As the prevalence of diabetes mellitus continues to rise, morbidity associated with nonhealing diabetic wounds is becoming more common. Hydrogen sulfide (H₂S) has been increasingly recognized as an important signaling molecule in wound healing and angiogenesis. Obesity and diabetes are associated with decreased levels of circulating and transdermal H₂S, but skin H₂S emissions during wound healing have not previously been established. This study aims to describe H₂S physiology during diabetic ischemic wound healing and revascularization.

Sprague Dawley and Zucker diabetic fatty (ZDF) rats underwent creation of full-thickness ischemic myocutaneous flap wounds. Revascularization was followed for 14 days by serial laser speckle contrast imaging and transdermal H₂S emissions during healing. The degree of ischemic tissue injury (panniculus carnosus thickness) and neovascularization (CD31 immunohistochemistry) were assessed histologically. Vascular endothelial growth factor was measured by Western immunoblot.

ZDF rats were observed to have impaired skin perfusion at baseline and during flap engraftment [64 perfusion units (PU) versus 184 PU, P < 0.01], which mirrored deficits in H₂S emissions of the healing flap wound (10 parts per billion [ppb] versus 28 ppb, P < 0.01). Significantly worse tissue ischemic injury and neovascularization were noted in ZDF animals compared to Sprague Dawley (12 CD31⁺ vessels/mm² versus 20, P = 0.02), which correlated with a two-fold deficit in vascular endothelial growth factor expression compared to nondiabetic animals.

Impairments in transdermal H₂S emissions are present in diabetic ischemic wounds and are associated with deficits in wound revascularization, perfusion, maintenance of tissue architecture, neovascularization, and angiogenic signaling. H₂S therapies may be a viable novel option for this challenging clinical problem.

To perform a descriptive analysis of a population diagnosed with DM2 in Alava, to correlate the CUN-BAE and BMI formulas and to analyse the use of GLP-1 analogue.

This is a descriptive, cross-sectional, retrospective and observational study. We included the type 2 diabetic population of Alava, over 18 years of age with BMI recorded in their clinical history in the last 2 years, the data were collected from the OBID database.

1,3705 patients were analysed, 56.4% men and 43.6% women. The mean age was 69.18 years. Mean BMI in men was 29.12 (SD 4.79) kg/m2 and in women 29.88 (SD 6) kg/m2. The CUN-BAE in men was 32.15 (SD 5.29) and in women 44.29 (SD 5.5).

41% of the population analysed by BMI would be considered obese, while with CUN-BAE 95.2% of men and 93.2% of women would be considered obese. Further studies are needed to make a more accurate estimation with CUN-BAE in other breeds.

To examine the association between predominant peripheral lesion (PPL) with systemic microvascular and macrovascular complications of diabetes mellitus (DM).

Cross-sectional, retrospective study.182 eyes from 100 diabetic patients were imaged using ultra-widefield color fundus photographs (UWF-CFP). UWF-CFP were assessed by 2 graders for presence and extent of PPL. Comprehensive demographic and clinical data were collected from electronic medical records. Generalized estimating equations were used to determine the association between PPL and systemic complications of DM.

PPL were identified in 69 out of 182 eyes [37.9%]. Both presence and extent of PPL were significantly associated with peripheral arterial disease (presence: OR=11.36, p=0.033; extent: OR=1.63, p=0.036), coronary artery disease (OR=5.86, p<0.001; OR=1.82, p=0.001), and stroke (OR=10.11, p=0.003; OR=1.99, p=0.007). The presence of PPL was also significantly associated with diabetic nephropathy (OR=2.97, p=0.016) and decreased estimated glomerular filtration rate (β = -12.66, p = 0.037). No significant associations were found between PPL and diabetic neuropathy or diabetic foot complications.

We highlight the strong link between PPL and diabetic vascular complications, suggesting their potential as an imaging biomarker of systemic vascular susceptibility. Early detection of PPL could facilitate risk stratification and proactive management of these severe complications, ultimately improving patient outcomes.

Background: Although COVID-19 vaccination has been effective in reducing severe illness and mortality, its differential clinical behavior in vaccinated and unvaccinated individuals during the early stages of the pandemic-especially in settings with partial coverage and real-world conditions-remains insufficiently characterized. Objective: To assess differences in clinical presentation, comorbidity prevalence, hospitalization, and mortality between vaccinated and unvaccinated patients diagnosed with SARS-CoV-2 during the early phase of the pandemic. Methods: An analytical cross-sectional study was conducted using 4625 electronic medical records of patients diagnosed with COVID-19 in Guerrero, Mexico, between 1 January and 31 December 2021. Variables included vaccination status, age, sex, comorbidities, symptom severity, clinical outcomes, and mortality. Statistical analyses involved chi-square tests, logistic regression for hospitalization probability, and Cox proportional hazards models for mortality risk. Results: Of the patients analyzed, 31.45% had received at least one vaccine dose. Fever, headache, cough, and anosmia were more frequent among vaccinated individuals (p < 0.001). Prostration and chest pain were strongly associated with hospitalization in both groups. In unvaccinated patients, smoking (OR = 4.75), obesity (OR = 3.85), and hypertension (OR = 2.94) increased hospitalization risk. Among vaccinated patients, diabetes mellitus (OR = 3.62) and hypertension (OR = 2.88) were key predictors. Vaccination was significantly associated with lower odds of hospitalization (OR = 0.38; 95% CI: 0.26-0.55) and reduced mortality risk (HR = 0.24; 95% CI: 0.08-0.71). Conclusions: Vaccination status was a significant protective factor for both hospitalization and mortality; however, clinical symptoms and comorbidity-related risks varied, highlighting the need for individualized patient management strategies.

