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1.
Yakugaku Zasshi ; 140(9): 1185-1193, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879250

RESUMO

Lipid lowering therapy using statins prevents the risk of cardiovascular events. However, since the year 2000, there have been some reports that statins increased the risk of developing diabetes (SIRDD). It is socially demanded that pharmacists must apply pharmacotherapy to patients by utilizing drug information like the above, such as selecting appropriate drugs and providing correct drug information. Accordingly, pharmacists must correct drug information, and they should analyze and evaluate such information. Therefore, we conducted a questionnaire survey for pharmacists in community pharmacies with an aim to verify relevance between methods of obtaining drug information and the utilization of the information of "SIRDD" as a subject. We sent a questionnaire by letter to 1522 pharmacists in Fukushima and Mie prefecture, and received the results of the questionnaire from them using "Google forms" that is software to make web questionnaire and letters. We obtained responses from 356 (23.4%) pharmacists out of 1522. The number of responses from the pharmacists that "know" the information of "SIRDD" was 135 (37.9%). We found that these pharmacists obtained the information by websites of pharmaceutical companies, m3, Inc. (Portal site for medical professionals), and Pharmaceuticals and Medical Devices Agency (PMDA), as the sources of information. Our results suggested that pharmacists responded that they "know" "SIRDD" utilized websites as a quick information tool. The difference in network environments will relate to the difference of providable medical quality. So, it is very important to maintain appropriate network environment in cooperation with medical institutions, professional associations and the government.


Assuntos
Conscientização , Serviços Comunitários de Farmácia , Diabetes Mellitus/induzido quimicamente , Serviços de Informação sobre Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Aceitação pelo Paciente de Cuidados de Saúde , Farmácias , Farmacêuticos/psicologia , Adulto , Serviços de Informação sobre Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Inquéritos e Questionários
2.
Pol Merkur Lekarski ; 48(285): 209-214, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32564049

RESUMO

Viral infections lead to many disorders with a different course and prognosis. Clinical trials are ongoing on new groups of antiviral drugs, which are very promising. However, treatment with antiviral drugs causes numerous adverse effects (AEs) including hormonal dysfunctions. The aim of this article is to discuss endocrine abnormalities induced by the antiviral drugs including frequency of their occurrence. The review is based on the available literature in the Medline database and considers the latest articles describing endocrine disorders with relation to antiviral therapy. The hormonal and metabolic dysfunctions were discussed, including the AEs like: osteoporosis, osteomalacia, hypoand hyperthyroidism, metabolic syndrome, lipodystrophy, hyperglycemia, diabetes mellitus and others. Awareness of frequency and type of complications caused by antiviral drugs, enables faster linking of the disease with the therapy, so it allows the personalization of treatment. It's necessary to monitor the general condition of the patients and appropriate diagnostic parameters that it can help diagnose hormonal disorders and adjust an individual antiviral therapy for the patient with endocrinopathy.


Assuntos
Antivirais , Diabetes Mellitus , Hiperglicemia , Osteoporose , Antivirais/efeitos adversos , Diabetes Mellitus/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Hiperglicemia/induzido quimicamente , Osteoporose/induzido quimicamente
3.
Diabetes Res Clin Pract ; 164: 108197, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32389742

RESUMO

AIM: To provide information on the balance between the cardiovascular (CV) benefit and the diabetogenic harm of statin therapy in the current clinical practice. METHODS: All the 115,939 residents (older than 50 years) in the Italian Lombardy Region newly treated with statins between 2003 and 2005, were followed from the first statin prescription until 2012 to identify those experiencing a macrovascular complication and those with at least one sign suggestive of new onset diabetes. The proportion of days of follow-up covered by statin prescriptions measured adherence with statins. Hazard ratio, and relative 95% confidence interval (CI), for the two considered outcomes associated with statin adherence, were separately estimated (proportional hazard models). Number needed to treat (NNT) and number needed to harm (NNH), i.e., number of individuals who must be treated with statins in order to prevent a macrovascular complication, or to generate a new onset diabetes, respectively, were calculated to evaluate the balance between CV benefit and diabetogenic harm of statin therapy. RESULTS: Compared to those at very low adherence with statins, patients at high adherence showed a significant reduction of macrovascular risk (28%, 95% CI: 23%-33%) and a greater risk of developing diabetic condition (67%, 50%-86%). In the whole cohort, the NNT was 26, whereas the NNH 65. NNT was lower than NNH also in all considered strata of age, gender, clinical profile. CONCLUSIONS: This large cohort investigation provides real-world evidence that the balance between CV benefit and diabetogenic harm of statin therapy is largely favourable to treatment benefits.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Doenças Cardiovasculares/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Risco
4.
J Biol Regul Homeost Agents ; 34(2): 509-515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32450680

