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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.
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Diferenciação Celular , Hiperglicemia , Neutrófilos , Humanos , Neutrófilos/metabolismo , Células HL-60 , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Antígeno CD11b/metabolismo , Glucose/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Consumo de Oxigênio , Antígenos CD15/metabolismo , Citrato (si)-Sintase/metabolismoRESUMO
(1) Background: Branched-chain and aromatic amino acids (BCAAs/AAAs) have been considered as markers of type 2 diabetes (T2D); however, studies on associations between these metabolites and T2D and cardiometabolic traits in Hispanic populations are limited. The aim of this study was to examine the associations between baseline BCAAs (isoleucine, leucine, valine)/AAAs (phenylalanine, tyrosine) and prevalent and incident T2D, as well as baseline and longitudinal (2 year) changes in cardiometabolic traits (measures of glycemia, dyslipidemia, inflammation, and obesity) in two large cohorts of adults of Puerto Rican descent. (2) Methods: We included participants of the Boston Puerto Rican Health Study (BPRHS, n = 670) and San Juan Overweight Adult Longitudinal study (SOALS, n = 999) with available baseline metabolite and covariate data. T2D diagnosis was defined based on American Diabetes Association criteria. Multivariable logistic (for baseline T2D), Poisson (for incident T2D), and linear (for cardiometabolic traits) regression models were used; cohort-specific results were combined in the meta-analysis and adjusted for multiple comparisons. (3) Results: Higher baseline BCAAs were associated with higher odds of prevalent T2D (OR1SD BCAA score = 1.46, 95% CI: 1.34-1.59, p < 0.0001) and higher risk of incident T2D (IRR1SD BCAA score = 1.24, 95% CI: 1.13-1.37, p < 0.0001). In multivariable longitudinal analysis, higher leucine and valine concentrations were associated with 2-year increase in insulin (beta 1SD leucine = 0.37 mcU/mL, 95% CI: 0.11-0.63, p < 0.05; beta 1SD valine = 0.43 mcU/mL, 95% CI: 0.17-0.68, p < 0.01). Tyrosine was a significant predictor of incident T2D (IRR = 1.31, 95% CI: 1.09-1.58, p < 0.05), as well as 2 year increases in HOMA-IR (beta 1SD tyrosine = 0.13, 95% CI: 0.04-0.22, p < 0.05) and insulin concentrations (beta 1SD tyrosine = 0.37 mcU/mL, 95% CI: 0.12-0.61, p < 0.05). (4) Conclusions: Our results confirmed the associations between BCAAs and prevalent and incident T2D, as well as concurrent measures of glycemia, dyslipidemia, and obesity, previously reported in predominantly White and Asian populations. Baseline leucine, valine, and tyrosine were predictors of 2 year increases in insulin, whereas tyrosine was a significant predictor of deteriorating insulin resistance over time. Our study suggests that BCAAs and tyrosine could serve as early markers of future glycemic changes in Puerto Ricans.
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Aminoácidos Aromáticos , Aminoácidos de Cadeia Ramificada , Fatores de Risco Cardiometabólico , Diabetes Mellitus Tipo 2 , Hispânico ou Latino , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Aminoácidos de Cadeia Ramificada/sangue , Aminoácidos Aromáticos/sangue , Adulto , Hispânico ou Latino/estatística & dados numéricos , Estudos Longitudinais , Porto Rico/epidemiologia , Porto Rico/etnologia , Idoso , Prevalência , Boston/epidemiologia , Incidência , Obesidade/epidemiologia , Obesidade/etnologiaRESUMO
This study aimed to perform exhaustive bioinformatic analysis by using GSE29221 micro-array maps obtained from healthy controls and Type 2 Diabetes (T2DM) patients. Raw data are downloaded from the Gene Expression Omnibus database and processed by the limma package in R software to identify Differentially Expressed Genes (DEGs). Gene ontology functional analysis and Kyoto Gene Encyclopedia and Genome Pathway analysis are performed to determine the biological functions and pathways of DEGs. A protein interaction network is constructed using the STRING database and Cytoscape software to identify key genes. Finally, immune infiltration analysis is performed using the Cibersort method. This study has implications for understanding the underlying molecular mechanism of T2DM and provides potential targets for further research.
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Biologia Computacional , Diabetes Mellitus Tipo 2 , Perfilação da Expressão Gênica , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/imunologia , Mapas de Interação de Proteínas/genética , Redes Reguladoras de Genes/genética , Ontologia Genética , Bases de Dados Genéticas , Estudos de Casos e ControlesRESUMO
BACKGROUND: To assess the efficiency of periodontal treatment (PT) in improving diabetes-related outcomes in adults with type 2 diabetes mellitus (T2DM) and periodontitis, providing an updated and comprehensive synthesis from economic evaluations (EE). METHODS: Seven databases and one register were independently searched by two reviewers for articles published up to 8 May 2024. Studies that assessed the efficiency of PT versus no treatment or other dental treatments were included. Risk of bias was assessed using the Cochrane RoB 2, ROBINS-I and ECOBIAS tools for the first stage of EE and the CHEERS checklist and NICE quality appraisal tool for overall EE. Qualitative and quantitative syntheses of the articles were conducted and assessed using the GRADE approach. RESULTS: Eleven studies were included. PT reduces total healthcare costs, including inpatient and outpatient, diabetes-related costs and other drug costs (low to moderate certainty). A total incremental net benefit of USD 12 348 (2022 currency, 95% CI 12 195-12 500) was estimated from three high-quality model-based cost-utility analyses (high certainty). DISCUSSION: The inclusion of PT in the comprehensive treatment of patients with T2DM and periodontitis is cost-effective. Future research is required to ensure the transferability of these findings and inform decision makers from different countries. REGISTRATION: PROSPERO CRD42023443146.
