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Background: Chronic kidney disease (CKD) and gout are risk factors for renal cancer. We analysed the effects of comorbid diabetic kidney disease and gout on renal cancer. Methods: This retrospective cohort study enrolled 847 884 patients with type 2 diabetes mellitus (T2DM) who underwent health assessments provided by the Korean National Health Insurance Service in 2009. Based on CKD occurrence (glomerular filtration rate <60 ml/min/1.73 m2) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD-Gout- (87.5%), CKD-Gout+ (2.5%), CKD+Gout- (9.3%) and CKD+Gout+ (0.7%). Patients with incident renal cancer (International Classification of Diseases code C64) were followed up until December 2018. Results: Renal cancer was diagnosed in 2376 patients (0.3%). Renal cancer incidence increased in sequential order of CKD-Gout- [0.29/1000 person-years (PY), CKD+Gout- and CKD-Gout+ (0.44 and 0.48/1000 PY, respectively) and CKD+Gout+ (1.14/1000 PY). Comorbid gout increased renal cancer risk depending on CKD occurrence {hazard ratio [HR] 1.28 [95% confidence interval (CI) 1.04-1.58 among those without CKD; HR 1.95 [95% CI 1.45-2.63] among those with CKD; P-value for interaction = 0.024}. The interaction was significant, particularly in men and patients with a shorter diabetes duration (<5 years) and lesser medication use (no insulin or fewer than three classes of oral hypoglycaemic agents). Conclusions: CKD and gout individually contributed to renal cancer incidence, and the risk is further increased when gout coexists with CKD. Screening for gout and appropriate management of CKD at an early T2DM stage may be beneficial.
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OBJECTIVES: We assessed the feasibility of ChatGPT for patients with type 2 diabetes seeking information about exercise. METHODS: In this pilot study, two physicians with expertise in diabetes care and rehabilitative treatment in Republic of Korea discussed and determined the 14 most asked questions on exercise for managing type 2 diabetes by patients in clinical practice. Each question was inputted into ChatGPT (V.4.0), and the answers from ChatGPT were assessed. The Likert scale was calculated for each category of validity (1-4), safety (1-4) and utility (1-4) based on position statements of the American Diabetes Association and American College of Sports Medicine. RESULTS: Regarding validity, 4 of 14 ChatGPT (28.6%) responses were scored as 3, indicating accurate but incomplete information. The other 10 responses (71.4%) were scored as 4, indicating complete accuracy with complete information. Safety and utility scored 4 (no danger and completely useful) for all 14 ChatGPT responses. CONCLUSION: ChatGPT can be used as supplementary educational material for diabetic exercise. However, users should be aware that ChatGPT may provide incomplete answers to some questions on exercise for type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Projetos Piloto , República da Coreia , Masculino , Feminino , Exercício Físico , Educação de Pacientes como Assunto , Pessoa de Meia-Idade , Inquéritos e Questionários , Terapia por Exercício , Estudos de ViabilidadeRESUMO
AIM: To explore the effect of mixed exposure to per- and polyfluoroalkyl substances (PFAS) on metabolic syndrome (MetS). METHODS: This cross-sectional study used data from the Korean National Environmental Health Survey Cycle 4 (2018-2020). The serum concentrations of five PFAS (perfluorooctanoic acid [PFOA], perfluorooctanesulfonic acid [PFOS], perfluorohexanesulfonic acid, perfluorononanoic acid [PFNA], and perfluorodecanoic acid [PFDeA]) were measured, and the relative potency factor approach was employed for the mixture of PFAS (Cmix) assessment. MetS was diagnosed if the patient satisfied three of five criteria: central obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure (BP), and elevated glycated hemoglobin (HbA1c). Age, sex, smoking, drinking, and exercise status were considered as covariates. The risk of MetS for single and mixed exposure to PFAS was analyzed using binomial regression and Bayesian kernel machine regression (BKMR). RESULTS: A total of 2984 (male:female = 1:1.3; age range, 19-80 years) adults were enrolled. The prevalence of MetS was 45.6%. Each PFAS and Cmix levels were higher in participants with MetS than in those without MetS. Cmix increased the risk of elevated BP and HbA1c, and eventually MetS (odds ratio [OR] = 2.00, 95% confidence interval [CI] 1.11-3.60 per log10Cmix; OR = 1.57, 95% CI 1.07-2.31 in the highest quartile of Cmix [Q4] vs. the lowest [Q1]). Sex-specific analyses revealed that the impact of Cmix was valid in females but not in males (Cmix Q4 vs. Q1: OR = 1.01, 95% CI 0.57-1.8 in males; OR = 2.30, 95% CI 1.38-3.84 in females). In the BKMR analysis, mixed exposure to PFAS dose-dependently increased the risk of MetS, particularly in females. Among single exposures, PFNA contributed significantly to the cumulative effect. CONCLUSION: Mixed exposure to PFAS was associated with a higher risk of MetS in females. Further studies on potential health concerns associated with PFAS mixtures are warranted.
