia and metabolic stress. Recent mechanistic, animal, and associative human studies further implicate amyloidogenic toxicity, particularly from human islet amyloid polypeptide (hIAPP), as a plausible contributory factor in peripheral nerve degeneration in T2DM, linking protein misfolding and aggregation to axonal damage and demyelination in DPN. Despite increased understanding of these mechanisms, current treatments remain mainly symptomatic. Emerging therapeutic strategies, including antioxidants, anti-inflammatory agents, modulators of mitochondrial function, amyloid oligomer modulators, neurotrophic enhancers, and regenerative approaches such as stem cells and gene-based therapies, offer potential to modify disease progression. The strength of evidence across these methods varies, ranging from mechanistic and animal studies to early human research and, in some cases, randomized clinical trials. Therefore, although several candidates show potential to alter the disease, few have demonstrated consistent benefits on objective measures of nerve structure or function in large clinical trials. This review summarizes the key mechanisms driving DPN in T2DM and highlights promising therapeutic innovations poised for clinical translation. Full article

Background: The global healthcare system faces a significant challenge due to the escalating prevalence of type 2 diabetes, affecting over 10% of the world’s population. Suppression of postprandial hyperglycemia through inhibition of carbohydrate-hydrolyzing enzymes is an effective therapeutic strategy. Although curcumin effectively inhibits α-amylase and α-glucosidase activities, its lower solubility and bioavailability restrict its clinical application. In this study, five mono-carbonyl curcumin analogues (CA1–CA5) were synthesized and evaluated for their antidiabetic potential following selective experimental methods both in vitro, and in vivo. Enhanced delivery for the most potent analogue was achieved through PEGylated graphene oxide (PEG-GO) to overcome the shortcomings of curcumin compounds. Methods: In silico ADME profiling was conducted using SwissADME, and molecular docking studies were performed with AutoDock Vina (v1.5.7) to assess enzyme binding interaction. The synthesized compounds were further evaluated using in vitro α-amylase and α-glucosidase inhibition assays, followed by in vivo blood profile analysis. The most active analogue CA3 (chloro derivative) was loaded onto PEG-GO and characterized using UV–visible spectroscopy, Fourier-transform infrared spectroscopy, and scanning electron microscopy. Results: Among all of the compounds, CA3 exhibits the strongest binding affinity and highest enzyme inhibitory activity, followed by CA2 and CA4. PEG-GO-CA3 demonstrated significantly enhanced biological activity compared to its free form. In vivo studies showed marked improvements in body weight and lipid profile, along with significant reductions in blood glucose, glycated hemoglobin, urea, creatinine, alanine aminotransferase, and aspartate aminotransferase levels over a 28-day treatment period as compared to a diabetic control. Spectroscopic and morphological analyses confirmed successful loading of CA3 onto PEG-GO (27.7–31.5%) with a release profile of 38–57% after 12 and 36 h in a controlled environment at pH 7. Conclusions: These findings suggest that PEG-GO-loaded mono-carbonyl curcumin analogues represent promising therapeutic candidates for the management of T2DM. Full article

The cardiovascular–kidney–metabolic (CKM) syndrome has emerged as an integrated framework linking obesity, type 2 diabetes, chronic kidney disease (CKD), and heart failure with preserved or mildly reduced ejection fraction through shared mechanisms including inflammation, oxidative stress, endothelial dysfunction, and fibrosis. Persistent mineralocorticoid receptor overactivation plays a central role in this continuum, contributing to progressive cardiac and renal injury despite optimized renin–angiotensin system blockade. Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has therefore gained increasing attention as a targeted strategy to reduce residual cardiorenal risk. This narrative review summarizes the mechanistic rationale and clinical evidence supporting finerenone across the CKM spectrum. Experimental data indicate that finerenone attenuates inflammation, fibrosis, myocardial hypertrophy, and adverse remodeling, while proteomic and translational analyses suggest biological complementarity with sodium–glucose cotransporter 2 inhibitors. Clinically, pivotal randomized trials have demonstrated that finerenone reduces kidney disease progression and major cardiovascular events in patients with CKD and type 2 diabetes, while the FINEARTS-HF trial extended these benefits to patients with heart failure with mildly reduced or preserved ejection fraction by reducing worsening heart failure events. Additional subgroup, pooled, and meta-analytic data reinforce the consistency of these effects across a broad range of cardiorenal phenotypes. Taken together, current evidence positions finerenone as an important component of contemporary CKM management, particularly in patients with diabetic CKD and selected heart failure phenotypes. Its principal value lies in targeting residual inflammatory and fibrotic risk beyond conventional hemodynamic and metabolic control. Future progress will depend on earlier phenotype recognition, improved implementation and adherence, and wider adoption of pathway-oriented combination therapy across the cardiorenal continuum. Full article

