Fructosamine and glycated hemoglobin as biomarkers of glycemic control in people with type 2 diabetes mellitus and cancer (GlicoOnco study)

Introduction: Glycemic control is important to avoid diabetes complications in individuals with cancer. There is no evidence for HbA1c and fructosamine as reliable biomarkers in these conditions. There are particularities in caring for patients with diabetes and cancer that can alter these biomarkers. Objective: The aim of this study was to evaluate HbA1c and fructosamine as glycemic biomarkers in people with type 2 diabetes and cancer, undergoing clinical or surgical oncological treatment. Methods: The authors conducted a single-center, retrospective analysis with people who have cancer and diabetes. Comparison of glycemic biomarkers (HbA1c, fructosamine, and Self-Monitoring of Blood Glucose [SMBG]) was performed including evaluation in individuals undergoing chemotherapy, using glucocorticoids, with anemia, hypoproteinemia or with reduced estimated Glomerular Filtration Rate (eGFR). Results: There was a strong positive correlation between fructosamine and HbA1c (n = 318, r = 0.66, p < 0.001) in people with diabetes and cancer even in those under chemotherapy (n = 101, r = 0.61, p < 0.001) or using glucocorticoids (n = 96, r = 0.67, p<0.001). There was a strong correlation between HbA1c and fructosamine in subjects with anemia (n = 111, r = 0.66, p < 0.001), hypoproteinemia (n = 54, r = 0.67, p < 0.001), or with eGFR ≥ 60 mL/min/1.73 m2 (n = 189, r = 0.70, p < 0.001), and moderate correlation with hypoalbuminemia (n = 21, r = 0.54, p = 0.001) and with reduced eGFR (n = 67, r = 0.57, p < 0.001). The correlations between fructosamine and HbA1c with SMBG were moderate (n = 164, r = 0.49, p < 0.001; n = 111, r = 0.55, p < 0.001, respectively), strong in subjects undergoing chemotherapy, with hypoalbuminemia or hypoproteinemia, and at least moderate, if eGFR < 60 mL/min/1.73 m2 or with anemia. Conclusions: Fructosamine and HbA1c can be used as glycemic biomarkers in people with diabetes and cancer, even in those with anemia, hypoproteinemia, or undergoing chemotherapy

RETRACTED ARTICLE: Fatal factitious Cushing\ud syndrome (Münchhausen’s syndrome) in a patient with macroprolactinoma and silent\ud corticotrophinoma: case report and literature review

Abstract\ud Münchhausen’s syndrome (MS) is a chronic factitious disorder\ud characterized by the intentional production of clinical symptoms without external\ud incentive. One type of MS is factitious Cushing syndrome, an extremely rare clinical\ud situation in which the diagnosis is challenging mainly due to interference of the\ud exogenous medication in cortisol immunoassays. We described a 26-year-old woman who\ud was originally diagnosed with a macroprolactinoma and during follow-up developed\ud clinical and laboratorial hypercortisolism. A transsphenoidal surgery was performed\ud and immunohistochemistry revealed positive and diffuse staining for both hormones.\ud Four years later, her hypercortisolism recurred and the confirmation of factitious\ud Cushing syndrome was delayed due to conflicting laboratorial results.\ud There are few cases in the literature of factitious Cushing syndrome,\ud and only one had a fatal outcome. The diagnosis of this condition is complex and\ud includes cyclic Cushing syndrome in the differential diagnosis. These patients have\ud high morbidity and increased mortality risk and are likely to have other psychiatric\ud disorders. Prednisone was identified as the culprit in the majority of the\ud cases.We would like to thank Dr. Wagner Farid Gattaz and Dr. Jose Gallucci Neto,\ud from the Psychiatric Division, for providing assistance during hospitalization.\ud This work was partially supported by grants from Conselho Nacional de\ud Desenvolvimento Científico e Tecnológico – CNPq (301339/2008-9 to B.B.M.)

Reduced albumin modification by advanced glycation end products in diabetes mellitus restores cholesterol homeostasis in macrophages