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Ácidos Alcanossulfônicos , Exposição Ambiental , Poluentes Ambientais , Fluorocarbonos , Síndrome Metabólica , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/induzido quimicamente , Fluorocarbonos/sangue , República da Coreia/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Poluentes Ambientais/sangue , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Ácidos Alcanossulfônicos/sangue , Inquéritos Epidemiológicos , Idoso , Estudos Transversais , Caprilatos/sangue , Adulto JovemRESUMO
Background/Objectives: Diabetic foot ulcers are one of the complications in patients with diabetes, which can be caused by infection, neuropathy, and blood vessel disorder. Among them, infection is the most common cause, and if it becomes worse, amputation may be necessary. So, it is important to detect and treat infections early, and determining indicators that can confirm infection is also important. Known infection markers include white blood cells (WBCs), the erythrocyte sediment rate (ESR), C-reactive protein (CRP), and procalcitonin, but they are not specific to diabetic foot ulcers. Presepsin, also known as soluble CD14, is known to be an early indicator of sepsis. Recent studies have reported that presepsin can be used as an early indicator of infection. This study investigated whether presepsin could be used as an early marker of severe infection in patients with diabetic foot ulcers. Methods: We retrospectively studied 73 patients who were treated for diabetic foot ulcerations from January 2021 to June 2023 at Yeungnam University Hospital. Results: Out of a total of 73 patients, 46 patients underwent amputations with severe infections, and the WBC level, ESR, and CRP, procalcitonin, and presepsin levels were significantly higher in the group of patients who underwent amputations. The cutoff of presepsin, which can predict serious infections that need amputation, was 675 ng/mL. A regression analysis confirmed that presepsin, HbA1c, and osteomyelitis significantly increased the risk of severe infections requiring amputation. Conclusions: Presepsin will be available as an early predictor of patients with severe infections requiring amputations for diabetic foot ulcerations.
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Molybdenum disulfide (MoS2), a semiconducting two-dimensional layered transition metal dichalcogenide (2D TMDC), with attractive properties enables the opening of a new electronics era beyond Si. However, the notoriously high contact resistance (RC) regardless of the electrode metal has been a major challenge in the practical applications of MoS2-based electronics. Moreover, it is difficult to lower RC because the conventional doping technique is unsuitable for MoS2 due to its ultrathin nature. Therefore, the metal-insulator-semiconductor (MIS) architecture has been proposed as a method to fabricate a reliable and stable contact with low RC. Herein, we introduce a strategy to fabricate MIS contact based on atomic layer deposition (ALD) to dramatically reduce the RC of single-layer MoS2 field effect transistors (FETs). We utilize ALD Al2O3 as an interlayer for the MIS contact of bottom-gated MoS2 FETs. Based on the Langmuir isotherm, the uniformity of ALD Al2O3 films on MoS2 can be increased by modulating the precursor injection pressures even at low temperatures of 150 °C. We discovered, for the first time, that film uniformity critically affects RC without altering the film thickness. Additionally, we can add functionality to the uniform interlayer by adopting isopropyl alcohol (IPA) as an oxidant. Tunneling resistance across the MIS contact is lowered by n-type doping of MoS2 induced by IPA as the oxidant in the ALD process. Through a highly uniform interlayer combined with strong doping, the contact resistance is improved by more than two orders of magnitude compared to that of other MoS2 FETs fabricated in this study.