Purpose: To determine the optimal treatment sequence for combination therapy using intravitreal faricimab (IVF) and direct photocoagulation (PC) in eyes with non-center-involved diabetic macular edema (DME). Methods: This retrospective study included 35 eyes with focal DME treated with IVF and PC targeting microaneurysms (MAs). Treatment success was defined as resolution of focal edema, indicated by disappearance of the white area (WA) on optical coherence tomography. Eyes were assigned to a PC-IVF group (initial PC followed by IVF if edema persisted after 2 months; n = 20) or an IVF-PC group (initial IVF followed by PC for residual edema; n = 15). Additional PC was performed every 2 months as needed. Results: Cumulative success rates at 2, 4, and 6 months were 35.0%, 70.0%, and 90.0% in the PC-IVF group and 60.0%, 93.3%, and 100% in the IVF-PC group, respectively. Macular volume significantly decreased at all time points in the IVF-PC group (all p < 0.01), whereas a significant reduction was observed only after 6 months in the PC-IVF group (p < 0.01). The number of MAs and the extent of edema were significantly reduced after 2 months in both groups, with greater reductions in the IVF-PC group (p < 0.05). The number of laser shots required for initial PC was significantly lower in the IVF-PC group (p < 0.0001), and the mean number of PC sessions was also reduced (0.6 vs. 1.8). In the PC-IVF group, baseline edema size was significantly smaller in successfully treated eyes (p < 0.001). Conclusions: Initiating treatment with IVF prior to PC may be advantageous in focal DME, particularly in eyes with larger edema, enabling faster anatomical improvement and reducing the need for laser treatment. Direct PC alone may be sufficient for small focal lesions with limited edema, supporting an individualized treatment strategy. Full article

Background: Routine fundus photography is widely accessible; however, its utility in stratifying systemic vascular risk in asymptomatic, general populations remains understudied. We utilized a large-scale health screening cohort in South Korea to evaluate the clinical validity of the retinal arteriosclerosis index (RAI) in a generally healthy population. Methods: We conducted a cross-sectional study of 74,608 adults who underwent routine health screening (2003–2010) at a tertiary center. Retinal arteriosclerosis was graded (0–4) by masked readers with a modified Scheie classification; a higher eye grade was defined as a person-level grade. High-grade RAI was prespecified as ≥2. Associations with systemic conditions (hypertension, type 2 diabetes, hyperlipidemia, metabolic syndrome, cardiovascular disease, and stroke) were examined by using multivariable logistic regression adjusted for demographic, lifestyle, and laboratory covariates; moreover, analyses were stratified by age and sex. Results: High-grade RAI was present in 4.5% of the participants and increased with age. After adjustment, high-grade RAI was associated with hypertension (OR, 2.97; 95% CI, 2.73–3.23), diabetes mellitus (OR, 1.35; 95% CI, 1.22–1.50), cardiovascular disease (OR, 1.46; 95% CI, 1.25–1.71), metabolic syndrome (OR, 1.63; 95% CI, 1.49–1.78), and stroke (OR, 1.98; 95% CI, 1.41–2.79) but not with hyperlipidemia. Sex-stratified analyses revealed broadly similar patterns, although high-grade RAI was associated with stroke in women and cardiovascular disease in men. Age-stratified analyses demonstrated consistent associations with hypertension, metabolic syndrome, and stroke across all age groups, with stronger effect sizes being observed in younger individuals. With respect to lifestyle factors, frequent alcohol consumption was associated with higher odds of high-grade RAI. Laboratory correlates included higher uric acid levels and lower red blood cell, albumin, and bilirubin levels (all p < 0.001). Conclusions: Fundus-defined arteriosclerotic changes were independently associated with multiple systemic vascular and metabolic conditions. An association with stroke in adults younger than 40 years of age was also observed, although this finding should be interpreted with caution given the cross-sectional design and limited number of events. These findings support the potential role of retinal vascular changes as cross-sectional correlates of systemic vascular health. Longitudinal studies are needed to clarify temporal relationships and causality. Full article

Background/Objectives: Diabetes is a prevalent chronic condition and a major contributor to morbidity, mortality, and healthcare costs in the U.S., particularly among older adults with comorbidities such as hypertension and dyslipidemia. Complex medication regimens increase the risk of nonadherence, which can worsen glycemic control, cardiovascular outcomes, and healthcare utilization. This study assessed longitudinal adherence patterns to oral antidiabetic medications among high-risk older adults and identified predictors using group-based trajectory modeling (GBTM). Methods: This retrospective cohort study used 2016–2017 Texas Medicare Advantage claims. Participants were older adults with diagnoses of diabetes, hypertension, and hyperlipidemia who had continuous plan coverage throughout the study period and at least one prescription fill for an oral antidiabetic, a statin, and a renin–angiotensin system (RAS) antagonist. Adherence was measured monthly over 12 months using the proportion of days covered (PDC). GBTM identified adherence trajectories, and multinomial logistic regression, based on the Andersen Behavioral Model, evaluated predictors using perfect adherence as the reference. Results: Among 7847 patients, three trajectories were observed: perfect adherence (59.50%), near-perfect adherence (29.21%), and rapid decline (11.29%). Female sex (OR, 1.38; 95% CI, 1.19–1.60) and absence of health plan subsidy (OR, 0.79; 95% CI, 0.68–0.92) were associated with rapid decline. Female sex (OR, 1.13; 95% CI, 1.02–1.25) and age ≥ 75 years (OR, 1.20; 95% CI, 1.00–1.43) were associated with near-perfect adherence. Conclusions: Older adults with diabetes and comorbidities exhibit distinct medication adherence patterns. Trajectory-based methods can identify those at risk for declining adherence and guide interventions to improve outcomes. Full article