Produtos de glicação avançada (AGEs) associam-se, independentemente, com o risco cardiovascular, e constituem uma das bases da memória metabólica, a qual fundamenta a manutenção do risco elevado de complicações do diabetes mellitus (DM) previamente descompensado, mesmo após a normalização da glicemia. Avaliou-se o efeito da redução da modificação da albumina por AGEs sobre o efluxo de colesterol, conteúdo intracelular de lípides, expressão de genes envolvidos no fluxo de lípides, taxa de decaimento e conteúdo do receptor ABCA-1 em macrófagos. Além disso, foi investigado o tempo de persistência do efeito da albumina modificada por AGEs na sensibilização de macrófagos à resposta inflamatória e no prejuízo da remoção de colesterol celular. Albumina foi isolada do soro de indivíduos com DM1 e DM2 antes e após melhora do controle glicêmico (pré- e pós-CG), por cromatografia rápida para separação de proteínas e extração alcoólica. Albumina bovina modificada in vitro por AGEs foi preparada pela incubação com glicolaldeído (albumina-GAD) e albumina controle, com tampão fosfato. Macrófagos derivados de células indiferenciadas da medula óssea de camundongos enriquecidos em 14C- colesterol foram incubados com albumina pré-CG e pós-CG e o efluxo de colesterol determinado após incubação com apoA-I ou HDL2. Coloração com Oil Red O foi utilizada para quantificação do conteúdo intracelular de lípides. A expressão gênica foi determinada em macrófagos J774 por RT-qPCR e a taxa de degração de ABCA-1, mediante tratamento destas células com ciclohexamida. O efluxo de colesterol (%; n = 3) foi maior nas células incubadas com albumina pós-CG (5,5 ± 0,6 e 11,1 ± 1,2; respectivamente para apo-AI e HDL2) em comparação com a albumina pré-CG (2,80 ± 0,7 e 4,4 ± 0,8; p < 0,05). O conteúdo de lípides (?m2 ) foi menor nas células tratadas com albumina pós-CG incubadas com apo-AI (0,6 ± 0,3) e HDL2 (1,2 ± 0,4) em comparação com a albumina pré-CG (2,8 ± 0,4 e 2,6 ± 0,03, respectivamente). A expressão de Abca1 foi semelhante entre os grupos, mas a de Nox4 e Jak2 foi, respectivamente, reduzida e aumentada pela albumina pós-CG em comparação com a albumina pré-CG. O conteúdo proteico de ABCA-1 foi 94% menor em macrófagos tratados com albumina pré-CG em comparação a pós-CG. Albumina isolada de indivíduos DM1 com controle glicêmico inadequado em comparação àquela de indivíduos controles, induziu maior taxa de decaimento (20%) do ABCA-1 em macrófagos. A albumina-GAD e a albumina isolada de DM pré-CG favoreceram maior secreção de TNF e IL-6 por macrófagos estimulados com lipopolissacarídeo e este efeito persistiu mesmo após 8 h da remoção do estímulo pela albumina modificada por AGEs. O mesmo foi observado para a redução do efluxo de colesterol, a qual persistiu após 9 h da retirada do insulto pela albumina modificada por AGEs. Em conclusão, a melhora do CG refletida pela redução da modificação de albumina por AGEs melhorou a expressão de genes que modulam a funcionalidade do ABCA-1, reduziu a taxa de degradação deste receptor e aumentou seu conteúdo em macrófagos, o que se vinculou à melhora do efluxo de colesterol e redução do acúmulo intracelular de lípides. Os efeitos da albumina modificada por AGEs são persistentes em macrófagos e condizem com alterações na homeostase de lípídes e estresse inflamatórios baseados em modelo de memória metabólica celular.Advanced glycation products (AGEs) are independently associated with cardiovascular risk and constitute one of the bases of metabolic memory, which supports the maintenance of high-risk complications in previously decompensated diabetes mellitus (DM), even after normalization of glycemia. It was evaluated the effect of the reduction in albumin modification by AGEs on the cholesterol efflux, intracellular lipid content, expression of genes involved in lipid flux, ABCA-1 content, and decay rate in macrophages. In addition, it was investigated the persistence time of AGE-albumin effect on macrophage sensitization to inflammation and damage in cholesterol efflux. Serum albumin was isolated from subjects with T1DM and T2DM before and after improvement of the glycemic control (GC) by fast protein liquid chromatography and alcoholic extraction. Bovine albumin was in vitro modified by AGEs by incubation with glycolaldehyde (GAD-albumin) and control albumin with phosphate buffer. Bone marrow-derived macrophages enriched with 14C-cholesterol were incubated with albumin isolated bGC and aGC and cholesterol efflux determined after incubation with apoA-I or HDL2. Staining with Oil Red O was used for the quantification of intracellular lipid content. Cholesterol efflux to apo-AI and HDL2 (%; n = 3) was higher in cells incubated with albumin isolated aGC (5.5 ± 0.6 and 11.1 ± 1.2, respectively) as compared to albumin isolated bGC (2.80 and 4.4 ± 0.8, respectively; p < 0.05). Lipid content (?m2 ) was lower in cells treated with albumin isolated aGC and incubated with apoA-I (0.6 ± 0.3) and HDL2 (1.2 ± 0.4) compared to albumin isolated bGC (2.8 ± 0.4 and 2.6 ± 0.03, respectively). The expression of Abca1 was similar between groups, but Nox4 and Jak2 were respectively reduced and increased by post-GC albumin compared to albumin in the bGC period. ABCA-1 protein levels were 94% lower in macrophages treated with albumin from bGC period as compared to albumin from aGC. Albumin from poorly controlled T1DM subjects induced a 20% increase in the ABCA-1 decay rate. As compared to non-modified control albumin and albumin isolated from control subjects, GAD-albumin and albumin isolated from subjects with DM bGC induced a higher secretion of tumor necrosis factor (TNF) and interleukin-6 (IL-6) by macrophages stimulated with lipopolysaccharides and this effect persisted even after 8 h of the removal of AGE-albumin from cells. The same was observed for the reduction in cholesterol efflux that persisted 9 h after the removal of AGE- albumin. In conclusion, the improvement in GC reflected by the reduction of albumin modification by AGEs, favored the expression. of genes that positively modulate ABCA-1 functionality, reduced ABCA-1 intracellular degradation, and increased the ABCA-1 protein level that was related to the improvement of cholesterol efflux and reduced intracellular lipid accumulation. The effects of AGE-albumin are persistent in macrophages favoring alteration in cellular lipid homeostasis and inflammatory stress according to a metabolic memory cell-based model