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Two-dimensional transition metal dichalcogenides (2D TMDCs) are considered promising alternatives to Si as channel materials because of the possibility of retaining their superior electronic transport properties even at atomic body thicknesses. However, the realization of high-performance 2D TMDC field-effect transistors remains a challenge owing to Fermi-level pinning (FLP) caused by gap states and the inherent high Schottky barrier height (SBH) within the metal contact and channel layer. This study demonstrates that high-quality van der Waals (vdW) heterojunction-based contacts can be formed by depositing semimetallic TiS2 onto monolayer (ML) MoS2. After confirming the successful formation of a TiS2/ML MoS2 heterojunction, the contact properties of vdW semimetal TiS2 were thoroughly investigated. With clean interfaces of the TiS2/ML MoS2 heterojunctions, atomic-layer-deposited TiS2 can induce gap-state saturation and suppress FLP. Consequently, compared with conventional evaporated metal electrodes, the TiS2/ML MoS2 heterojunctions exhibit a lower SBH of 8.54 meV and better contact properties. This, in turn, substantially improves the overall performance of the device, including its on-current, subthreshold swing, and threshold voltage. Furthermore, we believe that our proposed strategy for vdW-based contact formation will contribute to the development of 2D materials used in next-generation electronics.
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Progression of ß-cell loss in diabetes mellitus is significantly influenced by persistent hyperglycemia. At the cellular level, a number of signaling cascades affect the expression of apoptotic genes, ultimately resulting in ß-cell failure; these cascades have not been elucidated. Mitochondrial aldehyde dehydrogenase-2 (ALDH2) plays a central role in the detoxification of reactive aldehydes generated from endogenous and exogenous sources and protects against mitochondrial deterioration in cells. Here we report that under diabetogenic conditions, ALDH2 is strongly inactivated in ß-cells through CDK5-dependent glutathione antioxidant imbalance by glucose-6-phosphate dehydrogenase (G6PD) degradation. Intriguingly, CDK5 inhibition strengthens mitochondrial antioxidant defense through ALDH2 activation. Mitochondrial ALDH2 activation selectively preserves ß-cells against high-glucose-induced dysfunction by activating AMPK and Hydrogen Sulfide (H2S) signaling. This is associated with the stabilization and enhancement of the activity of G6PD by SIRT2, a cytoplasmic NAD+-dependent deacetylase, and is thereby linked to an elevation in the GSH/GSSG ratio, which leads to the inhibition of mitochondrial dysfunction under high-glucose conditions. Furthermore, treatment with NaHS, an H2S donor, selectively preserves ß-cell function by promoting ALDH2 activity, leading to the inhibition of lipid peroxidation by high-glucose concentrations. Collectively, our results provide the first direct evidence that ALDH2 activation enhances H2S-AMPK-G6PD signaling, leading to improved ß-cell function and survival under high-glucose conditions via the glutathione redox balance.