RESUMO

The aim of this study is to explore the regulatory effect of micro ribonucleic acid (miR)-19a on diabetic retinopathy (DR) through mediating the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/protein kinase B (Akt) signaling pathway. Thirty male Sprague-Dawley rats were first divided into Healthy group, DR group and miR-19a inhibitor group. The DR model was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). The retinal tissues were dissected and RGCs were isolated. The expression level of miR-19a therein was determined using quantitative polymerase chain reaction (qPCR). The pathological changes were observed through hematoxylin-eosin staining (HE) staining. The apoptosis was detected by flow cytometry. PTEN was predicted as a target gene of miR-19a through TargetScan biological software. The protein expression of PTEN was detected via immunofluorescence assay. The changes in the phosphatidylinositol 3-hydroxy kinase (PI3K)/Akt pathway-associated proteins were detected using Western blotting. The expression of miR-19a declined substantially in DR rats injected with miR-19a inhibitor (P<0.05). RGCs were arranged regularly, showing apoptosis and milder necrosis in miR-19a inhibitor group. The proportion of apoptotic cells was substantially decreased in miR-19a inhibitor group (P<0.05). It was found that miR-19a inhibitor group exhibited an evidently lower protein expression of PTEN and a higher activation degree of the Akt pathway than DR group (P<0.05). MiR-19a binds to PTEN protein in a targeted manner to mediate the PI3K/Akt pathway, thereby affecting the progression of DR.


Assuntos
Retinopatia Diabética/tratamento farmacológico , MicroRNAs/antagonistas & inibidores , Transdução de Sinais , Animais , Diabetes Mellitus/induzido quimicamente , Retinopatia Diabética/induzido quimicamente , Masculino , PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Sprague-Dawley
5.
Biomed Environ Sci ; 33(4): 260-268, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32438963

RESUMO

Objective: To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35-74 years. Methods: Data for this study were derived from the China Chronic Diseases and Behavioral Risk Factors Surveillance 2010 survey. Selenium concentrations in soil were obtained from the Atlas of Soil Environmental Background Values in China. A two-level binary logistic regression model was used to determine the association between soil selenium concentrations and the risk of diabetes, with participants nested within districts/counties. Results: A total of 69,332 participants aged 35-74 years, from 158 districts/counties were included in the analysis. Concentrations of selenium in soil varied greatly across the 158 districts/counties, with a median concentration of 0.219 mg/kg ( IQR: 0.185-0.248). The results showed that both Quartile 1 (0.119-0.185 mg/kg) and Quartile 4 (0.249-0.344 mg/kg) groups were positively associated with diabetes compared to a soil selenium concentration of 0.186-0.219 mg/kg (Quartile 2), crude odds ratios ( ORs) (95% CI) were 1.227 (1.003-1.502) and 1.280 (1.048-1.563). The P values were 0.045 and 0.013, for Quartile 1 and Quartile 4 groups, respectively. After adjusting for all confounding factors of interest, the Quartile 1 group became non-significant, and the Quartile 4 group had an adjusted OR (95% CI) of 1.203 (1.018-1.421) relative to the reference group (Quartile 2), the P values was 0.030. No significant results were seen for the Quartile 3 group (0.220-0.248 mg/kg) compared to the reference group. Conclusion: Excessive selenium concentrations in soil could increase the risk of diabetes among Chinese adults aged 35-74 years.


Assuntos
Diabetes Mellitus/epidemiologia , Selênio/metabolismo , Solo/química , Adulto , Idoso , China/epidemiologia , Diabetes Mellitus/induzido quimicamente , Dieta , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Selênio/deficiência
6.
Yakugaku Zasshi ; 140(4): 591-598, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32238642

RESUMO

Few studies have examined the relationship between the use of antidepressants and the onset of hyperglycemia and diabetes mellitus in Japan. We herein explored the possibility of this relationship using the Japanese Adverse Drug Event Report database (JADER). The present study included 20 individual antidepressants, consisting of 6 subclasses, which have been approved for use in Japan. We used Standardized MedDRA Queries 20000041 to extract patients who developed hyperglycemia/new onset diabetes mellitus (NODM) in JADER between April 2004 and September 2016. We calculated reporting odds ratios (RORs) with 95% confidence intervals (CI). We also calculated odds ratios defined as the ratio of odds of hyperglycemia/NODM to all other adverse drug events (ADEs) by the age cut-off group or sex in the cases of antidepressants. The lower limit of 95%CI of RORs for 13 antidepressants (imipramine, clomipramine, nortriptyline, amitriptyline, amoxapine, maprotiline, mianserin, sertraline, paroxetine, escitalopram, duloxetine, mirtazapine, and trazodone), which included all subclasses, exceeded 1. Younger age group was associated with hyperglycemia/NODM for 5 antidepressants (imipramine, amitriptyline, maprotiline, duloxetine, and trazodone), and female was associated with the ADEs for trazodone, although these results should be interpreted cautiously. Healthcare personnel need to be aware that the use of antidepressants may lead to hyperglycemia/NODM.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Antidepressivos/efeitos adversos , Diabetes Mellitus/induzido quimicamente , Hiperglicemia/induzido quimicamente , Adulto , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hiperglicemia/epidemiologia , Japão/epidemiologia , Masculino , Razão de Chances , Fatores de Tempo , Adulto Jovem
7.
Sci Rep ; 10(1): 6339, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286339

