The dose-effect response of combined red and infrared photobiomodulation on insulin resistance in skeletal muscle cells.

Obesity is a major public health problem and is a major contributor to the development of insulin resistance. In previous studies we observed that single-wavelength red or infrared photobiomodulation (PBM) improved insulin signaling in adipocytes and skeletal muscle of mice fed a high-fat diet, but information about the combination of different wavelengths, as well as the effect of different light doses (J/cm2) is lacking. Therefore, the aim of this study was to investigate the effects of different doses of dual-wavelength PBM on insulin signaling in muscle cell, and explore potential mechanisms involved. Mouse myoblasts (C2C12) were differentiated into myotubes and cultured in palmitic acid, sodium oleate and l-carnitine (PAL) to induce insulin resistance high or in glucose medium (CTRL). Then, they received SHAM treatment (lights off, 0 J/cm2) or PBM (660 + 850 nm; 2, 4 or 8 J/cm2). PAL induced insulin resistance (assessed by Akt phosphorylation at ser473), attenuated maximal citrate synthase activity, and increased the phosphorylation of c-Jun NH(2) terminal kinase (JNK) (T183/Y185). PBM at doses of 4 or 8 J/cm2 reversed these PAL-induced responses. Furthermore, at doses of 2, 4 or 8 J/cm2, PBM reversed the increase in mitofusin-2 content induced by PAL. In conclusion, the combination of dual-wavelength red and infrared PBM at doses of 4 and 8 J/cm2 improved intracellular insulin signaling in musculoskeletal cells, and this effect appears to involve the modulation of mitochondrial function and the attenuation of the activation of stress kinases.

Evaluation of the Effect of a Mobile Application on Glycated Hemoglobin in Older Adults with Type 2 Diabetes Mellitus-Protocol of a Randomized Clinical Trial.

BACKGROUND: Digital educational technologies in health have been an important instrument for promoting learning, self-care, self-esteem, and security regarding prevention and health promotion actions that lead to changes in behavior, mainly for non-communicable disease patients, such as type 2 Diabetes Mellitus (DM 2). OBJECTIVE: This study aimed to describe a protocol for evaluating the effect of an app for cell phones and tablets on the blood glucose of older adults with DM 2. METHODS: The protocol will be used to compare the effectiveness of an application for mobile devices concerning the educational booklet in reducing Glycated Hemoglobin in older adults with DM 2 in Primary Health Care. This protocol is part of a Randomized Clinical Trial project entitled Effectiveness of a Mobile Device Application on Glycated Hemoglobin in Elderly People with Type 2 Diabetes Mellitus: a Randomized Clinical Trial. RESULTS: The protocol was structured in the following phases: (i) sample calculation, (ii) invitation to participate in the study according to the eligibility criteria; (iii) participant registration; (iv) randomization and allocation of participants into groups (double blinding); (v) application of the intervention; (vi) post-intervention procedures (post-test); (vii) data analysis. CONCLUSION: It is expected that encouraging studies on the impact of a mobile application will improve and enhance health education focused on self-care for older adults with DM 2, potentially influencing the local health system by reducing hospitalizations due to conditions that are sensitive to primary care, since health promotion and prevention of DM-related illnesses will be the main focus of the application and booklet developed.

Association of the rs9896052 Polymorphism Upstream of GRB2 with Proliferative Diabetic Retinopathy in Patients with Less than 10 Years of Diabetes.

Growth factor receptor-bound protein 2 (GRB2) is a negative regulator of insulin signaling and a positive regulator of angiogenesis. Its expression is increased in a mouse model of retinal neovascularization and in patients with type 2 diabetes mellitus (T2DM). This case-control study aimed to investigate the association between the rs9896052 polymorphism (A>C) upstream of GRB2 and proliferative diabetic retinopathy (PDR) in patients with T2DM from Southern Brazil, taking into consideration self-reported skin color (white or non-white) and the known duration of diabetes (<10 years or ≥10 years). Genotypes were determined by real-time PCR in 838 patients with T2DM (284 cases with PDR and 554 controls without DR). In the total study group and in the analysis stratified by skin color, the genotype and allele frequencies were similar between cases and controls. However, among patients with less than 10 years of diabetes, the C allele was more frequent in cases than in controls (63.3% versus 51.8%, p = 0.032), and the CC genotype was independently associated with an increased risk of PDR (adjusted OR = 2.82, 95% CI 1.17-6.75). In conclusion, our findings support the hypothesis that the rs9896052 polymorphism near GRB2 is associated with PDR in Brazilian patients with T2DM.

