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1.
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
2.
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
3.
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
4.
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
5.
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
6.
Endocr J ; 66(7): 581-586, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31243183

RESUMO

Immune checkpoint inhibitors (ICIs) have become a promising treatment for advanced malignancies. However, these drugs can induce immune-related adverse events (irAEs) in several organs, including skin, gastrointestinal tract, liver, muscle, nerve, and endocrine organs. Endocrine irAEs comprise hypopituitarism, primary adrenal insufficiency, thyroid dysfunction, hypoparathyroidism, and type 1 diabetes mellitus. These conditions have the potential to lead to life-threatening consequences, such as adrenal crisis, thyroid storm, severe hypocalcemia, and diabetic ketoacidosis. It is therefore important that both endocrinologists and oncologists understand the clinical features of each endocrine irAE to manage them appropriately. This opinion paper provides the guidelines of the Japan Endocrine Society and in part the Japan Diabetes Society for the management of endocrine irAEs induced by ICIs.


Assuntos
Doenças do Sistema Endócrino/induzido quimicamente , Doenças do Sistema Endócrino/terapia , Doenças do Sistema Imunitário/induzido quimicamente , Doenças do Sistema Imunitário/terapia , Fatores Imunológicos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Doenças das Glândulas Suprarrenais/induzido quimicamente , Doenças das Glândulas Suprarrenais/terapia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/imunologia , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/imunologia , Diabetes Mellitus/terapia , Doenças do Sistema Endócrino/diagnóstico , Humanos , Doenças do Sistema Imunitário/diagnóstico , Fatores Imunológicos/uso terapêutico , Japão , Doenças das Paratireoides/induzido quimicamente , Doenças das Paratireoides/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Sociedades Médicas/organização & administração , Sociedades Médicas/normas , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/terapia
7.
Mol Cell Biol ; 39(17)2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31208980

RESUMO

The pancreatic-islet-enriched transcription factors MafA and MafB have unique expression patterns in ß cells in rodents. MafA is specifically expressed in ß cells and is a key regulatory factor for maintaining adult ß-cell function, whereas MafB plays an essential role in ß-cell development during embryogenesis, and its expression in ß cells gradually decreases and is restricted to α cells after birth in rodents. However, it was previously observed that MafB started to be reexpressed in insulin-positive (insulin+) ß cells in MafA-deficient adult mice. To elucidate how MafB functions in the adult ß cell under MafA-deficient conditions, we generated MafA and MafB double-knockout (A0B0) mice in which MafB was specifically deleted from ß cells. As a result, the A0B0 mice became more vulnerable to diabetes under a high-fat diet (HFD) treatment, with impaired islet formation and a decreased number of insulin+ ß cells because of increased ß-cell apoptosis, indicating MafB can take part in the maintenance of adult ß cells under certain pathological conditions.


Assuntos
Diabetes Mellitus/genética , Células Secretoras de Insulina/citologia , Fatores de Transcrição Maf Maior/genética , Fator de Transcrição MafB/genética , Animais , Apoptose , Células Cultivadas , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Desenvolvimento Embrionário , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Fator de Transcrição MafB/metabolismo , Camundongos , Camundongos Knockout
8.
J Pediatr Endocrinol Metab ; 32(5): 447-454, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31042641