RESUMO

Exposure to environment-polluting chemicals (EPC) is associated with the development of diabetes. Many EPCs exert toxic effects via aryl hydrocarbon receptor (AhR) and/or mitochondrial inhibition. Here we investigated if the levels of human exposure to a mixture of EPC and/or mitochondrial inhibitors could predict the development of diabetes in a prospective study, the Korean Genome and Epidemiological Study (KoGES). We analysed AhR ligands (AhRL) and mitochondria-inhibiting substances (MIS) in serum samples (n = 1,537), collected during the 2008 Ansung KoGES survey with a 4-year-follow-up. Serum AhRL, determined by the AhR-dependent luciferase reporter assay, represents the contamination level of AhR ligand mixture in serum. Serum levels of MIS, analysed indirectly by MIS-ATP or MIS-ROS, are the serum MIS-induced mitochondria inhibiting effects on ATP content or reactive oxygen species (ROS) production in the cultured cells. Among 919 normal subjects at baseline, 7.1% developed impaired glucose tolerance (IGT) and 1.6% diabetes after 4 years. At the baseline, diabetic and IGT sera displayed higher AhRL and MIS than normal sera, which correlated with indices of insulin resistance. When the subjects were classified according to ROC cut-off values, fully adjusted relative risks of diabetes development within 4 years were 7.60 (95% CI, 4.23-13.64), 4.27 (95% CI, 2.38-7.64), and 21.11 (95% CI, 8.46-52.67) for AhRL ≥ 2.70 pM, MIS-ATP ≤ 88.1%, and both, respectively. Gender analysis revealed that male subjects with AhRL ≥ 2.70 pM or MIS-ATP ≤ 88.1% showed higher risk than female subjects. High serum levels of AhRL and/or MIS strongly predict the future development of diabetes, suggesting that the accumulation of AhR ligands and/or mitochondrial inhibitors in body may play an important role in the pathogenesis of diabetes.


Assuntos
Poluentes Atmosféricos/toxicidade , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores/sangue , Diabetes Mellitus/sangue , Mitocôndrias/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/genética , Idoso , Fatores de Transcrição Hélice-Alça-Hélice Básicos/sangue , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/patologia , Biomarcadores Ambientais/genética , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/genética , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina/genética , Ligantes , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Receptores de Hidrocarboneto Arílico/sangue , República da Coreia
8.
Nutr. hosp ; 37(2): 343-348, mar.-abr. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-190600

RESUMO

INTRODUCTION: diabetes mellitus is considered a chronic disease, characterized by the presence of high glycemic concentrations and dyslipidemia or hyperlipidemia caused by absence or deficiency of insulin secretion by pancreatic β-cells. Micro and macrovascular complications may lead to nephropathy. Diabetic syndrome and oxidative damage are strongly related. The guarana plant (Paullinia cupana) has been described as an antioxidant agent. OBJECTIVE: this study aims to evaluate the protective action of the guarana compound on the biochemical profile of alloxan-induced diabetes in rats. METHOD: twenty-eight male Wistar Furth rats were divided into four groups of seven animals each: the control group (CG) was fed a standard diet; the guarana group (GG) was fed a standard diet supplemented with guarana; the diabetic group (DG) included alloxan-induced diabetic rats fed a standard diet; and the diabetic guarana group (DGG) included alloxan-induced diabetic rats fed a standard diet supplemented with guarana. Induction was performed by intraperitoneal injection of alloxan 150 mg/kg. RESULTS: LDL (CG: 24.64 ± 2,59; GG: 38.93 ± 7.19; DG: 14.9 ± 3.96; DGG: 20.8 ± 4.04 mg/dL); HDL (CG: 14.8 ± 4.86; GG: 13 ± 1.41; DG: 22.5 ± 7.81; DGG: 30.66 ± 9.02 mg/dL); ALT (CG: 31.8 ± 4.81; GG: 22.16 ± 1.83; DG: 38 ± 1.4; DGG: 26.83 ± 2.13 U/L); AST (CG: 101.8 ± 5.07; GG: 117.5 ± 9.73; DG: 183.6 ± 4.21; DGG: 116.16 ± 12 U/L); urea (CG: 51.4 ± 5.03; GG: 42.5 ± 8.24; DG: 129.16 ± 31.72; DGG: 150.5 ± 36.02 mg/dL); creatinine (CG: 0.6 ± 0.12; GG: 0.53 ± 0.05; DG: 0.78 ± 0.11; DGG: 0.61 ± 0.07 mg/dL). CONCLUSIONS: consumption of guarana (Paullinia cupana) by male Wistar Furth rats with alloxan induced diabetes without treatment had a beneficial effect on hepatic and renal function parameters, and raises the possibility of being used as supportive therapy in the treatment of diabetes