Evidence for a Pro-Inflammatory State of Macrophages from Non-Obese Type-2 Diabetic Goto-Kakizaki Rats.

Obesity causes insulin resistance (IR) through systemic low-grade inflammation and can lead to type 2 diabetes mellitus (T2DM). However, the mechanisms that cause IR and T2DM in non-obese individuals are unclear. The Goto-Kakizaki (GK) rat develops IR spontaneously and is a model of non-obese T2DM. These rats exhibit hyperglycemia beginning at weaning and exhibit lower body mass than control Wistar rats. Herein, we tested the hypothesis that macrophages of GK rats are permanently in a pro-inflammatory state, which may be associated with a systemic inflammation condition that mimics the pathogenesis of obesity-induced T2DM. Using eighteen-week-old GK and control Wistar rats, we investigated the proportions of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages isolated from the peritoneal cavity. Additionally, the production of inflammatory cytokines and reactive oxygen species (ROS) in cultured macrophages under basal and stimulated conditions was assessed. It was found that phorbol myristate acetate (PMA) stimulation increased GK rat macrophage ROS production 90-fold compared to basal levels. This response was also three times more pronounced than in control cells (36-fold). The production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), tended to be upregulated in cultured macrophages from GK rats under basal conditions. Macrophages from GK rats produced 1.6 times more granulocyte-macrophage colony-stimulating factor (GM-CSF), 1.5 times more monocyte chemoattractant protein-1 (MCP-1) and 3.3 times more TNF-α than control cells when stimulated with lipopolysaccharide (LPS) (p = 0.0033; p = 0.049; p = 0.002, respectively). Moreover, compared to control cells, GK rats had 60% more M1 (p = 0.0008) and 23% less M2 (p = 0.038) macrophages. This study is the first to report macrophage inflammatory reprogramming towards a pro-inflammatory state in GK rats.

Exploring plantar pressure distribution in patients with newly diagnosed diabetes: Implications for foot ulcer prevention in an overweight Mexican population.

INTRODUCTION: Elevated plantar pressure (PP) constitutes a risk factor for developing foot ulcers. Once present, elevated PP increases morbidity and mortality in patients with diabetes. Given the high prevalence of overweight and obesity in the Mexican population, this study aimed to describe the magnitudes and the distribution of the PP observed in a sample of newly diagnosed patients with diabetes, adjusting for body mass index (BMI) groups (normal weight, overweight, grade I obesity, and grade II and III obesity). MATERIALS AND METHODS: A total of 250 volunteers attending a comprehensive care program for the management of type 2 diabetes received foot assessments that included vascular and neurological evaluation, the identification of musculoskeletal changes, and measurements of PP. RESULTS: Diabetic neuropathy and peripheral arterial disease were present in 21.6% and 11.2% of all participants. Musculoskeletal alterations were present in 70.8% of participants. A positive and significant correlation (p<0.001) was observed between BMI and the peak PP of all anatomical regions assessed. After adjusting for BMI, significant differences (p<0.001) were seen between groups. The metatarsal region, particularly under the third metatarsal head, denoted the highest magnitudes across all BMI. CONCLUSIONS: Periodic PP assessment is recommended to identify the distribution of high-pressure points along the plantar surface. However, as a preventive measure, it is suggested to encourage patients with diabetes and overweight or obesity to wear appropriate footwear and pressure-relief insoles to relieve high-pressure areas - often seen in these populations - to help prevent foot complications.

Intestinal Motility Dysfunction in Goto-Kakizaki Rats: Role of the Myenteric Plexus.