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Sulfeto de Hidrogênio , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo , Sulfeto de Hidrogênio/farmacologia , Antioxidantes/farmacologia , Aldeído Desidrogenase/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Glutationa/metabolismo , Glucose/metabolismoRESUMO
INTRODUCTION: This meta-analysis aimed to analyze the effect of cadmium (Cd) exposure on thyroid hormone disruption. CONTENT: Databases including PubMed, Embase, Cochrane Library, and Scopus were searched for studies published up to December 14, 2022. Studies evaluating the association between Cd exposure (blood Cd [BCd] or urine Cd [UCd]) and thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [FT4], total triiodothyronine [TT3]) or thyroid autoimmunity (thyroglobulin antibody [TgAb] or thyroperoxidase Ab [TPOAb]) were included. SUMMARY AND OUTLOOK: This systematic review included 12 cross-sectional studies. Cd exposure showed a neutral association with TSH (pooled correlation=0.016, 95â¯% confidence interval [CI]=-0.013 to 0.045, p=0.277), FT4 (pooled correlation=0.028, 95â¯% CI=-0.005 to 0.061, p=0.098), and thyroid autoimmunity (pooled odds ratio=1.143, 95â¯% CI=0.820-1.591, p=0.430). However, Cd exposure showed a positive association with TT3 (pooled correlation=0.065, 95â¯% CI=0.050-0.080, p<0.001), which was consistent with the BCd and UCd subgroup analyses (pooled correlation=0.053 and 0.081, respectively, both p<0.001). Cd exposure was not associated with TSH, FT4, or thyroid autoimmunity but tended to increase with TT3.
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This study aimed to evaluate factors that predict lymph node metastasis (LNM) in papillary thyroid cancer (PTC). This retrospective cross-sectional study compared the demographic, clinical, and ultrasonographic findings of patients with PTC with and without LNM. Subgroup analysis was conducted for micro-PTCs (<1 cm). Among total (n = 512; mean age, 47.3 ± 12.7 years) and micro-PTC patients (n = 312), 35.7% and 19.6% had LNM, respectively. Younger age, male sex, tumor size, bilaterality, and suspicious ultrasound features of the tumor were associated with LNM. In multiple logistic regression analysis, among all patients, age, tumor size, and extrathyroidal extension were independent risk factors for LNM (all p<0.05). In the micro-PTC subgroup, age, extrathyroidal extension, bilaterality of tumor, and presence of autoimmune thyroid disease were independent risk and protective factors for LNM (all p<0.05). In the receiver operating characteristic analysis, the accuracy of the multivariable logistic regression model for predicting LNM among all patients and micro-PTC was acceptable (area under the curve = 0.729 and 0.733, respectively). Age, sex, tumor size, and extrathyroidal extension can assist in predicting LNM in PTC patients. Additionally, the bilaterality of tumors and presence of autoimmune thyroid disease can assist in predicting LNM in micro-PTCs.
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Carcinoma Papilar , Doença de Hashimoto , Neoplasias da Glândula Tireoide , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Metástase Linfática/patologia , Estudos Retrospectivos , Estudos Transversais , Carcinoma Papilar/patologia , Linfonodos/patologia , Fatores de Risco , Doença de Hashimoto/patologiaRESUMO
INTRODUCTION: Evidence of the adverse metabolic health effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) is increasing. However, the impact of PFAS on cardiovascular diseases remains controversial. This meta-analysis aimed to analyze the impact of PFAS on the stroke risk. CONTENT: Databases were searched for studies published up to November 1, 2022, which report the association between stroke and exposure to at least one of four main PFAS (perfluorooctanoic acid [PFOA], perfluorooctanesulfonic acid [PFOS], perfluorononanoic acid [PFNA], and perfluorohexane sulfonic acid [PFHxS]). Data extraction and quality assessment were performed according to the Newcastle-Ottawa scale. SUMMARY AND OUTLOOK: Four studies were included in this systematic review. Multivariate adjusted odds ratios (ORs) for incident stroke per 1-log unit increment in each serum PFAS were combined in the meta-analysis. The risk of development of stroke was not significantly associated with PFOA, PFOS, or PFNA exposure (PFOA: pooled odds ratio [OR]=1.001, 95â¯% confidence interval [CI]=0.975-1.028, p=0.934; PFOS: pooled OR=0.994, 95â¯% CI=0.972-1.017, p=0.601; PFNA: pooled OR=1.016, 95â¯% CI=0.920-1.123, p=0.752), whereas a moderately lower risk was associated with PFHxS exposure without statistical significance (pooled OR=0.953, 95â¯% CI=0.908-1.001, p=0.054). PFOA, PFOS, and PFNA exposure showed a neutral association, while PFHxS showed a possible inverse association with the risk of stroke. Therefore, this finding should be interpreted with caution. Further prospective observational studies with PFAS mixture analyses are warranted.