RESUMO

Background Too much consumption of carbonated beverages increases the risk of diabetes. Insulin deficiency and the body's decreased sensitivity to insulin cause diabetes. C-peptide can assess a person's own insulin secretion. The decrease of C-peptide is closely related to the occurrence of diabetes and its chronic complications. The present study assessed the effect of carbonated beverages on C-peptide in adolescents and analyzed the correlation between C-peptide and the drinking index (DI). Methods The subjects investigated including 463 adolescents were divided into a carbonated beverages group, a non-carbonated beverages group and a control group. The general demographic characteristics, beverage consumption status, physical activity and family history of hypertension and diabetes were interviewed with a questionnaire designed by us. All the subjects maintained their original lifestyle and received the oral glucose tolerance test. Various biochemical indicators and C-peptides were detected in these three groups. The data were analyzed by statistical analysis, and multivariate logistic regression analysis was used to examine the risk factors related to C-peptide. Results Blood glucose, blood lipid, liver function and renal function had no statistically significant difference among the three groups. C-peptide levels were lower in the carbonated beverages group and the non-carbonated beverages group than in the control group. Compared to the non-carbonated beverages group, there was a significant decrease in C-peptide levels in the carbonated beverages group. Logistic analysis demonstrated that DI was negatively correlated with C-peptide levels when the physical activity was adjusted. The odds ratio (OR) (OR = 2.540, 95% confidence interval [CI] 1.121-5.752) value difference was statistically significant at a stratification level of DI ≥ 6. Conclusions The C-peptide of adolescents was affected by the long-term consumption of beverages, and the effect of carbonated beverages was even more obvious. DI ≥ 6 bottle-years was a risk factor for diabetes, and we can constitute prevention and control measures accordingly so as to reduce the incidence of diabetes.


Assuntos
Peptídeo C/sangue , Bebidas Gaseificadas/efeitos adversos , Diabetes Mellitus/induzido quimicamente , Adolescente , Adulto , Estudos de Casos e Controles , Diabetes Mellitus/sangue , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Fatores de Risco , Adulto Jovem
9.
Environ Sci Pollut Res Int ; 26(19): 19272-19281, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31069655

RESUMO

As cadmium levels are increasing in the environment, the adverse effects of cadmium exposure specifically associated with chronic diseases are receiving increasing attention. Several population-based studies have been conducted on the association between cadmium and diabetes mellitus (DM) but have reported controversial results. Here, we aimed to evaluate the association between cadmium exposure and DM. In this meta-analysis, a random effects model was used because there was evidence of heterogeneity among studies. A dose-response relationship was assessed through a restricted cubic spline model with three knots. The results showed a positive association between cadmium levels in the body and DM (OR = 1.27; 95% CI, 1.07-1.52). The cadmium levels in the body were defined on the basis of combined urinary and blood cadmium. Subgroup analysis further indicated a positive association between urinary cadmium levels and DM (OR = 1.31; 95% CI, 1.02-1.69). The dose-response analysis results showed a positive association between levels of urinary cadmium above 2.43 µg/g creatinine and DM, and the risk of DM increased by 16% for each l µg/g creatinine increase in urinary cadmium levels. The results from our meta-analysis indicate that cadmium levels in the body are positively associated with DM, and urinary cadmium levels above 2.43 µg/g creatinine are associated with an increased risk of DM.


Assuntos
Cádmio/urina , Diabetes Mellitus/epidemiologia , Exposição Ambiental/análise , Poluentes Ambientais/urina , Cádmio/toxicidade , Creatinina/urina , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/urina , Relação Dose-Resposta a Droga , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Feminino , Humanos , Masculino
11.
PLoS One ; 14(5): e0217096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091299

RESUMO

As in mammals, high-sucrose diets lead to obesity and insulin resistance in the model organism Drosophila melanogaster (called Drosophila hereafter). To explore the relative contributions of glucose and fructose, sucrose's component monosaccharides, we compared their effects on larval physiology. Both sugars exhibited similar effects to sucrose, leading to obesity and hyperglycemia. There were no striking differences resulting from larvae fed high glucose versus high fructose. Some small but statistically significant differences in weight and gene expression were observed that suggest Drosophila is a promising model system for understanding monosaccharide-specific effects on metabolic homeostasis.