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AIMS: To evaluate insulin secretion and insulin resistance profiles in individuals with family history of prediabetes and type 2 diabetes. METHODS: This was a cross-sectional study to evaluate clinical and metabolic profiles between individuals with type 2 diabetes, prediabetes and their relatives. There were 911 subjects divided into five groups: (i) normoglycemic (NG), (ii) type 2 diabetes, (iii) prediabetes, (iv) first-degree relatives of patients with type 2 diabetes (famT2D), and (v) first-degree relatives of patients with prediabetes (famPD); anthropometrical, biochemical and nutritional evaluation, as well as insulin resistance and pancreatic beta cell function measurement was performed by oral glucose tolerance to compare between groups. RESULTS: The most prevalent type 2 diabetes risk factors were dyslipidemia (81%), family history of type 2 diabetes (76%), central obesity (73%), male sex (63%), and sedentary lifestyle (60%), and most of them were progressively associated to prediabetes and type 2 diabetes groups. Insulin sensitivity was lower in famT2D groups in comparison to NG group (p < 0.0001). FamPD and famT2D had a 10% lower pancreatic beta cell function (DI) than the NG group (NG group 2.78 ± 1.0, famPD 2.5 ± 0.85, famT2D 2.4 ± 0.75, pË0.001). CONCLUSIONS: FamPD and famT2D patients had lower pancreatic beta cell function than NG patients, highlighting that defects in insulin secretion and insulin sensitivity appear long time before the development of hyperglycemia in patients genetically predisposed.
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Introduction: Globally, up to 76.6% of the population may be affected by vitamin D (VD) deficiency, which has been linked to increased morbidity and mortality from COVID-19. This underscores the importance of further research into VD supplementation, particularly for health care workers, who are at higher risk due to indoor work environments and dietary challenges associated with shift schedules. Objective: This study aimed to identify factors associated with VD deficiency in Mexican health care workers exposed to SARS-CoV-2. Materials and methods: We conducted a cross-sectional study from June 2020 to January 2021 among frontline health care workers treating hospitalized COVID-19 patients. Blood samples were collected to measure 25-hydroxy VD levels via radioimmunoassay. We also assessed previous COVID-19 infection and comorbidities that could influence VD levels. Results: The study included 468 health care workers. The median serum VD concentration was 16.6 ng/mL. VD deficiency was found in 69.4% (n = 325) of participants, while only 5.1% (n = 24) had normal levels. Those with type 2 diabetes (13.3 ng/mL vs. 17.1 ng/mL) or obesity (15.7 ng/mL vs. 17.1 ng/mL) had significantly lower VD levels than their counterparts (p < 0.001 and p = 0.049, respectively). No significant differences were found among participants with high blood pressure. Multivariate analysis revealed that type 2 diabetes was independently associated with VD deficiency. Conclusion: There is a high prevalence of VD deficiency among health care workers, which is potentially linked to both personal health factors and occupational conditions.
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BACKGROUND: Type 2 diabetes has economic implications involving family income and out-of-pocket spending. OBJECTIVE: Determine family out-of-pocket expenditure for type 2 diabetes mellitus care and percentage of family income. MATERIAL AND METHODS: Study of family out-of-pocket spending in families with patients with type 2 diabetes treated at primary care level. Out-of-pocket expenses included expenses for transportation, food-drinks, and external medications. Family income corresponded to the total economic income contributed by family members. The percentage of out-of-pocket spending in relation to family income was identified with the relationship between these two variables. Statistical analysis included averages and percentages. RESULTS: The annual family out-of-pocket expenditure on transportation was $2,621.24, the family out-of-pocket expenditure on food and beverages was $1,075.67, and the family out-of-pocket expenditure on external medications was $722.08. The total annual family out-of-pocket expense was $4,418.89 and corresponds to 4.73% of family income. CONCLUSION: The family out-of-pocket expense in the family with a patient with diabetes mellitus 2 was $4,418.89 and represents 4.73% of the family income.
ANTECEDENTES: La diabetes tipo 2 tiene implicaciones económicas en el ingreso familiar y el gasto de bolsillo. OBJETIVO: Determinar el gasto de bolsillo familiar en la atención de la diabetes mellitus tipo 2 y el porcentaje que representa en el ingreso familiar. MATERIAL Y MÉTODOS: Estudio de gasto de bolsillo de las familias con pacientes con diabetes tipo 2 atendidos en el primer nivel de atención. El gasto de bolsillo familiar incluyó gasto en traslado, alimentos-bebidas y medicamentos externos. El ingreso familiar correspondió al total de ingresos económicos aportados por los miembros de la familia. El porcentaje del gasto de bolsillo con relación al ingreso familiar se identificó con la relación entre estas dos variables. El análisis estadístico incluyó promedios y porcentajes. RESULTADOS: El gasto de bolsillo familiar anual en transporte fue de $2621.24, en alimentos y bebidas fue de $1075.67 y en medicamentos externos fue de $722.08. El gasto familiar de bolsillo total anual fue de $4418.89 y correspondió a 4.73 % del ingreso familiar. CONCLUSIÓN: El gasto de bolsillo en las familias con un paciente con diabetes mellitus tipo 2 fue de $4418.89 y representó 4.73 % del ingreso familiar.
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Diabetes Mellitus Tipo 2 , Gastos em Saúde , Renda , Humanos , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/terapia , Gastos em Saúde/estatística & dados numéricos , Masculino , Feminino , Atenção Primária à Saúde/economia , Pessoa de Meia-Idade , Família , Efeitos Psicossociais da DoençaRESUMO
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.
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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.
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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.