INTRODUCCIÓN: la diabetes mellitus (DM) se considera una enfermedad crónica caracterizada por la presencia de altas concentraciones glucémicas, dislipidemia o hiperlipidemia causadas por ausencia o deficiencia de la secreción de insulina por las células β del páncreas. Sus complicaciones micro y macrovasculares pueden llevar a un cuadro de nefropatía. El síndrome diabético y el daño oxidativo están fuertemente relacionados. El guaraná (Paullinia cupana) se ha venido describiendo como un agente antioxidante. OBJETIVO: este estudio tiene el objetivo de evaluar la posible acción protectora de este compuesto sobre el perfil bioquímico de ratas con diabetes inducida por aloxano. MATERIAL Y MÉTODOS: veintiocho ratas macho Wistar Furth se dividieron en cuatro grupos de siete animales cada uno: el grupo de control (CG) se alimentó con la dieta estándar; el grupo de guaraná (GG) se alimentó con la dieta estándar complementada con guaraná; el grupo diabético (DG) se formó con ratas con diabetes inducida por aloxano que se alimentaron con la dieta estándar; el grupo diabético con guaraná (DGG) se formó con ratas con diabetes inducida por aloxano que se alimentaron con la dieta estándar complementada con guaraná. La inducción se realizó a través de una inyección intraperitoneal de aloxano en dosis de 150 mg/kg. RESULTADOS: LDL (CG: 24,64 ± 2,59; GG: 38,93 ± 7,19; DG: 14,9 ± 3,96; DGG: 20,8 ± 4,04 mg/dl); HDL (CG: 14,8 ± 4,86; GG: 13 ± 1,41; DG: 22,5 ± 7,81; DGG: 30,66 ± 9,02 mg/dl); ALT (CG: 31,8 ± 4,81; GG: 22,16 ± 1,83; DG: 38 ± 1,4; DGG: 26,83 ± 2,13 U/L); AST (CG: 101,8 ± 5,07; GG: 117,5 ± 9,73; DG: 183,6 ± 4,21; DGG: 116,16 ± 12 U/L); urea (CG: 51,4 ± 5,03; GG: 42,5 ± 8,24; DG: 129,16 ± 31,72; DGG: 150,5 ± 36,02 mg/dl); creatinina (CG: 0,6 ± 0,12; GG: 0,53 ± 0,05; DG: 0,78 ± 0,11; DGG: 0,61 ± 0,07 mg/dl). CONCLUSIÓN: el consumo de guaraná (Paullinia cupana) por ratas Wistar con diabetes inducida por aloxano y sin tratamiento actuó de forma beneficiosa sobre los parámetros hepáticos y de función renal, planteando la posibilidad de poder ser utilizado como terapia de soporte en el tratamiento de la diabetes


Assuntos
Animais , Feminino , Ratos , Paullinia , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/veterinária , Aloxano/efeitos adversos , Fígado/efeitos dos fármacos , Aloxano/administração & dosagem , Células Secretoras de Insulina/efeitos dos fármacos , Ratos Endogâmicos WF
9.
J Diabetes Res ; 2020: 6542346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998808

RESUMO

Objective: Posttransplantation diabetes mellitus (PTDM) is a known complication of transplantation that affects the prognosis. Tacrolimus (Tac or FK506) is a widely used immunosuppressant that has been reported to be a risk factor for PTDM and to further induce complications in heart and skeletal muscles, but the mechanism is still largely unknown. In our preliminary experiments, we found that after Tac treatment, blood glucose increased, and the weight of skeletal muscle declined. Here, we hypothesize that tacrolimus can induce PTDM and influence the atrophy of skeletal muscle. Methods: We designed preliminary experiments to establish a tacrolimus-induced PTDM model. Gene expression profiles in quadriceps muscle from this rat model were characterized by oligonucleotide microarrays. Then, differences in gene expression profiles in muscle from PTDM rats that received tacrolimus and control subjects were analyzed by using GeneSpring GX 11.0 software (Agilent). Functional annotation and enrichment analysis of differentially expressed genes (DEGs) helped us identify clues for the side effects of tacrolimus. Results: Our experiments found that the quadriceps in tacrolimus-induced PTDM group were smaller than those in the control group. The study identified 275 DEGs that may be responsible for insulin resistance and the progression of PTDM, including 86 upregulated genes and 199 downregulated genes. GO and KEGG functional analysis of the DEGs showed a significant correlation between PTDM and muscle development. PPI network analysis screened eight hub genes and found that they were related to troponin and tropomyosin. Conclusions: This study explored the molecular mechanism of muscle atrophy in a tacrolimus-induced PTDM model by bioinformatics analyses. We identified 275 DEGs and identified significant biomarkers for predicting the development and progression of tacrolimus-induced PTDM.