Assuntos
Diabetes Mellitus/induzido quimicamente , Sacarose na Dieta/administração & dosagem , Drosophila melanogaster/efeitos dos fármacos , Frutose/toxicidade , Glucose/toxicidade , Hiperglicemia/induzido quimicamente , Obesidade/induzido quimicamente , Animais , Modelos Animais de Doenças , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Feminino , Perfilação da Expressão Gênica , Resistência à Insulina , Masculino , Edulcorantes/toxicidade , Triglicerídeos/metabolismo
12.
BMC Med Imaging ; 19(1): 38, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088378

RESUMO

BACKGROUND: Recent studies have highlighted the correlation between diabetes and pancreatic fat infiltration. Notably, pancreatic fat content (PFC) is a potential biomarker in diabetic patients, and magnetic resonance imaging (MRI) provides an effective method for noninvasive assessment of pancreatic fat infiltration. However, most reports of quantitative measurement of pancreatic fat have lacked comparisons of pathology results. The primary objective of this study was to determine the feasibility and accuracy of pancreatic MRI by using pancreatic fat fraction (PFF) measurements with the IDEAL-IQ sequence; the secondary objective was to explore changes in PFC between pigs with and without diabetes. METHODS: In this prospective study, 13 Bama Mini-pigs (7 females, 6 males; median age, 2 weeks) were randomly assigned to diabetes (n = 7) or control (n = 6) groups. Pigs in the diabetes group received high fat/high sugar feed, combined with streptozotocin injections. At the end of 15 months, biochemical changes were evaluated. All pigs underwent axial MRI with the IDEAL-IQ sequence to measure PFF; PFC of fresh pancreatic parenchyma was measured by the Soxhlet extraction method; and pancreatic fat distribution was observed by histopathology. Results of all analyses were compared between the diabetes and control groups by using the Mann-Whitney U-test. Correlations of PFF and PFC, fasting blood glucose (GLU), and serum insulin (INS) were calculated by using the Spearman correlation coefficient. Single-measure intraclass correlation coefficient (ICC) was used to assess interreader agreement. RESULTS: There were significant differences between diabetes and control groups: GLU (mmol/L) was 18.06 ± 6.03 and 5.06 ± 1.41 (P < 0.001); INS (mU/L) was 21.59 ± 2.93 and 29.32 ± 3.27 (P = 0.003); PFC (%) was 34.60 ± 3.52 and 28.63 ± 3.25 (P = 0.027); and PFF (%) was 36.51 ± 4.07 and 27.75 ± 3.73 (P = 0.003). There was a strongly positive correlation between PFF and PFC (r = 0.934, P < 0.001); there were moderate correlations between PFF and GLU (r = 0.736, P = 0.004; positive correlation), and between PFF and INS (r = - 0.747, P = 0.003; negative correlation). Excellent interreader agreement was observed for PFF measurements (ICC, 0.954). CONCLUSIONS: Pancreatic fat infiltration shows a clear association with diabetes. MRI with the IDEAL-IQ sequence can be used to accurately and reproducibly quantify PFC.


Assuntos
Tecido Adiposo/patologia , Diabetes Mellitus/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Pâncreas/diagnóstico por imagem , Tecido Adiposo/diagnóstico por imagem , Animais , Glicemia/análise , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/patologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pâncreas/patologia , Estudos Prospectivos , Prótons , Distribuição Aleatória , Estreptozocina , Suínos
13.
Korean J Radiol ; 20(5): 830-843, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30993934

RESUMO

OBJECTIVE: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model. MATERIALS AND METHODS: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were calculated. RESULTS: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels. CONCLUSION: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.