Background/Objectives: To examine the association of social determinants of health (SDOHs) with primary and cost-related medication nonadherence among adults with diabetes. Methods: A retrospective cross-sectional analysis was conducted using 2021 data from the Medical Expenditure Panel Survey (MEPS), a nationally representative sample of the United States civilian noninstitutionalized population. Adults aged ≥ 18 years with a diagnosis of diabetes in 2021 were included. The outcomes include primary medication nonadherence (no antidiabetic prescriptions filled) and cost-related medication nonadherence (delaying prescriptions due to cost). The exposure variables include SDOHs such as financial stress, food insecurity, transportation barriers, social support, access to medical care in the neighborhood, and healthcare discrimination. Weighted multivariable logistic regression analyses were conducted to assess the association between SDOHs and medication nonadherence. Results: Among 21.9 million patients with diabetes, 6.5% reported cost-related nonadherence and 17.4% exhibited primary nonadherence. Difficulty paying rent or mortgage (OR 2.32, 95% CI: 1.27–4.23), food insecurity (OR 2.13, 95% CI: 1.27–3.58), and transportation barriers (OR = 2.15; 95% CI: 1.20–3.63) were significantly associated with cost-related nonadherence. In the Medicare subgroup, both difficulty paying rent or mortgage (OR = 2.41, 95% CI: 1.03–5.64) and food insecurity (OR = 2.16, 95% CI: 1.18–3.96) significantly increased cost-related nonadherence. Conclusions: Financial strain, food insecurity, and transportation barriers are associated with cost-related nonadherence. These findings suggest considering social and economic factors in strategies supporting diabetes medication adherence across populations, including Medicare beneficiaries. Full article

Background/Objectives: Both adiposity and nutritional–inflammatory status influence glucose metabolism; however, their longitudinal associations with glycemic changes in non-diabetic populations remain unclear. We examined the independent, interactive, and joint associations of body mass index (BMI) and prognostic nutritional index (PNI) with the 3-year change in HbA1c (ΔHbA1c). PNI, a composite marker of serum albumin and peripheral lymphocyte count, reflects both protein nutritional status and systemic immune competence. We hypothesized that BMI and PNI would each independently predict ΔHbA1c and that their joint profiling would identify higher-risk subgroups. Methods: A total of 9414 non-diabetic adults from the Shanghai Suburban Adult Cohort were included. Participants with diabetes at baseline (defined as fasting plasma glucose ≥ 7.0 mmol/L, 2-h post-load glucose ≥ 11.1 mmol/L, HbA1c ≥ 6.5%, or self-reported physician diagnosis of diabetes or use of glucose-lowering medications) were excluded. BMI was measured, and PNI was calculated as serum albumin + 5 × lymphocyte count. ΔHbA1c was assessed over a 3-year period. Multivariable linear regression, interaction testing, and joint stratification were performed. Covariate selection was guided by prior biological plausibility, and model adequacy was evaluated using the Akaike Information Criterion (AIC). Results: Both BMI (β = 0.013% per kg/m², 95% CI: 0.011–0.016, p < 0.001) and PNI (β = 0.002% per unit, 95% CI: 0.000–0.004, p = 0.019) were independently and positively associated with ΔHbA1c. No significant interaction was observed (p = 0.431). High BMI (≥24 kg/m²) was associated with glycemic worsening irrespective of PNI level (β ≈ 0.075%, p < 0.001). Among normal-weight individuals, higher PNI was associated with a modest increase in ΔHbA1c (β = 0.031%, p = 0.007). Conclusions: Although the absolute effect sizes were modest at the individual level, BMI was consistently and independently associated with glycemic deterioration therefore, even small per-unit increases may translate into meaningful risk at the population level given the high prevalence of overweight and obesity. PNI showed a small positive association, suggesting that in relatively healthy populations a higher PNI may partly capture subtle pro-glycemic factors—such as low-grade inflammation or higher protein intake—rather than representing unambiguous nutritional benefit. The absence of interaction suggests that BMI and PNI act through largely independent pathways. These findings extend prior evidence by demonstrating that PNI provides modest additional glycemic information beyond BMI in non-diabetic community-dwelling adults, particularly among those of normal weight. Full article