Assuntos
Diabetes Mellitus/induzido quimicamente , Expressão Gênica/efeitos dos fármacos , Imunossupressores/efeitos adversos , Músculo Quadríceps/efeitos dos fármacos , Tacrolimo/efeitos adversos , Animais , Glicemia/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Resistência à Insulina , Masculino , Músculo Quadríceps/metabolismo , Ratos , Ratos Sprague-Dawley , Transcriptoma
10.
Am J Cardiol ; 125(4): 534-541, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31848029

RESUMO

The association between statins and diabetes mellitus (DM) remains controversial. The Kaiser Permanente CHAMP Study identified adults without DM who had cardiovascular (CV) risk factors and no previous lipid lowering therapy (LLT) between 2008 and 2010. The CV risk factors included known atherosclerotic CV disease (ASCVD), elevated low-density lipoprotein cholesterol ≥190 mg/dl, or a low-density lipoprotein cholesterol between 70 and 189 mg/dl and an estimated 10-year ASCVD risk ≥7.5%. Incident DM was defined as ≥2 abnormal tests (i.e., A1C ≥6.5% or a fasting blood glucose ≥126 mg/dl) or ≥1 abnormal test result plus a new diagnostic code or medication for DM. Among 213,289 eligible adults, 28,149 patients initiating statins were carefully matched to an equal number of patients who remained off LLT during follow-up. Compared with matched patients not receiving statins, those initiating statin therapy had the same mean age (67.9 ± 9.4 years) and gender (42.8% women). The crude rate (per 100 person-years) of incident DM was low (0.55, 95% confidence interval [CI] 0.52 to 0.59) but was marginally higher in patients who were treated with a statin (0.69, 95% CI 0.64 to 0.74) versus no LLT (0.42, 95% CI 0.38 to 0.46). After additional adjustment, statin therapy was associated with a modestly increased risk of incident DM (adjusted hazard ratio 1.17, 95% CI 1.02 to 1.34). In conclusion, in adults without DM at increased ASCVD risk, initiation of statin therapy was independently associated with a modestly higher risk of incident DM.


Assuntos
Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Idoso , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Lipídeos/sangue , Masculino , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
11.
Ned Tijdschr Geneeskd ; 1632019 10 31.
Artigo em Holandês | MEDLINE | ID: mdl-31714042

RESUMO

Checkpoint inhibition has emerged as a promising therapeutic strategy for several types of cancer. Immune-related adverse effects (irAEs) commonly involve the endocrine system. Distinguishing endocrine side effect-related symptoms from disease progression or treatment-related toxicity can be challenging. If not recognized in time, endocrine irAEs may be life-threatening. As the use of checkpoint inhibitors is expected to increase, there is a need for more awareness of endocrine irAEs amongst health care professionals. We describe three cases that illustrate the importance of timely recognition, patient education and the management of endocrinopathies. Two patients who were treated with the checkpoint inhibitor ipilimumab developed hypophysitis and subsequent episodes of hypocortisolism. These cases underline both the frequency of diagnostic delay and the importance of patient education with regard to glucocorticoid stress dosage. The third patient presented with diabetes mellitus after administration of nivolumab. A multidisciplinary approach is warranted to ensure optimal care for patients with endocrine irAEs.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Diabetes Mellitus/induzido quimicamente , Hipofisite/induzido quimicamente , Ipilimumab/efeitos adversos , Neoplasias/tratamento farmacológico , Nivolumabe/efeitos adversos , Doença de Addison/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade
12.
Kidney Blood Press Res ; 44(6): 1352-1362, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31645044

RESUMO

BACKGROUND: Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults. Although various studies have demonstrated the efficacy of tacrolimus combined with corticosteroids for treating IMN, both tacrolimus and corticosteroids have been shown to be diabetogenic, particularly following organ transplantation. Furthermore, the frequency and risk factors for new-onset diabetes mellitus (NODM) in IMN patients treated with tacrolimus plus low-dose corticosteroids remain unclear. OBJECTIVES: To evaluate the incidence of NODM in IMN patients undergoing tacrolimus plus low-dose corticosteroid therapy and to confirm the risk factors for NODM development. METHODS: This retrospective study recruited 72 eligible patients with biopsy-proven IMN from our center, between September 2013 and June 2018. All subjects were treated with tacrolimus plus low-dose corticosteroids for a minimum of 3 months. The primary outcome was NODM development during the follow-up period. The secondary outcome was complete or partial remission. Patients were divided into 2 groups: patients with NODM (NODM group) and those without NODM (No-NODM group). Demographic and clinical data at baseline and follow-up were assessed. RESULTS: During follow-up, 31 of the 72 patients developed NODM (43.0%). The median time to occurrence was 3 months after treatment initiation. NODM patients were significantly older (median age 59 vs. 40 years) than No-NODM patients. Baseline fasting blood glucose levels were slightly higher in the NODM group; however, the difference was not significant (p = 0.07). Older age was an independent risk factor for NODM (OR 1.73 and 95% CI 1.20-2.47, p = 0.003). Overall kidney remission rates were 80.6%. There was no significant difference in remission rate between groups. There was a significant difference in development of pulmonary infection, which occurred in 7 NODM patients and only in 1 No-NODM patient (p = 0.018). IMN reoccurred in 5 NODM patients but only 1 No-NODM patient. CONCLUSIONS: Tacrolimus plus low-dose corticosteroid therapy was an efficient treatment for IMN; however, it was accompanied by increased NODM morbidity, which should be considered serious, due to the increased risk of life-threatening complications. Increasing age was a major risk factor for NODM in IMN patients treated with tacrolimus plus low-dose corticosteroid therapy.