Assuntos
Lesão Renal Aguda/diagnóstico por imagem , Meios de Contraste/efeitos adversos , Diabetes Mellitus/patologia , Rim/diagnóstico por imagem , Imagem por Ressonância Magnética , Oxigênio/sangue , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/etiologia , Animais , Meios de Contraste/administração & dosagem , Meios de Contraste/química , Diabetes Mellitus/induzido quimicamente , Modelos Animais de Doenças , Hemodinâmica , Iodo/química , Rim/irrigação sanguínea , Rim/patologia , Masculino , Coelhos
14.
Endocr J ; 66(6): 571-574, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30944270

RESUMO

Some categories of drugs are known for causing hyperglycemia or diabetes such as steroids, antipsychotics, and immunosuppressant. However, there has been little evidence from studies about the proportion of each drug in the context of drug-induced diabetes. In this study, we used data from the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system database maintained at the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan, reported between April 2004 and June 2017. Among 459,250 reports of adverse drug reactions in JADER database, reported instances of the adverse event of hyperglycemia or diabetes were extracted. After the exclusion of anti-diabetes drugs, the drugs frequently implicated in the development of hyperglycemia or diabetes, including prednisolone, tacrolimus, everolimus, ribavirin, quetiapine, aripiprazole, interferon alfa-2b, risperidone, atorvastatin, dexamethasone, ciclosporin, nilotinib, methylprednisolone, or nivolumab, were identified. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, was manifested as the third most frequently associated drug with hyperglycemia or diabetes (340 cases), following prednisolone (694 cases) and tacrolimus (393 cases), and the reporting odds ratio (ROR 8.56, 95% CI 7.65-9.57) of this drug was higher than that of the two aforementioned drugs (ROR 3.96, 95% CI 3.66-4.28 and ROR 3.51, 95% CI 3.17-3.89). These results suggest that there is a potent association of evelolimus with hyperglycemia in clinical practice in Japan.


Assuntos
Diabetes Mellitus/induzido quimicamente , Everolimo/efeitos adversos , Hiperglicemia/induzido quimicamente , Imunossupressores/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos , Humanos , Japão
15.
Biomed Res Int ; 2019: 2870647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30868068

RESUMO

We assess long-term changes in lipid levels in human immunodeficiency disease- (HIV-) infected patients undergoing highly active antiretroviral treatment (HAART) and their association with diabetes mellitus (DM) and thyroid dysfunction. We observed changes in the levels of total cholesterol (TC) and total triglyceride (TG) of 63 HIV-infected patients in the 6 years from starting HAART and analyzed correlations between relevant parameters. TC levels of patients with normal baseline TC levels as well as those diagnosed with DM or impaired fasting glucose (IFG) increased significantly (P < 0.05) as did the TG levels of patients with normal baseline TG levels (P < 0.05). TC levels of patients with hypercholesterolemia in the year HAART was initiated were significantly higher than those of patients with normal baseline TC levels (P < 0.05) for all 6 years. TC levels of patients diagnosed with DM were significantly higher than those with euglycemia (P < 0.05) 2 and 4 years after HAART commencement. Levels of TC, high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) were correlated negatively with viral load, whereas levels of TC and very-low-density lipoprotein-cholesterol (VLDL-C) were correlated positively with CD4+ cell counts before HAART commencement. Linear mixed-effect model demonstrated disturbance of glucose metabolism and HAART containing nevirapine and CD4+ cell count were positively correlated with TC levels after HAART commencement. These findings suggest that there are changes in the lipid levels of patients undergoing HAART, with the potential risk of dyslipidemia.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Diabetes Mellitus/metabolismo , Dislipidemias/metabolismo , Infecções por HIV/tratamento farmacológico , Doenças da Glândula Tireoide/metabolismo , Contagem de Linfócito CD4 , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/virologia , Dislipidemias/induzido quimicamente , Dislipidemias/complicações , Dislipidemias/virologia , HIV/efeitos dos fármacos , HIV/genética , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Humanos , Lipídeos/sangue , Nevirapina/efeitos adversos , Doenças da Glândula Tireoide/induzido quimicamente , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/virologia , Triglicerídeos/sangue , Carga Viral/genética
16.
Biomed Pharmacother ; 114: 108802, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30921704