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This propensity score-matched cohort study investigated the effects of blood cadmium (Cd) levels on body composition. Body composition was assessed by multifrequency bioelectrical impedance analysis and categorized into three groups: metabolically healthy obesity (MHO), adiposity obesity (AO), and sarcopenic obesity (SO). At baseline, 85 and 101 participants had MHO and AO, respectively (mean age, 51 ± 7 years; male-to-female ratio, 1.0:1.3). During the 14-year follow-up, the body composition of 40 MHO and 6 AO participants deteriorated to AO and SO, respectively. The incidence of AO and SO differed according to age, sex, and blood Cd level. High blood Cd level increased the risk of body composition deterioration, particularly among those aged 60-69 years (hazard ratio [HR] = 2.14), women (HR = 1.46), and those with AO at baseline (HR = 1.63; all p < 0.05). Cd exposure deteriorates body composition in older and female individuals, particularly from AO to SO.
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Cádmio , Sarcopenia , Humanos , Masculino , Feminino , Idoso , Adulto , Pessoa de Meia-Idade , Estudos de Coortes , Pontuação de Propensão , Obesidade/epidemiologia , Obesidade/complicações , Sarcopenia/epidemiologia , Sarcopenia/etiologia , Composição Corporal , Índice de Massa Corporal , Fatores de RiscoRESUMO
We assessed the risk factors for major amputation of diabetic foot ulcers (DFUs) in patients with diabetic kidney disease (DKD) stages 3b-5. For DFU assessment, in addition to DFU location and presence of infection, ischemia, and neuropathy, vascular calcification was assessed using the medial arterial calcification (MAC) score. Of 210 patients, 26 (12.4%) underwent major amputations. Only the location and extension of DFU, represented by Texas grade differed between the minor and major amputation groups. However, after adjusting for covariates, ulcer location of mid- or hindfoot (vs. forefoot, odds ratio [OR] = 3.27), Texas grades 2 or 3 (vs. grade 0, OR = 5.78), and severe MAC (vs. no MAC, OR = 4.46) was an independent risk factor for major amputation (all P < 0.05). The current use of antiplatelets was a possible protective factor for major amputations (OR = 0.37, P = 0.055). In conclusion, DFU with severe MAC is associated with major amputation in patients with DKD.
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Diabetes Mellitus , Pé Diabético , Nefropatias Diabéticas , Humanos , Pé Diabético/complicações , Pé Diabético/cirurgia , Nefropatias Diabéticas/complicações , Fatores de Risco , Amputação Cirúrgica , Estudos RetrospectivosRESUMO
AIM: To investigate the effects of gemigliptin on cardiac function and compare the effects of gemigliptin and glimepiride in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: Sixty T2D patients being treated with metformin were assigned to a gemigliptin group (50 mg daily) or a glimepiride group (2 mg daily) for 24 weeks. The preadjudicated extension period was up to 52 weeks. Glucose metabolism variables and cardiac biomarkers were measured. Echocardiography was used to evaluate cardiac functions. RESULTS: The HbA1c levels decreased significantly from 8.1% ± 0.6% to 6.8% ± 0.6% in the gemigliptin group and from 8.1% ± 0.6% to 7.0% ± 0.7% in the glimepiride group, without a between-group difference. Gemigliptin reduced insulin resistance, high sensitivity C-reactive protein and low-density lipoprotein cholesterol levels, and blood pressure, and increased adiponectin level compared with glimepiride therapy. Gemigliptin induced favourable changes in body composition. Left ventricular end-diastolic volume decreased in the gemigliptin group but increased in the glimepiride group, with a borderline between-group difference. Cardiac biomarkers did not change significantly in either group. At 52 weeks, the HbA1c levels in both groups increased slightly; 7.3% ± 0.8% in the gemigliptin group versus 7.7% ± 1.3% in the glimepiride group, without a between-group difference. CONCLUSIONS: Gemigliptin had a comparable glucose-lowering efficacy without deleterious effects on cardiac functions or on biomarkers reflective of myocardial injury or heart failure during the 24-week observation period. However, larger, longer-term studies are needed to confirm these findings.