Assuntos
Corticosteroides/uso terapêutico , Diabetes Mellitus/induzido quimicamente , Quimioterapia Combinada/efeitos adversos , Glomerulonefrite Membranosa/tratamento farmacológico , Tacrolimo/uso terapêutico , Adulto , Fatores Etários , Diabetes Mellitus/etiologia , Feminino , Glomerulonefrite Membranosa/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
13.
Br J Clin Pharmacol ; 85(11): 2559-2567, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31595525

RESUMO

AIMS: To determine statins' impact on skin infection risk in view of conflicting literature: that statins may reduce infection risk, but are also associated with diabetes mellitus, a risk factor for skin and soft tissue infections (SSTIs). METHODS: Sequence symmetry analysis was performed on prescription claims (2001-2011) from the Australian Department of Veterans' Affairs to determine the interrelationships between: (i) statins and SSTIs; (ii) statins and diabetes; and (iii) diabetes and SSTIs; as well as whether statins increased the risk of SSTIs, independent of diabetes status. Chi-square tests were performed to detect differences in Index of Relative Socio-economic Advantage and Disadvantage scores of patients within each interrelationship. Prescriptions for statins, antidiabetic medication, and antistaphylococcal antibiotics were evaluated using nonidentifiable client numbers, prescription dates filled, residential electorates, and pharmaceutical codes. Adjusted sequence ratio and confidence interval were calculated at intervals of 91, 182 and 365 days for sequence symmetry analysis studies. RESULTS: Statins were associated with: (i) significant SSTI risk (adjusted sequence ratio > 1; confidence interval >1), (ii) significant diabetes risk, and (iii) diabetic patients had increased risk of SSTIs. Diabetic and nondiabetic statin users had significantly increased risks of SSTIs, while the influence from socioeconomic status was not significant for each of the 3 relationships. CONCLUSIONS: Statins are associated with increased risk of SSTIs via direct and indirect mechanisms, probably independent of diabetes or socioeconomic statuses. We believe that clinicians should be aware of the association between statins and SSTIs, and, where appropriate, monitor blood glucose levels of statin users.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/epidemiologia , Prescrições de Medicamentos/estatística & dados numéricos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Infecções Cutâneas Estafilocócicas/epidemiologia , Adulto , Idoso , Austrália/epidemiologia , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/imunologia , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Farmacoepidemiologia/métodos , Fatores de Risco , Classe Social , Infecções Cutâneas Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/imunologia , Staphylococcus aureus/isolamento & purificação
14.
Clín. investig. arterioscler. (Ed. impr.) ; 31(5): 228-232, sept.-oct. 2019.
Artigo em Inglês | IBECS | ID: ibc-184166

RESUMO

Statins have been associated with an increased risk of new-onset diabetes mellitus (NODM), as confirmed in previous observational studies and meta-analyses. Controversy exists as to whether this risk varies depending on statin type or dose. However, there appears to be unanimity regarding the different associated factors that raise this risk. Furthermore, diverse pathophysiologic mechanisms have been described that could explain the increased risk of diabetes in patients with statin treatment. These fundamentally cause a rise in insulin resistance together with a decrease in insulin secretion. The present review aimed to describe the relationship between statin treatment and the presence of diabetes and provide an update of previous published evidence and the possible mechanisms involved


Las estatinas se han asociado con un incremento en el riesgo de aparición de diabetes mellitus de novo, siendo esto confirmado en estudios previos observacionales así como metaanálisis. Sin embargo, existe cierta controversia sobre si este riesgo varia en función de la dosis o tipo de estatina. Por otro lado, parece que hay unanimidad con respecto a los factores asociados a este incremento de riesgo. Asimismo, se han descrito diversos mecanismos fisiopatológicos que podrían explicar el aumento de riesgo de padecer diabetes en los pacientes tratados con estatinas. Estos mecanismos se basan fundamentalmente en un incremento en la resistencia a la insulina así como un descenso en su sensibilidad. La presente revisión está enfocada en describir la relación entre el tratamiento con estatinas y el riesgo de padecer diabetes y revisar los datos publicados hasta las fecha así como los posibles mecanismos fisiopatológicos involucrados en este aumento de riesgo


Assuntos
Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doenças Cardiovasculares/complicações , Diabetes Mellitus/induzido quimicamente , Medição de Risco , Diabetes Mellitus/fisiopatologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Resistência à Insulina
15.
Undersea Hyperb Med ; 46(4): 437-445, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509900