RESUMO

Endocrine disrupting chemicals (EDCs) have widespread environmental distribution originated from both natural and anthropogenic sources. From the last few decades, their contamination has been raised dramatically owing to continuous discharge in sewage and untreated industrial effluents. They have rapidly gained a considerable attention due to their critical role in the development of multiple endocrine-related disorders notably diabetes mellitus (DM). Cadmium and arsenic, among the most hazardous EDCs, are not only widely spread in our environment, but they are also found to be associated with wide range of health hazards. After entering into the human body, they are preferably accumulated in the liver, kidney and pancreas where they exhibit deleterious effects on carbohydrate metabolism pathways notably glycolysis, glucogenesis and gluconeogenesis through the modification and impairment of relevant key enzymes activity. Impairment of hepatic glucose homeostasis plays a crucial role in the pathogenesis of DM. Along with compromised function of pancreas and muscles, diminished liver and kidney functions also contribute considerably to increase the blood glucose level. These metals have potential to bring conformational changes in these enzymes and make them inactive. Additionally, these metals also disturb the hormonal balance, such as insulin, glucocorticoids and catecholamines; by damaging pancreas and adrenal gland, respectively. Moreover, these metals also enhance the production of reactive oxygen species and depress the anti-oxidative defense mechanism with subsequent disruption of multiple organs. In this article, we have briefly highlighted the impact of arsenic and cadmium on the metabolism of carbohydrates and the enzymes that are involved in carbohydrate metabolism and glucose homeostasis.


Assuntos
Arsênico/efeitos adversos , Cádmio/efeitos adversos , Metabolismo dos Carboidratos/efeitos dos fármacos , Disruptores Endócrinos/efeitos adversos , Animais , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/metabolismo , Poluentes Ambientais/efeitos adversos , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Humanos
17.
Infez Med ; 27(1): 103-105, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30882388

RESUMO

Glucose intolerance and diabetes are becoming increasingly common in HIV-infected patients in the cART era. Many factors are associated with the development of diabetes in HIV-infected individuals who receive cART, one of which is the assumption of specific antiretroviral classes or agents. We describe a case in a 72-year-old Caucasian man with long-term HIV infection. We observed the development of unbalanced diabetes treated with insulin and metformin which improved when we replaced zidovudine with rilpivirine. This switch improved diabetes to such an extent that insulin suspension was required. In several countries zidovudine has long been used due to its low cost, although several side effects have been observed, especially in the long term. In this case, the switch to rilpivirine was shown to be able to improve the toxicity of zidovudine on glucose metabolism, representing a good option to be used.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Diabetes Mellitus/induzido quimicamente , Substituição de Medicamentos , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/efeitos adversos , Rilpivirina/uso terapêutico , Zidovudina/efeitos adversos , Idoso , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Hemoglobina A Glicada/metabolismo , Humanos , Masculino
18.
Environ Res ; 172: 399-407, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30825691

RESUMO

Pyrethroid insecticides have been used widely as replacements for organophosphate insecticides over the past decades. While several animal studies suggest that exposure to pyrethroids can alter glucose homeostasis, there is only limited evidence of the association between environmental pyrethroid exposure and diabetes risk in human populations. Therefore, we examined the National Health and Nutrition Examination Survey (NHANES) 2007-2010 data to determine the association between environmental pyrethroid exposure and the prevalence of diabetes in the general U.S. population. Using data on 2796 participants aged 20-79 years from NHANES 2007-2010, we estimated odds ratios (ORs) and 95% confidence intervals (CI) of the association between diabetes and urinary metabolite concentration of pyrethroids using logistic regression. The weighted prevalence of diabetes was 10.3%. The weighted geometric means and detection rate of 3-phenoxybenzoic acid (3-PBA), the most common nonspecific pyrethroid metabolite, were 0.41 µg/L (95% CI: 0.38, 0.45) and 72.0%, respectively. After adjusting for sociodemographic, behavioral, and metabolic factors, we found a significant dose-response relationship between urinary 3-PBA as quartile and prevalent diabetes (p-trend=0.007). Compared to the lowest quartile of 3-PBA, the highest quartile had OR of 2.18 (95% CI: 1.18, 4.03) for diabetes. Our finding suggests pyrethroid insecticides as a potential risk factor for diabetes. Further studies should be conducted to confirm our finding and to determine if this association is causal.