Diabetes mellitus is associated with changes in intestinal morphology and the enteric nervous system. We previously reported constipation in Goto-Kakizaki (GK) rats, a non-obese model for type 2 diabetes mellitus. AIM: The morpho-quantitative analysis of myenteric plexus neurons in the small and large intestines of 120-day-old male GK rats was investigated. METHODS: The diabetes was confirmed by high fasting blood glucose levels. The myenteric plexus was evaluated through wholemount immunofluorescence. The morpho-quantitative analyses included evaluating neuronal density (neurons per ganglion) of the total neuronal population, the cholinergic and nitrergic subpopulations, and enteric glial cells per ganglion. The cell body area of 100 neurons per segment per animal was measured. RESULTS: The total neurons and nitrergic subpopulation were unaltered in the GK rats' small and large intestines. The cholinergic subpopulation exhibited decreased density in the three segments of the small intestine and an increased number in the proximal colon of the GK rats. The number of enteric glial cells increased in the ileum of the GK rats, which could indicate enteric gliosis caused by the intestinal inflammatory state. The area of the cell body was increased in the total neuronal population of the jejunum and ileum of the GK rats. Frequency histograms of the cell body area distribution revealed the contribution of cholinergic neurons to larger areas in the jejunum and nitrergic neurons in the ileum. CONCLUSION: The constipation previously reported in GK rats might be explained by the decrease in the density of cholinergic neurons in the small intestine of this animal model.

Low-Carbohydrate Dietary Interventions for Metabolic Control in Individuals With Type 2 Diabetes Mellitus: An Overview of Systematic Reviews.

CONTEXT: Dietary interventions providing different amounts of carbohydrates have been proposed as a means of achieving glycemic control and weight loss in type 2 diabetes mellitus (T2DM); however, the supporting evidence is heterogeneous, making this recommendation difficult to apply in nutritional clinical practice. OBJECTIVE: The aim was to assess the quality of evidence from meta-analyses on low-carbohydrate (LC) dietary interventions for glycemic control, weight loss, and lipid profile in individuals with T2DM. DATA SOURCES: The MEDLINE, Web of Science, and Scopus databases were searched until September 2023. DATA EXTRACTION: A systematic review was conducted. Systematic reviews with meta-analysis of randomized clinical trials designed to assess glycated hemoglobin (HbA1c) reductions in individuals with T2DM were eligible. The AMSTAR-2 critical appraisal tool was used to evaluate the methodological aspects of all included studies. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to assess the certainty of the evidence. DATA ANALYSIS: The LC interventions were associated with a reduction in HbA1c (%) of -0.42 (-1.45 to -0.09; high certainty of evidence) without considering follow-up time; at up to 3 months of follow-up of -0.28 (-0.13 to -0.43); at up to 6 months of follow-up of -0.40 (-0.61 to -0.09); at 6 to 12 months of follow-up of -0.32 (-0.49 to 0.11); and at >12 months of follow-up time of -0.31 (-0.14 to -0.65) compared with control diets. CONCLUSION: LC diets can help reduce HbA1c in individuals with T2DM in the short term (up to 3 months). However, dietary recommendations must always be individualized, as the studies reviewed herein analyzed different populations and used different definitions of what constitutes an LC diet. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42023404197.

Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular and Renal Outcomes in Heart Failure Patients With Type 2 Diabetes: A Literature Review.

The management of heart failure (HF) in patients with type 2 diabetes has significantly evolved with the introduction of sodium-glucose cotransporter 2 (SGLT2) inhibitors. This article aims to consolidate existing knowledge on the efficacy of these inhibitors in managing HF in this patient population. Major medical databases, including PubMed, Scopus, and Web of Science, were reviewed, prioritizing research from the last decade. The results of this review highlight the mechanisms of action of SGLT2 inhibitors, their clinical benefits, challenges in patient management, and outcomes associated with their use. These medications were found to not only improve glycemic control but also offer significant cardiovascular and renal benefits, reducing cardiovascular mortality and major adverse cardiovascular events. However, challenges and knowledge gaps persist, particularly regarding long-term effects and safety in diverse populations. The conclusions of this review underscore the importance of updating clinical guidelines to incorporate these findings and propose the need for future research to address existing gaps and optimize the use of SGLT2 inhibitors in clinical practice.

Dietary counseling, meal patterns, and diet quality in patients with type 2 diabetes mellitus with/without chronic kidney disease.