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Diabetes Mellitus Tipo 2 , Coração , Hipoglicemiantes , Piperidonas , Pirimidinas , Compostos de Sulfonilureia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Piperidonas/uso terapêutico , Pirimidinas/uso terapêutico , Hipoglicemiantes/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Metformina , Humanos , Ecocardiografia , Coração/efeitos dos fármacos , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
This cross-sectional study enrolled 267 patients with metabolic risk factors and established non-alcoholic fatty liver disease in the prospective cohort. The performance of fibrosis-4 (FIB-4) score (≥1.3) to diagnose advanced fibrosis using transient elastography (liver stiffness measurement [LSM] ≥8 kPa) was analyzed. Comparing patients with type 2 diabetes (T2D, n=87) and without (n=180), not FIB-4, but LSM was significantly higher in T2D (P=0.026). The prevalence of advanced fibrosis was 17.2% in T2D and 12.8% in non-T2D. FIB-4 exhibited higher proportion of false negatives in T2D patients (10.9%) than those without (5.2%). The diagnostic performance of FIB-4 was suboptimal in T2D (area under curve [AUC], 0.653; 95% confidence interval [CI], 0.462 to 0.844) compared to that in non-T2D (AUC, 0.826; 95% CI, 0.724 to 0.927). In conclusion, patients with T2D might be beneficial to conduct transient elastography without screening to avoid missing advanced fibrosis.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Cirrose Hepática/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Estudos Transversais , Estudos ProspectivosRESUMO
Pheochromocytomas and paragangliomas (PPGLs) may secrete hormones or bioactive neuropeptides such as interleukin-6 (IL-6), which can mask the clinical manifestations of catecholamine hypersecretion. We report the case of a patient with delayed diagnosis of paraganglioma due to the development of IL-6-mediated systemic inflammatory response syndrome (SIRS). A 58-year-old woman presented with dyspnea and flank pain accompanied by SIRS and acute cardiac, kidney, and liver injuries. A left paravertebral mass was incidentally observed on abdominal computed tomography (CT). Biochemical tests revealed increased 24-hour urinary metanephrine (2.12 mg/day), plasma norepinephrine (1,588 pg/mL), plasma normetanephrine (2.27 nmol/L), and IL-6 (16.5 pg/mL) levels. 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT showed increased uptake of FDG in the left paravertebral mass without metastases. The patient was finally diagnosed with functional paraganglioma crisis. The precipitating factor was unclear, but phendimetrazine tartrate, a norepinephrine-dopamine release drug that the patient regularly took, might have stimulated the paraganglioma. The patient's body temperature and blood pressure were well controlled after alpha-blocker administration, and the retroperitoneal mass was surgically resected successfully. After surgery, the patient's inflammatory, cardiac, renal, and hepatic biomarkers and catecholamine levels improved. In conclusion, our report emphasizes the importance of IL-6-producing PPGLs in the differential diagnosis of SIRS.