Knowledge of contraceptive methods in postpartum and its effective use after six months

Objetivo: Avaliar o conhecimento sobre métodos anticoncepcionais em mulheres no puerpério, bem como analisar a escolha e seu uso efetivo decorrido seis meses do parto. Método: Estudo prospectivo, transversal, realizado por entrevistas no puerpério precoce e após seis meses, com 107 mulheres internadas que aceitaram participar do estudo após a leitura do consentimento livre e esclarecido. Avaliaram-se os indicadores socioeconômicos, o conhecimento em anticoncepção, a orientação recebida, a oferta e uso de contraceptivos após seis meses do parto. Resultados: Os métodos anticoncepcionais mais conhecidos de forma espontânea foram a pílula (89%) e o condom masculino (65%). O DIU com hormônio foi o menos lembrado espontaneamente. Perto de 95% das puérperas referiram desejar evitar nova gravidez. Os métodos mais escolhidos foram a pílula (24%) e a ligadura tubária (18%). Ao se perguntar sobre o interesse em outros métodos contraceptivos após o questionário, 48% demonstraram interesse, sendo o mais citado o DIU (26%). Apenas um quarto das mulheres que disseram conhecer o DIU, faria a opção pelo método. Após seis meses, apenas 47 mulheres foram contatadas, e somente 31 delas haviam recebido orientação sobre anticoncepção (em média sobre três métodos diferentes). Houve apenas uma inserção de DIU de cobre, e três mulheres estavam grávidas naquele momento. Conclusões: O conhecimento da anticoncepção pelas mulheres no puerpério foi alto e melhorou após a estimulação. A avaliação dos resultados parece indicar que a simples leitura dos métodos anticoncepcionais disponíveis contribui para a escolha por métodos não relatados espontaneament

Persistent Effect of Advanced Glycated Albumin Driving Inflammation and Disturbances in Cholesterol Efflux in Macrophages

Advanced glycated albumin (AGE-albumin) impairs cholesterol efflux and contributes to inflammation in macrophages. The current study evaluated: (1) the persistence of the deleterious effect of AGE-albumin in cholesterol efflux and in inflammation, and (2) how metabolic control in diabetes mellitus (DM) contributes to attenuate the deleterious role of AGE-albumin in macrophage cholesterol homeostasis. Methods: AGE-albumin was produced in vitro or isolated from uncontrolled DM subjects’ serum before (bGC) and after improved glycemic control (aGC). Albumin samples were incubated with bone marrow-derived macrophages and 14C-cholesterol efflux or LPS- induced cytokine secretion were determined immediately, or after cell resting in culture media alone. The ABCA-1 degradation rate was determined after cell incubation with cycloheximide, and ABCA1 protein level by immunoblot. Oil Red O staining was used to assess intracellular lipid accumulation. Results: A persistent effect of AGE-albumin was observed in macrophages in terms of the secretion of inflammatory cytokines and reduced cholesterol efflux. HDL-mediated 14C-cholesterol efflux was at least two times higher in macrophages treated with aCG-albumin as compared to bGC-albumin, and intracellular lipid content was significantly reduced in aGC-albumin-treated cells. As compared to bGC-albumin, the ABCA-1 protein content in whole cell bulk was 94% higher in aCG-albumin. A 20% increased ABCA-1 decay rate was observed in macrophages treated with albumin from poorly controlled DM. AGE-albumin has a persistent deleterious effect on macrophage lipid homeostasis and inflammation. The reduction of AGEs in albumin ameliorates cholesterol efflux