BACKGROUND: Aim to this study is to investigate the association of Dietary Counseling, Meal Patterns, and Diet Quality (DietQ) in Patients with Type 2 Diabetes Mellitus (T2DM) with/without chronic kidney disease (CKD) in primary healthcare. METHODS: Cross-sectional study acquired data on dietary counseling and meal patterns by direct interview with a food-frequency questionnaire and one 24-h food-recall. The Healthy Eating Index (HEI) was used to classify DietQ ["good" DietQ (GDietQ, score ≥ 80) and "poor" DietQ (PDietQ, score < 80)]. PARTICIPANTS/SETTING: This study included 705 patients with T2DM: 306 with normal kidney function; 236 with early nephropathy, and 163 with overt nephropathy (ON). STATISTICAL ANALYSES PERFORMED: Multivariate linear-regression models for predicting HEI and χ2 tests for qualitative variables and one-way ANOVA for quantitative variables were employed. Mann-Whitney U and independent Student t were performed for comparisons between GDietQ and PDietQ. RESULTS: Only 18 % of the population was classified as GDietQ. Patients with ON and PDietQ vs. with GDietQ received significantly less dietary counseling from any health professional in general (45 % vs 72 %, respectively), or from any nutrition professional (36 % vs. 61 %, respectively). A better HEI was significantly predicted (F = 42.01; p = 0.0001) by lower HbA1C (ß -0.53, p = 0.0007) and better diet diversity (ß 8.09, p = 0.0001). CONCLUSIONS: Patients with more advanced stages of CKD had less nutritional counseling and worse dietary patterns, as well as more frequent PDietQ. Our findings reinforce the need for dietitians and nutritionists in primary healthcare to provide timely nutritional counseling.

Testosterone levels and risk of newly diagnosed type 2 diabetes mellitus in adult men: systematic review and meta-analysis.

INTRODUCTION: Testosterone is a metabolically active hormone in males for metabolic homeostasis. Although the coexistence of low testosterone levels and type 2 diabetes mellitus (T2DM) have been associated, there are no reports that evaluate alterations in total testosterone (TT) levels and the risk of newly diagnosed T2DM. This review evaluates this question in adult men with high or low levels of total testosterone (TT), as well as the role played by other hormones such as free testosterone (FT), sex hormone binding globulin (SHBG), dihydrotestosterone (DHT), estrogens and testosterone bioavailable (bT). METHODS: We searched for studies published up to July 30, 2023, in five databases, following a PECO strategy. We found twenty-two studies for quantitative analysis and meta-analyzed the same quantity of studies. RESULTS: This first meta-analysis incorporates the assessment of the risk of low TT and T2DM in longitudinal studies. 43,038 adult men are included. Our meta-analysis shows that there is an association between low TT levels and the risk of newly diagnosed T2DM (OR 1.52; 95% CI 1.10-2.10; p < 0.05; I²: 79%). It is also evident that SHBG in low TT studies behaves as a risk factor for T2DM in the same way as FT, although without statistical significance. bT behaves as a protective factor. There is no association between estrogen, DHT and T2DM. CONCLUSIONS: In adult men with low TT values, there is a greater risk of developing a newly diagnosed of T2DM. SHBG values in low TT patients also present a higher risk of T2DM as the same FT but without statistical significance. bT behaves as a protective factor We have not found an association between risk of T2DM and the levels of estrogen, DHT although there are very few studies that report these hormones.

Association Study of CACNA1D, KCNJ11, KCNQ1, and CACNA1E Single-Nucleotide Polymorphisms with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a complex chronic disease characterized by decreased insulin secretion and the development of insulin resistance. Previous genome-wide association studies demonstrated that single-nucleotide polymorphisms (SNPs) present in genes coding for ion channels involved in insulin secretion increase the risk of developing this disease. We determined the association of 16 SNPs found in CACNA1D, KCNQ1, KCNJ11, and CACNA1E genes and the increased probability of developing T2DM. In this work, we performed a case-control study in 301 Mexican adults, including 201 cases with diabetes and 100 controls without diabetes. Our findings indicate a moderate association between T2DM and the C allele, and the C/C genotype of rs312480 within CACNA1D. The CAG haplotype surprisingly showed a protective effect, whereas the CAC and CGG haplotypes have a strong association with T2DM. The C allele and C/C genotype of rs5219 were significantly associated with diabetes. Also, an association was observed between diabetes and the A allele and the A/A genotype of rs3753737 and rs175338 in CACNA1E. The TGG and CGA haplotypes were also found to be significantly associated. The findings of this study indicate that the SNPs examined could serve as a potential diagnostic tool and contribute to the susceptibility of the Mexican population to this disease.

Associations Between Habit and Its Determinants with Medication Adherence in Chilean Patients with Type 2 Diabetes Mellitus.