Assuntos
Diabetes Mellitus , Exposição Ambiental , Piretrinas , Adulto , Idoso , Diabetes Mellitus/induzido quimicamente , Feminino , Humanos , Inseticidas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Piretrinas/efeitos adversos , Adulto Jovem
19.
Horm Metab Res ; 51(3): 145-156, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30861560

RESUMO

Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced malignancies. The incidence of endocrine adverse events provoked by these immune checkpoint inhibitors (ICI) is based on data from randomized controlled trials, which have their drawbacks. PubMed was searched through August 22nd, 2017, by 2 reviewers independently (J.d.F. and C.E.A.). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. The weighted incidence and risk ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency, and diabetes mellitus. Their management is discussed in a systematic review. A total of 101 studies involving 19 922 patients were included. Ipilimumab-treated patients experienced hypophysitis in 5.6% (95% CI, 3.9-8.1), which was higher than nivolumab (0.5%; 95% CI, 0.2-1.2) and pembrolizumab (1.1%; 95% CI, 0.5-2.6). PD-1/PD-L1 inhibitors had a higher incidence of thyroid dysfunction - particularly hypothyroidism (nivolumab, 8.0%; 95% CI, 6.4-9.8; pembrolizumab, 8.5%; 95% CI, 7.5-9.7; PD-L1, 5.5%; 95% CI, 4.4-6.8; ipilimumab, 3.8%; 95% CI, 2.6-5.5). Combination therapy was associated with a high incidence of hypothyroidism (10.2-16.4%), hyperthyroidism (9.4-10.4%), hypophysitis (8.8-10.5%), and primary adrenal insufficiency (5.2-7.6%). Diabetes mellitus and primary adrenal insufficiency were less frequent findings on monotherapy. Our meta-analysis shows a high incidence of endocrine adverse events provoked by single agent checkpoint blockade, further reinforced by combined treatment.


Assuntos
Doença de Addison/induzido quimicamente , Antineoplásicos Imunológicos/efeitos adversos , Diabetes Mellitus/induzido quimicamente , Hipofisite/induzido quimicamente , Neoplasias/tratamento farmacológico , Doenças da Glândula Tireoide/induzido quimicamente , Antineoplásicos Imunológicos/uso terapêutico , Humanos
20.
Med Sci Monit ; 25: 1102-1104, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30739121

RESUMO

Widespread usage of the calcineurin inhibitors tacrolimus and cyclosporine A as post-transplantation immunosuppressive agents is fraught with severe nephrotoxic and diabetogenic side effects. More recently, tapering of calcineurin inhibitor-based immunotherapies with concurrent administration of the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been employed within pharmacological regimens designed to achieve better safety and efficacy for preservation of allograft kidney function. Collected preclinical data and recent clinical study, however, indicate that usage of calcineurin inhibitors and/or mTOR blockers as immunosuppressive agents promotes equivalent diabetogenic side effects. Based on a wealth of validating preclinical studies, we contend that the favorable metabolic effects of mineralocorticoid receptor antagonists, such as spironolactone, support their inclusion in novel immunosuppressive strategies to inhibit new onset type II diabetic symptoms in post-transplantation patient populations.


Assuntos
Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona/uso terapêutico , Calcineurina/metabolismo , Inibidores de Calcineurina , Ciclosporina , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/induzido quimicamente , Everolimo , Rejeição de Enxerto/tratamento farmacológico , Humanos , Imunossupressores/metabolismo , Imunossupressores/farmacologia , Transplante de Rim , Sirolimo , Espironolactona/farmacologia , Tacrolimo , Tolerância ao Transplante/fisiologia
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