RESUMO

Introduction: To determine if hyperbaric oxygen (HBO2) therapy has an effect on diabetic blood glucose levels (BGL) and, if so, the extent of this effect. Also, to examine factors that exacerbate any observed effect. Methods: This was a retrospective review of prospectively collected quality data on diabetics undergoing HBO2. Pre- and post-treatment BGL were recorded. Pre-treatment BGL ⟨120 mg/dL received glucose supplementation. Hypoglycemia was defined as BGL ⟨70 mg/dL. BGL ⟨90 mg/dL was included as an elevated hypoglycemia threshold. Results: 77 patients representing 1,825 treatments were included for analysis. No patient had deleterious side effects or required emergency care. BGL decreased in 75.4% of treatments in this group, with a median decrease of 25 mg/dL (IQR=54 mg/dL; range of decreased 374 mg/dL to increased 240 mg/dL). A statistically significant greater percentage of treatments of patients with type 2 diabetes resulted in a decrease in BGL (1598 or 77.5%) compared to treatments of patients with type 1 diabetes (169 or 51.5%) (χ2(1, N=1767) =55.37, p⟨0.001). 1.1% of treatments had post-HBO2 serum glucose ⟨90 mg/dL, and 0.2% of treatments had post-HBO2 serum glucose ⟨70 mg/dL. The majority (70%) of patients with post-HBO2 BGL ⟨90 mg/dL were maintained on insulin alone (χ2(2, N=20) =12.4, p=0.002). Well-controlled diabetics (i.e., those with all BGLs within 50 mg/dL over all pre-HBO2 treatments) had no post-HBO2 BGL ⟨70 mg/dL or ⟨90 mg/dL. Conclusion: Our results suggest that HBO2 does not cause a clinically significant decrease in diabetic patient BGL. No patient in our study had deleterious side effects or required emergency care. We found that glucose level of ⟨90 mg/dL occurred more often in those who use insulin. Hyperbaric patients who exhibit consistent BGL values may represent a group who could be managed similarly to the non-diabetic population.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Oxigenação Hiperbárica , Idoso , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Oxigenação Hiperbárica/efeitos adversos , Oxigenação Hiperbárica/estatística & dados numéricos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Estudos Retrospectivos , Esteroides/efeitos adversos
16.
Curr Diab Rep ; 19(10): 96, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31478094

RESUMO

PURPOSE OF REVIEW: The prevalence of diabetes is 2-3-fold higher in people with severe mental illness than the general population. There are concerns that antipsychotics increase the risk of diabetes. This review will examine the latest epidemiological studies linking antipsychotics and diabetes, as well as the mechanisms underlying the association and the clinical implications to minimise the impact of antipsychotics on metabolic health. RECENT FINDINGS: Although there is an increased risk of diabetes in people with first-episode psychosis, the prevalence increases rapidly after antipsychotics are started. Antipsychotics likely increase the risk of diabetes through weight gain and directly by adversely affecting insulin sensitivity and secretion. It is important to implement measures to prevent diabetes, to screen for diabetes to ensure prompt diagnosis and to provide effective diabetes care. Further research is needed to understand how antipsychotics cause diabetes and to improve the clinical management of diabetes in people with severe mental illness.


Assuntos
Antipsicóticos/efeitos adversos , Diabetes Mellitus/epidemiologia , Transtornos Psicóticos/epidemiologia , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/terapia , Humanos , Resistência à Insulina/fisiologia , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/etiologia , Ganho de Peso/efeitos dos fármacos , Ganho de Peso/fisiologia
17.
Schizophr Res ; 212: 150-156, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31395489

RESUMO

BACKGROUND: Long-term cataract risks associated with first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), and their associations with metabolism-related diseases are not yet elucidated. METHODS: Using Taiwan National Health Insurance data, we conducted a propensity score matched population-based cohort study consisting of 10,014 patients with newly diagnosed schizophrenia from 2005 to 2009 and followed them until the end of 2013. A Cox hazard model with metabolism-related diseases as time-dependent covariates was adapted to estimate the hazard ratio (HR) of cataracts between SGAs and FGAs groups. RESULTS: During the 8-year follow-up, patients receiving SGAs were associated with a higher risk of cataract than those receiving FGAs with an adjusted HR of 1.59 (95% confidence interval [CI] = 1.06-2.36). Patients receiving high-metabolic-risk SGAs (clozapine and olanzapine) showed the highest risk of cataracts among SGAs when compared with those receiving FGAs (aHR = 2.57, 95% CI: 1.35-4.88). SGAs demonstrated a stronger contribution in the risk of cataract in patients without diabetes mellitus (DM) and hyperlipidemia than in those developed these diseases. Patients who developed DM or hyperlipidemia after receiving antipsychotics had an approximately 2.5-fold increased cataract risk over those who did not develop these diseases. CONCLUSIONS: Regardless of the condition of metabolic-related diseases, SGAs were independently associated with an increased risk of cataract. DM and hyperlipidemia developed after antipsychotics contributed to the risk of cataract risk.