High rates of medication non-adherence have been reported in Chilean patients with type 2 diabetes mellitus (T2DM). Although habit is relevant to medication adherence, few studies have examined the antecedents of habit strength in taking diabetes medication. The aim of the present study was to assess the mediating role of habit strength in the association between determinants of habit formation and medication adherence in Chilean patients with T2DM. Participants were 245 T2DM patients from Chile. Variables were measured using self-report scales. Hypotheses were tested using a series of mediation models. Results supported the mediating role of habit strength in the relationships of medication adherence with planning, exposure to contextual cues, behavior repetition, perceived benefits, and intrinsic motivation. The theoretical and practical implications of these findings for the treatment of T2DM are discussed.

Nutritional Interventions in Older Persons with Type 2 Diabetes and Frailty: A Scoping Systematic Review.

In the elderly, the coexistence of type 2 diabetes mellitus (T2DM) and frailty is frequent. Much has been described about pharmacological management and glycemic control goals. However, there is a knowledge gap in terms of the objectives and characteristics of interventions, especially nutritional ones, for this population. A scoping review was performed to document the objectives, characteristics, and results of nutritional interventions in older people with T2DM and frailty. The five-stage framework of Arksey and O'Malley was used, as was the PRISMA extension for scoping reviews. The results stand out for three trends, as follows: (1) experimental studies with multicomponent intervention physical exercise programs and nutritional programs based on educational processes or behavioral intervention; (2) observational studies with an association of the kind of diet assessed by scales and their relation to stages of frailty; (3) a review that updates recommendations on pharmacological and non-pharmacological, diet, exercise, management, as well as glucose control goals for diabetes in frail older persons. Finally, the evidence shows that management of T2DM in older adults with frailty requires goals and interventions tailored to their functional capacity and health condition. The exercise, diet, and education programs reviewed have demonstrated their effectiveness in improving physical performance, reducing the risk of frailty or progression to more advanced stages, and achieving better glycemic control.

Influence of glucagon-like peptide-1 receptor agonists on hepatic events in type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND AND AIM: Type 2 diabetes mellitus (T2DM) is intrinsically linked to various etiologies of liver disease, with 69% of patients having concomitant metabolic dysfunction-associated steatotic liver disease (MASLD). Studies suggest glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorating liver disease. With this analysis, we address the gap in knowledge about the effectiveness of these agents in preventing different major adverse liver outcomes (MALOs). METHODS: PubMed, Embase, and The Cochrane Central of Trials were searched for articles reporting MALOs in T2DM patients. Publication bias-identifying methods, quality assessment and sensitivity analyses (subgroup analyses, leave-one-out meta-analyses, and meta-regression) were employed. Statistical analyses were performed in R using the "meta" and "metafor" packages. RESULTS: Nine cohort studies from 535 identified articles encompassing 579 256 T2DM patients were included in the main analyses. GLP-1RA use was associated with reduced risks of hepatocellular carcinoma (HR 0.74, 95% CI 0.56-0.96) and cirrhosis decompensation (HR 0.68, 95% CI 0.65-0.72). Within the latter, variceal bleeding and hepatic encephalopathy prevention were found to be significantly reduced. Egger's test, Begg's test, and funnel-plot analysis yielded no publication bias. No significant differences were observed in preventing cirrhosis or hepatic failure. Meta-regression analysis revealed a positive correlation between hepatocellular carcinoma incidence and both male sex and longer follow-up duration. CONCLUSIONS: This meta-analysis improves our understanding of the hepatoprotective effects of GLP-1RAs in T2DM patients and supports existing research, exhibiting superiority over other antidiabetic medications for hepatoprotection in this subgroup. Additional long-term follow-up studies are necessary to further validate these findings.

Insulin resistance in nonobese type 2 diabetic Goto Kakizaki rats is associated with a proinflammatory T lymphocyte profile.

Goto-Kakizaki (GK) rats develop a well-defined insulin resistance (IR) and type 2 diabetes mellitus (T2DM) without presenting obesity. The lymphocyte profile in nonobese diabetic conditions is not yet characterized. Therefore, GK rats were chosen to explore T lymphocyte (TL) dynamics at various stages (21, 60, and 120 days) compared to Wistar rats. GK rats exhibit progressive disruption of glucose regulation, with early glucose intolerance at 21 days and reduced insulin sensitivity at 60 days, confirming IR. Glucose transporter 1 (GLUT1) expression was consistently elevated in GK rats, suggesting heightened TL activation. T-regulatory lymphocyte markers diminished at 21 days. However, GK rats showed increased Th1 markers and reduced Gata-3 expression (crucial for Th2 cell differentiation) at 120 days. These findings underscore an early breakdown of anti-inflammatory mechanisms in GK rats, indicating a proinflammatory TL profile that may worsen chronic inflammation in T2DM.