Type 2 diabetes mellitus (T2DM) is an epidemic chronic disease that affects millions of people worldwide. This study aims to explore the impact of T2DM on the tear proteome, specifically investigating whether alterations occur before the development of diabetic retinopathy.

Flush tear samples were collected from healthy subjects and subjects with preDM and T2DM. Tear proteins were processed and analyzed by mass spectrometry-based shotgun proteomics using a data-independent acquisition parallel acquisition serial fragmentation (diaPASEF) approach. Machine learning algorithms, including random forest, lasso regression, and support vector machine, and statistical tools were used to identify potential biomarkers.

Machine learning models identified 17 proteins with high importance in classification. Among these, five proteins (cystatin-S, S100-A11, submaxillary gland androgen-regulated protein 3B, immunoglobulin lambda variable 3-25, and lambda constant 3) exhibited differential abundance across these three groups. No correlations were identified between proteins and clinical assessments of the ocular surface. Notably, the 17 important proteins showed superior prediction accuracy in distinguishing all three groups (healthy, preDM, and T2DM) compared to the five proteins that were statistically significant.

Alterations in the tear proteome profile were observed in adults with preDM and T2DM before the clinical diagnosis of ocular abnormality, including retinopathy.

The COVID-19 pandemic disrupted routine care for individuals with type 2 diabetes mellitus (T2DM), raising concerns about its impact on glycemic control and medication management. This study evaluated the relationship between insulin use and glycemic control among T2DM patients during the pandemic. A retrospective analysis was conducted using deidentified clinical and prescription data from two family medicine clinics, comparing data from the pre-COVID-19 period (1 March 2019-13 March 2020) and during the COVID-19 pandemic (14 March 2020-31 March 2021). Patients included had at least two A1c values before the COVID and one during the COVID. A1c control was defined as less than 8%. Among 992 patients, 238 experienced a change in A1c status: 128 improved and 110 worsened. Mean A1c remained stable at 8.2 across both periods. A majority of patients who improved were using insulin during the COVID-19 era, although some discontinued insulin at some point during the study period. These findings suggest that consistent insulin therapy may have helped maintain glycemic control despite healthcare disruptions. This study highlights the importance of sustained medication management and suggests that integrating telehealth and pharmacist-led care could support diabetes control during future healthcare system challenges.

Diabetes mellitus is a group of chronic metabolic disorders characterized by persistent hyperglycemia. Aldose reductase, the first enzyme in the polyol pathway, plays a key role in the onset of long-term diabetic complications. Aldose reductase inhibition has been widely established as a potential pharmacotherapeutic approach to prevent and treat diabetes mellitus-related comorbidities. Although several promising aldose reductase inhibitors have been developed over the past few decades, they have failed in clinical trials due to unacceptable pharmacokinetic properties and severe side effects. This paper describes the design, synthesis, and pharmacological evaluation of four novel 5-halogenated N-indolylsulfonyl-2-fluorophenol derivatives (3a-d) as aldose reductase inhibitors.

The design of compounds was based on a previously published lead compound (IIc) developed by our research group to enhance its inhibitory capacity. Compounds 3a-d were screened for their ability to inhibit in vitro partially purified aldose reductase from rat lenses, and their binding modes were investigated through molecular docking.

The presence of a sulfonyl linker between indole and o-fluorophenol aromatic rings is mandatory for potent aldose reductase inhibition. The 5-substitution of the indole core with halogens resulted in a slight decrease in the inhibitory power of 3a-c compared to IIc. Among halogens, bromine was the most capable of filling the selectivity pocket through hydrophobic interactions with Thr113 and Phe115 residues.

Although our strategy to optimize the inhibitory potency of IIc via inserting halogen atoms in the indole scaffold was not fruitful, aromatic ring halogenation can be still utilized as a promising approach for designing more potent aldose reductase inhibitors.

Cataracts remain one of the leading causes of reversible blindness in low- and middle-income countries such as Ecuador. This study assessed the efficacy of Small Incision Cataract Surgery (SICS) and analyzed sociodemographic and clinical factors associated with postoperative visual outcomes. A retrospective multicenter analysis was conducted across six ophthalmology clinics along the Ecuadorian coast between 2023 and 2024, including 558 patients aged 30 years or older. Postoperative visual acuity, measured using the LogMAR scale, improved significantly (mean improvement of 0.525 LogMAR units in the right eye (OD) and 0.489 LogMAR units in the left eye; p < 0.001). Ages between 60 and 69 years were associated with better outcomes in the right eye, while male sex was a protective factor against poor visual acuity in the left eye. Although diabetes mellitus and hypertension were prevalent, neither condition showed a significant association with postoperative visual outcomes. The findings confirm that SICS is a safe, effective, and cost-efficient surgical approach for restoring vision in resource-limited settings, supporting its inclusion in national public health strategies to reduce avoidable blindness in developing countries.