Assuntos
Antipsicóticos/efeitos adversos , Catarata/induzido quimicamente , Diabetes Mellitus/induzido quimicamente , Hiperlipidemias/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Catarata/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Humanos , Hiperlipidemias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esquizofrenia/epidemiologia , Taiwan/epidemiologia
18.
Food Funct ; 10(8): 4868-4876, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31334540

RESUMO

In this study, a polysaccharide was extracted from Physalis pubescens L. (named PP). Its antihyperglycemic and antihyperlipidemic activities were evaluated in STZ-induced diabetic mice. Results showed that PP was determined to be composed of rhamnose (Rha), arabinose (Ara), fucose (Fuc), xylose (Xyl), mannose (Man), glucose (Glc) and galactose (Gal) with molar percentages of 4.65%, 17.34%, 1.43%, 6.24%, 5.52%, 45.5%, and 19.31%, respectively. The average molecular weight (Mw) was found to be 20.0 kDa. It had a strong α-glucosidase inhibitory activity in vitro. PP treatment could enhance the oral glucose tolerance, and increase the levels of SOD, GSH, CAT, vitamin C, vitamin E, HDL-c, C-peptide, GCK and hepatic glycogen in diabetic mice. Besides, PP treatment could also decrease the levels of MDA, TG, TC, LDL-c, BUN and G-6-Pase. The regulating effects were stronger in high dose PP treatment than those in the low and medium dose treatments. In short, PP played an important role in protecting STZ-induced diabetic mice, and the effect was closely related to its activities in antioxidation and regulating glucose and lipid metabolism.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Physalis/química , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Animais , Glicemia/metabolismo , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/metabolismo , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/química , Hipolipemiantes/química , Insulina/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Extratos Vegetais/química , Polissacarídeos/química , Estreptozocina
19.
Transplant Proc ; 51(6): 1962-1971, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303410

RESUMO

BACKGROUND: The impact of immunosuppressive drugs in patients following liver transplantation (LT) is very individual. Despite the multiple beneficial effects of the mammalian target of rapamycin (mTOR) inhibitor everolimus (EVR) in LT recipients, some patients do not benefit from EVR administration. We investigated whether the presence of common single-nucleotide polymorphisms (SNPs) in the mTOR gene are predictive for adverse events following the introduction of EVR after LT. MATERIALS AND METHODS: The feasibility and efficacy of EVR in 127 liver transplant recipients who were converted to EVR-based immunosuppression was documented retrospectively. Blood samples of these patients were analyzed for the occurrence of 4 SNPs in the mTOR promoter region (mTOR3099/rs2295079 C>G, mTOR3162/rs2295080 A>C) and the mTOR 3' untranslated regio (mTOR8167/rs12139042 C>T, mTOR8600/rs2536 A>G); the specific allele variants were also associated with the incidence of adverse events (AEs). RESULTS: Of all patients, 21 (16.5%) did not tolerate the medication and had to discontinue. Of those patients who continued, 37% developed signs of reduced tolerance within the first 6 months, resolving after 12 months. When the cohort was divided according to genotype and allele frequency, patients with the mTOR3162/rs2295080 CC variant had a significantly higher risk (odds ratio = 5.89; 95% confidence interval = 1.48-23.40; P = .012) of developing new-onset diabetes mellitus following EVR treatment than AA or AC genotype carriers. CONCLUSION: Our results suggest that the SNP mTOR3162/rs2295080 CC genotype is associated with the development of new-onset diabetes mellitus following EVR treatment.


Assuntos
Diabetes Mellitus/induzido quimicamente , Everolimo/efeitos adversos , Imunossupressores/efeitos adversos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Serina-Treonina Quinases TOR/genética , Diabetes Mellitus/genética , Feminino , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Complicações Pós-Operatórias/genética , Estudos Retrospectivos
20.
Environ Sci Pollut Res Int ; 26(25): 26332-26338, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286379

RESUMO

Bisphenol A (BPA) is an endocrine-disrupting chemical widely used in the production of polycarbonate plastics and epoxy resins, which has been previously linked to diabetes among non-Hispanic populations. As part of a case control study for breast cancer, only controls with BPA information were included in this report. The final sample size comprises 70 self-reported diabetics and 334 non-diabetics. Urinary free bisphenol A (BPA-F) (µg/L) was determined by solid-phase extraction and HPLC/FLD analysis. Logistic regression models were used to evaluate the association between BPA-F and self-reported diabetes. After adjusting by age, urinary BPA-F (4.06-224.53 µg/g creatinine) was associated with diabetes exposure (OR = 1.85; 95% CI 1.04, 3.28) compared with women in the reference category (0.67-4.05 µg/g creatinine). BPA may be an environmental cofactor of diabetes. More studies are needed to confirm this result, especially in Hispanic populations.


Assuntos
Compostos Benzidrílicos/toxicidade , Diabetes Mellitus/induzido quimicamente , Exposição Ambiental/efeitos adversos , Fenóis/toxicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos Benzidrílicos/urina , Estudos de Casos e Controles , Creatinina/urina , Diabetes Mellitus/urina , Disruptores Endócrinos/toxicidade , Disruptores Endócrinos/urina , Feminino , Humanos , México , Pessoa de Meia-Idade , Fenóis/urina , Fatores de Risco
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