Periodontal disease: A silent factor in the development and progression of diabetic retinopathy.

The global increase in the prevalence of type 2 diabetes mellitus (T2DM) and its complications presents significant challenges to public health. Recently, per-iodontal disease (PD) was recognized as a factor that is likely to influence the progression of T2DM and its complications due to its potential to exacerbate systemic inflammation and oxidative stress. In this editorial, we comment on the article published by Thazhe Poyil et al in the very recent issue of the World Journal of Diabetes in 2024, which investigated the correlation between PD and diabetic retinopathy (DR) in T2DM patients, with emphasis on the association between periodontal swollen surface area, glycated hemoglobin (HbA1c), interleukin-6 (IL-6), and lipoprotein (a). The findings by Thazhe Poyil et al are significant as they demonstrate a strong link between PD and DR in T2DM patients. This correlation highlights the importance of addressing periodontal health in diabetes management to potentially reduce the risk and severity of DR, a complication of diabetes. The integration of periodontal evaluation and treatment into diabetes care protocols may lead to improved glycemic control and better overall outcomes for T2DM patients . A few studies have established an interconnection between PD and diabetic complication, specifically DR, in T2DM patients, which we aim to highlight in this editorial. Emphasis was placed on the different mechanisms that suggest a bidirectional relationship between PD and T2DM, where the presence of periodontal inflammation negatively influenced glycemic control and contributed to the development and progression of DR through shared inflammatory and vascular mechanisms. This article highlights the importance of collaboration amongst diabetes specialists, ophthalmologists, periodontists, and public health professionals to advance the prevention, early detection, and treatment of PD and DR. This will improve the health and quality of life of T2DM patients. Moreover, the editorial highlights the need for further research on the specific molecular and immunological mechanisms that underlie the link between periodontitis and DR, with identification of common inflammatory biomarkers and signaling pathways. This is expected to facilitate effective direction of therapeutic objectives, thereby improving the management of diabetes and its complications through integrated care that incorporates oral health.

Electronic Glycemic Management System Improved Glycemic Control and Reduced Complications in Patients With Diabetes Undergoing Coronary Artery Bypass Surgery: A Randomized Controlled Trial.

BACKGROUND: In-hospital hyperglycemia poses significant risks for patients with diabetes mellitus undergoing coronary artery bypass graft (CABG) surgery. Electronic glycemic management systems (eGMSs) like InsulinAPP offer promise in standardizing and improving glycemic control (GC) in these settings. This study evaluated the efficacy of the InsulinAPP protocol in optimizing GC and reducing adverse outcomes post-CABG. METHODS: This prospective, randomized, open-label study was conducted with 100 adult type 2 diabetes mellitus (T2DM) patients post-CABG surgery, who were randomized into two groups: conventional care (gCONV) and eGMS protocol (gAPP). The gAPP used InsulinAPP for insulin therapy management, whereas the gCONV received standard clinical care. The primary outcome was a composite of hospital-acquired infections, renal function deterioration, and symptomatic atrial arrhythmia. Secondary outcomes included GC, hypoglycemia incidence, hospital stay length, and costs. RESULTS: The gAPP achieved lower mean glucose levels (167.2 ± 42.5 mg/dL vs 188.7 ± 54.4 mg/dL; P = .040) and fewer patients-day with BG above 180 mg/dL (51.3% vs 74.8%, P = .011). The gAPP received an insulin regimen that included more prandial bolus and correction insulin (either bolus-correction or basal-bolus regimens) than the gCONV (90.3% vs 16.7%). The primary composite outcome occurred in 16% of gAPP patients compared with 58% in gCONV (P < .010). Hypoglycemia incidence was lower in the gAPP (4% vs 16%, P = .046). The gAPP protocol also resulted in shorter hospital stays and reduced costs. CONCLUSIONS: The InsulinAPP protocol effectively optimizes GC and reduces adverse outcomes in T2DM patients' post-CABG surgery, offering a cost-effective solution for inpatient diabetes management.