Background/Objectives: Diabetic ketoacidosis (DKA) is an acute and severe complication of diabetes mellitus, marked by hyperglycemia, ketosis, and acidosis. It is associated with significant metabolic and inflammatory adjustments that can impact multiple biochemical pathways. This study aimed to determine the serum sphingolipid profile in DKA and investigate its relationship with neutral sphingomyelinase (N-SMase), pro-inflammatory cytokines, β-hydroxybutyrate (β-OHB), and lactate levels. Methods: Thirty-three participants were divided into three groups: control (BMI ≤ 30, no health issues), obese (BMI > 30), and DKA (BMI ≤ 30). Sphingomyelins (16:0-24:0 SMs) and ceramides (C16-C24 CERs) were measured using ultra-fast liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). N-SMase, interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were assessed by enzyme-linked immunosorbent assay. Evaluations were done in the DKA group before and after standard clinical treatment for DKA (post-DKA group), which included intravenous insulin therapy, fluid resuscitation, and electrolyte replacement, as per established clinical guidelines. Results: β-OHB levels were significantly higher in the DKA group than in the control, obese, and post-DKA groups. Although β-OHB levels decreased in the post-DKA group, they remained elevated compared to the control and obese groups. Lactate levels were also higher in the DKA group, with a significant decrease in the post-DKA group. TNF-α and IL-1β were higher in the obese group compared to control and DKA groups, and TNF-α decreased significantly in the post-DKA group compared to DKA. N-SMase, 16:0-18:0 SMs, and C18-C24 CER levels were lower in the DKA and post-DKA groups compared to obese and control groups. Serum β-OHB and lactate levels were significantly correlated with S1P, total CER, total SM, and N-SMase values. Conclusions: The study reveals significant metabolic and inflammatory differences in DKA and post-DKA states, suggesting a relationship between sphingolipids, N-SMase, and these alterations, which could offer insights into DKA pathophysiology and therapeutic targets.

Protein catabolism and chronic inflammation drive sarcopenia and frailty in individuals with diabetes mellitus and chronic kidney disease (CKD). The difference between estimated glomerular filtration rates derived from cystatin C and creatinine (eGFRcys and eGFRcr, respectively), termed eGFRdiff, along with growth differentiation factor-15 (GDF-15) levels, have emerged as markers of metabolic and inflammatory dysregulation. Lower eGFRdiff and elevated GDF-15 levels are associated with sarcopenia, frailty, CKD progression and mortality. However, their interplay and respective impacts on CKD progression and mortality remain unclear.

A total of 638 Japanese individuals with diabetes mellitus were stratified into tertiles based on eGFRdiff. Serum GDF-15 levels were measured using enzyme-linked immunosorbent assays. The relationships between eGFRdiff and GDF-15 were assessed using Spearman's correlation coefficients. Multivariate ordered logistic regression was used to evaluate the association between eGFRdiff and GDF-15 tertiles, with GDF-15 as the dependent variable and eGFRdiff as the independent variable, adjusting for covariates including age, sex, urinary albumin-to-creatinine ratio (UACR) and eGFRcr or eGFRcys. Cox proportional hazards models with restricted cubic splines were used to examine associations between eGFRdiff and GDF-15 (independent variables) with CKD progression (≥ 30% decline in eGFRcr from baseline) and mortality (dependent variables). These models were adjusted for age, sex, glycated haemoglobin, UACR and eGFRcr.

The median age was 65 years (interquartile range: 58-73), and 53.9% of participants were male. Over median follow-up periods of 5.3 years for CKD progression and 5.4 years for mortality, 75 participants (11.8%) experienced CKD progression and 44 (6.9%) died. GDF-15 levels inversely correlated with eGFRdiff (r = -0.35, p < 0.001). Higher eGFRdiff values were associated with lower odds of being in a higher GDF-15 tertile (odds ratio 0.86; 95% confidence interval [CI]: 0.76-0.97; p = 0.01). Both lower eGFRdiff and higher GDF-15 levels were independently associated with adverse outcomes: CKD progression (GDF-15, hazard ratio [HR] 1.36, 95% CI: 1.02-1.81, p < 0.05; eGFRdiff, HR 0.67, 95% CI: 0.58-0.78, p < 0.0001) and mortality (GDF-15, HR 2.35, 95% CI: 1.63-3.41, p < 0.0001; eGFRdiff: 0.80, 95% CI: 0.65-0.99, p < 0.05).

Both eGFRdiff and GDF-15 were independently associated with adverse outcomes in individuals with diabetes mellitus. GDF-15 showed a stronger association with mortality, whereas eGFRdiff was more strongly linked to CKD progression. These findings underscore the potential utility of these markers in risk stratification for diabetes-related complications and may guide individualized interventions in clinical practice.