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Endocrine-disrupting chemical perfluorooctane sulfonate (PFOS) acute exposure stimulates insulin secretion from pancreatic ß-cells. However, chronic exposure to PFOS on pancreatic ß-cells, its role in insulin secretion, and the underlying mechanisms have not been studied. We used rat insulinoma INS-1 and human 1.1b4 islet cells to investigate the chronic effects of PFOS on glucose-stimulated insulin secretion and toxicity implicated in the downregulation of ß-cell functionality. Chronic exposure of INS-1 cells or human pancreatic 1.1b4 ß-cells to PFOS stimulated the small G-protein RAC1-guanosine triphosphate-dependent nicotinamide adenine dinucleotide phosphate oxidase (NOX2/gp91phox) subunit expression and activation. Upregulated NOX2/gp91phox activation led to elevated reactive oxygen species (ROS) production with a decrease in the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway in both cell types. Inhibition of cAMP/PKA signaling induces ß-cell mitochondrial dysfunction and endoplasmic stress via the loss of PDX1-SERCA2B and glucose-stimulated insulin release. Inhibiting RAC1-NOX2/gp91phox activation or elevating cAMP by pentoxifylline, a Food and Drug Administration-approved phosphodiesterase inhibitor, significantly reduced PFOS-induced ROS production and restored insulin secretory function of pancreatic ß-cells. Enhanced secretory function in pentoxifylline-treated cells was associated with increased stability of PDX1-SERCA2B protein levels. Intriguingly, inhibition of cAMP/PKA signaling impaired pentoxifylline-induced insulin secretion caused by the activation of ROS production and mitochondrial dysfunction. Overall, our findings show that PFOS has a new and first-ever direct chronic effect on pancreatic ß-cell failure through increased RAC1-NOX2/gp91phox activation and pentoxifylline-induced cAMP/PKA signaling, which inhibits PFOS-mediated mitochondrial dysfunction.
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Pentoxifilina , Ratos , Animais , Humanos , Pentoxifilina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Insulina/metabolismo , AMP Cíclico/metabolismo , Glucose , Apoptose , Monofosfato de Adenosina/metabolismo , Monofosfato de Adenosina/farmacologiaRESUMO
BACKGROUND: The endocrine disruption of perfluorinated compounds is an emerging issue. We aimed to examine the association of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels with incident diabetes and fasting serum glucose concentration. METHODS: This prospective cohort study was based on an urban-based cohort subpopulation from the Korean Genome and Epidemiology Study. Serum samples (600 µL) were received from 100 participants in the normoglycemic baseline survey (2004-2013), and concentrations of PFOA and PFOS were measured using mass spectrometry. The incidence of diabetes was tracked in the follow-up survey (2012-2016). RESULTS: The mean age was 56.4 years (men, 59%). The median serum PFOA and PFOS concentrations were 4.29 ng/mL and 9.44 ng/mL, respectively. PFOA and PFOS concentrations differed according to age, sex, and residential area. After 60 months, 23 patients had diabetes. Log-transformed PFOA (lnPFOA) and log-transformed PFOS (lnPFOS) were significantly higher in those who transitioned to diabetes than in those who did not (both p < 0.05). After multivariate adjustment, lnPFOA (coefficient = 6.98, 95% CI -0.04-14, p = 0.054) and lnPFOS (coefficient = 7.06, 95% CI -0.96-15.08, p = 0.088) predicted increased fasting glucose without statistical significance. In addition, lnPFOA, but not lnPFOS, significantly predicted incident diabetes (HR = 3.98, 95% CI 1.42-11.1, p < 0.01). CONCLUSION: Exposure to PFOA and PFOS may have a potential dysglycemic effect. In particular, exposure to PFOA increased the risk of diabetes. Further research with larger sample size is warranted.