Metabolic features of neutrophilic differentiation of HL-60 cells in hyperglycemic environments.

INTRODUCTION: Chronic hyperglycemia affects neutrophil functions, leading to reduced pathogen killing and increased morbidity. This impairment has been directly linked to increased glycemia, however, how this specifically affects neutrophils metabolism and their differentiation in the bone marrow is unclear and difficult to study. RESEARCH DESIGN AND METHODS: We used high-resolution respirometry to investigate the metabolism of resting and activated donor neutrophils, and flow cytometry to measure surface CD15 and CD11b expression. We then used HL-60 cells differentiated towards neutrophil-like cells in standard media and investigated the effect of doubling glucose concentration on differentiation metabolism. We measured the oxygen consumption rate (OCR), and the enzymatic activity of carnitine palmitoyl transferase 1 (CPT1) and citrate synthase during neutrophil-like differentiation. We compared the surface phenotype, functions, and OCR of neutrophil-like cells differentiated under both glucose concentrations. RESULTS: Donor neutrophils showed significant instability of CD11b and OCR after phorbol 12-myristate 13-acetate stimulation at 3 hours post-enrichment. During HL-60 neutrophil-like cell differentiation, there was a significant increase in surface CD15 and CD11b expression together with the loss of mitochondrial mass. Differentiated neutrophil-like cells also exhibited higher CD11b expression and were significantly more phagocytic. In higher glucose media, we measured a decrease in citrate synthase and CPT1 activities during neutrophil-like differentiation. CONCLUSIONS: HL-60 neutrophil-like differentiation recapitulated known molecular and metabolic features of human neutrophil differentiation. Increased glucose concentrations correlated with features described in hyperglycemic donor neutrophils including increased CD11b and phagocytosis. We used this model to describe metabolic features of neutrophil-like cell differentiation in hyperglycemia and show for the first time the downregulation of CPT1 and citrate synthase activity, independently of mitochondrial mass.

The unexpected silent manifestation of myocardial infarctions in ischemic heart failure patients: Insights from a case-control study.

BACKGROUND: Recent studies show Silent Myocardial Infarction (SMI) as a quite frequent event. However, regarding severe tertiary care patients that frequently present consequences of Coronary Artery Disease (CAD) and Left Ventricular Dysfunction (LVD), the occurrence of this manifestation is unexpected and its associated factors aren't clear in the literature. AIM: To compare clinical, laboratorial, ventricular and angiographic factors between silent and classical presentation of MI in patients with CAD and LVD. METHODS: Patients with multivessel CAD with over 70 % obstructive lesions and LVD with EF less than 35 % were evaluated for MASS VI trial and later included in the present study. The ventricular function and coronary assessment were measured by echocardiography and SYNTAX score, respectively. The population was stratified in a SMI group and Clinically Manifested Myocardial Infarction (CMMI) group based on MI presentation for a comparison of medical parameters. RESULTS: From 132 patients, 47 (35.6 %) were classified as SMI and 85 (64.4 %) as CMMI. No differences were observed between groups regarding age, sex, diabetes mellitus, SYNTAX score, or collateral circulation. Higher proportion of NYHA II classification, inferior wall MI and lower creatinine clearance were found in SMI group. After multivariate analysis, peripheral diabetic neuropathy (OR = 4.6 [1.1‒12.7] p = 0.032) and inferior wall MI (OR = 4.1 [1.5‒11.4] p = 0.007) were significantly associated with SMI. CONCLUSION: Peripheral diabetic neuropathy and inferior wall MI were associated with SMI presentation. Overall, associated factors tend to be similar comparing SMI and CMMI, but in the specific population of diabetic patients with chronic neuropathy a special care should be taken.

Antidiabetic drugs in Parkinson's disease.

This review explores the intricate connections between type 2 diabetes (T2D) and Parkinson's disease (PD), both prevalent chronic conditions that primarily affect the aging population. These diseases share common early biochemical pathways that contribute to tissue damage. This manuscript also systematically compiles potential shared cellular mechanisms between T2D and PD and discusses the literature on the utilization of antidiabetic drugs as potential therapeutic options for PD. This review encompasses studies investigating the experimental and clinical efficacy of antidiabetic drugs in the treatment of Parkinson's disease, along with the proposed mechanisms of action. The exploration of the benefits of antidiabetic drugs in PD presents a promising avenue for the treatment of this neurodegenerative disorder.