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Ácidos Alcanossulfônicos , Diabetes Mellitus , Fluorocarbonos , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Glucose , Jejum , Estudos Prospectivos , Caprilatos , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/epidemiologia , Estudos de CoortesRESUMO
OBJECTIVE: This study aimed to evaluate the effect of early glycaemic variability (GV) on 28-day mortality in critically ill patients with pneumonia. PATIENTS AND METHODS: This single-centre retrospective study included patients admitted to the intensive care unit (ICU) due to pneumonia between 2018 and 2019. A total of 282 patients (mean age, 68.6 years) with blood sugar test (BST) results measured more than three times within 48 h after hospitalization and haemoglobin A1c (HbA1c) levels recorded within 2 months were enrolled. Coefficient of variation (CV) was calculated using the BST values. The effects of GV on 28-day mortality and prolonged ICU stay (>14 days) were also assessed. RESULTS: The mean age was 60.6 years (male to female ratio, 2.5:1). The 28-day mortality rate was 31.6% (n = 89) and was not different according to the presence of diabetes (DM vs. non-DM) or HbA1c levels (≥7.5 vs. <7.5%; both p > .05). However, the mortality rate was significantly higher in patients with high GV (CV ≥ 36%) than in those with low GV (CV < 36%; 37.5 vs. 25.4%, p = .028). The risk of mortality in patients with high GV was prominent in the subgroups with DM or low HbA1c levels. Among the surviving patients (n = 193), 44 remained in the ICU for more than 14 days. Compared to low GV, high GV was associated with a higher rate of prolonged ICU stay, although not statistically significant (27.8 vs. 18.5%, p = .171). After adjusting for the severity of illness and treatment strategy, CV was an independent risk factor for 28-day mortality (hazard ratio [HR], 1.01, p = .04) and prolonged ICU stay (odds ratio, 1.02; p = .04). CONCLUSIONS: High GV within 48 h of ICU admission was associated with an increased 28-day mortality risk and prolonged ICU stay. Early phase GV should be carefully managed in critically ill patients with pneumonia.KEY MESSAGESThe presence of diabetes or HbA1c alone is insufficient to predict 28-day mortality and prolonged ICU stay in critically ill patients with pneumonia.High glycaemic variability (GV) within 48 h of ICU admission increases 28-day mortality and prolongs ICU stay, which is consistent after adjusting for severity of illness and treatment strategy.Patients with high GV, especially those with DM or low HbA1c levels (<7.5%) should be more carefully treated to reduce mortality.
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Diabetes Mellitus , Hiperglicemia , Hipoglicemia , Pneumonia , Idoso , Glicemia , Estado Terminal , Feminino , Hemoglobinas Glicadas , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGRUOUND: This study aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death. METHODS: This retrospective observational study used data from 2009 to 2018 from the National Health Insurance in Korea. Among the patients with type 2 diabetes, those taking antidiabetic drugs and who did not have CV events until 2009 were included. Patients were divided into quartiles (Q1 [lowest]-4 [highest]) according to the 2009 diabetes drug cost. In addition, the 10-year incidences of CV events (non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death (death due to CV events) were analyzed. RESULTS: A total of 441,914 participants were enrolled (median age, 60 years; men, 57%). CV events and death occurred in 28.1% and 8.36% of the patients, respectively. The 10-year incidences of CV events and deaths increased from Q1 to 4. After adjusting for sex, age, income, type of diabetes drugs, comorbidities, and smoking and drinking status, the risk of CV events significantly increased according to the sequential order of the cost quartiles. In contrast, the risk of CV death showed a U-shaped pattern, which was the lowest in Q3 (hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.913 to 0.995) and the highest in Q4 (HR, 1.266; 95% CI, 1.213 to 1.321). CONCLUSION: Diabetes drug expenditure affects 10-year CV events and mortality. Therefore, affording an appropriate diabetes drug cost at a similar risk of CV is an independent protective factor against CV death.
Assuntos
Diabetes Mellitus Tipo 2 , Infarto do Miocárdio , Masculino , Humanos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Custos de Medicamentos , Fatores de Risco , Infarto do Miocárdio/epidemiologia , Hipoglicemiantes/uso terapêutico , Programas Nacionais de SaúdeRESUMO
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